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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-Q
(Mark One)
☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the quarterly period ended March 31, 2025
or
☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from to
Commission File Number: 0-22705
NEUROCRINE BIOSCIENCES, INC.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of
incorporation or organization)
6027 Edgewood Bend Court
San Diego, CA
(Address of principal executive office)
33-0525145
(IRS Employer
Identification No.)
92130
(Zip Code)
(858) 617-7600
(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
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Title of each class |
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Trading Symbol |
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Name of each exchange on which registered |
Common Stock, $0.001 par value |
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NBIX |
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Nasdaq Global Select Market |
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days: Yes ☒ No ☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act:
Large accelerated filer ☒ Accelerated filer ☐ Non-accelerated filer ☐ Smaller reporting company ☐ Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
The number of outstanding shares of the registrant’s common stock, par value $0.001 per share, was 98,965,820 as of April 30, 2025.
NEUROCRINE BIOSCIENCES, INC.
TABLE OF CONTENTS
Part I. Financial Information
Item 1. Financial Statements
NEUROCRINE BIOSCIENCES, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(unaudited)
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(in millions, except per share data) |
March 31, 2025 |
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December 31, 2024 |
Assets |
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Current assets: |
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Cash and cash equivalents |
$ |
194.1 |
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$ |
233.0 |
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Available-for-sale debt securities |
749.4 |
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843.1 |
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Accounts receivable |
516.0 |
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479.1 |
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Inventory |
59.1 |
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57.4 |
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Other current assets |
119.3 |
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112.1 |
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Total current assets |
1,637.9 |
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1,724.7 |
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Deferred tax assets |
499.4 |
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485.7 |
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Available-for-sale debt securities |
815.3 |
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739.5 |
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Right-of-use assets |
502.2 |
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509.4 |
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Equity investments |
94.2 |
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124.8 |
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Property and equipment, net |
87.0 |
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82.6 |
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Intangible assets, net |
36.4 |
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36.5 |
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Other noncurrent assets |
15.3 |
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15.5 |
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Total assets |
$ |
3,687.7 |
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$ |
3,718.7 |
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Liabilities and Stockholders' Equity |
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Current liabilities: |
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Accounts payable and accrued liabilities |
$ |
475.2 |
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$ |
461.6 |
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Other current liabilities |
47.7 |
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46.1 |
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Total current liabilities |
522.9 |
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507.7 |
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Noncurrent operating lease liabilities |
447.5 |
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455.1 |
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Other noncurrent liabilities |
181.6 |
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166.2 |
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Total liabilities |
1,152.0 |
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1,129.0 |
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Stockholders’ equity: |
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Preferred stock, $0.001 par value; 5.0 shares authorized; no shares issued and outstanding |
— |
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— |
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Common stock, $0.001 par value; 220.0 shares authorized; 99.0 and 99.4 shares issued and outstanding, respectively |
0.1 |
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0.1 |
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Additional paid-in capital |
2,531.9 |
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2,554.6 |
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Accumulated other comprehensive income |
9.0 |
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5.8 |
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(Accumulated deficit) Retained earnings |
(5.3) |
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29.2 |
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Total stockholders’ equity |
2,535.7 |
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2,589.7 |
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Total liabilities and stockholders’ equity |
$ |
3,687.7 |
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$ |
3,718.7 |
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See accompanying notes to the condensed consolidated financial statements.
NEUROCRINE BIOSCIENCES, INC.
CONDENSED CONSOLIDATED STATEMENTS OF INCOME
AND COMPREHENSIVE INCOME
(unaudited)
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Three Months Ended March 31, |
(in millions, except per share data) |
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2025 |
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2024 |
Revenues: |
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Net product sales |
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$ |
563.7 |
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$ |
509.0 |
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Collaboration revenues |
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8.9 |
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6.3 |
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Total revenues |
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572.6 |
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515.3 |
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Operating expenses: |
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Cost of revenues |
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9.2 |
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7.5 |
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Research and development |
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263.2 |
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159.4 |
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Acquired in-process research and development |
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0.1 |
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6.0 |
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Selling, general, and administrative |
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276.5 |
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243.1 |
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Total operating expenses |
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549.0 |
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416.0 |
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Operating income |
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23.6 |
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99.3 |
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Other (expense) income: |
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Unrealized (loss) gain on equity investments |
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(30.6) |
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1.6 |
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Charges associated with convertible senior notes |
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— |
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(88.7) |
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Investment income and other, net |
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21.7 |
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22.3 |
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Total other expense, net |
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(8.9) |
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(64.8) |
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Income before provision for income taxes |
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14.7 |
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34.5 |
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Provision for (Benefit from) income taxes |
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6.8 |
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(8.9) |
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Net income |
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$ |
7.9 |
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$ |
43.4 |
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Foreign currency translation adjustments, net of tax |
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1.5 |
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(0.5) |
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Unrealized gain (loss) on available-for-sale debt securities, net of tax |
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1.7 |
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(3.2) |
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Comprehensive income |
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$ |
11.1 |
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$ |
39.7 |
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Earnings per share: |
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Basic |
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$ |
0.08 |
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$ |
0.43 |
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Diluted |
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$ |
0.08 |
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$ |
0.42 |
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Weighted-average shares outstanding: |
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Basic |
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99.7 |
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99.8 |
Diluted |
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102.5 |
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103.6 |
See accompanying notes to the condensed consolidated financial statements.
NEUROCRINE BIOSCIENCES, INC.
CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY
(unaudited)
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Accumulated Other Comprehensive Income (Loss) |
|
Retained Earnings (Accumulated Deficit) |
|
|
|
Common Stock |
|
Additional Paid-In Capital |
|
|
|
|
(in millions) |
Shares |
|
$ |
|
|
|
|
Total |
Balance at December 31,2024 |
99.4 |
|
|
$ |
0.1 |
|
|
$ |
2,554.6 |
|
|
$ |
5.8 |
|
|
$ |
29.2 |
|
|
$ |
2,589.7 |
|
Net income |
— |
|
|
— |
|
|
— |
|
|
— |
|
|
7.9 |
|
|
7.9 |
|
Other comprehensive income, net of tax |
— |
|
|
— |
|
|
— |
|
|
3.2 |
|
|
— |
|
|
3.2 |
|
Stock-based compensation expense |
— |
|
|
— |
|
|
52.8 |
|
|
— |
|
|
— |
|
|
52.8 |
|
Issuances of common stock under stock plans |
1.2 |
|
|
— |
|
|
32.1 |
|
|
— |
|
|
— |
|
|
32.1 |
|
Repurchases of common stock |
(1.6) |
|
|
— |
|
|
(107.6) |
|
|
— |
|
|
(42.4) |
|
|
(150.0) |
|
Balance at March 31, 2025 |
99.0 |
|
|
$ |
0.1 |
|
|
$ |
2,531.9 |
|
|
$ |
9.0 |
|
|
$ |
(5.3) |
|
|
$ |
2,535.7 |
|
|
|
|
|
|
|
|
|
|
|
|
|
Balance at December 31,2023 |
98.7 |
|
|
$ |
0.1 |
|
|
$ |
2,382.0 |
|
|
$ |
7.0 |
|
|
$ |
(157.1) |
|
|
$ |
2,232.0 |
|
Net income |
— |
|
|
— |
|
|
— |
|
|
— |
|
|
43.4 |
|
|
43.4 |
|
Other comprehensive loss, net of tax |
— |
|
|
— |
|
|
— |
|
|
(3.7) |
|
|
— |
|
|
(3.7) |
|
Stock-based compensation expense |
— |
|
|
— |
|
|
44.5 |
|
|
— |
|
|
— |
|
|
44.5 |
|
Issuances of common stock under stock plans |
1.9 |
|
|
— |
|
|
69.9 |
|
|
— |
|
|
— |
|
|
69.9 |
|
|
|
|
|
|
|
|
|
|
|
|
|
Balance at March 31, 2024 |
100.6 |
|
|
$ |
0.1 |
|
|
$ |
2,496.4 |
|
|
$ |
3.3 |
|
|
$ |
(113.7) |
|
|
$ |
2,386.1 |
|
|
|
|
|
|
|
|
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|
|
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|
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|
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|
|
|
|
See accompanying notes to the condensed consolidated financial statements.
NEUROCRINE BIOSCIENCES, INC.
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended March 31, |
(in millions) |
2025 |
|
2024 |
Cash flows from operating activities: |
|
|
|
Net income |
$ |
7.9 |
|
|
$ |
43.4 |
|
Adjustments to reconcile net income to net cash from operating activities: |
|
|
|
Stock-based compensation expense |
52.8 |
|
|
44.5 |
|
Charges associated with convertible senior notes |
— |
|
|
88.7 |
|
Depreciation |
6.6 |
|
|
5.3 |
|
Accretion of discount on available-for-sale debt securities, net |
(4.6) |
|
|
(7.1) |
|
Amortization of intangible assets |
1.0 |
|
|
0.9 |
|
Changes in fair values of equity investments |
30.6 |
|
|
(1.6) |
|
Deferred income taxes |
(13.7) |
|
|
(15.6) |
|
Other |
7.9 |
|
|
3.4 |
|
Change in operating assets and liabilities: |
|
|
|
Accounts receivable |
(36.9) |
|
|
(11.3) |
|
Inventory |
(1.7) |
|
|
1.1 |
|
Accounts payable and accrued liabilities |
12.4 |
|
|
(18.6) |
|
Other assets and liabilities, net |
2.5 |
|
|
(2.8) |
|
Cash flows from operating activities |
64.8 |
|
|
130.3 |
|
|
|
|
|
Cash flows from investing activities: |
|
|
|
Purchases of available-for-sale debt securities |
(273.2) |
|
|
(320.1) |
|
Sales and maturities of available-for-sale debt securities |
298.1 |
|
|
276.3 |
|
|
|
|
|
Capital expenditures |
(10.7) |
|
|
(11.2) |
|
Cash flows from investing activities |
14.2 |
|
|
(55.0) |
|
|
|
|
|
Cash flows from financing activities: |
|
|
|
Issuances of common stock under benefit plans |
32.1 |
|
|
69.9 |
|
Repurchases of common stock |
(150.0) |
|
|
— |
|
|
|
|
|
Cash flows from financing activities |
(117.9) |
|
|
69.9 |
|
|
|
|
|
Change in cash, cash equivalents and restricted cash |
(38.9) |
|
|
145.2 |
|
Cash, cash equivalents and restricted cash at beginning of period |
241.0 |
|
|
259.1 |
|
Cash, cash equivalents and restricted cash at end of period |
$ |
202.1 |
|
|
$ |
404.3 |
|
|
|
|
|
Supplemental disclosures: |
|
|
|
Accrued capital expenditures |
$ |
2.7 |
|
|
$ |
1.1 |
|
|
|
|
|
|
|
|
|
Cash paid for income taxes |
$ |
0.6 |
|
|
$ |
0.2 |
|
See accompanying notes to the condensed consolidated financial statements.
NEUROCRINE BIOSCIENCES, INC.
NOTES TO THE CONDENSED CONSOLIDATED FINANCIAL STATEMENTS
(unaudited)
1. Organization and Significant Accounting Policies
Basis of Presentation
The accompanying unaudited condensed consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States (GAAP) for interim financial information and with the instructions of the Securities and Exchange Commission (SEC) on Form 10-Q and Rule 10-01 of Regulation S-X. Accordingly, they do not include all of the information and disclosures required by GAAP for complete financial statements. In the opinion of management, the condensed consolidated financial statements include all adjustments necessary, which are of a normal and recurring nature, for the fair presentation of our financial position and of the results of operations and cash flows for the periods presented. The accompanying unaudited condensed consolidated financial statements include the accounts of Neurocrine Biosciences and our wholly owned subsidiaries. All significant intercompany balances and transactions have been eliminated in consolidation.
These financial statements should be read in conjunction with the audited consolidated financial statements and notes thereto for the year ended December 31, 2024, included in our Annual Report on Form 10-K (the 2024 Form 10-K) filed with the SEC. The results of operations for the interim period shown in this report are not necessarily indicative of the results that may be expected for any other interim period or the full year. The condensed consolidated balance sheet as of December 31, 2024, has been derived from the audited financial statements as of that date, but does not include all of the information and footnotes required by GAAP for complete financial statements.
There were no significant changes to our significant accounting policies as disclosed in the 2024 Form 10-K.
Recently Adopted Accounting Pronouncements
In November 2023, the Financial Accounting Standards Board (FASB) issued Accounting Standards Update (ASU) 2023-07, Segment Reporting (Topic 280): Improvements to Reportable Segment Disclosures, which requires public entities to disclose information about their reportable segments’ significant expenses and other segment items on an interim and annual basis. Public entities with a single reportable segment are required to apply the disclosure requirements in ASU 2023-07, as well as all existing segment disclosures and reconciliation requirements in ASC 280 on an interim and annual basis. We adopted ASU 2023-07 for annual reporting periods beginning January 1, 2024 and interim reporting periods beginning January 1, 2025. The adoption of ASU 2023-07 had no significant impact on our financial statement disclosures.
Recently Issued Accounting Pronouncements Not Yet Adopted
In December 2023, the FASB issued ASU 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures, which requires public entities, on an annual basis, to provide disclosure of specific categories in the rate reconciliation, as well as disclosure of income taxes paid disaggregated by jurisdiction. ASU 2023-09 is effective for annual reporting periods beginning after December 15, 2024, with early adoption permitted. We are currently evaluating the impact that adoption of ASU 2023-09 will have on our financial statement disclosures.
In November 2024, the FASB issued ASU 2024-03, Income Statement–Reporting Comprehensive Income–Expense Disaggregation Disclosures (Subtopic 220-40): Disaggregation of Income Statement Expenses, which requires public entities to disclose specified information about certain costs and expenses on an interim and annual basis. ASU 2024-03 is effective for annual reporting periods beginning after December 15, 2026, and interim reporting periods beginning after December 15, 2027, with early adoption permitted. We are currently evaluating the impact that adoption of ASU 2024-03 will have on our financial statement disclosures.
2. Collaboration and License Agreements
Nxera Pharma UK Limited (Nxera)
In 2021, we entered into a collaboration and license agreement with Nxera (formerly Sosei Heptares) to develop and commercialize certain compounds containing sub-type selective muscarinic M1, M4, or dual M1/M4 receptor agonists, which we have the exclusive rights to develop, manufacture and commercialize worldwide, excluding in Japan, where Nxera retains the rights to develop, manufacture, and commercialize all compounds comprised of M1 receptor agonists, subject to certain exceptions. With respect to such rights retained by Nxera, we retain the rights to opt in to profit sharing arrangements, pursuant to which we and Nxera will equally share in the operating profits and losses for such compounds in Japan. Subject to specified conditions, we may elect to exercise such opt-in rights with respect to each such compound either before initiation of the first proof of concept Phase 2 clinical trial for such compound or following our receipt from Nxera of the top-line data from such clinical trial for such compound. We are responsible for all development, manufacturing, and commercialization costs of any collaboration product.
Under the terms of the agreement, Nxera may be entitled to receive potential future payments of up to $2.5 billion upon the achievement of certain event-based milestones and is entitled to receive royalties on the future net sales of any collaboration product.
Unless earlier terminated, the agreement will continue on a licensed product-by-licensed product and country-by-country basis until the date on which the royalty term for such licensed product has expired in such country. On a licensed product-by-licensed product and country-by-country basis, royalty payments would commence on the first commercial sale of a licensed product and terminate on the later of (i) the expiration of the last patent covering such licensed product in such country, (ii) a number of years from the first commercial sale of such licensed product in such country and (iii) the expiration of regulatory exclusivity for such licensed product in such country.
We may terminate the agreement in its entirety or with respect to one or more targets upon 180 days’ written notice to Nxera during the research collaboration term and upon 90 days’ written notice to Nxera following the expiration of the research collaboration term. Following the expiration of the research collaboration term, Nxera may terminate the agreement on a target-by-target basis in the event that we do not conduct any material development activities outside of Japan with respect to a certain compound or licensed product within the applicable target class for a continuous period of not less than 365 days and do not commence any such activities within 120 days of receiving written notice. Either party may terminate the agreement, subject to specified conditions, (i) in the event of material breach by the other party, subject to a cure period, (ii) if the other party challenges the validity or enforceability of certain intellectual property rights, subject to a cure period, or (iii) if the other party becomes insolvent or takes certain actions related to insolvency.
Takeda Pharmaceutical Company Limited (Takeda)
In 2020, we entered into an exclusive license agreement with Takeda (the 2020 Takeda Agreement), pursuant to which we acquired the exclusive rights to develop and commercialize certain early to mid-stage psychiatry compounds, including luvadaxistat, NBI-1070770, osavampator (formerly NBI-1065845), NBI-1065846, and three non-clinical stage compounds. Pursuant to the 2020 Takeda Agreement, osavampator was designated as a profit-share product, meaning we and Takeda would equally share in the operating profits and losses. Takeda also retained the right to opt-out of the profit-sharing arrangement, pursuant to which Takeda would be entitled to receive potential future payments upon the achievement of certain event-based milestones with respect to osavampator and receive royalties on the future net sales of osavampator (in lieu of equally sharing in the operating profits and losses).
In October 2024, we provided Takeda with written notice of termination of the license under the 2020 Takeda Agreement to develop and commercialize luvadaxistat and NBI-1065846, which became effective in April 2025. In January 2025, we and Takeda amended and restated the exclusive license agreement (the Restated Takeda Agreement) to, among other things, reflect the conversion from sharing operating profits and losses with respect to the development and commercialization of osavampator to a royalty-bearing license, the return of rights to osavampator in Japan to Takeda, and our previous termination of DAAO inhibitors under the 2020 Takeda Agreement, including luvadaxistat, and GPR139 agonists, including NBI-1065846.
Under the Restated Takeda Agreement, we will retain exclusive rights to develop and commercialize osavampator for all indications in all territories worldwide except Japan, where Takeda will reacquire exclusive development and commercialization rights. In addition, each party is responsible for development costs for osavampator in its respective territory, and each party is eligible to receive royalty payments based on the other party’s net sales of osavampator in the other party’s territory. Pursuant to the Restated Takeda Agreement and upon the successful development and commercialization of osavampator, we will incur tiered based royalties payable to Takeda in the mid-to-upper teens in the U.S. and low double-digits outside of the U.S. on a blended basis as a percentage of net sales. Additionally, we are entitled to receive royalties from Takeda on the future net sales of osavampator in Japan.
In connection with the initiation of a Phase 3 clinical study for osavampator in major depressive disorder, we expensed a milestone of $37.5 million payable to Takeda as research and development (R&D) in the first quarter of 2025. The milestone was paid in the second quarter of 2025.
Takeda may be entitled to receive potential future payments of up to $0.7 billion upon the achievement of certain event-based milestones and is entitled to receive royalties on the future net sales of any royalty-bearing product.
Unless earlier terminated, the Restated Takeda Agreement will continue on a licensed product-by-licensed product and country-by-country basis until the date on which, (i) for any royalty-bearing product, the royalty term has expired in such country; and (ii) for any profit-share product, for so long as we continue to develop, manufacture, or commercialize such licensed product. On a licensed product-by-licensed product and country-by-country basis, royalty payments would commence on the first commercial sale of a royalty-bearing product and terminate on the later of (i) the expiration of the last patent covering such royalty-bearing product in such country, (ii) a number of years from the first commercial sale of such royalty-bearing product in such country and (iii) the expiration of regulatory exclusivity for such royalty-bearing product in such country.
We may terminate the Restated Takeda Agreement in its entirety or in one or more (but not all) of the U.S., Japan, the European Union and the United Kingdom, or, collectively, the major markets, upon six months’ written notice to Takeda (i) with respect to all licensed products prior to the first commercial sale of the first licensed product for which first commercial sale occurs, or (ii) with respect to all licensed products in one or more given target classes, as defined in the Restated Takeda Agreement, prior to the first commercial sale of the first licensed product in such target class for which first commercial sale occurs. We may terminate the Restated Takeda Agreement in its entirety or in one or more (but not all) of the major markets upon 12 months’ written notice to Takeda (i) with respect to all licensed products following the first commercial sale of the first licensed product for which first commercial sale occurs, or (ii) with respect to all licensed products in one or more given target classes following the first commercial sale of the first licensed product in such target class for which first commercial sale occurs. Takeda may terminate the Restated Takeda Agreement, subject to specified conditions, (i) if we challenge the validity or enforceability of certain Takeda intellectual property rights or (ii) on a target class-by-target class basis, in the event that we do not conduct any material development or commercialization activities with respect to any licensed product within such target class for a specified continuous period. Subject to a cure period, either party may terminate the Restated Takeda Agreement in the event of any material breach, solely with respect to the target class of a licensed product to which such material breach relates, or in its entirety in the event of any material breach that relates to all licensed products, or if either party challenges the validity or enforceability of certain intellectual property rights.
Xenon Pharmaceuticals Inc. (Xenon)
In 2019, we entered into a collaboration and license agreement with Xenon to identify, research and develop sodium channel inhibitors, including NBI-921352 and three preclinical candidates, which compounds we have the exclusive rights to develop and commercialize. In connection with the agreement, we purchased 1.4 million shares (at $14.196 per share) of Xenon common stock in 2019, 0.3 million shares (at $19.9755 per share) of Xenon common stock in 2021, and 0.3 million shares (at $31.855 per share) of Xenon common stock in 2022. We are responsible for all development and manufacturing costs of any collaboration product, subject to certain exceptions.
In connection with the initiation of a Phase 1 clinical study for NBI-921355, an investigational, selective inhibitor of voltage-gated sodium channels Nav1.2 and Nav1.6, as a potential treatment of certain types of epilepsy, we expensed a milestone of $7.5 million payable to Xenon as R&D in the first quarter of 2025. The milestone was paid in the second quarter of 2025.
Under the terms of the agreement, Xenon may be entitled to receive potential future payments of up to $1.7 billion upon the achievement of certain event-based milestones and is entitled to receive royalties on the future net sales of any collaboration product. Xenon retains the right to elect to co-develop one product in a major indication, pursuant to which Xenon would receive a mid-single digit percentage increase in royalties earned on the future net sales of such product in the United States and we and Xenon would equally share in the development costs of such product in the applicable indication, except where such development costs relate solely to the regulatory approval of such product outside the United States.
Unless earlier terminated, the agreement will continue on a licensed product-by-licensed product and country-by-country basis until the expiration of the royalty term for such product in such country. Upon the expiration of the royalty term for a particular licensed product and country, the license obtained by us with respect to such product and country will become fully paid, royalty free, perpetual and irrevocable. We may terminate the agreement upon 90 days’ written notice to Xenon, provided that such unilateral termination will not be effective for certain products until we have used commercially reasonable efforts to complete certain specified clinical studies. Either party may terminate the agreement in the event of a material breach in whole or in part, subject to specified conditions.
Voyager Therapeutics, Inc. (Voyager)
2019 Voyager Agreement
In 2019, we entered into a collaboration and license agreement with Voyager (the 2019 Voyager Agreement), pursuant to which we retain certain rights to develop and commercialize the Friedreich’s ataxia (FA) program and two undisclosed programs. We are responsible for all development and commercialization costs of any collaboration product under the 2019 Voyager Agreement, subject to certain co-development and co-commercialization rights retained by Voyager.
In connection with the 2019 Voyager Agreement, we purchased 4.2 million shares (at $11.9625 per share) of Voyager common stock (the 2019 Voyager Shares), which are subject to certain transfer, beneficial ownership, and voting restrictions for a period of up to three years from the effective date of the 2023 Voyager Agreement (defined below).
In connection with the selection of a development candidate under the FA program pursuant to our collaboration with Voyager, we expensed a milestone of $5.0 million as R&D in the first quarter of 2024.
Under the terms of the 2019 Voyager Agreement, Voyager may be entitled to receive potential future payments of up to $1.3 billion upon the achievement of certain event-based milestones and is entitled to receive royalties on the future net sales of any collaboration product, subject to certain co-development and co-commercialization rights retained by Voyager.
Unless terminated earlier, the 2019 Voyager Agreement will continue in effect until the expiration of the last to expire royalty term with respect to any collaboration product under the agreement or the last expiration or termination of any exercised co-development and co-commercialization rights by Voyager as provided for in the 2019 Voyager Agreement. We may terminate the 2019 Voyager Agreement upon 180 days’ written notice to Voyager prior to the first commercial sale of any collaboration product under the 2019 Voyager Agreement or upon one year after the date of notice if such notice is provided after the first commercial sale of any collaboration product under the 2019 Voyager Agreement.
2023 Voyager Agreement
In 2023, we entered into a collaboration and license agreement with Voyager, which we amended in April 2024 (as amended, the 2023 Voyager Agreement), pursuant to which we acquired the global rights to the gene therapy products directed to the gene that encodes glucosylceramidase beta 1 (GBA1) for the treatment of Parkinson's disease and other diseases associated with GBA1 (the GBA1 Program), and three gene therapy programs directed to rare central nervous system (CNS) targets, each enabled by Voyager's next-generation TRACERTM capsids. With respect to collaboration products subject to the GBA1 Program, we are responsible for all development and commercialization costs of any such products, including in the U.S., where Voyager retains certain co-development and co-commercialization rights. Voyager may elect to exercise such rights, pursuant to which we and Voyager would equally share in the operating profits and losses of such products in the U.S. (in lieu of Voyager being entitled to receive potential future payments of certain event-based milestones upon their achievement in the U.S. and receive royalties on the future net sales of such products in the U.S.), following Voyager’s receipt of the top-line data from a first clinical trial Parkinson’s disease. However, if we and Voyager elect to focus on an indication other than Parkinson’s disease prior to Voyager’s receipt of top-line data from a first clinical trial for Parkinson’s disease, then Voyager may elect to exercise such co-development and co-commercialization rights after the later of: (i) Voyager’s receipt of top-line data from the first clinical trial of a product that is the subject of the GBA1 Program or (ii) the date we and Voyager decide not to pursue Parkinson’s disease as an indication for development under the GBA1 Program. Irrespective of Voyager’s election to exercise such rights, Voyager may be entitled to receive potential future payments upon the achievement of certain event-based milestones outside the U.S. and would be entitled to receive royalties on the future net sales of any such product outside the U.S. With respect to collaboration products subject to the three gene therapy programs directed to rare CNS targets, we are responsible for all development and commercialization costs for any such products. In addition, as part of the collaboration, Jude Onyia, Ph.D., Chief Scientific Officer of Neurocrine Biosciences, was appointed to Voyager's board of directors. Dr. Onyia (or another individual designated by us) will be nominated for election to Voyager's board of directors annually for a maximum duration of 10 years from the effective date of the 2023 Voyager Agreement.
In connection with the 2023 Voyager Agreement, we purchased 4.4 million shares (at $8.88 per share) of Voyager common stock (the 2023 Voyager Shares), which are subject to certain transfer, beneficial ownership, and voting restrictions for a period of up to three years from the effective date of the 2023 Voyager Agreement. Our equity investment in Voyager became subject to the equity method of accounting, and Voyager became a related party, following our purchase of the 2023 Voyager Shares, after which, together with the 2019 Voyager Shares, we owned approximately 19.9% of the voting stock of Voyager. We elected the fair value option to account for our equity investment in Voyager as we believe it creates greater transparency regarding the investment's fair value at future reporting dates.
Under the terms of the 2023 Voyager Agreement, Voyager may be entitled to receive potential future payments of up to $6.1 billion upon the achievement of certain event-based milestones and is entitled to receive royalties on the future net sales of any collaboration product, subject to certain co-development and co-commercialization rights retained by Voyager.
Unless terminated earlier, the 2023 Voyager Agreement will continue in effect until the expiration of the last to expire royalty term with respect to any collaboration product under the 2023 Voyager Agreement or the last expiration or termination of any exercised co-development and co-commercialization rights by Voyager as provided for in the 2023 Voyager Agreement. We may terminate the 2023 Voyager Agreement upon 180 days’ written notice to Voyager prior to the first commercial sale of any collaboration product under the 2023 Voyager Agreement or upon one year after the date of notice if such notice is provided after the first commercial sale of any collaboration product under the 2023 Voyager Agreement.
Sanofi S.A. (Sanofi)
In 2014, we entered into a license agreement with Sanofi, pursuant to which we acquired the global rights to develop and commercialize certain corticotropin-releasing factor type 1 receptor (CRF1) antagonists, including crinecerfont. We launched CRENESSITYTM (crinecerfont) in the U.S. as a first-in-class U.S. Food and Drug Administration (FDA)-approved treatment of classic congenital adrenal hyperplasia (CAH) in December 2024. We are responsible for all manufacturing, development, and commercialization costs of any licensed product.
Under the terms of our license agreement with Sanofi, Sanofi may be entitled to receive potential future payments of up to $10.0 million upon the achievement of certain event-based milestones and is entitled to receive royalties at tiered percentage rates ranging from 3.0% to 5.0% on our future net sales of CRENESSITY in the U.S. for the longer of 16 years or the life of the related patent rights.
Mitsubishi Tanabe Pharma Corporation (MTPC)
In 2015, we out-licensed the rights to valbenazine in Japan and other select Asian markets to MTPC. In 2020, we entered into a commercial supply agreement with MTPC, pursuant to which we supply MTPC with valbenazine drug product for commercial use in such markets. MTPC launched DYSVAL® (valbenazine) in Japan for the treatment of tardive dyskinesia in June 2022 and subsequently in other select Asian markets, where it is marketed as REMLEAS® (valbenazine). MTPC is responsible for all development, manufacturing, and commercialization costs of valbenazine in such markets.
Under the terms of our license agreement with MTPC, we may be entitled to receive potential future payments of up to $30.0 million upon the achievement of certain sales-based milestones and are entitled to receive royalties at tiered percentage rates on future MTPC net sales of valbenazine for the longer of 10 years or the life of the related patent rights. MTPC may terminate the agreement upon 180 days’ written notice to us. In such event, all out-licensed product rights would revert to us.
AbbVie Inc. (AbbVie)
In 2010, we out-licensed the global rights to elagolix to AbbVie. AbbVie launched ORILISSA® (elagolix tablets) in the U.S. for the treatment of moderate to severe pain associated with endometriosis in August 2018 and ORIAHNN® (elagolix, estradiol and norethindrone acetate capsules and elagolix capsules) in the U.S. for the treatment of heavy menstrual bleeding due to uterine fibroids in June 2020. AbbVie is responsible for all development and commercialization costs of elagolix.
Under the terms of our license agreement with AbbVie, we may be entitled to receive potential future payments of up to $366.0 million upon the achievement of certain event-based milestones and are entitled to receive royalties at tiered percentage rates on future AbbVie net sales of elagolix for the longer of 10 years or the life of the related patent rights. We recognized royalty revenue of $6.7 million and $3.0 million, respectively, on AbbVie net sales of elagolix for the first quarter of 2025 and 2024. AbbVie may terminate the agreement upon 180 days’ written notice to us. In such event, all out-licensed product rights would revert to us.
3. Fair Value Measurements
The fair value hierarchy consists of the following three levels:
Level 1 – Quoted prices (unadjusted) in active markets for identical assets or liabilities.
Level 2 – Quoted prices for similar assets or liabilities in active markets, quoted prices for identical or similar assets or liabilities in markets that are not active or inputs that are observable, either directly or indirectly, for substantially the full term of the asset or liability.
Level 3 – Unobservable inputs that reflect our own assumptions about the assumptions that market participants would use in pricing the asset or liability when there is little, if any, market activity for the asset or liability at the measurement date.
The following table presents a summary of certain financial assets, which were measured at fair value on a recurring basis.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
March 31, 2025 |
|
December 31, 2024 |
|
Fair Value |
|
Leveling |
|
Fair Value |
|
Leveling |
(in millions) |
|
Level 1 |
|
Level 2 |
|
|
Level 1 |
|
Level 2 |
Cash and cash equivalents |
$ |
194.1 |
|
|
$ |
194.1 |
|
|
$ |
— |
|
|
$ |
233.0 |
|
|
$ |
233.0 |
|
|
$ |
— |
|
Available-for-sale debt securities |
1,564.7 |
|
|
— |
|
|
1,564.7 |
|
|
1,582.6 |
|
|
— |
|
|
1,582.6 |
|
Equity investments |
94.2 |
|
|
94.2 |
|
|
— |
|
|
124.8 |
|
|
124.8 |
|
|
— |
|
|
$ |
1,853.0 |
|
|
$ |
288.3 |
|
|
$ |
1,564.7 |
|
|
$ |
1,940.4 |
|
|
$ |
357.8 |
|
|
$ |
1,582.6 |
|
Concentration of Credit Risk
Financial instruments that potentially subject us to concentrations of credit risk include cash and cash equivalents, investments in available-for-sale debt securities, and accounts receivable.
To minimize the risks related to cash and cash equivalents and investments in available-for-sale debt securities, we have established guidelines related to credit ratings and maturities intended to safeguard principal balances and maintain liquidity. Our investment portfolio is maintained in accordance with our investment policy, which defines allowable investments, specifies credit quality standards, and limits the credit exposure of any single issuer.
As of March 31, 2025 and December 31, 2024, we held available-for-sale debt securities with a total fair value of $317.3 million and $458.7 million, respectively, that were in unrealized loss positions totaling $0.6 million and $1.7 million, respectively. Available-for-sale debt securities that had been in unrealized loss positions for longer than twelve months were not significant as of March 31, 2025 or December 31, 2024. Unrealized losses on available-for-sale debt securities are primarily caused by changes in interest rates. Our investments in available-for-sale debt securities are of high credit quality, and we do not intend to sell these investments and it is not more likely than not that we will be required to sell these investments before their maturity. Accrued interest receivables on available-for-sale debt securities totaled $14.5 million and $14.4 million, respectively, as of March 31, 2025 and December 31, 2024 and are included in other current assets on the condensed consolidated balance sheets. We do not measure an allowance for credit losses for accrued interest receivables. For the purposes of identifying and measuring an impairment, accrued interest is excluded from both the fair value and amortized cost basis of the debt security. Uncollectible accrued interest receivables associated with an impaired debt security are reversed against interest income upon identification of the impairment.
To minimize the risks related to accounts receivable, which are typically unsecured, we monitor the financial performance and creditworthiness of our customers so that we can properly assess and respond to changes in their credit profiles.
The following table presents the percent of total gross product sales for each of our customers who individually accounted for 10% or more of total gross product sales.
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended March 31, |
(in millions) |
2025 |
|
2024 |
Customer A |
41 |
% |
|
43 |
% |
Customer B |
30 |
% |
|
28 |
% |
Customer C |
14 |
% |
|
14 |
% |
|
|
|
|
The following table presents the percent of total accounts receivable for each of our customers who individually accounted for 10% or more of total accounts receivable.
|
|
|
|
|
|
|
|
|
|
|
|
(in millions) |
March 31, 2025 |
|
December 31, 2024 |
Customer A |
45 |
% |
|
41 |
% |
Customer B |
31 |
% |
|
37 |
% |
Customer C |
11 |
% |
|
11 |
% |
Customer D |
10 |
% |
|
< 10 % |
4. Earnings per Share
Earnings per share were calculated as follows:
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|
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|
|
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|
|
|
|
|
|
|
|
Three Months Ended March 31, |
(in millions, except per share data) |
|
|
|
|
2025 |
|
2024 |
Net income - basic and diluted |
|
|
|
|
$ |
7.9 |
|
|
$ |
43.4 |
|
Weighted-average common shares outstanding: |
|
|
|
|
|
|
|
Basic |
|
|
|
|
99.7 |
|
|
99.8 |
|
Effect of dilutive securities |
|
|
|
|
2.8 |
|
|
3.8 |
|
Diluted |
|
|
|
|
102.5 |
|
|
103.6 |
|
Earnings per share: |
|
|
|
|
|
|
|
Basic |
|
|
|
|
$ |
0.08 |
|
|
$ |
0.43 |
|
Diluted |
|
|
|
|
$ |
0.08 |
|
|
$ |
0.42 |
|
|
|
|
|
|
|
|
|
Shares excluded from diluted per share amounts because their effect would have been anti-dilutive |
|
|
|
|
3.3 |
|
|
1.7 |
|
5. Leases
Our operating leases that have commenced have terms that expire beginning 2025 through 2036 and consist of office space and research and development laboratories, including our corporate headquarters. Certain of these lease agreements contain clauses for renewal at our option. As we were not reasonably certain to exercise any of these renewal options at commencement of the associated leases, no such options were recognized as part of our right-of-use (ROU) assets or operating lease liabilities.
The following table presents supplemental operating lease information for operating leases that have commenced.
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended March 31, |
(in millions, except weighted average data) |
2025 |
|
2024 |
Operating lease cost |
$ |
16.5 |
|
|
$ |
9.4 |
|
Sublease income |
(0.9) |
|
|
(0.4) |
|
Net operating lease cost |
$ |
15.6 |
|
|
$ |
9.0 |
|
Cash paid for amounts included in the measurement of operating lease liabilities |
$ |
9.3 |
|
|
$ |
6.1 |
|
|
|
|
|
|
March 31, |
|
2025 |
|
2024 |
Weighted average remaining lease term |
10.6 years |
|
10.6 years |
Weighted average discount rate |
4.9 |
% |
|
5.1 |
% |
Restricted cash related to letters of credit issued in lieu of cash security deposits |
$ |
7.8 |
|
|
$ |
7.8 |
|
The following table presents approximate future non-cancelable minimum lease payments under operating leases and sublease income as of March 31, 2025.
|
|
|
|
|
|
|
|
|
|
|
|
(in millions) |
Operating
Leases (1)
|
|
Sublease Income |
2025 (9 months remaining) |
$ |
32.5 |
|
|
$ |
(2.6) |
|
2026 |
58.3 |
|
|
(3.5) |
|
2027 |
59.2 |
|
|
(3.5) |
|
2028 |
60.7 |
|
|
(3.5) |
|
2029 |
60.8 |
|
|
(3.5) |
|
Thereafter |
374.4 |
|
|
(5.4) |
|
Total operating lease payments (sublease income) |
645.9 |
|
|
$ |
(22.0) |
|
Less imputed interest |
152.8 |
|
|
|
Total operating lease liabilities |
493.1 |
|
|
|
Less current operating lease liabilities included in other current liabilities |
45.6 |
|
|
|
Noncurrent operating lease liabilities |
$ |
447.5 |
|
|
|
_________________________
(1) Amounts presented in the table above exclude $0.9 million for 2025, $1.7 million for 2026, and $0.9 million for 2027 of approximate non-cancelable future minimum lease payments under operating leases that have not yet commenced.
6. Stockholders’ Equity
Share Repurchases
In February 2025, our Board of Directors authorized a new share repurchase program (the 2025 Repurchase Program) under which we may repurchase up to $500.0 million of our common stock, subject to market conditions. Under the 2025 Repurchase Program, we repurchased 1.4 million shares on the open market for a cost of $150.0 million during the first quarter of 2025. As of March 31, 2025, we had $350.0 million remaining under the 2025 Repurchase Program.
Under the 2025 Repurchase Program, share repurchases may be made from time to time at management's discretion through a variety of methods, such as open-market transactions including pre-set trading plans, privately negotiated transactions, accelerated share repurchases, and other transactions in accordance with applicable securities laws. Shares repurchased under the 2025 Repurchase Program are retired immediately, resulting in an immediate reduction of the outstanding shares used to calculate the weighted-average common shares for both basic and diluted earnings per share, and included in the category of authorized but unissued shares. The excess of the purchase price over the par value of the common shares was recorded as a reduction to additional paid-in capital.
In November 2024, we entered into an accelerated share repurchase transaction (the 2024 Repurchase Program) with a third-party financial institution to repurchase an aggregate of $300.0 million of our common stock. Shares repurchased under the 2024 Repurchase Program were retired immediately upon receipt, resulting in an immediate reduction of the outstanding shares used to calculate the weighted-average common shares for both basic and diluted earnings per share in the period received, and included in the category of authorized but unissued shares. At inception, we paid the financial institution $300.0 million using cash on hand and took initial delivery of 2.0 million shares in November 2024. The fair market value of the 2.0 million initial shares received was $240.5 million, with the excess of the fair market value over the par value of the initial shares received recorded as reductions to retained earnings and additional paid-in capital. The remaining $59.5 million of the repurchase price was recorded as a reduction to additional paid-in capital. The 2024 Repurchase Program was completed in February 2025, at which time we received an additional 0.3 million shares upon settlement, with the excess of the fair market value over the par value of the settlement shares received recorded as an increase to additional paid-in capital and a reduction to retained earnings. In total, we repurchased 2.3 million shares under the 2024 Repurchase Program at an average price of $131.83 per share, which represents the daily volume-weighted average price of our common stock over the term of the transaction, less a negotiated discount.
The following table presents information relating to purchases of our common stock.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended March 31, |
(in millions, except per share data) |
|
2025 |
|
2024 |
Total number of shares repurchased |
|
1.6 |
|
|
— |
|
Amount repurchased |
|
$ |
209.5 |
|
|
$ |
— |
|
Average price per share |
|
$ |
128.03 |
|
|
$ |
— |
|
7. Intangible Assets
The following table presents information relating to our recognized intangible assets.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
March 31, 2025 |
|
December 31, 2024 |
(dollars in millions) |
|
Gross Carrying Amount |
|
Accumulated Amortization |
|
Net Carrying Amount |
|
Gross Carrying Amount |
|
Accumulated Amortization |
|
Net Carrying Amount |
Developed product rights (1) |
|
$ |
41.6 |
|
|
$ |
9.0 |
|
|
$ |
32.6 |
|
|
$ |
40.5 |
|
|
$ |
7.7 |
|
|
$ |
32.8 |
|
Acquired IPR&D (2) |
|
$ |
3.8 |
|
|
$ |
— |
|
|
3.8 |
|
|
$ |
3.7 |
|
|
$ |
— |
|
|
3.7 |
|
Total intangible assets, net |
|
|
|
|
|
$ |
36.4 |
|
|
|
|
|
|
$ |
36.5 |
|
_________________________
(1) Developed product rights have a useful life of 10 to 16 years.
(2) Acquired IPR&D is considered indefinite lived until the completion or abandonment of the associated research and development efforts.
The following table presents approximate future annual amortization expense for our finite-lived intangible assets as of March 31, 2025.
|
|
|
|
|
|
(in millions) |
Amount |
Year ending December 31, 2025 (9 months remaining) |
$ |
3.0 |
|
Year ending December 31, 2026 |
$ |
4.0 |
|
Year ending December 31, 2027 |
$ |
4.0 |
|
Year ending December 31, 2028 |
$ |
4.0 |
|
Year ending December 31, 2029 |
$ |
4.0 |
|
Thereafter |
$ |
13.6 |
|
8. Convertible Senior Notes
On May 2, 2017, we completed a private placement of $517.5 million in aggregate principal amount of 2.25% fixed-rate convertible senior notes due May 15, 2024 (the 2024 Notes) and entered into the 2017 Indenture with respect to the 2024 Notes. Interest on the 2024 Notes was due semi-annually on May 15 and November 15 of each year.
In 2020, we repurchased $136.2 million in aggregate principal amount of the 2024 Notes for an aggregate repurchase price of $186.9 million in cash. In 2022, we repurchased $210.8 million in aggregate principal amount of the 2024 Notes for an aggregate repurchase price of $279.0 million in cash.
In January 2024, we provided notice to the holders of the 2024 Notes electing to settle all conversions of the 2024 Notes which occur on or after January 15, 2024 in cash. Consequently, the embedded conversion option of the 2024 Notes (the conversion feature) required bifurcation and separate accounting from the 2024 Notes as it no longer qualified for the equity scope exception under ASC 815, Derivatives and Hedging. Upon bifurcation of the conversion feature in the first quarter of 2024, we recorded a derivative liability at a fair value of $126.6 million (Level 3) and a corresponding debt discount that was accreted over the remaining term of the 2024 Notes using the straight-line method. Subsequent changes in the fair value of the derivative liability and accretion of the associated debt discount were recorded in other expense, net on the condensed consolidated statements of income and comprehensive income.
The following table presents a summary of charges recognized in connection with the bifurcation of the conversion feature of the 2024 Notes in the first quarter of 2024.
|
|
|
|
|
|
(in millions) |
|
Accretion of debt discount associated with derivative liability |
$ |
79.1 |
|
Change in fair value of derivative liability |
9.6 |
|
|
|
Charges associated with convertible senior notes |
$ |
88.7 |
|
During the second quarter of 2024, holders of the 2024 Notes converted $169.8 million in aggregate principal amount of the 2024 Notes for $308.2 million in cash, reflecting a conversion premium of $138.4 million calculated based on the per share volume-weighted average price (VWAP) for each of the 30 consecutive trading days during the observation period (as more fully described in the 2017 Indenture). The 2024 Notes were settled in full upon maturity on May 15, 2024.
9. Other Balance Sheet Details
Inventory consisted of the following:
|
|
|
|
|
|
|
|
|
|
|
|
(in millions) |
March 31, 2025 |
|
December 31, 2024 |
Raw materials |
$ |
31.9 |
|
|
$ |
33.7 |
|
Work in process |
13.8 |
|
|
10.9 |
|
Finished goods |
13.6 |
|
|
12.8 |
|
|
59.3 |
|
|
57.4 |
|
Less inventory reserves |
(0.2) |
|
|
— |
|
Total inventory |
$ |
59.1 |
|
|
$ |
57.4 |
|
Prior to FDA approval of CRENESSITY in December 2024, all costs related to its manufacturing were expensed as R&D in the period incurred. As a result, our physical inventories as of March 31, 2025 and December 31, 2024 included active pharmaceutical product with no cost basis. Costs related to the manufacturing of bulk drug product, finished bottling, and other labeling activities that occurred post-FDA approval are included in the inventory values as of March 31, 2025 and December 31, 2024.
Accounts payable and accrued liabilities consisted of the following:
|
|
|
|
|
|
|
|
|
|
|
|
(in millions) |
March 31, 2025 |
|
December 31, 2024 |
Sales rebates and reserves |
$ |
154.6 |
|
|
$ |
144.2 |
|
Accrued development costs (including unpaid development milestones) |
89.7 |
|
|
50.8 |
|
Accrued employee related costs |
57.5 |
|
|
107.5 |
|
Current branded prescription drug fee |
38.0 |
|
|
49.2 |
|
Current income taxes payable |
25.4 |
|
|
10.0 |
|
Accounts payable and other accrued liabilities |
110.0 |
|
|
99.9 |
|
Total accounts payable and accrued liabilities |
$ |
475.2 |
|
|
$ |
461.6 |
|
Other noncurrent liabilities consisted of the following:
|
|
|
|
|
|
|
|
|
|
|
|
(in millions) |
March 31, 2025 |
|
December 31, 2024 |
Noncurrent income taxes payable |
$ |
166.0 |
|
|
$ |
160.7 |
|
Other noncurrent liabilities |
15.6 |
|
|
5.5 |
|
Total other noncurrent liabilities |
$ |
181.6 |
|
|
$ |
166.2 |
|
The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported within the condensed consolidated balance sheets that sum to the total of the same such amounts shown in the condensed consolidated statements of cash flows.
|
|
|
|
|
|
|
|
|
|
|
|
(in millions) |
March 31, 2025 |
|
March 31, 2024 |
Cash and cash equivalents |
$ |
194.1 |
|
|
$ |
396.3 |
|
Restricted cash included in other noncurrent assets |
8.0 |
|
|
8.0 |
|
Total cash, cash equivalents, and restricted cash |
$ |
202.1 |
|
|
$ |
404.3 |
|
10. Segment Reporting and Disaggregation of Relevant Expense Captions
Neurocrine Biosciences operates as a single global business segment dedicated to the research and development, commercialization, and sale of pharmaceuticals primarily in the U.S. for the treatment of neurological, neuroendocrine, and neuropsychiatric disorders. There were no changes to the accounting policies of the segment as disclosed in the 2024 Form 10-K.
The determination of a single business segment is consistent with the consolidated financial information regularly reviewed by the Chief Executive Officer as chief operating decision maker (CODM) in assessing segment performance and deciding how to allocate resources on a consolidated basis.
The CODM assesses performance for the segment and decides how to allocate resources based on net income that also is reported on the consolidated statements of income and comprehensive income as consolidated net income. The CODM uses net income to monitor budget and forecast versus actual results in assessing segment performance and to evaluate income generated from segment assets in deciding how to allocate resources. The measure of segment assets is reported on the consolidated balance sheets as total consolidated assets.
The following table presents information about reported segment revenues, segment profit, and significant segment expenses.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended March 31, |
(in millions) |
|
|
|
|
2025 |
|
2024 |
Revenues: |
|
|
|
|
|
|
|
INGREZZA net product sales |
|
|
|
|
$ |
545.2 |
|
|
$ |
506.0 |
|
CRENESSITY net product sales |
|
|
|
|
14.5 |
|
|
— |
|
Other revenues (1) |
|
|
|
|
12.9 |
|
|
9.3 |
|
Total revenues |
|
|
|
|
572.6 |
|
|
515.3 |
|
Less: |
|
|
|
|
|
|
|
Cost of revenues |
|
|
|
|
9.2 |
|
|
7.5 |
|
Research and development: |
|
|
|
|
|
|
|
External research and development |
|
|
|
|
107.9 |
|
|
77.6 |
|
Payroll and benefits |
|
|
|
|
75.0 |
|
|
57.6 |
|
Milestones |
|
|
|
|
45.4 |
|
|
6.1 |
|
Other research and development (2) |
|
|
|
|
34.9 |
|
|
18.1 |
|
Total research and development |
|
|
|
|
263.2 |
|
|
159.4 |
|
Acquired in-process research and development |
|
|
|
|
0.1 |
|
|
6.0 |
|
Selling, general, and administrative |
|
|
|
|
276.5 |
|
|
243.1 |
|
Unrealized loss (gain) on equity investments |
|
|
|
|
30.6 |
|
|
(1.6) |
|
Charges associated with convertible senior notes |
|
|
|
|
— |
|
|
88.7 |
|
Interest income and other, net |
|
|
|
|
(21.7) |
|
|
(22.3) |
|
Provision for (Benefit from) income taxes |
|
|
|
|
6.8 |
|
|
(8.9) |
|
Net income |
|
|
|
|
$ |
7.9 |
|
|
$ |
43.4 |
|
_________________________
(1) Other revenues primarily consist of net product sales for ALKINDI and EFMODY and royalties earned on AbbVie net sales of elagolix and MTPC net sales of valbenazine.
(2) Other research and development consists of indirect costs incurred for the benefit of multiple research and development programs, including facility-based expenses (such as rent expense) and other overhead allocations.
11. Legal Proceedings
In March 2025, we received a notice from Zydus Lifesciences Global FZE (Zydus FZE) that it had filed an abbreviated new drug application, or ANDA, with the FDA seeking approval of a generic version of INGREZZA SPRINKLE (valbenazine). The ANDA contained a Paragraph IV Patent Certification alleging that certain of our patents covering INGREZZA SPRINKLE are invalid and/or will not be infringed by Zydus FZE’s importation, manufacture, use or sale of the medicine for which the ANDA was submitted. We filed suit in the U.S. District Court for the District of Delaware in April 2025 against Zydus Pharmaceuticals (USA) Inc. and its affiliates Zydus FZE, Zydus Worldwide DMCC, Zydus Lifesciences Limited, and Zydus Healthcare (USA) LLC (collectively, Zydus). We also filed suit in the U.S. District Court for the District of New Jersey in April 2025 against Zydus seeking to prevent Zydus from selling a generic version of INGREZZA SPRINKLE.
In January 2025, we filed suit in the United States District Court for the District of Delaware against Spruce Biosciences, Inc. (Spruce), seeking to invalidate one of Spruce’s patents. In addition, we have initiated (1) administrative proceedings against another Spruce patent in the U.S. Patent and Trademark Office, and (2) both judicial and administrative proceedings against Spruce patents in other jurisdictions.
From time to time, we may also become subject to other legal proceedings or claims arising in the ordinary course of our business. We currently believe that none of the claims or actions pending against us is likely to have, individually or in the aggregate, a material adverse effect on our business, financial condition or results of operations. Given the unpredictability inherent in litigation, however, we cannot predict the outcome of these matters.
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following Management’s Discussion and Analysis of Financial Condition and Results of Operations section contains forward-looking statements, which involve risks and uncertainties. Our actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors, including those set forth in Part II, Item 1A under the caption “Risk Factors.” The interim financial statements and this Management’s Discussion and Analysis of Financial Condition and Results of Operations should be read in conjunction with the financial statements and notes thereto for the year ended December 31, 2024 and the related Management’s Discussion and Analysis of Financial Condition and Results of Operations, which are contained in our Annual Report on Form 10-K for the year ended December 31, 2024.
Overview
Neurocrine Biosciences is a neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neuropsychiatric, neurological, and neuroendocrine disorders.
Our portfolio of products includes U.S. Food and Drug Administration (FDA) approved treatments for tardive dyskinesia (TD), chorea associated with Huntington's disease, classic congenital adrenal hyperplasia (CAH), and endometriosis and uterine fibroids in collaboration with AbbVie Inc. (AbbVie). In addition, we have a diversified portfolio of multiple compounds in mid- to late-phase development across our core therapeutic areas and an expanding early-phase pipeline that includes a range of modalities including small molecules, peptides, proteins, antibodies, and gene therapy.
We launched INGREZZA® (valbenazine) in the U.S. as the first FDA-approved drug for the treatment of TD in May 2017 and for the treatment of chorea associated with Huntington's disease in August 2023 and launched CRENESSITYTM (crinecerfont) in the U.S. as a first-in-class FDA-approved treatment of CAH in December 2024.
We estimate that TD affects approximately 800,000 people in the U.S., that approximately 90% of the 40,000 people in the U.S. affected by Huntington’s disease will develop chorea, and that CAH affects at least 20,000 people in the U.S. Key elements of our commercial strategy include maximizing the opportunities in INGREZZA and CRENESSITY through consistent and effective commercial execution, continued development of valbenazine as the best-in-class treatment for new patient populations, and to lead the evolving understanding of vesicular monoamine transporter 2 (VMAT2) biology and its role in disease. INGREZZA net product sales totaled $545.2 million and $506.0 million, respectively, for the first quarter of 2025 and 2024 and accounted for substantially all of our total net product sales during each of these reporting periods. CRENESSITY net product sales totaled $14.5 million for the first quarter of 2025.
Our partner Mitsubishi Tanabe Pharma Corporation (MTPC) launched DYSVAL® (valbenazine) in Japan for the treatment of TD in June 2022 and subsequently in other select Asian markets, where it is marketed as REMLEAS® (valbenazine). We receive royalties at tiered percentage rates on MTPC net sales of valbenazine.
Our partner AbbVie launched ORILISSA® (elagolix tablets) in the U.S. for the treatment of endometriosis in August 2018 and ORIAHNN® (elagolix, estradiol and norethindrone acetate capsules and elagolix capsules) in the U.S. for the treatment of heavy menstrual bleeding due to uterine fibroids in June 2020. We receive royalties at tiered percentage rates on AbbVie net sales of elagolix.
Business Highlights
•In February 2025, our Board of Directors authorized a new share repurchase program (the 2025 Repurchase Program) under which we may repurchase up to $500.0 million of our common stock, subject to market conditions. The 2025 Repurchase Program is in addition to the $300.0 million accelerated repurchase program (the 2024 Repurchase Program) that was announced in October 2024 and completed in February 2025. During the first quarter of 2025, we repurchased 1.4 million shares on the open market under the 2025 Repurchase Program and received an additional 0.3 million shares upon settlement of the 2024 Repurchase Program in February 2025.
•In January 2025, we received Centers for Medicare and Medicaid Services (CMS) notification that INGREZZA qualifies for the small biotech exception under the Medicare Drug Price Negotiation Program, which provides exemption from selection until 2027 for initial price applicability in 2029. In addition, in April 2025, we expanded formulary access for INGREZZA, significantly improving coverage to now include two-thirds of TD and Huntington's disease Medicare beneficiaries.
•Appointed Sanjay Keswani, M.D., as Chief Medical Officer (CMO) and member of the Company's executive management team effective June 2, 2025.
Pipeline Highlights
•Initiated a Phase 3 clinical study for osavampator (formerly NBI-1065845) in major depressive disorder (MDD), which resulted in the expense of a $37.5 million milestone payable to Takeda Pharmaceutical Company Limited (Takeda) as research and development (R&D) in the first quarter of 2025 and payment in the second quarter of 2025.
•Initiated a Phase 1 clinical study for NBI-921355, an investigational, selective inhibitor of voltage-gated sodium channels Nav1.2 and Nav1.6, as a potential treatment of certain types of epilepsy, which resulted in the expense of a $7.5 million milestone payable to Xenon Pharmaceuticals Inc. (Xenon) as R&D in the first quarter of 2025 and payment in the second quarter of 2025.
•Initiated a Phase 1 clinical study for NBI-1140675, an investigational, oral, selective second-generation small molecule VMAT2 inhibitor in development for the potential treatment of certain neurological and neuropsychiatric conditions.
•Announced top-line data from a Phase 4 study, KINECT-PRO™, demonstrating clinically meaningful and sustained effects of INGREZZA capsules on the physical, social, and emotional impacts experienced by patients living with TD, irrespective of TD severity or underlying psychiatric condition.
•Initiated a Phase 3 clinical study for NBI-1117568 in the second quarter of 2025, which triggered a milestone of $15.0 million payable to Nxera Pharma UK Limited upon initiation of the Phase 3 study.
Results of Operations for the Three Months Ended March 31, 2025 and 2024
Revenues
Net Product Sales
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Three Months Ended March 31, |
(in millions) |
|
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|
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2025 |
|
2024 |
INGREZZA |
|
|
|
|
$ |
545.2 |
|
|
$ |
506.0 |
|
CRENESSITY |
|
|
|
|
14.5 |
|
|
— |
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Other |
|
|
|
|
4.0 |
|
|
3.0 |
|
Total net product sales |
|
|
|
|
$ |
563.7 |
|
|
$ |
509.0 |
|
Compared with the comparable period last year, the increase primarily reflected increased net product sales of INGREZZA, driven by underlying patient demand and improved gross-to-net dynamics, and CRENESSITY, which was launched in the U.S. as a first-in-class FDA-approved treatment of CAH in December 2024.
Collaboration Revenues
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Three Months Ended March 31, |
(in millions) |
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2025 |
|
2024 |
Royalties |
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|
|
|
$ |
8.2 |
|
|
$ |
4.1 |
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Other |
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|
|
|
0.7 |
|
|
2.2 |
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Total collaboration revenues |
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|
|
|
$ |
8.9 |
|
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$ |
6.3 |
|
Total collaboration revenues for all periods presented primarily reflected royalties earned on AbbVie net sales of elagolix and MTPC net sales of valbenazine.
Operating Expenses
Cost of Revenues
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Three Months Ended March 31, |
(in millions) |
|
|
|
|
2025 |
|
2024 |
Cost of revenues |
|
|
|
|
$ |
9.2 |
|
|
$ |
7.5 |
|
Compared with the comparable period last year, the increase primarily reflected increased net product sales of INGREZZA and increased royalties payable on net product sales of CRENESSITY.
Research and Development
We support our drug discovery and development efforts through the commitment of significant resources to discovery, research and development programs, and business development opportunities. Costs are reflected in the applicable development stage based upon the program status when incurred. Therefore, the same program could be reflected in different development stages in the same reporting period. For several of our programs, the research and development activities are part of our collaborative arrangements.
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Three Months Ended March 31, |
(in millions) |
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2025 |
|
2024 |
Late stage |
|
|
|
|
$ |
35.3 |
|
|
$ |
24.2 |
|
Early stage |
|
|
|
|
21.7 |
|
|
27.2 |
|
Research and discovery |
|
|
|
|
50.9 |
|
|
26.2 |
|
Milestones |
|
|
|
|
45.4 |
|
|
6.1 |
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Payroll and benefits |
|
|
|
|
75.0 |
|
|
57.6 |
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Facilities and other |
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|
|
|
34.9 |
|
|
18.1 |
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Total research and development |
|
|
|
|
$ |
263.2 |
|
|
$ |
159.4 |
|
Late Stage. Late stage consists of costs incurred for product candidates in Phase 2 registrational studies and all subsequent activities.
Compared with the comparable period last year, the increase primarily reflected increased investment in the Phase 3 programs for osavampator in MDD and NBI-1117568 in schizophrenia, partially offset by the successful completion of the Phase 3 program for crinecerfont in CAH.
Early Stage. Early stage consists of costs incurred for product candidates after the approval of an investigational new drug application by the applicable regulatory agency through Phase 2 non-registrational studies.
Compared with the comparable period last year, the decrease primarily reflected the successful completions of the Phase 2 programs for osavampator in MDD and NBI-1117568 in schizophrenia and lower spend on early-stage epilepsy programs, partially offset by increased investment in certain early-stage muscarinic programs.
Research and Discovery. Research and discovery consists of costs incurred prior to the approval of an investigational new drug application by the applicable regulatory agency.
Compared with the comparable period last year, the increase reflected increased investments in gene therapy and other preclinical development programs.
Milestones. Milestones consists of costs incurred in connection with the achievement of development milestones under our collaborative arrangements.
Compared with the comparable period last year, the increase primarily reflected first quarter 2025 expenses of $37.5 million and $7.5 million, respectively, for development milestones achieved under our collaborations with Takeda and Xenon.
Payroll and Benefits. Payroll and benefits consists of costs incurred for salaries and wages, payroll taxes, benefits, and stock-based compensation associated with employees involved in research and development activities. Stock-based compensation may fluctuate from period to period based on factors that are not within our control, such as our stock price on the dates stock-based grants are issued.
Compared with the comparable period last year, the increase primarily reflected higher headcount and a $6.0 million increase in non-cash stock-based compensation expense.
Facilities and Other. Facilities and other consists of indirect costs incurred for the benefit of multiple programs, including facility-based expenses (such as rent expense) and other overhead allocations.
Compared with the comparable period last year, the increase primarily reflected increased facility-based expenses related to our new campus facility.
Selling, General, and Administrative
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Three Months Ended March 31, |
(in millions) |
|
|
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2025 |
|
2024 |
Selling, general, and administrative |
|
|
|
|
$ |
276.5 |
|
|
$ |
243.1 |
|
Compared with the comparable period last year, the increase primarily reflected continued investment in our commercial organization, including the expansion of our psychiatry and long-term care sales team completed in September 2024 and CRENESSITY-related headcount and commercial launch activities, and a $2.3 million increase in non-cash stock-based compensation expense.
Other (Expense) Income
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Three Months Ended March 31, |
(in millions) |
|
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|
2025 |
|
2024 |
Unrealized (loss) gain on equity investments |
|
|
|
|
(30.6) |
|
|
1.6 |
|
Charges associated with convertible senior notes |
|
|
|
|
— |
|
|
(88.7) |
|
Investment income and other, net |
|
|
|
|
21.7 |
|
|
22.3 |
|
Total other expense, net |
|
|
|
|
$ |
(8.9) |
|
|
$ |
(64.8) |
|
Compared with the comparable period last year, the change primarily reflected prior year charges associated with the convertible senior notes that matured in May 2024 and periodic fluctuations in the fair values of our equity investments.
Provision for (Benefit from) Income Taxes
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Three Months Ended March 31, |
(in millions) |
|
|
|
|
2025 |
|
2024 |
Provision for (Benefit from) income taxes |
|
|
|
|
$ |
6.8 |
|
|
$ |
(8.9) |
|
The effective tax rate for the first quarter of 2025 varied from the federal and state statutory rates primarily due to credits generated for research activities, certain nondeductible expenses, excess tax benefits related to stock-based compensation, fluctuations in state effective tax rates, and losses in foreign and domestic jurisdictions for which no tax benefit was recorded as management cannot conclude that it is more likely than not that the tax benefit of such losses will be realized in the future. For the comparable period last year, the effective tax rate varied from the federal and state statutory rates primarily due to credits generated for research activities, certain nondeductible expenses including debt extinguishment, excess tax benefits related to stock-based compensation, and losses incurred in foreign jurisdictions for which no tax benefit was recorded as management cannot conclude that it is more likely than not that the tax benefit of such losses will be realized in the future.
Net Income
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|
Three Months Ended March 31, |
(in millions) |
|
|
|
|
2025 |
|
2024 |
Net income |
|
|
|
|
$ |
7.9 |
|
|
$ |
43.4 |
|
Compared with the comparable period last year, the decrease primarily reflected increased expense for development milestones achieved under our collaborations with Takeda and Xenon, periodic fluctuations in the fair values of our equity investments, and continued investments in our commercial organization, including the expansion of our psychiatry and long-term care sales team completed in September 2024 and CRENESSITY-related headcount and commercial launch activities, and expanded pre-clinical and clinical portfolio, partially offset by increased net product sales of INGREZZA and CRENESSITY and prior year charges associated with the convertible senior notes that matured in May 2024.
Liquidity and Capital Resources
Sources of Liquidity
We believe that our existing capital resources, funds generated by anticipated INGREZZA net product sales, and investment income will be sufficient to satisfy our current and projected funding requirements for at least the next 12 months. However, we cannot guarantee that our existing capital resources and anticipated revenues will be sufficient to conduct and complete all of our research and development programs or commercialization activities as planned. We may seek to access the public or private equity markets whenever conditions are favorable or pursue opportunities to obtain debt financing in the future. We may also seek additional funding through strategic alliances or other financing mechanisms. However, we cannot provide assurance that adequate funding will be available on terms acceptable to us, if at all.
Information Regarding Our Financial Condition
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|
|
(in millions) |
March 31, 2025 |
|
December 31, 2024 |
Total cash, cash equivalents, and marketable securities |
$ |
1,758.8 |
|
|
$ |
1,815.6 |
|
Working Capital: |
|
|
|
Total current assets |
$ |
1,637.9 |
|
|
$ |
1,724.7 |
|
Less total current liabilities |
522.9 |
|
|
507.7 |
|
Total working capital |
$ |
1,115.0 |
|
|
$ |
1,217.0 |
|
Information Regarding Our Cash Flows
|
|
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|
|
|
|
|
|
|
|
Three Months Ended March 31, |
(in millions) |
2025 |
|
2024 |
Cash flows from operating activities |
$ |
64.8 |
|
|
$ |
130.3 |
|
Cash flows from investing activities |
14.2 |
|
|
(55.0) |
|
Cash flows from financing activities |
(117.9) |
|
|
69.9 |
|
|
|
|
|
Change in cash, cash equivalents, and restricted cash |
$ |
(38.9) |
|
|
$ |
145.2 |
|
Cash Flows from Operating Activities
Compared with the comparable period last year, the decrease primarily reflected continued investments in our commercial organization, including the expansion of our psychiatry and long-term care sales team completed in September 2024 and CRENESSITY-related headcount and commercial launch activities, and expanded pre-clinical and clinical portfolio, partially offset by increased net product sales of INGREZZA. In addition, we experienced an increase in accounts receivable primarily due to the timing impacts of customer orders received and cash collections on outstanding receivables.
Cash Flows from Investing Activities
Periodic fluctuations in cash flows from investing activities primarily reflected timing differences related to our purchases, sales, and maturities of debt security investments and changes in our portfolio-mix.
Cash Flows from Financing Activities
Cash flows from financing activities for all periods presented reflected proceeds from issuances of our common stock.
Compared with the comparable period last year, cash flows from financing activities also reflected $150.0 million in repurchases of our common stock under the $500.0 million 2025 Repurchase Program that was authorized by our Board of Directors in February 2025.
Material Cash Requirements
In the pharmaceutical industry, it can take a significant amount of time and capital resources to successfully complete all stages of research and development and commercialize a product candidate, which ultimate length of time and spend required cannot be accurately estimated as it varies substantially according to the type, complexity, novelty and intended use of a product candidate.
The funding necessary to execute our business strategies is subject to numerous uncertainties and we may be required to make substantial expenditures if unforeseen difficulties arise in certain areas of our business. In particular, our future capital requirements will depend on many factors, including:
•the commercial success of INGREZZA and CRENESSITY;
•continued scientific progress in our research and clinical development programs;
•the magnitude and complexity of our research and development programs;
•progress with preclinical testing and clinical trials;
•the time and costs involved in obtaining regulatory approvals;
•the costs involved in filing and pursuing patent applications, enforcing patent claims, or engaging in interference proceedings or other patent litigation;
•costs associated with securing adequate coverage and reimbursement for our products;
•competing technological and market developments;
•developments related to any future litigation;
•the cost of commercialization activities and arrangements, including our advertising campaigns; and
•the cost of manufacturing our product candidates.
In addition to the foregoing factors, we have significant future capital requirements, including:
External Business Developments
In addition to our independent efforts to develop and market products, we may enter into collaboration and license agreements or acquire businesses from time-to-time to enhance our drug development and commercial capabilities. With respect to our existing collaboration and license agreements, we may be required to make potential future payments of up to $14.8 billion upon the achievement of certain milestones.
Refer to Note 2 to the condensed consolidated financial statements for more information on our significant collaboration and license agreements.
Share Repurchase Program
In addition to the foregoing future capital requirements, in February 2025, our Board of Directors authorized the 2025 Repurchase Program under which we may repurchase up to $500.0 million of our common stock, subject to market conditions. The 2025 Repurchase Program is in addition to the $300.0 million 2024 Repurchase Program that was announced in October 2024 and completed in February 2025. Under the 2025 Repurchase Program, we repurchased 1.4 million shares on the open market for a cost of $150.0 million during the first quarter of 2025. As of March 31, 2025, we had $350.0 million remaining under the 2025 Repurchase Program.
Critical Accounting Policies and Estimates
There were no changes to our critical accounting policies as disclosed in our Annual Report on Form 10-K for the year ended December 31, 2024.
Interest Rate Risk
We maintain a diversified investment portfolio consisting of low-risk, investment-grade debt securities with maturities of up to three years, including investments in commercial paper, securities of government-sponsored entities and corporate bonds that are subject to interest rate risk. The primary objective of our investment activities is to preserve principal and maintain liquidity. If a 1% unfavorable change in interest rates were to have occurred on March 31, 2025, it would not have had a material effect on the fair value of our investment portfolio as of that date.
Forward-Looking Statements
This Quarterly Report on Form 10-Q contains forward-looking statements that involve a number of risks and uncertainties. Although our forward-looking statements reflect the good faith judgment of our management, these statements can only be based on facts and factors currently known by us. Consequently, these forward-looking statements are inherently subject to risks and uncertainties, and actual results and outcomes may differ materially from results and outcomes discussed in the forward-looking statements.
Forward-looking statements can be identified by the use of forward-looking words such as “believes,” “expects,” “hopes,” “may,” “will,” “plan,” “intends,” “estimates,” “could,” “should,” “would,” “continue,” “seeks,” “proforma,” or “anticipates,” or other similar words (including their use in the negative), or by discussions of future matters such as the development of new products, technology enhancements, possible changes in legislation and other statements that are not historical. These statements include but are not limited to statements under the captions “Risk Factors,” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” as well as other sections in this report. You should be aware that the occurrence of any of the events discussed under the heading in Part II titled “Item 1A. Risk Factors” and elsewhere in this report could substantially harm our business, results of operations and financial condition and that if any of these events occurs, the trading price of our common stock could decline and you could lose all or a part of the value of your shares of our common stock.
The cautionary statements made in this report are intended to be applicable to all related forward-looking statements wherever they may appear in this report. We urge you not to place undue reliance on these forward-looking statements, which speak only as of the date of this report. Except as required by law, we assume no obligation to update our forward-looking statements, even if new information becomes available in the future.
Item 3. Quantitative and Qualitative Disclosures About Market Risk
A discussion of our exposure to, and management of, market risk appears in Part I, Item 2 of this Quarterly Report on Form 10-Q under the heading “Interest Rate Risk” and is incorporated into this Part I, Item 3 by reference.
Item 4. Controls and Procedures
We maintain disclosure controls and procedures that are designed to ensure that information required to be disclosed in our reports required by the Exchange Act of 1934, as amended, is recorded, processed, summarized and reported within the timelines specified in the SEC’s rules and forms, and that such information is accumulated and communicated to our management, including our Chief Executive Officer and Chief Financial Officer, as appropriate, to allow timely decisions regarding required disclosure. In designing and evaluating the disclosure controls and procedures, management recognized that any controls and procedures, no matter how well designed and operated, can only provide reasonable assurance of achieving the desired control objectives, and in reaching a reasonable level of assurance, management necessarily was required to apply its judgment in evaluating the cost-benefit relationship of possible controls and procedures.
As required by SEC Rule 13a-15(b), we carried out an evaluation, under the supervision and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer, of the effectiveness of the design and operation of our disclosure controls and procedures as of the end of the quarter covered by this report. Based on the foregoing, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective at the reasonable assurance level for the period covered by this report.
Changes in Internal Control over Financial Reporting
An evaluation was also performed under the supervision and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer, of any changes to our internal control over financial reporting that occurred during the quarter ended March 31, 2025, and that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
There were no significant changes in our internal controls over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Securities Exchange Act of 1934) that occurred during the quarter ended March 31, 2025, that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
Part II. Other Information
Item 1. Legal Proceedings
In March 2025, we received a notice from Zydus Lifesciences Global FZE (Zydus FZE) that it had filed an abbreviated new drug application, or ANDA, with the FDA seeking approval of a generic version of INGREZZA SPRINKLE (valbenazine). The ANDA contained a Paragraph IV Patent Certification alleging that certain of our patents covering INGREZZA SPRINKLE are invalid and/or will not be infringed by Zydus FZE’s importation, manufacture, use or sale of the medicine for which the ANDA was submitted. We filed suit in the U.S. District Court for the District of Delaware in April 2025 against Zydus Pharmaceuticals (USA) Inc. and its affiliates Zydus FZE, Zydus Worldwide DMCC, Zydus Lifesciences Limited, and Zydus Healthcare (USA) LLC (collectively, Zydus). We also filed suit in the U.S. District Court for the District of New Jersey in April 2025 against Zydus seeking to prevent Zydus from selling a generic version of INGREZZA SPRINKLE.
In January 2025, we filed suit in the United States District Court for the District of Delaware against Spruce Biosciences, Inc. (Spruce), seeking to invalidate one of Spruce’s patents. In addition, we have initiated (1) administrative proceedings against another Spruce patent in the U.S. Patent and Trademark Office, and (2) both judicial and administrative proceedings against Spruce patents in other jurisdictions.
From time to time, we may also become subject to other legal proceedings or claims arising in the ordinary course of our business. We currently believe that none of the claims or actions pending against us is likely to have, individually or in the aggregate, a material adverse effect on our business, financial condition or results of operations. Given the unpredictability inherent in litigation, however, we cannot predict the outcome of these matters.
Item 1A. Risk Factors
The following information sets forth risk factors that could cause our actual results to differ materially from those contained in forward-looking statements we have made in this Quarterly Report on Form 10-Q and those we may make from time to time. If any of the following risks actually occur, our business, operating results, prospects or financial condition could be harmed. Additional risks not presently known to us, or that we currently deem immaterial, may also affect our business operations. The risk factors set forth below with an asterisk (*) contain changes to the risk factors set forth in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024.
Summary Risk Factors
We face risks and uncertainties related to our business, many of which are beyond our control. In particular, risks associated with our business include:
•We may not be able to continue to successfully commercialize INGREZZA or any of our product candidates if they are approved in the future.
•We may not be able to successfully launch CRENESSITY.
•If physicians and patients do not continue to accept INGREZZA or do not accept CRENESSITY, or our sales and marketing efforts are not effective, we may not generate sufficient revenue.
•We face intense competition, and if we are unable to compete effectively, the demand for our products may be reduced.
•Government and third-party payors may impose sales and pharmaceutical pricing controls on our products or limit coverage and/or reimbursement for our products or impose policies and/or make decisions regarding the status of our products that could limit our product revenues and delay sustained profitability.
•Because the development of our product candidates is subject to a substantial degree of technological uncertainty, we may not succeed in developing any of our product candidates.
•Our clinical trials may be delayed for safety or other reasons, or fail to demonstrate the safety and efficacy of our product candidates, which could prevent or significantly delay their regulatory approval.
•Enacted healthcare reform, drug pricing measures and other recent legislative initiatives, including the Inflation Reduction Act of 2022, could adversely affect our business.
•We have increased the size of our organization and will need to continue to increase the size of our organization. We may encounter difficulties with managing our growth, which could adversely affect our results of operations.
•We are transforming our research and development strategies to include the development of biologics, which requires substantial investment, including in personnel and facilities. We may encounter difficulties as we expand and may fail to successfully develop or commercialize our biologic product candidates, which could adversely affect our results of operations.
•If we are unable to retain and recruit qualified scientists and other employees or if any of our key senior executives discontinues his or her employment with us, it may delay our development efforts or impact our commercialization of INGREZZA, CRENESSITY, or any product candidate approved by the FDA in the future.
•Use of our approved products or those of our collaborators could be associated with side effects or adverse events.
•We currently depend on a limited number of third-party suppliers. The loss of these suppliers, or delays or problems in the supply of INGREZZA, CRENESSITY, or our product candidates, could materially and adversely affect our ability to successfully develop or commercialize INGREZZA, CRENESSITY, or any of our product candidates.
•We currently have no manufacturing capabilities. If third-party manufacturers of INGREZZA, CRENESSITY, or any of our product candidates fail to devote sufficient time and resources to our concerns, or if their performance is substandard, our ability to commercialize existing products, conduct clinical trials and develop new products could be impaired and our costs may rise.
•We depend on our current collaborators for the development and commercialization of several of our products and product candidates and may need to enter into future collaborations to develop and commercialize certain of our product candidates.
•We license some of our core technologies and drug candidates from third parties. If we default on any of our obligations under those licenses, or violate the terms of these licenses, we could lose our rights to those technologies and drug candidates or be forced to pay damages.
•If we are unable to protect our intellectual property, our competitors could develop and market products based on our discoveries, which may reduce demand for our products.
•Our customers are concentrated and therefore the loss of a significant customer may harm our business.
•We may need additional capital in the future. If we cannot raise additional funding, we may be unable to fund our business plan and our future research, development, commercial and manufacturing efforts.
•We expect to increase our expenses for the foreseeable future, and we may not be able to sustain growth and profitability.
Risks Related to Our Company
We may not be able to continue to successfully commercialize INGREZZA or any of our product candidates if they are approved in the future.
We launched INGREZZA in the U.S. as the first FDA-approved drug for the treatment of tardive dyskinesia in May 2017 and for the treatment of chorea associated with Huntington's disease in August 2023. Our ability to produce INGREZZA revenues consistent with expectations ultimately depends on our ability to continue to successfully commercialize INGREZZA and secure and maintain adequate third-party reimbursement. Our experience in marketing and selling pharmaceutical products began with INGREZZA’s approval in 2017, when we hired our sales force and established our distribution and reimbursement capabilities, all of which are necessary to successfully commercialize our current and future products. We have continued to invest in our commercial infrastructure and distribution capabilities, including the recent expansion of our psychiatry and long-term care sales teams for INGREZZA in September 2024. While our team members and consultants have experience marketing and selling pharmaceutical products, we may face difficulties related to managing the rapid growth of our personnel and infrastructure, and there can be no guarantee that we will be able to maintain the personnel, systems, arrangements and capabilities necessary to continue to successfully commercialize INGREZZA or any product candidate approved by the FDA, or equivalent foreign authorities, in the future.
We may not be able to successfully launch CRENESSITY.
In December 2024, we announced FDA approval and launched CRENESSITY capsules and oral solution as an adjunctive treatment to glucocorticoid replacement to control androgens in adult and pediatric patients four years of age and older with classic CAH. We have also established our commercial team and hired our U.S. sales force for CRENESSITY. The successful commercial launch of CRENESSITY depends on the extent to which patients and physicians accept and adopt CRENESSITY as a treatment for CAH, and we do not know whether our expectations or estimates in this regard, or those of investors or securities analysts, will be accurate. Physicians may not prescribe CRENESSITY and patients may be unwilling to use CRENESSITY. In addition, patients may be unwilling to use CRENESSITY if reimbursement is not provided or reimbursement is inadequate to cover a significant portion of the cost to the patient. CRENESSITY is a first-in-class therapy for children and adults with classic CAH and will therefore require us to expend substantial time and resources to educate physicians and other healthcare providers about the benefits of CRENESSITY. If we are unable to provide our sales force with effective materials, including medical and sales literature to help them inform and educate potential customers about the benefits of CRENESSITY, our efforts to commercialize CRENESSITY may not be successful. Further, any negative publicity related to CRENESSITY, or negative development for CRENESSITY in our post-marketing commitments or in regulatory processes in other jurisdictions, may adversely impact the potential of CRENESSITY and our commercial results. If the commercialization of CRENESSITY and future sales are less successful than anticipated by us or our investors or securities analysts, our stock price could decline and our business may be harmed.
If physicians and patients do not continue to accept INGREZZA or do not accept CRENESSITY, or our sales and marketing efforts are not effective, we may not generate sufficient revenue.
The commercial success of INGREZZA and CRENESSITY will depend upon the acceptance of these products as safe and effective by the medical community and patients.
The market acceptance of INGREZZA and CRENESSITY could be affected by a number of factors, including:
•the timing of receipt of marketing approvals for additional indications;
•the safety and efficacy of the products;
•the pricing of these products;
•the availability of healthcare payor coverage and adequate reimbursement for the products;
•public perception regarding these products;
•the success of existing competitor products addressing our target markets or the emergence of equivalent or superior products; and
•the cost-effectiveness of the products.
If the medical community, patients and payors do not continue to accept our products as being safe, effective, superior and/or cost effective, we may not generate sufficient revenue.
We face intense competition, and if we are unable to compete effectively, the demand for our products may be reduced.
The biotechnology and pharmaceutical industries are subject to rapid and intense technological change. We face, and will continue to face, competition in the development and marketing of our products and product candidates from academic institutions, government agencies, research institutions and biotechnology and pharmaceutical companies.
Competition may also arise from, among other things:
•other drug development technologies;
•methods of preventing or reducing the incidence of disease, including vaccines; and
•new small molecule or other classes of therapeutic agents.
Developments by others (including the development of generic equivalents) may render our product candidates or technologies obsolete or noncompetitive.
We are commercializing and performing research on or developing products for the treatment of several disorders, including tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, uterine fibroids, endometriosis, pain, Parkinson’s disease, schizophrenia, epilepsy, and other neurology, neuroendocrinology, and neuropsychiatry-related diseases and disorders, and there are a number of competitors to our products and product candidates. If one or more of our competitors’ products or programs are successful (including the development of generic equivalents), the market for our products may be reduced or eliminated.
•INGREZZA competes with AUSTEDO® (deutetrabenazine), marketed by Teva Pharmaceuticals Industries, for the treatment of tardive dyskinesia in adults and chorea associated with Huntington's disease. A once-daily dosing of AUSTEDO (AUSTEDO XR) was introduced in February 2023. Additionally, there are a number of commercially available medicines used to treat tardive dyskinesia off-label, such as XENAZINE® (tetrabenazine) and generic equivalents, and various antipsychotic medications (e.g., clozapine), anticholinergics, benzodiazepines (off-label), and botulinum toxin. In addition, there are several programs in clinical development by other companies targeting Huntington's disease.
•CRENESSITY competes with high dose corticosteroid monotherapy which is the current standard of care to both correct the endogenous cortisol deficiency as well as reduce the excessive adrenocorticotropic hormone levels for patients with CAH. In the U.S. alone, there are more than two dozen companies manufacturing steroid-based products. In addition, there are several programs in clinical development by other companies targeting CAH.
•Our investigational treatments for potential use in schizophrenia and depression may in the future compete with several development-stage programs being pursued by other companies. In addition, there are a number of different anti-psychotic and anti-depressant medications currently used in these patient populations.
•Our investigational treatments for potential use in neurology, neuroendocrinology and neuropsychiatry may in the future compete with numerous approved products and development-stage programs being pursued by several other companies.
Compared to us, many of our competitors and potential competitors have substantially greater:
•capital resources;
•sales and marketing experience;
•research and development resources, including personnel and technology;
•regulatory experience;
•preclinical study and clinical testing experience;
•manufacturing, marketing and distribution experience; and
•production facilities.
Moreover, increased competition in certain disorders or therapies may make it more difficult for us to recruit or enroll patients in our clinical trials for similar disorders or therapies.
Government and third-party payors may impose sales and pharmaceutical pricing controls on our products or limit coverage and/or reimbursement for our products or impose policies and/or make decisions regarding the status of our products that could limit our product revenues and delay sustained profitability.
Our ability to continue to commercialize INGREZZA and successfully launch and commercialize CRENESSITY will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available. The continuing efforts of government and third-party payors to contain or reduce the costs of healthcare and the price of prescription drugs through various means may impact our revenues. These payors’ efforts could decrease the price that we receive for any products we may develop and sell in the future.
Assuming we obtain coverage for a given product by a third-party payor, the resulting reimbursement rates may not be adequate or may require co-payments that patients find unacceptably high. Patients who are prescribed medications for the treatment of their conditions, and their prescribing physicians, generally rely on third-party payors to reimburse all or part of the costs associated with their prescription drugs. Patients are unlikely to use our products unless coverage is provided and reimbursement is adequate to cover all or a significant portion of the out-of-pocket cost of our products. Coverage decisions may depend upon clinical and economic standards that disfavor new drug products when more established or lower cost therapeutic alternatives are already available or subsequently become available regardless of whether they are approved by the FDA for that particular use. Coverage decisions by payors for our competitors' products may also impact coverage for our products.
Government authorities and other third-party payors are developing increasingly sophisticated methods of controlling healthcare costs, such as by limiting coverage and the amount of reimbursement for particular medications. Further, no uniform policy requirement for coverage and reimbursement for drug products exists among third-party payors in the U.S. Therefore, coverage and reimbursement for drug products can differ significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. In addition, communications from government officials, media outlets, and others regarding healthcare costs and pharmaceutical pricing could have a negative impact on our stock price, even if such communications do not ultimately impact coverage or reimbursement decisions for our products.
There may also be significant delays in obtaining coverage and reimbursement for newly approved drugs or indications, and coverage may be more limited than the purposes for which the drug is approved by the FDA or comparable foreign regulatory authorities. Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. In addition, we could also be subject to amendments in our rebate agreements with pharmaceutical benefit managers that require us to pay larger rebate amounts or modify our formulary position, which could have a material adverse effect on our business. Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. For example, government authorities could make a decision that adversely impacts the status of one of our products, which could impact the eligibility and/or the amount of government reimbursement for that product.
As a pharmaceutical manufacturer, we are subject to various federal statutes and regulations requiring the reporting of price data and the subsequent provision of concessions to certain purchasers/payors, including state Medicaid programs. Federal agencies issue guidance to manufacturers related to the interpretation of laws and regulations, and this guidance has changed and may change or be updated over time. In interpreting these laws, regulations and guidance, manufacturers may make reasonable assumptions to fill gaps, and these reasonable assumptions may need to be updated upon issuance of additional agency guidance.
If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may be unable to successfully commercialize INGREZZA, CRENESSITY, or any of our product candidates for which we obtain marketing approval in the future. Our inability to promptly obtain coverage and profitable reimbursement rates from both government-funded and private payors for any approved products that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products and our overall financial condition. Further, a majority of our current revenue is derived from federal healthcare program payors, including Medicare and Medicaid. Thus, changes in government reimbursement policies, government negotiation of the price of any of products, reductions in payments and/or our suspension or exclusion from participation in federal healthcare programs could have a material adverse effect on our business.
Further, the use of physician telehealth services has continued to increase, fueled by an unprecedented expansion of coverage and reimbursement for telehealth services across public and private insurers. The limitations that telehealth places on the ability to conduct a thorough physical examination may impact the ability of providers to screen for tardive dyskinesia or chorea associated with Huntington’s disease, leading to fewer patients being diagnosed and/or treated.
Outside the U.S., reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. The EU provides options for EU Member States to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. An EU Member State may approve a specific price for the medicinal product, it may refuse to reimburse a product at the price set by the manufacturer or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.
To obtain reimbursement for our products in some European countries, including some EU Member States, we may be required to compile additional data comparing the cost-effectiveness of our products to other available therapies. The Health Technology Assessment (HTA) of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in some EU Member States, including those representing the larger markets. The extent to which pricing and reimbursement decisions are influenced by the HTA of the specific medicinal product currently varies between EU Member States. If we are unable to obtain favorable pricing and reimbursement status in EU Member States for product candidates that we may successfully develop and for which we may obtain regulatory approval, any anticipated revenue from and growth prospects for those products in the EU could be negatively affected.
Legislators, policymakers, and payors may continue to propose and implement cost-containing measures to keep healthcare costs down. These measures could include limitations on the prices we would be able to charge for product candidates that we may successfully develop and for which we may obtain regulatory approval or the level of reimbursement available for these products from governmental authorities or third-party payors. Further, an increasing number of countries use prices for medicinal products established in other countries as “reference prices” to help determine the price of the product in their own territory. Consequently, a downward trend in prices of medicinal products in some countries could contribute to similar downward trends elsewhere, including in the U.S.
Because the development of our product candidates is subject to a substantial degree of technological uncertainty, we may not succeed in developing any of our product candidates.
Only a small number of research and development programs ultimately result in commercially successful drugs.
Potential products that appear to be promising at early stages of development may not reach the market for a number of reasons. These reasons include the possibilities that the potential products may:
•be found ineffective or cause harmful side effects during preclinical studies or clinical trials;
•fail to receive necessary regulatory approvals on a timely basis or at all;
•be precluded from commercialization by proprietary rights of third parties;
•be difficult to manufacture on a large scale; or
•be uneconomical to commercialize or fail to achieve market acceptance.
If any of our product candidates encounters any of these potential problems, we may never successfully market that product candidate.
* Our clinical trials may be delayed for safety or other reasons, or fail to demonstrate the safety and efficacy of our product candidates, which could prevent or significantly delay their regulatory approval.
Before obtaining regulatory approval for the sale of any of our potential products, we must subject these product candidates to extensive preclinical and clinical testing to demonstrate their safety and efficacy for humans. Clinical trials are expensive, time consuming and may take years to complete and the outcomes are uncertain.
In connection with the clinical trials of our product candidates, we face the risks that:
•the FDA or similar foreign regulatory authority may not allow an IND or foreign equivalent filings required to initiate human clinical studies for our drug candidates or the FDA or similar foreign regulatory authorities may require additional preclinical studies as a condition of the initiation of Phase 1 clinical studies, or additional clinical studies for progression from Phase 1 to Phase 2, or Phase 2 to Phase 3, or for NDA approval;
•the product candidate may not prove to be effective or as effective as other competing product candidates;
•we may discover that a product candidate may cause harmful side effects or results of required toxicology or other studies may not be acceptable to the FDA or similar foreign regulatory authorities;
•clinical trial results may not replicate the results of previous trials;
•we or the FDA or similar foreign regulatory authorities may suspend or vary the trials;
•the results may not be statistically significant;
•clinical site initiation or patient recruitment and enrollment may be slower or more difficult than expected;
•the FDA or similar foreign regulatory authorities may not accept the data from any trial or trial site outside of the U.S.;
•a study is compromised due to patients dropping out and not completing the trials;
•unforeseen disruptions or delays may occur, caused by man-made or natural disasters, public health pandemics or epidemics, armed conflicts, trade restrictions, tariffs or other business interruptions; and
•regulatory requirements may change.
These risks and uncertainties impact all of our clinical programs and any of the clinical, regulatory or operational events described above could change our planned clinical and regulatory activities. Geopolitical tensions could also affect our ability to obtain supplies of our investigational products, which could cause delays or otherwise disrupt our clinical trials and research and development efforts. Some of our suppliers and research collaborators are located in China, exposing us to the possibility of supply disruption in the event of changes to the laws, rules, regulations, and policies of the governments of the U.S. or China. Any such changes to laws or the adoption of tariffs or other restrictions could impact our ability to contract with certain Chinese biotechnology companies, cause delays, or have other adverse effects on the development of certain of our research programs.
In addition, late-stage clinical trials are often conducted with patients having the most advanced stages of disease. During the course of treatment, these patients can die or suffer other adverse medical effects for reasons that may not be related to the pharmaceutical agent being tested but which can nevertheless adversely affect clinical trial conduct, completion and results. Any failure or substantial delay in completing clinical trials for our product candidates may severely harm our business.
Even if the clinical trials are successfully completed, we cannot guarantee that the FDA or similar foreign regulatory authorities will interpret the results as we do, and more trials could be required before we submit our product candidates for approval. The FDA and similar foreign regulatory authorities have substantial discretion in the approval process and may either refuse to accept an application for substantive review or may form the opinion after review of an application that the application is insufficient to allow approval of a product candidate. To the extent that the FDA or similar foreign regulatory authorities do not accept our application for review or approve our application, we may be required to expend significant additional resources, which may not be available to us, to conduct additional trials in support of potential approval of our product candidates. Depending on the extent of these additional trials or any other studies that might be required, approval of any applications that we submit may be significantly delayed. It is also possible that any such additional studies, if performed and completed, may not be considered sufficient by the FDA or similar foreign regulatory authorities and we may be forced to delay or abandon our applications for approval.
* We have increased the size of our organization and will need to continue to increase the size of our organization. We may encounter difficulties with managing our growth, which could adversely affect our results of operations.
Since 2017, our number of full-time employees has grown from approximately 200 to over 1,800. Although we have substantially increased the size of our organization, we may need to add additional qualified personnel and resources, especially with the recent increase in the size of our sales force. Our current infrastructure may be inadequate to support our development and commercialization efforts and expected growth. Future growth will impose significant added responsibilities on our organization, including the need to identify, recruit, maintain and integrate additional employees and implement and expand managerial, operational and financial systems and may be costly and take time away from running other aspects of our business, including development and commercialization of our product candidates. For example, we implemented a new company-wide enterprise resource planning (ERP) system in 2024 to streamline certain existing business, operational, and financial processes. This project has required and may continue to require investment of capital and human resources, the re-engineering of processes of our business, and the attention of many employees who would otherwise be focused on other aspects of our business. Any deficiencies in the design of the ERP system could adversely affect the effectiveness of our internal control over financial reporting or our ability to accurately maintain our books and records, provide accurate, timely and reliable reports on our financial and operating results, or otherwise operate our business. Any of these consequences could have an adverse effect on our results of operations and financial condition.
Our future financial performance and our ability to commercialize INGREZZA, CRENESSITY, or any of our product candidates that receive regulatory approval in the future, will partially depend on our ability to manage any future growth effectively. In particular, as we commercialize INGREZZA and CRENESSITY, we will need to support the training and ongoing activities of our sales force and will likely need to continue to expand the size of our employee base for managerial, operational, financial and other resources. To that end, we must be able to successfully:
•manage our development efforts effectively;
•integrate additional management, administrative and manufacturing personnel;
•further develop our marketing and sales organization;
•compensate our employees on adequate terms in an increasingly competitive, inflationary market;
•attract and retain personnel; and
•maintain sufficient administrative, accounting and management information systems and controls.
We may not be able to accomplish these tasks or successfully manage our operations and, accordingly, may not achieve our research, development and commercialization goals. Our failure to accomplish any of these goals could harm our financial results and prospects.
We are transforming our research and development strategies to include the development of biologics, which requires substantial investment, including in personnel and facilities. We may encounter difficulties as we expand and may fail to successfully develop or commercialize our biologic product candidates, which could adversely affect our results of operations.
We are transforming our research and development strategies to include the development of biologics, including peptides, antibodies and gene therapies. As a company, we do not have experience successfully developing and commercializing biologics and our current infrastructure may be inadequate to support the expected growth and transformation of processes, personnel, and technologies required for these new programs. We have hired employees with expertise in these modalities, but we will need to hire additional qualified personnel and expand our management, administrative, and manufacturing functions to support the research and development organization. If we are unable to identify, recruit and integrate additional employees with the requisite skills, or effectively manage our transformation activities, the development of our biologic product candidates may not be successful, or be delayed or paused indefinitely. Additionally, the manufacture of biologics is more complex than the manufacture of small molecule therapies. We may encounter delays in production and delivery of our biologic product candidates by our third-party manufacturers or other vendors, which would result in corresponding delays to our development and commercialization of such biologic candidates. In addition, the regulatory requirements in the United States and in other countries governing biologics are evolving and the FDA or comparable foreign regulatory authorities may change the requirements, or identify different regulatory pathways, for approval for any of our biologic candidates. As a result, we may be required to change our regulatory strategy or to modify our applications for regulatory approval, which could delay and impair our ability to complete the preclinical and clinical development and manufacture of, and obtain regulatory approval for, our biologic candidates. We have made, and expect to continue making, substantial investments in our research and development personnel and facilities, as well in external innovation to support our expansion into the development of our biologics. If any of these risks occur and we fail to successfully develop or commercialize our biologic product candidates, we may not realize a return on our investments which could have an adverse effect on our results of operations and financial condition.
If we are unable to retain and recruit qualified scientists and other employees or if any of our key senior executives discontinues his or her employment with us, it may delay our development efforts or impact our commercialization of INGREZZA, CRENESSITY, or any product candidate approved by the FDA in the future.
We are highly dependent on the principal members of our management, commercial and scientific staff. The loss of any of these people could impede the achievement of our objectives, including the successful commercialization of INGREZZA, the launch of CRENESSITY, or the commercialization of any product candidate approved by the FDA in the future. Furthermore, recruiting and retaining qualified scientific personnel to perform research and development work in the future, along with personnel with experience marketing and selling pharmaceutical products, is critical to our success. We may be unable to attract and retain personnel on acceptable terms given the competition among biotechnology, pharmaceutical and healthcare companies, universities and non-profit research institutions for experienced scientists and individuals with experience marketing and selling pharmaceutical products. We may face particular retention challenges in light of the recent rapid growth in our personnel and infrastructure and the perceived impact of those changes upon our corporate culture. In addition, we rely on a significant number of consultants to assist us in formulating our research and development strategy and our commercialization strategy. Our consultants may have commitments to, or advisory or consulting agreements with, other entities that may limit their availability to us.
On October 11, 2024, Kevin Gorman, Ph.D., retired as the Company's President and Chief Executive Officer and Kyle Gano, Ph.D., formerly our Chief Business Development and Strategy Officer, succeeded Dr. Gorman in the CEO role. Dr. Gano also joined our Board of Directors effective as of October 11, 2024. Dr. Gorman founded Neurocrine in 1992 and has held numerous positions across the Company, including Chief Operating Officer, Chief Business Officer, and Senior Vice President of Business Development, before being appointed CEO in 2008. Dr. Gano was appointed Neurocrine’s Chief Business Development Officer in 2011, and Chief Business Development and Strategy Officer in 2020, and is responsible for all of Neurocrine’s business and corporate development activities. Our Board of Directors worked closely with Dr. Gorman on succession planning and believes Dr. Gano and the senior leadership team are well-positioned to continue to execute our strategy. Although Dr. Gorman will continue to serve on our Board of Directors and provide strategic direction to the Company, this leadership transition may be viewed negatively by investors, our strategic partners, or other stakeholders. Further, if the transition is not managed effectively, it could disrupt our operations and impact our financial condition and results.
Use of our approved products or those of our collaborators could be associated with side effects or adverse events.
As with most pharmaceutical products, use of our approved products or those of our collaborators could be associated with side effects or adverse events which can vary in severity (from minor adverse reactions to death) and frequency (infrequent or prevalent). Side effects or adverse events associated with the use of our products or those of our collaborators may be observed at any time, including after a product is commercialized, and reports of any such side effects or adverse events may negatively impact demand for our or our collaborators’ products or affect our or our collaborators’ ability to maintain regulatory approval for such products. Side effects or other safety issues associated with the use of our approved products or those of our collaborators could require us or our collaborators to modify or halt commercialization of these products or expose us to product liability lawsuits which will harm our business. We or our collaborators may be required by regulatory agencies to conduct additional studies regarding the safety and efficacy of our products which we have not planned or anticipated. Furthermore, there can be no assurance that we or our collaborators will resolve any issues related to any product related adverse events to the satisfaction of the FDA or any regulatory agency in a timely manner or ever, which could harm our business, prospects and financial condition.
* We currently depend on a limited number of third-party suppliers. The loss of these suppliers, or delays or problems in the supply of INGREZZA, CRENESSITY, or our product candidates, could materially and adversely affect our ability to successfully develop or commercialize INGREZZA, CRENESSITY, or any of our product candidates.
The manufacture of pharmaceutical products requires significant expertise and capital investment, including the development of process controls required to consistently produce the active pharmaceutical ingredients (API), the finished drug product and packaging in sufficient quantities while meeting detailed product specifications on a repeated basis. Manufacturers of pharmaceutical products may encounter difficulties in production, such as difficulties with production costs and yields, process controls and validation, quality control and quality assurance, including testing of stability, impurities and impurity levels and other product specifications by validated test methods, compliance with strictly enforced U.S., state and non-U.S. regulations, and disruptions or delays caused by man-made or natural disasters, public health pandemics or epidemics, armed conflicts, trade restrictions, tariffs, or other business interruptions. We depend on a limited number of suppliers for the production (including API) of INGREZZA, CRENESSITY and our product candidates and for the packaging of INGREZZA and CRENESSITY. If our third-party suppliers for INGREZZA, CRENESSITY, or any of our product candidates encounter these or any other manufacturing, quality or compliance difficulties, our ability to successfully develop or commercialize INGREZZA, CRENESSITY, or any of our product candidates could be materially and adversely affected.
In addition, if our suppliers fail or refuse to supply us with INGREZZA, CRENESSITY, or any of our product candidates, or their APIs for any reason, or terminate our supply agreements or do not perform as agreed, it would take a significant amount of time and expense to qualify a new supplier. The FDA and similar foreign regulatory authorities must approve manufacturers of the active and inactive pharmaceutical ingredients and certain packaging materials used in pharmaceutical products. The loss of a supplier could require us to obtain regulatory clearance and to incur validation and other costs associated with the transfer of the API or product manufacturing processes. If there are delays in qualifying new suppliers or facilities or if a new supplier is unable to meet FDA or a similar foreign regulatory authority’s requirements for approval, there could be a shortage of INGREZZA, CRENESSITY, or any of our product candidates, which could materially and adversely affect our ability to successfully develop or commercialize INGREZZA, CRENESSITY, or any of our product candidates.
* We currently have no manufacturing capabilities. If third-party manufacturers of INGREZZA, CRENESSITY, or any of our product candidates fail to devote sufficient time and resources to our concerns, or if their performance is substandard, our ability to commercialize existing products, conduct clinical trials and develop new products could be impaired and our costs may rise.
We have in the past utilized, and intend to continue to utilize, third-party manufacturers to produce the drug compounds we use in our clinical trials and for the commercialization of our products. We have limited experience in manufacturing products for commercial purposes and do not currently have any manufacturing facilities. Establishing internal commercial manufacturing capabilities would require significant time and resources, and we may not be able to timely or successfully establish such capabilities. Consequently, we depend on, and will continue to depend on, several contract manufacturers for all production of products for development and commercial purposes, including INGREZZA and CRENESSITY. If we are unable to obtain or retain third-party manufacturers, we will not be able to develop or commercialize our products, including INGREZZA and CRENESSITY. The manufacture of our products for clinical trials and commercial purposes is subject to specific FDA and equivalent foreign regulations, including current Good Manufacturing Practice regulations. Our third-party manufacturers might not comply with FDA or equivalent foreign regulations relating to manufacturing our products for clinical trials and commercial purposes or other regulatory requirements now or in the future. Our reliance on contract manufacturers also exposes us to the following risks:
•contract manufacturers may encounter difficulties in achieving volume production, quality control or quality assurance, and also may experience shortages in qualified personnel or materials and ingredients necessary to conduct their operations. As a result, our contract manufacturers might not be able to meet our clinical schedules or adequately manufacture our products in commercial quantities when required;
•switching manufacturers may be difficult because the number of potential manufacturers is limited. It may be difficult or impossible for us to find a replacement manufacturer quickly on acceptable terms, or at all;
•our contract manufacturers may not perform as agreed or may not remain in the contract manufacturing business for the time required to successfully produce, store or distribute our products or product candidates; and
•drug manufacturers are subject to ongoing periodic unannounced inspection by the FDA, the U.S. Drug Enforcement Administration, equivalent foreign regulatory authorities, and other agencies to ensure strict compliance with current good manufacturing practices (cGMP) and other government regulations and corresponding foreign standards. Any delay, interruption, or other issue that arises in the manufacture of our products or product candidates as a result of a failure of a third-party manufacturer to pass regulatory inspections or maintain cGMP compliance could significantly impair our ability to develop, obtain approval for, or successfully commercialize our products.
Further, changes in federal policy could affect the geopolitical landscape and could give rise to circumstances that negatively affect our business. The third parties that manufacture our products have manufacturing facilities located in Europe. The U.S. has implemented, and has proposed to further implement, tariffs that may increase the costs of our third-party manufacturers and the expense to us to produce the drug compounds we use in our clinical trials and for the commercialization of our products. If such actions were to materially affect us or our third-party manufacturers, we may not be able to successfully develop our product candidates or commercialize our products.
Our current dependence upon third parties for the manufacture of our products may reduce our profit margin, if any, on the sale of INGREZZA, CRENESSITY, or our future products and our ability to develop and deliver products on a timely and competitive basis.
We depend on our current collaborators for the development and commercialization of several of our products and product candidates and may need to enter into future collaborations to develop and commercialize certain of our product candidates.
We depend on our current collaborators for the development and commercialization of several of our products and product candidates and may need to enter into future collaborations to develop and commercialize certain of our product candidates. For example, we depend on AbbVie for the manufacture and commercialization of ORILISSA and ORIAHNN and for the continued development of elagolix. We collaborate with MTPC for the commercialization of DYSVAL in Japan and for the continued development and commercialization of valbenazine for movement disorders in other select Asian markets. Some of our other collaborators include Nxera Pharma UK Limited (formerly Sosei Heptares), Takeda Pharmaceutical Company Limited, Voyager Therapeutics, Inc., and Xenon Pharmaceuticals Inc.
Our current and future collaborations and licenses could subject us to a number of risks, including:
•strategic collaborators may sell, transfer or divest assets or programs related to our partnered product or product candidates;
•we may be required to undertake the expenditure of substantial operational, financial and management resources;
•we may be required to assume substantial actual or contingent liabilities;
•we may not be able to control the amount and timing of resources that our strategic collaborators devote to the development or commercialization of our products or product candidates;
•we may not be able to influence our strategic collaborator’s decisions regarding the development and collaboration of our partnered product and product candidates, and as a result, our collaboration partners may not pursue or prioritize the development and commercialization of those partnered products and product candidates in a manner that is in our best interest;
•strategic collaborators may select indications or design clinical trials in a way that may be less successful than if we were doing so;
•strategic collaborators may not conduct collaborative activities in a timely manner, provide insufficient funding, terminate a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new version of a product candidate for clinical testing;
•strategic collaborators may not pursue further development and commercialization of products resulting from the strategic collaboration arrangement or may elect to discontinue research and development programs;
•disagreements or disputes may arise between us and our strategic collaborators that result in delays or in costly litigation or arbitration that diverts management’s attention and consumes resources;
•strategic collaborators may experience financial difficulties;
•strategic collaborators may not properly maintain, enforce or defend our intellectual property rights or may use our proprietary information in a manner that could jeopardize or invalidate our proprietary information or expose us to potential litigation;
•we or strategic collaborators could terminate the arrangement (in whole or in part) or allow it to expire, which would delay the development and commercialization, result in disagreements or disputes or may increase the cost of developing and commercializing our products or product candidates;
•strategic collaborators could develop, either alone or with others, products or product candidates that may compete with ours; and
•our strategic collaborator’s decisions regarding the development and commercialization of a partnered product or product candidate within their territory(ies) could negatively impact us in the territories where we have development and commercialization rights for such product or product candidate.
If any of these issues arise, it may delay and/or negatively impact the development and commercialization of drug candidates and, ultimately, our generation of product revenues.
We license some of our core technologies and drug candidates from third parties. If we default on any of our obligations under those licenses, or violate the terms of these licenses, we could lose our rights to those technologies and drug candidates or be forced to pay damages.
We are dependent on licenses from third parties for some of our key technologies. These licenses typically subject us to various commercialization, reporting and other obligations. If we fail to comply with these obligations, we could lose important rights. If we were to default on our obligations under any of our licenses, we could lose some or all of our rights to develop, market and sell products covered by these licenses. In addition, several of our collaboration and license agreements allow our licensors to terminate such agreements if we challenge the validity or enforceability of certain intellectual property rights or if we commit a material breach in whole or in part of the agreement and do not cure such breach within the agreed upon cure period. In addition, if we were to violate any of the terms of our licenses, we could become subject to damages. Likewise, if we were to lose our rights under a license to use proprietary research tools, it could adversely affect our existing collaborations or adversely affect our ability to form new collaborations. We also face the risk that our licensors could, for a number of reasons, lose patent protection or lose their rights to the technologies we have licensed, thereby impairing or extinguishing our rights under our licenses with them.
* Our customers are concentrated and therefore the loss of a significant customer may harm our business.
We have entered into agreements for the distribution of INGREZZA with a limited number of specialty pharmacy providers and distributors. Four of these customers represent over 90% of our total gross product sales. In addition, CRENESSITY is distributed by one specialty pharmacy provider. If any of our significant customers becomes subject to bankruptcy, is unable to pay us for our products or wants to terminate their relationship with us, or if we otherwise lose any of these significant customers, our revenue, results of operations and cash flows would be adversely affected. Also, we may need to enter into agreements with additional distributors or specialty pharmacy providers, and there is no guarantee that we will be able to do so on commercially reasonable terms or at all. Even if we replace the loss of a significant customer, we cannot predict with certainty that such transition would not result in a decline in our revenue, results of operations and cash flows.
We may need additional capital in the future. If we cannot raise additional funding, we may be unable to fund our business plan and our future research, development, commercial and manufacturing efforts.
Our future funding requirements will depend on many factors and we may need to raise additional capital to fund our business plan and our future research, development, commercial and manufacturing efforts.
Our future capital requirements will depend on many factors, including:
•the commercial success of INGREZZA and CRENESSITY;
•the cost of commercialization activities and arrangements, including advertising campaigns;
•continued scientific progress in our R&D and clinical development programs;
•the magnitude and complexity of our research and development programs;
•progress with preclinical testing and clinical trials;
•the time and costs involved in obtaining regulatory approvals;
•the cost involved in filing and pursuing patent applications, enforcing patent claims, or engaging in interference proceedings or other patent litigation;
•costs associated with securing adequate coverage and reimbursement for our products;
•competing technological and market developments;
•developments related to any future litigation;
•the cost of manufacturing our product candidates;
•the impact of pandemics or epidemics on our business; and
•the cost of any strategic alliances, collaborations, product in-licensing, or acquisitions.
We may seek additional funding through public or private sales of our securities, including equity securities. In addition, we have previously financed capital purchases and may continue to pursue opportunities to obtain debt financing in the future. Additional equity or debt financing might not be available on reasonable terms, if at all. Any additional equity financings will be dilutive to our stockholders and any debt financings may involve operating covenants that restrict our business.
We expect to increase our expenses for the foreseeable future, and we may not be able to sustain growth and profitability.
We received FDA approval for INGREZZA for tardive dyskinesia in April 2017 and for chorea associated with Huntington's disease in August 2023. We received FDA approval for CRENESSITY capsules and oral solution as an adjunctive treatment to glucocorticoid replacement to control androgens in adult and pediatric patients four years of age and older with classic CAH in December 2024. Our partner AbbVie received FDA approval for ORILISSA for endometriosis in July 2018 and for ORIAHNN for uterine fibroids in May 2020. Additionally, our partner MTPC received Japanese Ministry of Health, Labour, and Welfare approval for DYSVAL for the treatment of tardive dyskinesia in March 2022. However, we have not yet obtained regulatory approvals for any other product candidates. Even if we continue to succeed in commercializing INGREZZA, or are successful in commercializing CRENESSITY or any of our product candidates, we may not be able to sustain profitability. We also expect to continue to incur significant operating and capital expenditures as we:
•commercialize INGREZZA for tardive dyskinesia and chorea associated with Huntington's disease;
•commercially launch CRENESSITY as an adjunctive treatment to glucocorticoid replacement to control androgens in adult and pediatric patients four years of age and older with classic CAH;
•seek regulatory approvals for our product candidates or for additional indications for our current products;
•develop, formulate, manufacture and commercialize our product candidates;
•in-license or acquire new product development opportunities;
•implement additional internal systems and infrastructure; and
•hire additional clinical, scientific, sales, marketing and administrative personnel.
We expect to increase our expenses and other investments in the coming years as we fund our operations and capital expenditures. Thus, our future operating results and profitability may fluctuate from period to period due to the factors described above, and we will need to generate significant revenues to achieve and maintain profitability and positive cash flow on a sustained basis. We may not be able to generate these revenues, and we may never achieve profitability on a sustained basis in the future. In addition, there is no guarantee that our prioritization determinations regarding our R&D and clinical development programs, including the acceleration or discontinuation of certain programs and product candidates, will generate their expected benefits and/or meet investor expectations. Our prioritization decisions may also adversely affect other internal programs and initiatives as well as our ability to recruit and retain skilled and motivated personnel. Our failure to maintain or increase profitability on a sustained basis could negatively impact the market price of our common stock.
* The independent clinical investigators and contract research organizations that we rely upon to conduct our clinical trials may not be diligent, careful or timely, or may make mistakes in the conduct of our trials.
We depend on independent clinical investigators and CROs to conduct our clinical trials under their agreements with us. The investigators are not our employees, and we cannot control the amount or timing of resources that they devote to our programs. If our independent investigators fail to devote sufficient time and resources to our drug development programs, or if their performance is substandard, or not in compliance with good clinical practices (GCPs), it may delay or prevent the approval of our regulatory applications and our introduction of new treatments. The CROs we contract with for execution of our clinical trials play a significant role in the conduct of the trials and the subsequent collection and analysis of data. Failure of the CROs to meet their obligations could adversely affect clinical development of our product candidates. Moreover, these independent investigators and CROs may also have relationships with other commercial entities, some of which may compete with us. If independent investigators and CROs assist our competitors at our expense, it could harm our competitive position.
We are subject to ongoing obligations and continued regulatory review for INGREZZA and CRENESSITY. Additionally, our product candidates, if approved, could be subject to labeling and other post-marketing requirements and restrictions.
Regulatory approvals for any of our product candidates may be subject to limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials, and surveillance to monitor the safety and efficacy of the product candidate. For INGREZZA, CRENESSITY, and any product candidate that the FDA or a comparable foreign regulatory authority approves, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for the product is subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with GCPs for any clinical trials that we conduct post-approval. In addition, advertising and promotional materials for approved products must comply with FDA regulations and those of foreign regulatory authorities and may be subject to other potentially applicable federal and state laws.
Failure to comply with these ongoing regulatory requirements, or later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, may result in, among other things:
•restrictions on the marketing or manufacturing of the product, changes in the product’s label, withdrawal of the product from the market, or voluntary or mandatory product recalls;
•fines, warning or untitled letters or holds on clinical trials;
•refusal by the FDA or similar foreign regulatory authorities to approve pending applications or supplements to approved applications filed by us, or suspension or revocation of product license approvals;
•adverse inspection findings, enforcement actions, or other activities that temporarily delay manufacture and distribution of our products;
•product seizure or detention, or refusal to permit the import or export of products; and
•product injunctions or the imposition of civil or criminal penalties.
The occurrence of any of these events may adversely affect our business, prospects and ability to achieve or sustain profitability on a sustained basis.
The U.S. Supreme Court’s June 2024 decision in Loper Bright Enterprises v. Raimondo overturned the longstanding Chevron doctrine, under which courts were required to give deference to regulatory agencies’ reasonable interpretations of ambiguous federal statutes. The Loper decision could result in additional legal challenges to regulations and guidance issued by federal agencies, including the FDA, on which we rely. Any such legal challenges, if successful, could have a material impact on our business. Additionally, the Loper decision may result in increased regulatory uncertainty, inconsistent judicial interpretations, and other impacts to the agency rulemaking process, any of which could adversely impact our business and operations. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action or as a result of legal challenges, either in the United States or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, our business could be materially harmed.
If the market opportunities for our products and product candidates are smaller than we believe they are, our expected revenues may be adversely affected, and our business may suffer.
Certain of the diseases that INGREZZA, CRENESSITY, and our product candidates are being developed to address are in underserved and underdiagnosed populations. Our projections of both the number of people who have these diseases, as well as the subset of people with these diseases who will seek treatment utilizing our products or product candidates, may not be accurate. If our estimates of the prevalence or number of patients potentially on therapy prove to be inaccurate, the market opportunities for INGREZZA, CRENESSITY, and our product candidates may be smaller than we believe they are, our prospects for generating expected revenue may be adversely affected and our business may suffer.
* Because our operating results may vary significantly in future periods, our stock price may decline.
Our quarterly revenues, expenses and operating results have fluctuated in the past and are likely to fluctuate significantly in the future. Our financial results are unpredictable and may fluctuate, for among other reasons, due to seasonality and timing of customer purchases and commercial sales of INGREZZA and CRENESSITY, royalties from out-licensed products, the impact of Medicare Part D coverage, including redesign of the Part D benefit enacted as part of the Inflation Reduction Act, our achievement of product development objectives and milestones, clinical trial enrollment and expenses, research and development expenses and the timing and nature of contract manufacturing, contract research payments, fluctuations in our effective tax rate, disruptions caused by man-made or natural disasters, public health pandemics or epidemics, armed conflicts, trade restrictions, tariffs, or other business interruptions. Because a majority of our costs are predetermined on an annual basis, due in part to our significant research and development costs, small declines in revenue could disproportionately affect financial results in a quarter. Thus, our future operating results and profitability may fluctuate from period to period, and even if we become profitable on a quarterly or annual basis, we may not be able to sustain or increase our profitability. Moreover, as our company and our market capitalization have grown, our financial performance has become increasingly subject to quarterly and annual comparisons with the expectations of securities analysts or investors. The failure of our financial results to meet these expectations, either in a single quarterly or annual period over a sustained period of time, could cause our stock price to decline.
Changes in tax laws or regulations that are applied adversely to us or our customers may have a material adverse effect on our business, cash flows, financial condition or results of operations.
New tax laws or regulations could be enacted at any time, and existing tax laws or regulations could be interpreted, modified or applied in a manner that is adverse to us or our customers, which could adversely affect our business and financial condition. For example, the Tax Cuts and Jobs Act of 2017, the Coronavirus Aid, Relief, and Economic Security Act and the Inflation Reduction Act enacted many significant changes to the U.S. tax laws. Among other changes, the Tax Cuts and Jobs Act eliminated the option to deduct research and development expenses for tax purposes in the year incurred and requires taxpayers to capitalize and subsequently amortize such expenses over five years for research activities conducted in the U.S. and over 15 years for research activities conducted outside the U.S. If the requirement to amortize research and development expenditures is not repealed or otherwise modified, it will continue to have an adverse effect on our tax liability. Furthermore, our tax obligations and effective tax rate in the jurisdictions in which we conduct business could increase as a result of international tax developments, including the implementation of the Organization for Economic Co-operation and Development’s (OECD) Base Erosion and Profit Shifting “Two-Pillar” framework, which involves the reallocation of taxing rights in respect of certain multinational enterprises above a fixed profit margin to the jurisdictions in which they carry on business (referred to as Pillar One) and the imposition of a minimum effective corporate tax rate (referred to as Pillar Two). Certain countries in which we conduct business have enacted, or are in the process of enacting, core provisions of the Pillar Two rules. We continue to evaluate and assess the potential impact of these new rules, including on our effective tax rate, and our eligibility to qualify for transition and safe harbor. Any changes in tax laws, including any new tax legislation or initiatives, could not only significantly increase our tax provision, cash tax liabilities, and effective tax rate, but could also have a material impact on the value of our deferred tax assets, result in significant one-time charges and ongoing compliance costs, and increase our future tax expense.
Our effective tax rate may fluctuate, and we may incur obligations in tax jurisdictions in excess of accrued amounts.
We have a multinational tax structure and are subject to income tax in the U.S. and various foreign jurisdictions, including the United Kingdom and Switzerland. Our effective tax rate is influenced by many factors including changes in our operating structure, changes in the mix of our earnings among countries, our allocation of profits and losses among our subsidiaries, our intercompany transfer pricing agreements and rules relating to transfer pricing, our inability to secure or sustain acceptable agreements with tax authorities, the impact of stock-based compensation, the availability of U.S. research and development tax credits, the results of examinations and audits of our tax filings, changes in accounting for income taxes, and future changes in tax laws and regulations in the U.S. and foreign countries. Significant judgment is required in determining our tax liabilities including management’s judgment for uncertain tax positions. The Internal Revenue Service, other domestic taxing authorities, or foreign taxing authorities may disagree with our interpretation of tax laws as applied to our operations. Our reported effective tax rate and after-tax cash flows may be materially and adversely affected by tax assessments in excess of amounts accrued for our financial statements. This could cause us to experience an effective tax rate significantly different from previous periods or our current expectations.
* The price of our common stock is volatile.
The market prices for securities of biotechnology and pharmaceutical companies historically have been highly volatile, and the market for these securities has from time to time experienced significant price and volume fluctuations that are unrelated to the operating performance of particular companies. For example, the applicability of the Medicare drug price negotiation provisions in the Inflation Reduction Act negatively affected investor sentiment and resulted in significant volatility. Furthermore, especially as we and our market capitalization have grown, the price of our common stock has been increasingly affected by quarterly and annual comparisons with the valuations and recommendations of the analysts who cover our business. If our results do not meet these analysts’ forecasts, the expectations of our investors or the financial guidance we provide to investors in any period, which is based on assumptions that may be incorrect or that may change from quarter to quarter, the market price of our common stock could decline. Over the course of the last 12 months, the price of our common stock has ranged from approximately $84 per share to approximately $158 per share.
The market price of our common stock may fluctuate in response to many factors, including:
•sales of INGREZZA and CRENESSITY;
•failure of CRENESSITY to achieve commercial success;
•the results of our clinical trials;
•reports of safety issues related to INGREZZA or CRENESSITY;
•any delay in filing an IND, NDA, marketing authorization application (MAA), or other regulatory submission for any of our product candidates and any adverse development or perceived adverse development with respect to the applicable regulatory agency's review of that IND, NDA, MAA, or other regulatory submission;
•developments concerning new and existing collaboration agreements;
•announcements of technological innovations or new therapeutic products by us or others, including our competitors;
•general economic and market conditions, including economic and market conditions affecting the biotechnology industry;
•developments in patent or other proprietary rights;
•developments related to the FDA, CMS and foreign regulatory agencies;
•government regulation, including the Inflation Reduction Act;
•future sales of our common stock by us or our stockholders;
•any trading activity pursuant to a share repurchase program;
•comments by securities analysts;
•additions or departures of key personnel;
•fluctuations in our operating results;
•potential litigation matters;
•government and third-party payor coverage and reimbursement;
•failure of any of our product candidates to achieve commercial success even if approved;
•disruptions caused by man-made or natural disasters, public health pandemics or epidemics, armed conflicts, trade restrictions, tariffs, including protectionist or retaliatory measures taken by the United States or other countries, or other business interruptions; and
•public concern as to the safety of our drugs.
In addition, we are a member of the S&P MidCap 400 index. If we cease to be represented in the S&P MidCap 400 index, or other indexes or indexed products, as a result of our market capitalization falling below the threshold for inclusion in the index, certain institutional shareholders may, due to their internal policies and investment guidelines, be required to sell their shareholdings. Such sales may result in further negative pressure on our stock price and, when combined with reduced trading volume and liquidity, could adversely affect the value of your investment and your ability to sell your shares.
* There can be no assurance that any share repurchases will enhance long-term stockholder value.
In October 2024, our Board of Directors authorized a share repurchase program to repurchase up to $300 million of our common stock and we subsequently entered into an accelerated share repurchase (ASR) transaction to repurchase the entirety of this authorized amount. The purchase period for this ASR transaction ended in February 2025 and an aggregate of 2.3 million shares were delivered to us at an average repurchase price of $131.83 per share. Additionally, in February 2025, our Board of Directors authorized a share repurchase program under which we may repurchase up to $500 million of our common stock (of which $350 million remained available as of March 31, 2025). This subsequent share repurchase authorization was in addition to the $300 million accelerated share repurchase program that was announced in October 2024 and completed in early February 2025. Our share repurchases may change from time to time, and we can provide no assurance that we will repurchase shares of our common stock at favorable prices, in particular amounts, or at all, and any repurchases may not enhance long-term stockholder value or prove to be the best use of our cash. If our Board of Directors authorizes any additional share repurchase programs, it could affect the trading price of our stock and increase volatility.
* Compliance with changing laws, regulations and standards relating to various aspects of our business, including corporate governance, workforce initiatives and public disclosure, may result in additional expenses and failure to comply with such laws, regulations and standards could adversely affect our business.
Changing laws, regulations and standards relating to various aspects of our business, including corporate governance, workforce initiatives and public disclosure, including as a result of the Dodd-Frank Wall Street Reform and Consumer Protection Act, new SEC regulations and Nasdaq rules and executive orders, are creating uncertainty for companies such as ours. These laws, regulations and standards are subject to varying interpretations in some cases due to their lack of specificity, and as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies, which could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure, policies and governance practices. We are committed to maintaining high standards of corporate governance, workforce initiatives and public disclosure. As a result, our efforts to comply with evolving laws, regulations and standards have resulted in, and are likely to continue to result in, increased selling, general and administrative expenses and management time related to compliance activities. If we fail, or are perceived to fail, to comply with these laws, regulations and standards, our reputation may be harmed and we might be subject to litigation, sanctions, investigations or other regulatory proceedings by regulatory authorities, such as the SEC. Any such action could adversely affect our financial results and the market price of our common stock.
Increasing use of social media could give rise to liability and result in harm to our business.
Our employees are increasingly utilizing social media tools and our website as a means of communication. Despite our efforts to monitor social media communications, there is risk that the unauthorized use of social media by our employees to communicate about our products or business, or any inadvertent disclosure of material, nonpublic information through these means, may result in violations of applicable laws and regulations, which may give rise to liability and result in harm to our business. In addition, there is also risk of inappropriate disclosure of sensitive information, which could result in significant legal and financial exposure and reputational damages that could potentially have a material adverse impact on our business, financial condition and results of operations. Furthermore, negative posts or comments about us or our products on social media could seriously damage our reputation, brand image and goodwill.
We may be subject to claims that we or our employees have wrongfully used or disclosed alleged trade secrets of their former employers.
As is commonplace in the biotechnology industry, we employ individuals who were previously employed at other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although no claims against us are currently pending, we may be subject to claims that these employees or we have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers. Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management.
Risks Related to Our Industry
*Enacted healthcare reform, drug pricing measures and other recent legislative initiatives, including the Inflation Reduction Act of 2022, could adversely affect our business.
The business and financial condition of pharmaceutical and biotechnology companies are affected by the efforts of government and third-party payors to contain or reduce the costs of healthcare and to lower drug prices. In the U.S., comprehensive drug pricing legislation enacted by the Federal government implements, for the first time, government control over the pricing of certain prescription pharmaceuticals. Moreover, in some foreign jurisdictions, pricing of prescription pharmaceuticals is also subject to government control. Additionally, other federal and state laws impose obligations on manufacturers of pharmaceutical products, among others, related to disclosure of new drug products introduced to the market and increases in drug prices above a specified threshold.
For example, the Inflation Reduction Act of 2022, or the IRA, provides for, among other things: (1) the Secretary of the HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare; (2) the redesign of the Medicare Part D prescription drug benefit to lower patient out-of-pocket costs and increase manufacturer liability; and (3) drug manufacturers to pay rebates on drugs whose prices increase greater than the rate of inflation. The IRA also extends enhanced subsidies for individuals purchasing health insurance coverage in the ACA marketplaces through plan year 2025 and in 2025, eliminated the “donut hole” under the Medicare Part D program and created a new, permanent cap on beneficiary out-of-pocket spending for Part D drugs, in addition to a newly established manufacturer discount program. The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has issued and updated and will continue to issue and update guidance as these programs are implemented. These provisions took effect progressively beginning in 2023. On August 15, 2024, HHS announced the negotiated prices of the first 10 drugs that were subject to price negotiations (for initial price applicability year 2026), although the Medicare drug price negotiation program is currently subject to legal challenges. On January 17, 2025, HHS announced its selection of fifteen additional drugs covered under Part D for negotiation in 2025 (for initial price applicability year 2027). Certain high-expenditure Part B and Part D drugs/biologics will be selected for negotiation in 2026 (for initial price applicability year 2028) and annually thereafter. We were notified in January 2025 that INGREZZA qualifies for the small biotech exception, which provides an exemption from selection until 2027 (for initial price applicability year 2029, pursuant to which negotiated pricing would go into effect, if selected). If negotiated for initial price applicability year 2029, we expect that the negotiated price for INGREZZA would be constrained by the "short monopoly" price ceiling and temporary price floor for small biotech drugs.
Additionally, on January 1, 2025, the Centers for Medicare & Medicaid Services (CMS) implemented those provisions of the IRA establishing a new Medicare Part D manufacturer discount program. Under this discount program and subject to certain exceptions, manufacturers must give a 10 percent discount on Part D program drugs in the initial coverage phase, and a 20 percent discount on Part D drugs when the beneficiary enters the catastrophic coverage phase (the phase after the patient incurs costs above the initial phase out-of-pocket threshold, which is $2,000). However, the IRA allows the 10 and 20 percent discounts to be phased in over a multi-year period for “specified manufacturers” and “specified small manufacturers”. During this phase-in period, such manufacturers would pay a lower percentage discount on Medicare Part D program drugs. In April 2024, the Company was notified by CMS that it qualified as a “specified small manufacturer” and will receive the discount phase-in discussed above for INGREZZA. INGREZZA is reimbursed under Medicare Part D, and increased discounts could impact INGREZZA revenues, while also having an industry-wide impact on the cost of other Part D program drugs such as AUSTEDO and AUSTEDO XR, marketed by Teva Pharmaceutical Industries. The overall impact on INGREZZA revenues is inherently uncertain and difficult to predict, and we are still evaluating the potential impact of this discount program and our designation as a “specified small manufacturer.”
Our designation as a “specified small manufacturer” under the new Medicare Part D manufacturer discount program and INGREZZA’s qualification for the small biotech exception for purposes of the Medicare drug price negotiation program are subject to various requirements and there is no assurance that we will continue to qualify for these exemptions in the future. The loss or potential loss of these exemptions, including as a result of a third party acquiring us, could have an adverse impact on our business.
Prior to the IRA’s enactment, the most significant recent federal legislation impacting the pharmaceutical industry occurred in March 2010, when the ACA was signed into law. The ACA was intended to broaden access to health insurance and reduce the number of uninsured individuals, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose taxes and fees on the health industry and impose additional health policy reforms.
Other legislative changes have been adopted since the ACA was enacted. These changes include aggregate reductions to Medicare payments to providers of up to 2% per fiscal year pursuant to the Budget Control Act of 2011, which began in 2013 and, due to subsequent legislative amendments to the statute, including the Infrastructure Investment and Jobs Act and Consolidated Appropriations Act of 2023, will remain in effect until 2032. The American Taxpayer Relief Act of 2012, among other things, further reduced Medicare payments to several providers, including hospitals and cancer treatment centers, increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. For example, on January 5, 2024, the FDA approved Florida’s SIP proposal to import certain drugs from Canada for specific state healthcare programs. It is unclear how this program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the U.S. or Canada. Other states have also submitted SIP proposals that are pending review by the FDA. Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs. Further, certain states through legislation have created a state PDAB to help control costs of drugs for that state. The functions of the PDABs vary by state, and may include among other things, recommending or setting upper limits on the price the state pays for certain drugs, performing drug affordability reviews, and advising state lawmakers on additional ways to reduce the state’s drug spending. It is possible that the actions taken by the PDABs may result in lower prices for certain drug products sold in their states.
The implementation of these cost containment measures may prevent us from being able to generate revenue, attain sustained profitability or commercialize our drugs, particularly since the majority of our current revenue is derived from federal healthcare programs, including Medicare and Medicaid.
If we are unable to protect our intellectual property, our competitors could develop and market products based on our discoveries, which may reduce demand for our products.
Our success will depend on our ability to, among other things:
•obtain patent protection for our products;
•preserve our trade secrets;
•prevent third parties from infringing upon our proprietary rights; and
•operate without infringing upon the proprietary rights of others, both in the U.S. and internationally.
Because of the substantial length of time and expense associated with bringing new products through the development and regulatory approval processes in order to reach the marketplace, the pharmaceutical industry places considerable importance on obtaining patent and trade secret protection for new technologies, products and processes. Accordingly, we intend to seek patent protection for our proprietary technology and compounds. However, we face the risk that we may not obtain any of these patents and that the breadth of claims we obtain, if any, may not provide adequate protection of our proprietary technology or compounds. Additionally, if our employees, commercial collaborators or consultants use generative artificial intelligence (AI) technologies to develop our proprietary technology and compounds, it may impact our ability to obtain or successfully defend certain intellectual property rights.
We also rely upon unpatented trade secrets and improvements, unpatented know-how and continuing technological innovation to develop and maintain our competitive position, which we seek to protect, in part, through confidentiality agreements with our commercial collaborators, employees and consultants. We also have invention or patent assignment agreements with our employees and some, but not all, of our commercial collaborators and consultants. However, if our employees, commercial collaborators or consultants breach these agreements, we may not have adequate remedies for any such breach, and our trade secrets may otherwise become known or independently discovered by our competitors.
In addition, although we own a number of patents, the issuance of a patent is not conclusive as to its validity or enforceability, and third parties may challenge the validity or enforceability of our patents. We cannot assure you how much protection, if any, will be given to our patents if we attempt to enforce them and they are challenged in court or in other proceedings. It is possible that a competitor may successfully challenge our patents or that challenges will result in limitations of their coverage. Moreover, competitors may infringe our patents or successfully avoid them through design innovation. In addition, potential competitors have in the past and may in the future file an abbreviated new drug application (ANDA) with the FDA seeking approval to market a generic version of our products, or our competitors’ products, before the expiration of the patents covering our products or our competitors’ products, as applicable. To prevent infringement or unauthorized use, we have in the past and may in the future need to file infringement claims, which are expensive and time-consuming. In addition, in an infringement proceeding a court may decide that a patent of ours or a patent of a competitor is not valid or is unenforceable or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover its technology. Derivation proceedings declared by the U.S. Patent and Trademark Office may be necessary to determine the priority of inventions with respect to our patent applications (or those of our licensors) or a patent of a competitor. Litigation or derivation proceedings may fail and, even if successful, may result in substantial costs and be a distraction to management. Litigation or derivation proceedings, including proceedings of a competitor, may also result in a competitor entering the marketplace faster than expected. We cannot assure you that we will be able to prevent misappropriation of our proprietary rights, particularly in countries where the laws may not protect such rights as fully as in the U.S.
* Changes in the FDA, other government agencies or comparable foreign regulatory authorities could hinder their ability to hire and retain key leadership and other personnel, delay the development and commercialization of new products or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
The ability of the FDA or comparable foreign regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and manage user fee programs, and statutory, regulatory, and policy changes. FDA review performance has fluctuated in recent years as a result. In addition, government funding of other government agencies or comparable foreign regulatory authorities on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable.
Disruptions at the FDA, other government agencies or comparable foreign regulatory authorities may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical employees and stop critical activities. If a prolonged government shutdown occurs, including as a result of reaching the debt ceiling, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business. Further, government shutdowns could impact our ability to access the public markets and obtain additional capital in the future.
Proposed healthcare reform, drug pricing measures and other prospective legislative initiatives could adversely affect our business.
We expect that there will continue to be a number of federal and state proposals to implement additional government controls over the pricing of prescription pharmaceuticals. Increasing emphasis on reducing the cost of healthcare in the U.S. will continue to put pressure on the pricing and reimbursement of prescription pharmaceuticals.
In addition, certain jurisdictions outside of the U.S., including the EU, have instituted price ceilings on specific products and therapies, as described further in the risk factor titled “Government and third-party payors may impose sales and pharmaceutical pricing controls on our products or limit coverage and/or reimbursement for our products or impose policies and/or make decisions regarding the status of our products that could limit our product revenues and delay sustained profitability.”
We are currently unable to predict what other additional legislation or regulation, if any, relating to the healthcare industry may be enacted in the future or what effect recently enacted federal or equivalent foreign legislation or any such additional legislation or regulation would have on our business, particularly in light of the recent U.S. Presidential and Congressional elections. The pendency or approval of such proposals or reforms could result in a decrease in our stock price or limit our ability to raise capital or to enter into collaboration agreements for the further development and commercialization of our programs and products.
Any relationships with healthcare professionals, principal investigators, consultants, customers (actual and potential) and third-party payors in connection with our current and future business activities are and will continue to be subject, directly or indirectly, to federal and state healthcare laws. If we are unable to comply, or have not fully complied, with such laws, we could face penalties, contractual damages, reputational harm, diminished profits and future earnings and curtailment or restructuring of our operations.
Our business operations and activities may be directly, or indirectly, subject to various federal and state healthcare laws, including without limitation, fraud and abuse laws, false claims laws, data privacy and security laws, as well as transparency laws regarding payments or other items of value provided to healthcare providers. These laws may restrict or prohibit a wide range of business activities, including, but not limited to, research, manufacturing, distribution, pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. These laws may impact, among other things, our current activities with principal investigators and research subjects, as well as current and future sales, marketing, patient co-payment assistance and education programs.
Such laws include:
•the federal Anti-Kickback Statute which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid;
•the federal civil and criminal false claims laws, including the federal civil False Claims Act, and Civil Monetary Penalties Laws, which impose criminal and civil penalties against individuals or entities for, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;
•HIPAA, which imposes criminal and civil liability for, among other things, executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
•HIPAA, as amended by HITECH and its implementing regulations, which also imposes obligations, including mandatory contractual terms, on covered entities, including certain healthcare providers, health plans and healthcare clearinghouses, as well as their business associates and their covered subcontractors, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;
•the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate family members; and
•analogous state, local and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third party payors, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures or drug pricing; state laws that require disclosure of price increases above certain identified thresholds as well as of new commercial launches in the state; state laws that create Prescription Drug Price Affordability Boards to review or attempt to cap drug spending; state and local laws that require the registration of pharmaceutical sales representatives; state and local “drug take back” laws and regulations; and state and foreign laws governing the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Efforts to ensure that our business arrangements will comply with applicable healthcare laws may involve substantial costs. While our interactions with healthcare professionals, including our speaker programs and other arrangements have been structured to comply with these laws and related guidance, it is possible that governmental and enforcement authorities will conclude that our business practices, business practices of our vendors or consultants, or a rogue employee’s activities, may not comply with current or future statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws. For example, we maintain a patient assistance program to help eligible patients afford our products. These and other types of programs have become the subject of governmental scrutiny, and numerous organizations, including pharmaceutical manufacturers, have been subject to litigation, enforcement actions and settlements related to their patient assistance programs. If our operations or activities or those of our vendors are found to be in violation of any of the laws described above or any other applicable governmental regulations, we may be subject to, without limitation, significant civil, criminal and administrative penalties, damages, monetary fines, disgorgement, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, contractual damages, reputational harm, diminished profits and future earnings and curtailment or restructuring of our operations, any of which could adversely affect our ability to operate.
Any sales of our product once commercialized outside the U.S. will also likely subject us to foreign equivalents of the healthcare laws mentioned above, among other foreign laws. Additionally, because of our U.S. and international operations, we are also subject to anti-corruption laws and regulations, in the United States and internationally, including but not limited the U.S. Foreign Corrupt Practices (FCPA), the U.K. Bribery Act 2010, and other applicable anti-bribery and corruption laws. Anti-corruption laws are interpreted broadly and prohibit corporations and individuals from engaging in certain activities to obtain or retain business or to influence a person working in an official capacity. It is illegal to pay, offer to pay or authorize the payment of anything of value to any foreign government official, government staff member, political party, or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity. The FCPA also imposes accounting standards and requirements on publicly traded U.S. corporations and their foreign affiliates, which are intended to prevent the diversion of corporate funds to the payment of bribes and other improper payments. Recent years have seen substantial increase in the global enforcement of anti-corruption laws. Our operations outside the United States could increase the risk of such violations. Our business is also heavily regulated and involves significant interaction with foreign officials. In many countries outside the U.S., independent clinical investigators conducting our clinical trials and prescribers of our products are employed by government entities, and purchasers themselves can be government entities. As such, our interactions with such investigators, prescribers and purchasers may be subject to regulation under the FCPA, as well as other similar under anti-corruption laws and/or regulations enacted by other countries. Failure to comply with these laws, where applicable, can result in significant penalties, including the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, disgorgement, imprisonment, possible exclusion from participation in Medicare, Medicaid and other federal and equivalent foreign healthcare programs, and additional reporting requirements and regulatory oversight, any of which could adversely affect our ability to operate our business and our results of operations.
* International trade policies, including tariffs, sanctions and trade barriers may adversely affect our business, financial condition, results of operations and prospects.
We operate in a global economy, and our business depends on a global supply chain for the development, manufacturing, and distribution of our products, and for the advancement of our development programs. There is inherent risk, based on the complex relationships among the U.S. and the countries in which we conduct our business, that political, diplomatic, and national security factors can lead to global trade restrictions and changes in trade policies and export regulations that may adversely affect our business and operations.
We source and procure APIs, precursor chemicals, and specialized equipment from international suppliers, with substantial reliance on foreign contract manufacturers in Europe. Tariff policies, particularly those affecting pharmaceutical products, could increase our costs and reduce our profitability. Additionally, recent policy discussions have included potential targeted tariffs or other trade measures specifically aimed at pharmaceutical products and ingredients as part of broader healthcare cost control or national security initiatives. Unlike consumer goods, pharmaceuticals face unique regulatory constraints that make rapid supply chain adjustments particularly difficult and costly. Should tariffs be imposed specifically targeting pharmaceutical imports, our production costs could rise, and it would be difficult and costly to qualify alternative sources within another country with a lower tariff rate or within the United States, as developing and qualifying alternative sources typically requires substantial time, investment, and regulatory approvals.
Unlike many industries, our ability to pass increased costs to customers is limited by the structure of pharmaceutical pricing and reimbursement systems. As a result, cost increases due to tariffs may be difficult or impossible to pass through to customers.
Current or future tariffs will also result in increased research and development expenses, including with respect to increased costs associated with APIs, raw materials, laboratory equipment and research materials and components. Trade restrictions affecting the import of materials necessary for clinical trials could result in delays to our development timelines. Increased development costs and extended development timelines could place us at a competitive disadvantage compared to companies operating in regions with more favorable trade relationships and could reduce investor confidence and negatively impact our business, results of operations, financial condition and growth prospects.
Trade disputes, tariffs, restrictions and other political tensions between the United States and other countries may also exacerbate unfavorable macroeconomic conditions including inflationary pressures, foreign exchange volatility, financial market instability, and economic recessions or downturns. The ultimate impact of current or future tariffs and trade restrictions remains uncertain and could materially and adversely affect our business, financial condition, and prospects. While we actively monitor these risks, any prolonged economic downturn, escalation in trade tensions, or deterioration in international perception of U.S.-based companies could materially and adversely affect our business, ability to access the capital markets or other financing sources, results of operations, financial condition and prospects. In addition, tariffs and other trade developments have and may continue to heighten the risks related to the other risk factors described elsewhere in this report.
We could face liability if a regulatory authority determines that we are promoting INGREZZA, CRENESSITY, or any of our product candidates that receives regulatory approval, for “off-label” uses.
A company may not promote “off-label” uses for its drug products. An off-label use is the use of a product for an indication that is not described in the product’s FDA-approved label in the U.S. or for uses in other jurisdictions that differ from those approved by the applicable regulatory agencies. Physicians, on the other hand, may prescribe products for off-label uses. Although the FDA and other regulatory agencies do not regulate a physician’s choice of drug treatment made in the physician’s independent medical judgment, they do restrict promotional communications from companies or their sales force with respect to off-label uses of products for which marketing clearance has not been issued. However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA approved labeling. A company that is found to have promoted off-label use of its product may be subject to significant liability, including civil and criminal sanctions.
If the FDA or any other governmental agency, including equivalent foreign authorities, initiates an enforcement action against us, or if we are the subject of a qui tam suit brought by a private plaintiff on behalf of the government, and it is determined that we violated prohibitions relating to the promotion of products for unapproved uses, we could be subject to substantial civil or criminal fines or damage awards and other sanctions such as consent decrees and corporate integrity agreements pursuant to which our activities would be subject to ongoing scrutiny and monitoring to ensure compliance with applicable laws and regulations. Any such fines, awards or other sanctions would have an adverse effect on our revenue, business, financial prospects and reputation.
If our information technology systems, those third parties upon which we rely, or our data is or were compromised, we could experience adverse impacts resulting from such compromise, including, but not limited to, interruptions to our operations such as our clinical trials, claims that we breached our data protection obligations, harm to our reputation, regulatory investigations or actions, litigation, fines and penalties, and a loss of customers or sales.
We are increasingly dependent on information technology systems and infrastructure, including mobile technologies and technology systems and infrastructure of third parties upon whom we rely, including CROs and other vendors, to operate our business. In the ordinary course of our business, we and the third parties upon which we rely, collect, receive, store, process, generate, disclose, make accessible, protect, dispose of, transmit, use, safeguard, share and transfer, or collectively, process, confidential and sensitive electronic information on our networks and in our data centers. This information includes, among other things, de-identified or pseudonymous sensitive personal data (including health data), our intellectual property and proprietary information, the confidential information of our collaborators and licensees, and the personal data of our employees. It is important to our operations and business strategy that this electronic information remains secure and is perceived to be secure.
The size and complexity of our information technology systems, and those of third-party vendors with whom we contract, and the volume of data we retain, make such systems potentially vulnerable to a variety of evolving threats, including but not limited to social-engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code, malware (such as malicious code, adware, and command and control (C2)), denial-of-service attacks, credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, attacks enhanced or facilitated by AI, telecommunications failures, and other similar threats.
Cyber-attacks, malicious internet-based activity, online and offline fraud, and other similar activities threaten the confidentiality, integrity, and availability of our sensitive information and information technology systems, and those of the third parties upon which we rely. Such threats continue to rise, are increasingly difficult to detect, and come from a variety of sources, including traditional computer “hackers,” threat actors, “hacktivists,” organized criminal threat actors, personnel (such as through theft or misuse), sophisticated nation states, and nation-state-supported actors (also referred to as APTs). Some actors now engage and are expected to continue to engage in cyber-attacks, including without limitation nation-state actors for geopolitical reasons and in conjunction with military conflicts and defense activities. During times of war and other major conflicts, we and the third parties upon which we rely may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, which could materially disrupt our systems and operations, as well as our ability to conduct clinical trials.
Ransomware attacks are also becoming increasingly prevalent and severe, and can lead to significant interruptions in our operations (including our ability to conduct clinical trials), loss of sensitive data (including related to our clinical trials) and income, reputational harm, and diversion of funds. To alleviate the financial, operational and reputational impact of a ransomware attack, it may be preferable to make extortion payments, but we may be unwilling or unable to do so (including, for example, if applicable laws or regulations prohibit such payments). Similarly, supply chain attacks have increased in frequency and severity, and we cannot guarantee that third parties in our supply chain have not been compromised or that they do not contain exploitable defects, vulnerabilities, or bugs that could result in a breach of or disruption to our information technology systems and infrastructure or the information technology systems and infrastructure of third parties that support our operations.
Remote work has increased risks to our information technology systems and data, as certain of our employees work from home, utilizing network connections, computers and devices outside our premises, including at home, while in transit or in public locations.
Additionally, natural disasters, public health pandemics or epidemics, terrorism, war and geopolitical conflicts, and telecommunication and electrical failures may result in damage to or the interruption or impairment of key business processes, or the loss or corruption of confidential information, including intellectual property, proprietary business information and personal data.
Future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies. Furthermore, we may discover security issues that were not found during due diligence of such acquired or integrated entities, and it may be difficult to integrate companies into our information technology environment and security program.
As cyber threats continue to evolve, we may be required to expend significant additional resources to continue to modify or enhance our protective measures or to investigate and remediate any information security vulnerabilities or modify our business activities (including our clinical trial activities) to try to protect against security incidents.
We take steps designed to detect, mitigate, and remediate vulnerabilities in our information security systems (such as our hardware and/or software, including that of third parties upon which we rely). We may not, however, detect and remediate all such vulnerabilities including on a timely basis. Further, we may experience delays in developing and deploying remedial measures and patches designed to address identified vulnerabilities. Vulnerabilities could be exploited and result in a security incident.
We rely on third-party service providers and technologies to operate critical business systems to process sensitive information in a variety of contexts, including, without limitation, cloud-based infrastructure, data center facilities, encryption and authentication technology, employee email and other functions. We also rely on third-party service providers to provide other products, services, parts, or otherwise to operate our business, including clinical trial sites and investigators, contractors, manufacturers, suppliers and consultants. Our ability to monitor these third parties’ information security practices is limited, and these third parties may not have adequate information security measures in place. If our third-party service providers or CROs experience a security incident or other interruption, we could experience adverse consequences. In addition, supply-chain attacks have increased in frequency and severity, and we cannot guarantee that third parties’ infrastructure in our supply chain or our third-party partners’ supply chains have not been compromised or otherwise subject to a security incident. While we may be entitled to damages if our third-party service providers fail to satisfy their privacy or security-related obligations to us, any award may be insufficient to cover our damages, or we may be unable to recover such award.
Although to our knowledge we, or the third parties upon who we rely, have not experienced a security incident or disruption to date that is material to us, we and our vendors have been, either directly or indirectly, the target of cybersecurity incidents and expect them to continue. While we have implemented security measures designed to protect our data security and information technology systems, such measures may not prevent such events. Furthermore, while we have implemented certain redundancies designed to avoid interruptions to our operations, not all potential events can be anticipated and interruptions to our operations could lead to decreased productivity.
If we (or a third party upon whom we rely) experience a security incident, ransomware attack or are perceived to have experienced a security incident, we may experience material adverse consequences. Such material consequences may include: government enforcement actions (for example, investigations, fines, penalties, audits and inspections); additional reporting requirements and/or oversight; restrictions on processing sensitive information (including personal data); litigation (including class claims); indemnification obligations; negative publicity; reputational harm (including but not limited to damage to our patient, partner, or employee relationships); monetary fund diversions; diversion of management’s attention; interruptions in our operations (including availability of data, loss of connectivity to our network or internet); financial loss (including decreased productivity resulting from interruptions in our operations); and other similar harms. Similarly, the loss of clinical trial data from completed or ongoing or planned clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. In addition, theft of our intellectual property or proprietary business information could require substantial expenditures to remedy. Applicable data privacy and security obligations may also require us to notify relevant stakeholders, including affected individuals, customers, regulators, and investors, of security incidents. Such disclosures are costly, and the disclosure or the failure to comply with such requirements could lead to adverse consequences.
Our contracts, with for example third parties or CROs, may not contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in our contracts are sufficient to protect us from liabilities, damages, or claims related to our data privacy and security obligations. We also cannot be sure that our insurance coverage will be adequate or sufficient to protect us from or to mitigate liabilities arising out of our privacy and security practices, that such coverage will continue to be available on commercially reasonable terms or at all, or that such coverage will pay future claims.
In addition to experiencing a security incident, third parties may gather, collect, or infer sensitive information about us from public sources, data brokers, or other means that reveals competitively sensitive details about our organization and could be used to undermine our competitive advantage or market position. Additionally, our sensitive information could be leaked, disclosed, or revealed as a result of or in connection with our employees’, personnel’s, or vendors’ potential use of generative AI technologies.
If we fail to obtain or maintain orphan drug designation or other regulatory exclusivity for some of our product candidates, our competitive position would be harmed.
In addition to any patent protection, we rely on forms of regulatory exclusivity to protect our products such as orphan drug designation. A product candidate that receives orphan drug designation can benefit from a streamlined regulatory process as well as potential commercial benefits following approval. Currently, this designation provides market exclusivity in the U.S. for seven years and EU for 10 years if a product is the first such product approved for such orphan indication. This market exclusivity does not, however, pertain to indications other than those for which the drug was specifically designated in the approval, nor does it prevent other types of drugs from receiving orphan designations or approvals in these same indications. Further, even after an orphan drug is approved, the FDA can subsequently approve the same drug for the same condition if the FDA concludes that the product is clinically superior to the orphan product or a market shortage occurs.
In the EU, orphan exclusivity may be reduced to six years if the drug no longer satisfies the original designation criteria or can be lost altogether if the marketing authorization holder consents to a second orphan drug application or cannot supply enough drug, or when a second applicant demonstrates its drug is “clinically superior” to the original orphan drug.
If we do not have adequate patent protection for our products, then the relative importance of obtaining regulatory exclusivity is even greater. We may not be successful obtaining orphan drug designations for any indications and, even if we succeed, such product candidates with such orphan drug designations may fail to achieve FDA approval. Even if a product candidate with orphan drug designation may receive marketing approval from the FDA, it may fail to result in or maintain orphan drug exclusivity upon approval, which would harm our competitive position.
The technologies we use in our research as well as the drug targets we select may infringe the patents or violate the proprietary rights of third parties.
We cannot assure you that third parties will not assert patent or other intellectual property infringement claims against us or our collaborators with respect to technologies used in potential products. If a patent infringement suit were brought against us or our collaborators, we or our collaborators could be forced to stop or delay developing, manufacturing or selling potential products that are claimed to infringe a third party’s intellectual property unless that party grants us or our collaborators rights to use its intellectual property. In such cases, we could be required to obtain licenses to patents or proprietary rights of others in order to continue to commercialize our products. However, we may not be able to obtain any licenses required under any patents or proprietary rights of third parties on acceptable terms, or at all. Even if our collaborators or we were able to obtain rights to the third party’s intellectual property, these rights may be non-exclusive, thereby giving our competitors access to the same intellectual property. Ultimately, we may be unable to commercialize some of our potential products or may have to cease some of our business operations as a result of patent infringement claims, which could severely harm our business.
Our business operations may subject us to disputes, claims and lawsuits, which may be costly and time-consuming and could materially and adversely impact our financial position and results of operations.
From time to time, we may become involved in disputes, claims and lawsuits relating to our business operations. In particular, we may face claims related to the safety of our products, intellectual property matters, employment matters, tax matters, commercial disputes, competition, sales and marketing practices, environmental matters, personal injury, insurance coverage and acquisition or divestiture-related matters. Any dispute, claim or lawsuit may divert management’s attention away from our business, we may incur significant expenses in addressing or defending any dispute, claim or lawsuit, and we may be required to pay damage awards or settlements or become subject to equitable remedies that could adversely affect our operations and financial results.
Litigation related to these disputes may be costly and time-consuming and could materially and adversely impact our financial position and results of operations if resolved against us. In addition, the uncertainty associated with litigation could lead to increased volatility in our stock price.
Our employees, independent contractors, principal investigators, consultants, commercial partners and vendors may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements.
We are exposed to the risk of employee fraud or other misconduct. Misconduct by employees and independent contractors, such as principal investigators, consultants, commercial partners and vendors, or by employees of our commercial partners could include failures to comply with FDA regulations, to provide accurate information to the FDA, to comply with manufacturing standards we have established, to comply with federal and state healthcare fraud and abuse laws, to report financial information or data accurately, to maintain the confidentiality of our trade secrets or the trade secrets of our commercial partners, or to disclose unauthorized activities to us. In particular, sales, marketing and other business arrangements in the healthcare industry are subject to extensive laws intended to prevent fraud, kickbacks, self-dealing and other abusive practices. Employee and independent contractor misconduct could also involve the improper use of individually identifiable information, including, without limitation, information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. Any action against our employees, independent contractors, principal investigators, consultants, commercial partners or vendors for violations of these laws could result in significant civil, criminal and administrative penalties, fines and imprisonment.
We face potential product liability exposure far in excess of our insurance coverage.
The use of any of our potential products in clinical trials, and the sale of any approved products, including INGREZZA and CRENESSITY, may expose us to liability claims. These claims might be made directly by consumers, healthcare providers, pharmaceutical companies or others selling our products. We have product liability insurance coverage for both our clinical trials as well as related to the sale of INGREZZA and CRENESSITY in amounts consistent with customary industry practices. However, our insurance may not reimburse us or may not be sufficient to reimburse us for any expenses or losses we may suffer. Moreover, insurance coverage is becoming increasingly expensive, and we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability from any current or future clinical trials or approved products. A successful product liability claim, or series of claims, brought against us would decrease our cash reserves and could cause our stock price to fall. Furthermore, regardless of the eventual outcome of a product liability claim, any product liability claim against us may decrease demand for our approved products, including INGREZZA and CRENESSITY, damage our reputation, result in regulatory investigations that could require costly recalls or product modifications, cause clinical trial participants to withdrawal, result in costs to defend the related litigation, decrease our revenue, and divert management’s attention from managing our business.
Our activities involve hazardous materials, and we may be liable for any resulting contamination or injuries.
Our research activities involve the controlled use of hazardous materials. We cannot eliminate the risk of accidental contamination or injury from these materials. If an accident occurs, a court may hold us liable for any resulting damages, which may harm our results of operations and cause us to use a substantial portion of our cash reserves, which would force us to seek additional financing.
We are subject to stringent and changing obligations related to data privacy and information security. Our actual or perceived failure to comply with such obligations could have a material adverse effect on our reputation, business, financial condition or results of operations.
In the ordinary course of our business, we process confidential and sensitive information, including personal data, proprietary and confidential business data, trade secrets, intellectual property, data we collect about clinical trial participants in connection with clinical trials, and sensitive third-party data, on our networks and in our data centers. We are subject to numerous federal, state, local and foreign laws, orders, codes, regulations and regulatory guidance regarding privacy, data protection, information security and the processing of personal information (including clinical trial data), the number and scope of which are expanding, changing, subject to differing applications and interpretations, and may be inconsistent among jurisdictions. Our data processing activities may also subject us to other data privacy and security obligations, such as industry standards, external and internal privacy and security policies, contracts and other obligations that govern the processing of data by us and by third parties on our behalf.
Laws regarding privacy, data protection, information security and the processing of personal data are becoming increasingly common in the U.S. at both the federal and state level. Additionally, in the past few years, numerous U.S. states—including California, Virginia, Colorado, Connecticut, and Utah—have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data. As applicable, such rights may include the right to access, correct, or delete certain personal data, and to opt-out of certain data processing activities, such as targeted advertising, profiling, and automated decision-making. The exercise of these rights may impact our business and ability to provide our products and services. Certain states also impose stricter requirements for processing certain personal data, including sensitive information, such as conducting data privacy impact assessments. These state laws allow for statutory fines for noncompliance. For example, the California Consumer Privacy Act, as amended by the California Privacy Rights Act of 2020 (collectively, CCPA), requires businesses to provide specific disclosures in privacy notices, and honor requests of California residents to exercise certain privacy rights. The CCPA allows for fines for noncompliance (up to $7,500 per intentional violation). Although some U.S. comprehensive privacy laws and the CCPA exempt some data processed in the context of clinical trials, these laws may increase compliance costs and potential liability with respect to other personal data we may maintain about California residents. Other states have also enacted data privacy laws and we expect more jurisdictions to pass similar laws in the future. These developments may further complicate compliance efforts, and may increase legal risk and compliance costs for us and the third parties upon whom we rely.
Additionally, HIPAA, as amended by HITECH, imposes specific requirements relating to the privacy, security, and transmission of individually identifiable health information.
Laws in Europe regarding privacy, data protection, information security and the processing of personal data have also been significantly reformed and continue to undergo reform. For example, the EU’s General Data Protection Regulation (EU GDPR) and the UK’s GDPR (UK GDPR) (collectively, GDPR) impose strict requirements for processing the personal data of individuals located, respectively, within the European Economic Area (EEA) and the UK, and the Swiss Federal Act on Data Protection similarly applies to the collection and processing of personal data, including health-related information, in Switzerland. The GDPR provides for enhanced data protection obligations for processors and controllers of personal data, including, for example, obligations relating to: processing health and other sensitive data; obtaining consent of individuals; providing notice to individuals regarding data processing activities; responding to data subject requests; taking certain measures when engaging third-party processors; notifying data subjects and regulators of data breaches; and implementing safeguards to protect the security and confidentiality of personal data. The GDPR impose substantial fines for breaches of data protection requirements. For example, under the GDPR, such fines can be up to four percent of global revenue or 20 million euros under the EU GDPR / 17.5 million pounds sterling under the UK GDPR, whichever is greater in either case, and also allow for private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests. The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of sensitive data, such as EU regulations governing clinical trial data and other healthcare data, could require us to change our business practices or lead to government enforcement actions, private litigation or significant penalties against us and could have a material adverse effect on our business, financial condition or results of operations.
We may be subject to additional foreign data laws. For example, in Canada, the Personal Information Protection and Electronic Documents Act (PIPEDA) and various related provincial laws, as well as Canada’s Anti-Spam Legislation (CASL), may apply to our operations. As another example, the General Data Protection Law, Lei Geral de Proteção de Dados Pessoais (LGPD) (Law No. 13,709/2018), may apply to our operations. The LGPD broadly regulates processing personal data of individuals in Brazil and imposes compliance obligations and penalties comparable to those of the EU GDPR. We also target customers in Asia and may be subject to new and emerging data privacy regimes in Asia, including Japan’s Act on the Protection of Personal Information and Singapore’s Personal Data Protection Act.
In the ordinary course of business, we may transfer personal data from Europe and other jurisdictions to the U.S. or other countries. Certain jurisdictions have enacted data localization laws and cross-border personal data transfers laws. For example, countries in the EEA and the UK have significantly restricted the transfer of personal data to the U.S. and other countries, whose privacy laws it generally believes are inadequate. Although there are currently various mechanisms that may be used to transfer personal data from the EEA and UK to the U.S. in compliance with law, such as the EEA standard contractual clauses, the UK’s International Data Transfer Agreement / Addendum, and the EU-U.S. Data Privacy Framework and the UK extension thereto (which allows for transfers for to relevant U.S.-based organizations who self-certify compliance and participate in the Framework), these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the U.S. If we cannot implement a valid compliance mechanism for cross-border personal data transfers or if the requirements for a legally-compliant transfer are too onerous, we may face increased exposure to regulatory actions, substantial fines and injunctions against processing or transferring personal data from Europe or elsewhere. The inability to import personal data to the U.S. may significantly and negatively impact our business operations, including by limiting our ability to conduct clinical trial activities in Europe and elsewhere; limiting our ability to collaborate with parties subject to European and other data protection laws or requiring us to increase our personal data processing capabilities in Europe and/or elsewhere at significant expense. Other jurisdictions may adopt or have already adopted similarly stringent interpretations of their data localization and cross-border data transfer laws. Additionally, companies that transfer personal data out of the EEA and UK to other jurisdictions, particularly to the U.S., are subject to increased scrutiny from regulators, individual litigants, and activist groups. Some European regulators have ordered certain companies to suspend or permanently cease certain transfers out of Europe for allegedly violating the GDPR’s cross-border data transfer limitations.
Our employees and personnel are permitted to use generative AI technologies to perform some of their work, and the disclosure and use of personal information data in generative AI technologies is subject to various privacy laws and other privacy obligations. Governments have passed and are likely to pass additional laws regulating generative AI. Our use of this technology could result in additional compliance costs, regulatory investigations and actions, and consumer lawsuits. Furthermore, any use of generative AI to develop our proprietary technology and compounds may also impact our ability to obtain or successfully defend certain intellectual property rights. If we are unable to use generative AI, it could make our business less efficient and result in competitive disadvantages.
In addition to data privacy and security laws, we may contractually be subject to industry standards adopted by industry groups and, we are, or may become subject to such obligations in the future. We are also bound by contractual obligations related to data privacy and security, and our efforts to comply with such obligations may not be successful. We publish privacy policies, marketing materials and other statements regarding data privacy and security. Regulators in the U.S. are increasingly scrutinizing these statements, and if these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, misleading, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators or other adverse consequences.
Our obligations related to data privacy and security (and consumers’ data privacy expectations) are quickly changing in an increasingly stringent fashion and creating uncertainty. These obligations may be subject to differing applications and interpretations, which may be inconsistent among jurisdictions or in conflict. Preparing for and complying with these obligations requires us to devote significant resources (including, without limitation, financial and time-related resources). These obligations may necessitate changes to our information technologies, systems and practices and those of any third parties that process personal data on our behalf. In addition, these obligations may even require us to change our business model.
Although we endeavor to comply with all applicable data privacy and security obligations, we may at times fail (or be perceived to have failed) to do so. Moreover, despite our efforts, our personnel or third-parties upon whom we rely may fail to comply such obligations that impacts our compliance posture. If we fail, or are perceived to have failed, to address or comply with data privacy and security obligations, we could face significant consequences. These consequences may include, but are not limited to, government enforcement actions, litigation (including class claims), additional reporting requirements and/or oversight, bans on processing personal data, imprisonment of company officials, and orders to destroy or not use personal data. In particular, plaintiffs have become increasingly more active in bringing privacy-related claims against companies, including class claims and mass arbitration demands. Some of these claims allow for the recovery of statutory damages on a per violation basis, and, if viable, carry the potential for monumental statutory damages, depending on the volume of data and the number of violations. Any of these events could have a material adverse effect on our reputation, business, financial condition or results of operations.
Item 2. Unregistered Sales of Equity Securities and Use of Proceeds
Issuer Purchases of Equity Securities
The following table presents information relating to purchases of our common stock during the first quarter of 2025.
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Period |
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Total Number of Shares
Repurchased (1) (2)
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Average Price
Paid
Per Share (1) (2)
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Total Number of
Shares Purchased as
Part of Publicly
Announced Program (1) (2)
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Dollar Value of
Shares that May Yet
Be Purchased
Under the Program (1) (2)
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January 2025 |
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— |
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$ |
— |
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— |
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$ |
59,481,180 |
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February 2025 |
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280,182 |
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$ |
212.29 |
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280,182 |
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$ |
500,000,000 |
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March 2025 |
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1,355,967 |
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$ |
110.62 |
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1,355,967 |
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$ |
350,000,000 |
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1,636,149 |
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$ |
128.03 |
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1,636,149 |
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_________________________
(1) In October 2024, our Board of Directors authorized a share repurchase program to repurchase up to $300.0 million of our common stock (the 2024 Repurchase Program) and we subsequently entered into an accelerated share repurchase transaction with a third-party financial institution to repurchase the entirety of this authorized amount. In November 2024, we paid the financial institution $300.0 million using cash on hand and took initial delivery of 2.0 million shares. The 2024 Repurchase Program was completed in February 2025, at which time we received an additional 0.3 million shares upon settlement. In total, we repurchased 2.3 million shares under the 2024 Repurchase Program at an average price of $131.83 per share, which represents the daily volume-weighted average price of our common stock over the term of the transaction, less a negotiated discount. The average price paid per share for February 2025 was calculated as the implied dollar value of the forward stock purchase contract at inception of the 2024 Repurchase Program, or $59.5 million, divided by the additional shares received upon settlement.
(2) In February 2025, our Board of Directors authorized a share repurchase program (the 2025 Repurchase Program) under which we may repurchase up to $500.0 million of our common stock, subject to market conditions. The 2025 Repurchase Program is in addition to the $300.0 million 2024 Repurchase Program that was announced in October 2024 and completed in February 2025. Under the 2025 Repurchase Program, share repurchases may be made from time to time at management's discretion through a variety of methods, such as open-market transactions including pre-set trading plans, privately negotiated transactions, accelerated share repurchases, and other transactions in accordance with applicable securities laws.
Item 5. Other Information
During the period from January 1, 2025 to March 31, 2025, our executive officers and/or directors adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted below:
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Name and Title |
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Action |
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Date |
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Trading Arrangement |
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Total Shares Authorized
to be Sold***
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Expiration Date |
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Rule 10b5-1* |
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Non-Rule 10b5-1** |
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Kevin Gorman, Ph.D. |
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Termination |
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2/24/2025 |
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X |
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252,427 |
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2/04/2026 |
Director |
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Kevin Gorman, Ph.D. |
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Adoption |
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2/24/2025 |
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X |
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115,935 |
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2/04/2026 |
Director |
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______________
* Intended to satisfy the affirmative defense of Rule 10b5-1(c)
** Not intended to satisfy the affirmative defense of Rule 10b5-1(c)
*** Represents the maximum number of shares that may be sold pursuant to the 10b5-1 arrangement. The number of shares sold is dependent on the satisfaction of certain conditions as set forth in the written plan and the satisfaction of applicable vesting conditions of equity awards.
In addition, our executive officers have entered into sell-to-cover arrangements adopted pursuant to Rule 10b5-1 authorizing the pre-arranged sale of shares to satisfy tax withholding obligations of the Company arising exclusively from the vesting of time-vesting or performance-vesting restricted stock units and the related issuance of shares. The amount of shares to be sold to satisfy the Company’s tax withholding obligations under these arrangements is dependent on future events which cannot be known at this time, including the future trading price of Company shares. The expiration date relating to these arrangements is dependent on future events which cannot be known at this time, including the final vest date of the applicable time-vesting or performance-vesting restricted stock units and the officer’s termination of service.
Item 6. Exhibits
The following exhibits are filed as part of, or incorporated by reference into, this report:
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Exhibit |
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3.1 |
Description: |
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Reference: |
Incorporated by reference to Exhibit 3.1 of the Company’s Quarterly Report on Form 10-Q filed on November 5, 2018 |
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3.2 |
Description: |
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Reference: |
Incorporated by reference to Exhibit 3.2 of the Company's Quarterly Report on Form 10-Q filed on October 30, 2024 |
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4.1 |
Description: |
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Reference: |
Incorporated by reference to the Company’s Registration Statement on Form S-1 (Registration No. 333-03172) |
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10.1+ |
Description: |
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10.2+ |
Description: |
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Reference: |
Incorporated by reference to Exhibit 10.26 of the Company’s Annual Report on Form 10-K filed on February 10, 2025 |
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10.3+ |
Description: |
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Reference: |
Incorporated by reference to Exhibit 10.31 of the Company’s Annual Report on Form 10-K filed on February 10, 2025 |
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10.4+ |
Description: |
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Reference: |
Incorporated by reference to Exhibit 10.32 of the Company’s Annual Report on Form 10-K filed on February 10, 2025 |
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10.5+ |
Description: |
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Reference: |
Incorporated by reference to Exhibit 10.33 of the Company’s Annual Report on Form 10-K filed on February 10, 2025 |
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10.6+ |
Description: |
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Reference: |
Incorporated by reference to Exhibit 10.34 of the Company’s Annual Report on Form 10-K filed on February 10, 2025 |
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10.7+ |
Description: |
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Reference: |
Incorporated by reference to Exhibit 10.35 of the Company’s Annual Report on Form 10-K filed on February 10, 2025 |
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10.8* |
Description: |
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31.1 |
Description: |
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31.2 |
Description: |
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32** |
Description: |
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101.INS |
Description: |
Inline XBRL Instance Document. – the instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document. |
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101.SCH |
Description: |
Inline XBRL Taxonomy Extension Schema Document. |
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101.CAL |
Description: |
Inline XBRL Taxonomy Extension Calculation Linkbase Document. |
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101.DEF |
Description: |
Inline XBRL Taxonomy Extension Definition Linkbase Document. |
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101.LAB |
Description: |
Inline XBRL Taxonomy Extension Label Linkbase Document. |
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101.PRE |
Description: |
Inline XBRL Taxonomy Extension Presentation Linkbase Document. |
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104 |
Description: |
Cover Page Interactive Data File (formatted as Inline XBRL with applicable taxonomy extension information contained in Exhibit 101) |
______________
+ Management contract or compensatory arrangement.
* Certain information in this exhibit has been omitted pursuant to Item 601 of Regulation S-K.
** These certifications are being furnished solely to accompany this quarterly report pursuant to 18 U.S.C. Section 1350, and are not being filed for purposes of Section 18 of the Securities Exchange Act of 1934 and are not to be incorporated by reference into any filing of Neurocrine Biosciences, Inc., whether made before or after the date hereof, regardless of any general incorporation language in such filing.
Except as specifically noted above, the Company’s Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K have a Commission File Number of 000-22705.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
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NEUROCRINE BIOSCIENCES, INC. |
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Dated: May 5, 2025 |
/s/ Matthew C. Abernethy |
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Matthew C. Abernethy |
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Chief Financial Officer (Duly authorized officer and Principal Financial Officer) |
EX-10.1
2
q1-2025exhibit101.htm
EX-10.1
q1-2025exhibit101
Exhibit 10.1 NEUROCRINE BIOSCIENCES, INC. 2020 EQUITY INCENTIVE PLAN OPTION GRANT NOTICE Neurocrine Biosciences, Inc. (the “Company”) has granted to you (“Participant”) an option to purchase the number of shares of Common Stock set forth below (the “Option”) under the Neurocrine Biosciences, Inc. 2020 Equity Incentive Plan (the “Plan”). The Option is subject to all of the terms and conditions set forth in this Option Grant Notice (the “Grant Notice”), the Option Agreement (the “Agreement”) and the Plan, all of which are available by logging into your E*TRADE account and which are incorporated herein in their entirety. Capitalized terms not explicitly defined in this Grant Notice but defined in the Agreement or the Plan will have the meanings set forth in the Agreement or the Plan, as applicable. Participant: Date of Grant: Vesting Commencement Date: Number of Shares of Common Stock: Exercise Price (Per Share): Total Exercise Price: Expiration Date: Type of Grant: You have been granted an Incentive Stock Option. However, due to the $100,000 Rule (as described below), the Option (or a certain portion thereof) may be treated as a Nonstatutory Stock Option. Please log into your E*TRADE account to see the exact details of your grant. Vesting Schedule: Subject to Section 2 of the Agreement, the Option will vest as follows: [________]. Exercise Schedule: Same as Vesting Schedule Participant Acknowledgements: By your electronic acceptance of the Option via your E*TRADE account, you understand and agree that: • The Option is governed by this Grant Notice, the Agreement and the Plan, all of which are made a part of this document. Unless otherwise provided in the Plan, this Grant Notice and the Agreement may not be modified, amended or revised except in a writing signed by you and a duly authorized officer of the Company. • If the Option is an Incentive Stock Option, it (plus other outstanding Incentive Stock Options granted to you) cannot be first exercisable for more than $100,000 in value (measured by exercise price) in any calendar year. Any excess over $100,000 is a Nonstatutory Stock Option. For purposes of this Grant Notice, such rule is referred to as the “$100,000 Rule”. • Copies of this Grant Notice, the Agreement, the Plan and the Prospectus are available via your E*TRADE account and may be viewed and printed by you. You consent to receive this Grant Notice, the Agreement, the Plan, the Prospectus and any other Plan-related documents by electronic delivery and to participate in the Plan through an on-line or electronic system established and maintained by the Company or another third party designated by the Company. • You have read and are familiar with the provisions of this Grant Notice, the Agreement, the Plan and the Prospectus. In the event of any conflict between the provisions in this Grant Notice, the Agreement or the Prospectus and the provisions of the Plan, the provisions of the Plan will control. • As of the Date of Grant, this Grant Notice, the Agreement and the Plan set forth the entire understanding between you and the Company regarding the Option and supersede all prior oral and written agreements, promises and/or representations regarding the Option, with the exception of any written employment, offer letter, severance or other agreement, or any written severance plan or policy, in each case that specifies the terms that should govern the Option. NEUROCRINE BIOSCIENCES, INC. 2020 EQUITY INCENTIVE PLAN OPTION AGREEMENT Pursuant to the accompanying Option Grant Notice (the “Grant Notice”) and this Option Agreement (the “Agreement”), Neurocrine Biosciences, Inc. (the “Company”) has granted you an option under the Neurocrine Biosciences, Inc. 2020 Equity Incentive Plan (the “Plan”) to purchase the number of shares of Common Stock set forth in the Grant Notice at the exercise price set forth in the Grant Notice (the “Option”). Capitalized terms not explicitly defined in this Agreement but defined in the Grant Notice or the Plan will have the meanings set forth in the Grant Notice or the Plan, as applicable. The general terms and conditions applicable to your Option are as follows: 1. GOVERNING PLAN DOCUMENT. Your Option is subject to all the provisions of the Plan, including but not limited to the provisions in: (a) Section 6 of the Plan regarding the impact of a Capitalization Adjustment, dissolution, liquidation, or Transaction on your Option; (b) Section 9(f) of the Plan regarding the Company’s and any Affiliate’s (if applicable) retained rights to terminate your Continuous Service notwithstanding the grant of your Option; and (c) Section 8(c) of the Plan regarding the tax consequences of your Option. Your Option is further subject to all interpretations, amendments, rules and regulations, which may from time to time be promulgated and adopted pursuant to the Plan. In the event of any conflict between the provisions in this Agreement or the Grant Notice and the provisions of the Plan, the provisions of the Plan will control. 2. VESTING. (a) Subject to the limitations contained in this Agreement, your Option will vest in accordance with the vesting schedule set forth in the Grant Notice, provided that vesting will cease upon the termination of your Continuous Service, except as otherwise explicitly provided in the Plan (in connection with a Transaction or certain terminations of Continuous Service following such Transaction) or this Agreement. (b) If you are an Employee or Director, in each case as of the date of termination of your Continuous Service, then in the event of a termination of your Continuous Service due to your death or Disability, your Option will become vested, as of the date of such termination, in accordance with the vesting schedule set forth in the Grant Notice as if you had provided an additional six months of Continuous Service as of the date of such termination. (c) If you are an Employee and your employment with the Company or an Affiliate terminates due to your Retirement, then your Option will become fully vested as of the date of such Retirement. For purposes of this Agreement, “Retirement” means a termination of your employment with the Company or an Affiliate upon or after you have reached age 60 with at least 5 years of Continuous Service, provided that you comply with any other requirements in the Company’s then-current policy regarding Retirement. (d) If you are a Director as of the date of a Transaction, then in the event of a Transaction during your Continuous Service, your Option will become fully vested as of the date of such Transaction. 3. EXERCISE. (a) You may generally exercise the vested portion of your Option (and the unvested portion of your Option if permitted by the Grant Notice) for whole shares of Common Stock at any time during its term by delivery of payment of the exercise price and any Withholding Obligation, as set forth in Section 6, and other required documentation to the Plan Administrator in accordance with the exercise procedures established by the Plan Administrator, which may include an electronic submission. Please review Sections 4(i), 4(j) and 7(b)(v) of the Plan, which may restrict or prohibit your ability to exercise your Option during certain periods. (b) To the extent permitted by Applicable Law, you may pay the exercise price of your Option by cash or check or as follows: (i) pursuant to a “cashless exercise” program, as provided in Section 4(c)(ii) of the Plan, if at the time of exercise the Common Stock is publicly traded; (ii) by delivery of already owned shares of Common Stock, as provided in Section 4(c)(iii) of the Plan, if at the time of exercise the Common Stock is publicly traded; or (iii) subject to approval by the Company and/or the Committee, as applicable, at or prior to the time of exercise, if your Option is a Nonstatutory Stock Option, by a “net exercise” arrangement, as provided in Section 4(c)(iv) of the Plan. 4. TERM. You may not exercise your Option before the commencement of its term or after its term expires. The term of your Option commences on the Date of Grant and expires upon the earliest of the following: (a) immediately upon the termination of your Continuous Service for Cause; (b) if you are an Employee as of the date of termination of your Continuous Service, then three months after the termination of your Continuous Service for any reason other than Cause, Disability, death or Retirement; (c) if you are a Director as of the date of termination of your Continuous Service, then three years after the termination of your Continuous Service for any reason other than Cause; (d) if you are a Consultant as of the date of termination of your Continuous Service, then 30 days after the termination of your Continuous Service for any reason other than Cause; (e) if you are an Employee as of the date of termination of your Continuous Service due to your Disability, then 12 months after the termination of your Continuous Service due to your Disability; (f) if you are an Employee as of the date of termination of your Continuous Service due to your death, then 18 months after your death if you die during your Continuous Service; (g) if you are an Employee as of the date of termination of your employment with the Company or an Affiliate due to Retirement, then 12 months after the termination of your employment with the Company or an Affiliate due to your Retirement; (h) immediately upon a Transaction if the Board has determined that your Option will terminate in connection with such Transaction; (i) the Expiration Date set forth in the Grant Notice; or (j) the day before the 10th anniversary of the Date of Grant. If you are an Employee as of the date of termination of your Continuous Service, then notwithstanding the foregoing, if you die during the period provided in Section 4(b) above, the term of your Option will not expire until the earlier of (i) 18 months after the termination of your Continuous Service, (ii) a Transaction if the Board has determined that your Option will terminate in connection with such Transaction, (iii) the Expiration Date set forth in the Grant Notice, or (iv) the day before the 10th anniversary of the Date of Grant. In addition, the Post-Termination Exercise Period of your Option may be extended as provided in Section 4(i) of the Plan. To obtain the federal income tax advantages associated with an Incentive Stock Option, the Code requires that at all times beginning on the date of grant of your Option and ending on the day three months before the date of your Option’s exercise, you must be an employee of the Company or an Affiliate, except in the event of your death or Disability. If the Company provides for the extended exercisability of your Option under certain circumstances for your benefit, your Option will not necessarily be treated as an Incentive Stock Option if you exercise your Option more than three months after the date your employment terminates. 5. TRANSFERABILITY. Except as otherwise provided in Section 4(e) of the Plan, your Option is not transferable, except by will or by the applicable laws of descent and distribution, and is exercisable during your life only by you. Notwithstanding the foregoing, by delivering written notice to the Company, in a form satisfactory to the Company, you may designate a third party who, in the event of your death, will thereafter be entitled to exercise your Option.
6. WITHHOLDING OBLIGATIONS. (a) As provided in Section 8 of the Plan, at the time you exercise your Option, in whole or in part, or at any time thereafter as requested by the Company, you hereby authorize withholding from payroll and any other amounts payable to you, and otherwise agree to make adequate provision for (including by means of a “cashless exercise” pursuant to a program developed under Regulation T as promulgated by the Federal Reserve Board to the extent permitted by the Company), any sums required to satisfy the federal, state, local and foreign tax withholding obligations, if any, which arise in connection with your Option (the “Withholding Obligation”) in accordance with the withholding procedures established by the Company. (b) Upon your request and subject to approval by the Company and/or the Committee, as applicable, and in compliance with any applicable legal conditions or restrictions, the Company may withhold from fully vested shares of Common Stock otherwise issuable to you upon exercise of your Option a number of whole shares of Common Stock with a Fair Market Value on the date of exercise not in excess of the maximum amount of tax that may be required to be withheld by law (or such other amount as may be permitted while still avoiding classification of your Option as a liability for financial accounting purposes). (c) You may not exercise your Option unless the Withholding Obligation is satisfied. Accordingly, you may not be able to exercise your Option even though your Option is vested, and the Company will have no obligation to issue any shares of Common Stock subject to your Option, unless and until the Withholding Obligation is satisfied. In the event that the amount of the Withholding Obligation was greater than the amount actually withheld by the Company (or an Affiliate, if applicable), you agree to indemnify and hold the Company (and Affiliate, if applicable) harmless from any failure to withhold the proper amount. 7. INCENTIVE STOCK OPTION DISPOSITION REQUIREMENT. If your Option is an Incentive Stock Option, you must notify the Company in writing within 15 days after the date of any disposition of any of the shares of Common Stock issued upon exercise of your Option that occurs within two years after the date of grant of your Option or within one year after such shares of Common Stock are transferred upon exercise of your Option. 8. TRANSACTION. Your Option is subject to the terms of any agreement governing a Transaction involving the Company, including, without limitation, a provision for the appointment of a stockholder representative that is authorized to act on your behalf with respect to any escrow, indemnities and any contingent consideration. 9. NO LIABILITY FOR TAXES. As a condition to accepting your Option, you hereby (a) agree to not make any claim against the Company, or any of its Officers, Directors, Employees or Affiliates related to tax liabilities arising from your Option or other Company compensation and (b) acknowledge that you were advised to consult with your own personal tax, financial and other legal advisors regarding the tax consequences of your Option and have either done so or knowingly and voluntarily declined to do so. Additionally, you acknowledge that your Option is exempt from Section 409A only if the exercise price of your Option is at least equal to the “fair market value” of the Common Stock on the date of grant as determined by the Internal Revenue Service and there is no other impermissible deferral of compensation associated with your Option. Additionally, as a condition to accepting your Option, you agree to not make any claim against the Company, or any of its Officers, Directors, Employees or Affiliates in the event that the Internal Revenue Service asserts that such exercise price is less than the “fair market value” of the Common Stock on the date of grant as subsequently determined by the Internal Revenue Service. 10. SEVERABILITY. If any part of this Agreement, the Grant Notice or the Plan is declared by any court or governmental authority to be unlawful or invalid, such unlawfulness or invalidity will not invalidate any portion of this Agreement, the Grant Notice or the Plan not declared to be unlawful or invalid. Any Section of this Agreement, the Grant Notice or the Plan (or part of such a Section) so declared to be unlawful or invalid will, if possible, be construed in a manner which will give effect to the terms of such Section or part of a Section to the fullest extent possible while remaining lawful and valid. 11. OTHER DOCUMENTS. You hereby acknowledge receipt of or the right to receive a document providing the information required by Rule 428(b)(1) promulgated under the Securities Act, which includes the Prospectus. In addition, you acknowledge receipt of the Company’s Trading Policy. * * * *
EX-10.8
3
q1-2025exhibit108.htm
EX-10.8
q1-2025exhibit108
Exhibit 10.8 Certain identified information has been excluded from the exhibit because it is both (i) not material and (ii) is the type of information that the registrant treats as private or confidential. Triple asterisks denote omissions. CONFIDENTIAL Execution Version AMENDED AND RESTATED EXCLUSIVE LICENSE AGREEMENT BY AND BETWEEN TAKEDA PHARMACEUTICAL COMPANY LIMITED AND NEUROCRINE BIOSCIENCES, INC. JANUARY 24, 2025 i TABLE OF CONTENTS 1. DEFINITIONS ........................................................................................................ 2 2. LICENSE GRANT ................................................................................................ 21 2.1. License Grant to Neurocrine ..................................................................... 21 2.2. License Grant to Takeda ........................................................................... 21 2.3. Sublicensing Terms ................................................................................... 22 2.4. Subcontractors ........................................................................................... 23 2.5. [***] .......................................................................................................... 23 2.6. Third Party IP for TAK-653 Products ....................................................... 24 2.7. Knowledge and Technology Transfer. ...................................................... 26 2.8. No Other Rights and Retained Rights ....................................................... 26 3. DEVELOPMENT ................................................................................................. 27 3.1. Development Responsibilities ................................................................... 27 3.2. Neurocrine Development Diligence Obligations ...................................... 27 3.3. Licensed Products Development Reports ................................................. 27 3.4. Scientific Records ..................................................................................... 28 3.5. Scientific Records ..................................................................................... 28 3.6. Scientific Records ..................................................................................... 28 4. REGULATORY MATTERS ................................................................................ 28 4.1. Regulatory Responsibilities ....................................................................... 28 4.2. Regulatory Submissions, Study Reports and Data not Controlled by Takeda. ...................................................................................................... 29 4.3. Regulatory Information Obligations ......................................................... 29 4.4. TAK-653 Product Data Sharing ................................................................ 29 4.5. Costs of Regulatory Affairs ....................................................................... 30 4.6. No Harmful Actions .................................................................................. 30 4.7. Adverse Events Reporting ......................................................................... 30 4.8. Data Privacy .............................................................................................. 31 5. COMMERCIALIZATION .................................................................................... 31 5.1. Commercialization of the Licensed Products. ........................................... 31 5.2. Commercialization Diligence Obligations ................................................ 31 5.3. Licensed Products Commercialization Reporting ..................................... 31 5.4. Commercialization Information Sharing ................................................... 31 5.5. Recalls, Market Withdrawals, or Corrective Actions ................................ 31 ii 5.6. Cross-Territorial Restrictions ..................................................................... 32 5.7. Supply of TAK-653 Products for Japan ..................................................... 32 6. MEDICAL AFFAIRS ............................................................................................ 32 6.1. Responsibilities........................................................................................... 32 7. GOVERNANCE .................................................................................................... 33 7.1. Alliance Manager ....................................................................................... 33 7.2. Joint Steering Committee ........................................................................... 33 7.3. Decisions of the JSC ................................................................................... 35 7.4. Resolution of JSC Disputes ........................................................................ 35 7.5. JSC Disbandment ....................................................................................... 36 7.6. Joint Commercialization Committee .......................................................... 36 8. PAYMENTS .......................................................................................................... 37 8.1. Payments for the Licensed Assets and Licensed Products ......................... 37 8.2. Other Amounts Payable .............................................................................. 42 8.3. Payment Terms ........................................................................................... 42 9. CONFIDENTIALITY AND PUBLICATION ....................................................... 46 9.1. Nondisclosure and Non-Use Obligations ................................................... 46 9.2. Publication and Publicity ........................................................................... 48 10. REPRESENTATIONS, WARRANTIES AND COVENANTS ............................ 49 10.1. Mutual Representations and Warranties as of the Restatement Date ......... 49 10.2. Representations and Warranties by Takeda ................................................ 50 10.3. Warranty Disclaimer .................................................................................. 53 10.4. Certain Covenants ...................................................................................... 53 11. INDEMNIFICATION; LIMITATION OF LIABILITY; INSURANCE .............. 54 11.1. Indemnification by Takeda ........................................................................ 54 11.2. Indemnification by Neurocrine .................................................................. 55 11.3. Indemnification Procedure ......................................................................... 55 11.4. Limitation of Liability ................................................................................ 56 11.5. Insurance .................................................................................................... 56 12. INTELLECTUAL PROPERTY ............................................................................. 57 12.1. Inventions. .................................................................................................. 57 12.2. Prosecution and Maintenance of Patent Rights .......................................... 58 12.3. Third Party Infringement and Defense ....................................................... 59 12.4. Patent Right Extensions ............................................................................. 62 iii 12.5. Third Party Rights ...................................................................................... 62 12.6. Orange Book Listing. ................................................................................. 62 12.7. Trademarks. ................................................................................................ 63 12.8. Common Interest ........................................................................................ 63 13. TERM AND TERMINATION .............................................................................. 63 13.1. Term ........................................................................................................... 63 13.2. Termination for Convenience ..................................................................... 64 13.3. Termination for Cause ................................................................................ 64 13.4. Effects of Termination ................................................................................ 67 13.5. Survival ...................................................................................................... 73 14. MISCELLANEOUS ............................................................................................... 73 14.1. Assignment ................................................................................................. 73 14.2. Governing Law ........................................................................................... 73 14.3. Dispute Resolution ..................................................................................... 73 14.4. Entire Agreement; Amendments ................................................................ 74 14.5. Severability ................................................................................................. 75 14.6. Headings ..................................................................................................... 75 14.7. Waiver of Rule of Construction ................................................................. 75 14.8. Interpretation .............................................................................................. 75 14.9. No Implied Waivers; Rights Cumulative ................................................... 76 14.10. Notices. ....................................................................................................... 76 14.11. Compliance with Export Regulations ........................................................ 77 14.12. Force Majeure ............................................................................................ 77 14.13. Independent Parties .................................................................................... 77 14.14. Further Assurances ..................................................................................... 78 14.15. Performance by Affiliates .......................................................................... 78 14.16. Binding Effect; No Third Party Beneficiaries ............................................ 78 14.17. Counterparts ............................................................................................... 78
iv SCHEDULES SCHEDULE 1.33 Defensive Patent Rights SCHEDULE 1.80 Licensed Assets SCHEDULE 1.150 Takeda Know-How SCHEDULE 3.5 [***] Dispute Resolution SCHEDULE 9.2.3 Press Release SCHEDULE 10.2.1 Takeda Patent Rights SCHEDULE 10.2.2 Takeda Technology SCHEDULE 10.2.4 Ownership of Takeda Technology SCHEDULE 12.2.1(a) Annuities and Maintenance Fees SCHEDULE 13.4.3 [***] Dispute Resolution AMENDED AND RESTATED EXCLUSIVE LICENSE AGREEMENT THIS AMENDED AND RESTATED EXCLUSIVE LICENSE AGREEMENT (this “Agreement”), effective as of January 24, 2025 (the “Restatement Date”), is entered into by and between Takeda Pharmaceutical Company Limited, a Japanese corporation (“Takeda”), and Neurocrine Biosciences, Inc., a corporation organized and existing under the Laws of Delaware (“Neurocrine”). Takeda and Neurocrine are referred to in this Agreement individually as a “Party” and collectively as the “Parties.” RECITALS WHEREAS, Takeda is a global pharmaceutical company with expertise in developing and commercializing neuroscience therapeutics; WHEREAS, Neurocrine is a biopharmaceutical company focused on advancing therapies for neurological, psychiatric, and endocrine-related disorders; WHEREAS, Takeda Controls certain Patent Rights, Know-How, and other intellectual property rights related to the Licensed Assets and Licensed Products; WHEREAS, Takeda and Neurocrine are parties to an Exclusive License Agreement, dated June 12, 2020 (the “Execution Date”) and effective July 28, 2020 (the “Effective Date”, and such agreement, as clarified by the letter agreements dated February 10, 2021 and July 22, 2022, the “Original Agreement”), pursuant to which Takeda granted to Neurocrine a license under certain Patent Rights, Know-How, and other intellectual property rights Controlled by Takeda to Exploit the Licensed Assets and Licensed Products (each as defined in the Original Agreement) worldwide on the terms and conditions set forth therein; WHEREAS, pursuant to Section 3.1.1 of the Original Agreement, Takeda exercised its Phase I Opt-Out Right (as defined in the Original Agreement) with respect to the Phase I Asset (as defined in the Original Agreement) referred to as TAK-653 (NBI-1065845), such that the Parties will no longer share Operating Profits or Losses (as defined in the Original Agreement) with respect to such Licensed Asset; WHEREAS, by letter to Takeda dated September 27, 2024, Neurocrine terminated the Original Agreement with respect to certain Target Classes (as defined in the Original Agreement); WHEREAS, the Parties desire that from and after the Restatement Date, Takeda will have the exclusive rights to Develop and Commercialize Licensed Products containing TAK-653 in Japan, and that Neurocrine will retain all rights granted under the Original Agreement to Develop and Commercialize TAK-653 outside of Japan; and WHEREAS, the Parties now desire to amend and restate the Original Agreement in accordance with Section 16.4 thereof, such that this Agreement is in effect from and after the Restatement Date, and the Original Agreement governs the Parties’ rights and obligations thereunder during the period from the Effective Date until the Restatement Date (including with respect to the effects of termination of the Original Agreement with respect to those Target Classes for which Neurocrine terminated the Original Agreement). NOW, THEREFORE, the Parties hereby agree to amend and restate the Original Agreement as of the Restatement Date, so that it reads in its entirety as follows: 2 1. DEFINITIONS Unless specifically set forth to the contrary herein, the following terms, whether used in the singular or plural, will have the respective meanings set forth below: 1.1. “Accounting Standards” means International Financial Reporting Standards (IFRS), with respect to Takeda, and U.S. Generally Accepted Accounting Principles (GAAP), with respect to Neurocrine, or GAAP or IFRS, as applicable, in each case, as generally and consistently applied throughout the Party’s organization. 1.2. “Adverse Event” means any unwanted or harmful medical occurrence in a patient or subject who is administered a Licensed Product, whether or not considered related to such Licensed Product, including any undesirable sign (including abnormal laboratory findings of clinical concern). 1.3. “Affiliate” means, with respect to a Person, any other Person that controls, is controlled by, or is under common control with such Person. For purposes of this Agreement, a Person will be deemed to control another Person if it owns or controls, directly or indirectly, more than 50% of the equity securities of such other Person entitled to vote in the election of directors (or, in the case that such other Person is not a corporation, for the election of the corresponding managing authority), or otherwise has the power to direct the management and policies of such other Person. The Parties acknowledge that in the case of certain entities organized under the laws of certain countries outside the United States, the maximum percentage ownership permitted by law for a foreign investor may be less than 50%, and that in such case such lower percentage will be substituted in the preceding sentence, provided that such foreign investor has the power to direct the management and policies of such entity. Neither of the Parties will be deemed to be an “Affiliate” of the other solely as a result of their entering into this Agreement. 1.4. “Agreement” has the meaning set forth in the preamble. 1.5. “Alliance Manager” has the meaning set forth in Section 7.1 (Alliance Manager). 1.6. “Annual Ex-US Net Sales” has the meaning set forth in Section 8.1.2 (Royalties). 1.7. “Annual Net Sales” means the Annual US Net Sales and the Annual Ex-US Net Sales. 1.8. “Annual US Net Sales” has the meaning set forth in Section 8.1.2 (Royalties). 1.9. “Auditor” has the meaning set forth in Section 8.3.3 (Records and Audits). 1.10. “Business Day” means a calendar day other than a Saturday, Sunday, or a bank or other public holiday in Boston, Massachusetts or San Diego, California in the United States, or Tokyo in Japan. 1.11. “Calendar Quarter” means the respective periods of three consecutive calendar months ending on March 31, June 30, September 30, and December 31 of each Calendar Year. 1.12. “Calendar Year” means each successive period of twelve months commencing on January 1 and ending on December 31. 1.13. “cGMP” means the then-current good manufacturing practice standards, practices, and procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time, including those as 3 set forth in FDA regulations in 21 C.F.R. Parts 210 and 211 and all applicable FDA rules, regulations, orders, and guidances, and the requirements with respect to current good manufacturing practices prescribed by the European Community under provisions of “The Rules Governing Medicinal Products in the European Community, Volume 4, Good Manufacturing Practices, Annex 13, Manufacture of Investigational Medicinal Products, July 2003,” or as otherwise required by applicable Laws. 1.14. “Change of Control” means, with respect to a Party, (a) a merger, consolidation, recapitalization, or reorganization of such Party with a Third Party that results in the holders of beneficial ownership (other than by virtue of obtaining irrevocable proxies for purposes of management voting on matters as directed by beneficial owners) of the voting securities of such Party outstanding immediately prior thereto, or any securities into which such voting securities have been converted or exchanged, ceasing to hold beneficial ownership of more than 50% of the combined voting power of the surviving entity or the parent of the surviving entity immediately after such merger, consolidation, recapitalization, or reorganization, (b) a transaction or series of related transactions in which a Third Party, together with its Affiliates, becomes the direct or indirect beneficial owner of more than 50% of the combined voting power of the outstanding securities of such Party, or (c) the sale or other transfer to a Third Party of all or substantially all of such Party’s and its controlled Affiliates’ assets. Notwithstanding the foregoing, any transaction or series of transactions effected for the purpose of financing the operations of the applicable Party or changing the form or jurisdiction of organization of such Party (such as an initial public offering or other offering of equity securities to non-strategic investors or corporate reorganization) will not be deemed a “Change of Control” for purposes of this Agreement. 1.15. “Clinical Trial” means any study in humans (including a non-interventional study) conducted to obtain information regarding a pharmaceutical or biologic product, including information relating to the safety, tolerability, pharmacological activity, pharmacokinetics, dose ranging, or efficacy of such pharmaceutical or biologic product. 1.16. “CMO” means a contract manufacturing organization or a contract testing organization. 1.17. “Code” means the Internal Revenue Code of 1986, as amended. 1.18. “Combination Product” means a Licensed Product that is (a) sold in the form of a combination that contains or comprises one or more additional therapeutically active pharmaceutical agents (whether coformulated or copackaged or otherwise sold for a single price) other than a Licensed Asset; (b) sold for a single price together with any delivery device (each of the therapeutically active pharmaceutical agents in clause (a) and the delivery device in clause (b), an “Other Component”); or (c) defined as a “combination product” by the FDA pursuant to 21 C.F.R. §3.2(e) or its foreign equivalent, where such “combination product” is sold for a single price. 1.19. “Commercialization” or “Commercialize” means any and all activities directed to the marketing, promotion, distribution matters, offering for sale, sale, having sold, importing, having imported, exporting, having exported or other commercialization of a pharmaceutical or biologic product (including pricing matters), but expressly excluding activities directed to Manufacturing, Development, or performance of Medical Affairs. “Commercialize,” “Commercializing,” and “Commercialized” will be construed accordingly. 1.20. “Commercially Reasonable Efforts” means, with respect to the efforts to be expended by a Party or its Affiliates with respect to any objective or activity under this Agreement by a Party, those efforts and resources, including [***], in each case, [***], taking into account [***].
4 1.21. “Commercial Milestone Event” has the meaning set forth in Section 8.1.1(b) (Commercial Milestones). 1.22. “Commercial Milestone Payment” has the meaning set forth in Section 8.1.1(b) (Commercial Milestones). 1.23. “Competitive Infringement” means (a) the making, using, selling, offering for sale, importing, or exporting by a Third Party of a pharmaceutical or biologic product in a country that actually or potentially infringes a Valid Claim of a Takeda Patent Right, Defensive Patent Right or Program Patent Right in such country, but excluding any TAK-653 Competitive Infringement, or (b) the filing of an ANDA under Section 505(j) of the FD&C Act or an application under Section 505(b)(2) of the FD&C Act naming a Licensed Product as a reference listed drug and including a certification under Section 505(j)(2)(A)(vii)(IV) or 505(b)(2)(A)(IV), respectively. 1.24. “Confidential Information” means (a) any and all confidential or proprietary information and data, including scientific, pre-clinical, clinical, regulatory, manufacturing, marketing, financial and commercial information or data, unpublished patent applications and information related thereto and set forth therein, in each case, that is or has been provided by or on behalf of one Party to the other Party or its Affiliates in connection with the Original Agreement or this Agreement or any related negotiations, discussions, or diligence, whether communicated in writing or orally or by any other method, and (b) the terms of the Original Agreement and this Agreement. Notwithstanding the foregoing, “Confidential Information” excludes any information that the receiving Party can show by competent evidence (i) is known by the receiving Party at the time of its receipt, and not through a prior disclosure by the disclosing Party, as documented by the receiving Party’s business records; (ii) is known to the public before its receipt from the disclosing Party, or thereafter becomes generally known to the public through no breach of the Original Agreement or this Agreement by the receiving Party; (iii) is subsequently disclosed to the receiving Party without obligation of confidentiality by a Third Party who has rightfully obtained such information and who is not under an obligation of confidentiality or other contractual obligation with respect to such information; or (iv) is developed by the receiving Party independently of Confidential Information received from the disclosing Party, as documented by the receiving Party’s business records. 1.25. “Control” means the possession by a Party (whether by ownership, license, or otherwise), other than pursuant to the Original Agreement or this Agreement, of, (a) with respect to any tangible Know-How, the legal authority or right to physical possession of such tangible Know-How, with the right to provide such tangible Know-How to the other Party on the terms set forth herein, or (b) 5 with respect to Patent Rights, Regulatory Approvals, Regulatory Submissions, intangible Know- How, or other intellectual property, the legal authority or right to grant a license, sublicense, access, or right to use (as applicable) to the other Party under such Patent Rights, Regulatory Approvals, Regulatory Submissions, intangible Know-How, or other intellectual property on the terms set forth herein, in each case ((a) and (b)), (i) without breaching or otherwise violating the terms of any arrangement or agreement with a Third Party in existence as of the time such Party or its Affiliates would first be required hereunder to grant the other Party such access, right to use, licenses, or sublicense or (ii) with respect to Know-How or Patent Rights developed, acquired, or licensed by a Party after the Effective Date, without incurring any additional payment obligations to a Third Party that are not subject to an agreed allocation between the Parties. Notwithstanding the foregoing, a Party and its Affiliates will not be deemed to “Control” any of the foregoing (a)-(b) that is [***]. Furthermore, notwithstanding the foregoing, Takeda and its Affiliates will not be deemed to “Control” any of the foregoing (a)-(b) that (1) [***], (2) [***], and (3) [***]. 1.26. [***]. 1.27. [***]. 1.28. [***]. 1.29. [***]. 1.30. [***]. 1.31. “Cover,” “Covering,” or “Covered” means, with respect to a particular subject matter at issue and a relevant Patent Right or individual claim in such Patent Right, as applicable, that the manufacture, use, sale, offer for sale, or importation of such subject matter would fall within the scope of one or more claims in such Patent Right. 1.32. “CRO” means a contract research organization. 6 1.33. “Defensive Patent Right” means any Patent Right set forth on Schedule 1.33 (Defensive Patent Rights) or claiming priority to any such Patent Right. 1.34. “Develop” and “Development” means all internal and external research, discovery, development, and regulatory activities related to pharmaceutical or biologic products, including (a) research, non- clinical testing, toxicology, testing and studies, non-clinical and preclinical activities, and Clinical Trials, and (b) preparation, submission, review, and development of data or information for the purpose of submission to a Regulatory Authority to obtain authorization to conduct Clinical Trials and to obtain, support, or maintain Regulatory Approval of a pharmaceutical or biologic product and interacting with Regulatory Authorities following receipt of Regulatory Approval in the applicable country or region for such pharmaceutical or biologic product regarding the foregoing, but expressly excluding activities directed to Manufacturing, performance of Medical Affairs, or Commercialization. Development will include development and regulatory activities for additional forms, formulations, or indications for a pharmaceutical or biologic product after receipt of Regulatory Approval of such product (including label expansion), including Clinical Trials initiated following receipt of Regulatory Approval or any Clinical Trial to be conducted after receipt of Regulatory Approval that was mandated by the applicable Regulatory Authority as a condition of such Regulatory Approval with respect to an approved formulation or indication (such as observational studies, implementation and management of registries and analysis thereof, in each case, if required by any Regulatory Authority in any region in the Territory or in Japan to support or maintain Regulatory Approval for a pharmaceutical or biologic product in such region). “Develop,” “Developing,” and “Developed” will be construed accordingly. 1.35. “Development Milestone Event” has the meaning set forth in Section 8.1.1(a) (Development Milestones). 1.36. “Development Milestone Payment” has the meaning set forth in Section 8.1.1(a) (Development Milestones). 1.37. “Development Plan” has the meaning set forth in Section 3.1.3 (Development Responsibilities). 1.38. “Disputes” has the meaning set forth in Section 14.3.1 (Exclusive Dispute Resolution Mechanism). 1.39. “Dollars” or “$” means the legal tender of the United States of America. 1.40. “Effective Date” has the meaning set forth in the recitals. 1.41. “EU” means the European Union, as its membership may be constituted from time to time, and any successor thereto. 1.42. “Execution Date” has the meaning set forth in the recitals. 1.43. “Executive Officer” means, for Neurocrine, an executive officer, and for Takeda, its president- level officer of Research and Development or Commercialization, as applicable, or another senior executive officer or their respective designee with appropriate responsibilities, seniority, and decision-making authority. If the position of any of the Executive Officers identified in this Section 1.43 (Executive Officer) no longer exists due to a Change of Control, corporate reorganization, corporate restructuring, or the like of a Party that results in the elimination of the identified position, then the applicable Party will replace the applicable Executive Officer with another executive officer with responsibilities and seniority comparable to the eliminated Executive Officer. 7 1.44. “Exploit” or “Exploitation” means to make, have made, import, have imported, export, have exported, distribute, have distributed, use, have used, sell, have sold, offer for sale, or have offered for sale, including to Develop, Manufacture, Commercialize, and perform Medical Affairs activities. 1.45. “Ex-US Royalty” has the meaning set forth in Section 8.1.2 (Royalties). 1.46. “FD&C Act” means the United States Federal Food, Drug, and Cosmetic Act, as amended. 1.47. “FDA” means the United States Food and Drug Administration or any successor Governmental Authority having substantially the same function. 1.48. “Field” means all fields of use. 1.49. “First Commercial Sale” means, [***]. 1.50. “Force Majeure” has the meaning set forth in Section 14.12 (Force Majeure). 1.51. “FTE” means the equivalent of a full-time person’s work time, carried out by an appropriately qualified employee of a Party or its Affiliates, on the performance of Development, Manufacturing, Commercialization, or Medical Affairs activities, based on [***] person-hours per year, pro-rated as necessary. Overtime, and work on weekends, holidays, and the like [***]. 1.52. “FTE Costs” means, for any period, the FTE Rate multiplied by the number of FTEs in such period. 1.53. “FTE Rate” means (a) for personnel other than those described in clause (b), $[***] per one full FTE per full 12-month Calendar Year, which rate includes all direct and indirect costs of the performing Party’s FTE, including personnel and travel expenses, and (b) [***]. Each such rate, [***].
8 1.54. “GCP” means the then-current good clinical practice standards, practices, and procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time, including those as set forth in FDA regulations in 21 C.F.R. Parts 11, 50, 54, 56, 312, 314, and 320 and all related FDA rules, regulations, orders, and guidances, and by the International Conference on Harmonization E6: Good Clinical Practices Consolidated Guideline (the “ICH Guidelines”). 1.55. “Generic Product” means with respect to a given Licensed Other Product or TAK-653 Product in a given country, a product that (a) (i) contains the same active pharmaceutical ingredient as such Licensed Other Product or TAK-653 Product [***] and is approved in reliance on a prior Regulatory Approval of such Licensed Other Product or TAK-653 Product and (ii) is [***], and (b) is sold or marketed for sale in such country by a Third Party that has not obtained the rights to market or sell such product as a Sublicensee, subcontractor, or Third Party Distributor of a Party or any of its Affiliates, Sublicensees, or subcontractors with respect to such Licensed Other Product in the case of Neurocrine, or TAK-653 Product in the case of Takeda or Neurocrine, as applicable. 1.56. “GLP” means the then-current good laboratory practice standards, practices, and procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time, including those as set forth in FDA regulations in 21 C.F.R. Part 58 and all applicable FDA rules, regulations, orders, and guidances, and the requirements with respect to good laboratory practices prescribed by the European Community, the OECD (Organization for Economic Cooperation and Development Council) and the ICH Guidelines. 1.57. “Governmental Authority” means any applicable government authority, court, council, tribunal, arbitrator, agency, department, bureau, branch, office, legislative body, commission or other instrumentality of (a) any government of any country or territory, (b) any nation, state, province, county, city, or other political subdivision thereof, or (c) any supranational body. 1.58. “Grantback IP” has the meaning set forth in Section 13.4.3 (Intellectual Property License to Takeda). 1.59. “H-W Suit Notice” has the meaning set forth in Section 12.3.2(d) (Hatch-Waxman). 1.60. “Hatch-Waxman Act” means rights conferred in the U.S. under the Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. §355, as amended (or any successor statute or regulation). 1.61. “ICH Guidelines” has the meaning set forth in Section 1.54 (GCP). 1.62. “Identified TAK-653 Rights” has the meaning set forth in Section 2.6.1 (Notice). 9 1.63. “IND” means an Investigational New Drug Application (as defined in the FD&C Act), clinical trial application, or similar application or submission for approval to conduct human clinical investigations filed with or submitted to a Regulatory Authority anywhere in the world in conformance with the requirement of such Regulatory Authority, and any amendments thereto. 1.64. “IND Effective Date” means, with respect to an IND for a Licensed Other Product, (a) in the U.S., the date that is 30 days (or any different time period pursuant to a change in applicable Laws after the Restatement Date) following the filing of such IND for such Licensed Other Product, [***]; provided that, [***]. 1.65. “Indemnified Party” has the meaning set forth in Section 11.3.1 (Notice). 1.66. “Indemnifying Party” has the meaning set forth in Section 11.3.1 (Notice). 1.67. “Initiation” means, with respect to a Clinical Trial of a pharmaceutical or biologic product, the first dosing of the first human subject pursuant to the applicable protocol for such Clinical Trial. 1.68. [***]. 1.69. [***]. 1.70. [***]. 1.71. [***]. 1.72. [***]. 1.73. “Joint Program Know-How” means any and all Program Know-How made jointly by or on behalf of the Parties or their respective Affiliates. 1.74. “Joint Program Patent Rights” means the Program Patent Rights Covering any Joint Program Know-How. 1.75. “Joint Program Technology” means the Joint Program Know-How and Joint Program Patent Rights. 1.76. “JSC” has the meaning set forth in Section 7.2.1 (Joint Steering Committee: Purpose; Formation). 10 1.77. “Know-How” means all commercial, technical, scientific, and other know-how and information, inventions, discoveries, trade secrets, knowledge, technology, methods, processes, practices, formulae, amino acid sequences, nucleotide sequences, instructions, skills, techniques, procedures, experiences, ideas, technical assistance, designs, drawings, assembly procedures, computer programs, specifications, data and results (including biological, chemical, pharmacological, toxicological, pharmaceutical, physical and analytical, preclinical, clinical, safety, manufacturing and quality control data and know-how, including regulatory data, study designs and protocols), and materials, in all cases, whether or not confidential, proprietary, patentable, in written, electronic or any other form now known or hereafter developed, but expressly excluding all Patent Rights. 1.78. “Knowledge” means, with respect to Takeda, the actual knowledge of a fact or other matter, after reasonable inquiry of intellectual property counsel, of the applicable Global Program Leader for the applicable Licensed Asset, and the transition leader for the Licensed Assets. 1.79. “Laws” means all applicable laws, statutes, rules, regulations, orders, judgments, injunctions, ordinances, codes, principles of common law, or other pronouncements having the binding effect of law of any Governmental Authority, including if either Party is or becomes subject to a legal obligation to a Regulatory Authority or other Governmental Authority (such as a corporate integrity agreement or settlement agreement with a Governmental Authority). 1.80. “Licensed Asset” means any of the TAK-653 Asset and the Nonclinical Assets. 1.81. “Licensed Other Product” has the meaning set forth in Section 1.82 (Licensed Product). 1.82. “Licensed Product” means any (a) pharmaceutical or biologic product comprising a Nonclinical Asset, either alone or as a Combination Product, (such products in this clause (a), “Licensed Other Products”) and (b) TAK-653 Product. 1.83. “Licensed Takeda Technology” means the Takeda Technology, excluding (i) all Patent Rights in Japan that Cover TAK-653 Assets or TAK-653 Products, and (ii) Know-How that is useful solely to Exploit TAK-653 Assets or TAK-653 Products in Japan. 1.84. “Loss of Market Exclusivity” means an event where, with respect to any Licensed Product in any country: (a) [***]; and (b) [***]. 1.85. “Losses” has the meaning set forth in Section 11.1 (Indemnification by Takeda). 1.86. “LP Commercialization Report” has the meaning set forth in Section 5.3 (Licensed Products Commercialization Reporting). 1.87. “LP Development Report” has the meaning set forth in Section 3.3 (Licensed Products Development Reports). 1.88. “MAA” means any new drug application or other marketing authorization application, in each case, filed with the applicable Regulatory Authority in a country or other regulatory jurisdiction (and all 11 supplements and amendments thereto), which application is required to commercially market or sell a pharmaceutical or biologic product in such country or jurisdiction, including all New Drug Applications submitted to the FDA in the United States in accordance with the FD&C Act with respect to a pharmaceutical product or any analogous application or submission with any Regulatory Authority in any other country or regulatory jurisdiction. 1.89. “Major Market” means each of the U.S., Japan, the EU, and the United Kingdom. 1.90. “Manufacturing” or “Manufacture” means activities directed to process, analytical and formulation development, manufacturing, processing, packaging, labeling, filling, finishing, assembly, quality assurance, quality control, testing, and release, shipping, or storage of any pharmaceutical or biologic product (or any components or process steps involving any product or any companion diagnostics), placebo, or comparator agent, as the case may be, including process development, qualification, and validation, scale-up, pre-clinical, clinical, and commercial manufacture and analytic development, product characterization, and stability testing, but expressly excluding activities directed to Development, performance of Medical Affairs, or Commercialization. “Manufacturing” and “Manufactured” will be construed accordingly. 1.91. “Manufacturing Cost” means, with respect to any Licensed Product, the consolidated fully burdened Manufacturing costs in accordance with the applicable Accounting Standards, which will be the sum of: (a) [***]; and (b) [***]. 1.92. “Medical Affairs” means activities conducted by a Party’s medical affairs departments (or, if a Party does not have a medical affairs department, the equivalent function thereof), including patient advocacy, medical science liaisons, medical directors, health economics and outcomes research, communications with key opinion leaders (including key opinion leader selection and management, health care professional and patient speakers programs), medical education, symposia, advisory boards (to the extent related to medical affairs or clinical guidance), activities performed in
12 connection with patient registries and other medical programs and communications, including investigator sponsored studies, educational grants, research grants, and charitable donations to the extent related to medical affairs and not to other activities that are not conducted by a Party’s medical affairs (or equivalent) departments. 1.93. “Milestone Events” has the meaning set forth in Section 8.1.1(b) (Commercial Milestones). 1.94. “Milestone Payments” has the meaning set forth in Section 8.1.1(b) (Commercial Milestones). 1.95. “NDA” means a New Drug Application, as defined in the FD&C Act and applicable regulations promulgated thereunder by the FDA, or any analogous application or submission with any Regulatory Authority outside of the U.S. 1.96. “Net Sales” means with respect to a Licensed Product and Party, the gross amount invoiced in a country by such [***] (each of the foregoing Persons, a “Selling Party” of such Party) for the sale or other disposition of such Licensed Product in such country to Third Parties [***], less the following deductions calculated in accordance with the applicable Accounting Standards, consistently applied throughout the territory in which such Licensed Product is sold [***]: (a) [***]; (b) [***]; (c) [***]; (d) [***]; (e) [***]; 13 (f) [***]; and (g) [***]. [***]. Notwithstanding the foregoing, and subject to the remainder of this paragraph, [***]. Net Sales will not include [***]. In the case of any Combination Product sold in a given country in any Calendar Year, Net Sales for the purpose of determining Royalties and Commercial Milestone Events of the Combination Product in such country will be calculated by multiplying actual Net Sales of such Combination Product in such country by the fraction A/(A+B), where A is the invoice price of the Licensed Asset included in such Combination Product if sold separately as a stand-alone product in such country during the same Calendar Year, and B is the total invoice price of the Other Components in the Combination Product, if sold separately in such country during the same Calendar Year. If, on a country-by-country basis, the Licensed Asset included in such Combination Product is sold separately as a stand-alone product in a country during the same Calendar Year, but the Other Components in the Combination Product are not sold separately in such country during the same Calendar Year, then Net Sales for the purpose of determining Royalties and Commercial Milestone Events of the Combination Product for such country will be calculated by multiplying actual Net Sales of the Combination Product in 14 such country by the fraction A/C, where A is the invoice price of the Licensed Asset if sold separately as a stand-alone product in such country during the same Calendar Year, and C is the invoice price of the Combination Product in such country during the applicable Calendar Quarter. If, on a country-by-country basis, the Licensed Asset included in the Combination Product is not sold separately as a stand-alone product in such country during the same Calendar Year, but the Other Components included in the Combination Product are sold separately in such country during the same Calendar Year, then Net Sales for the purpose of determining Royalties and Commercial Milestone Events of the Combination Product for such country will be calculated by multiplying actual Net Sales of the Combination Product in such country by the fraction C-B/C, where B is the invoice price of the Other Components included in such Combination Product if sold separately in such country during the same Calendar Year, and C is the invoice price of the Combination Product in such country during the applicable Calendar Quarter. If neither the Licensed Asset nor the Other Components included in the Combination Product are sold separately in a given country during the same Calendar Year, then Net Sales for the purpose of determining Royalties and Commercial Milestone Events in such country will be calculated [***]. [***]. 1.97. “Neurocrine Manufacturing Technology” means Neurocrine’s interest in (a) the Neurocrine Sole Program Patent Rights in the Neurocrine Territory and (b) the Program Know-How, in each case (a) and (b), that is (i) Controlled by Neurocrine or its Affiliates during the period starting on the Effective Date and ending on the last day of the Term, (ii) related to the TAK-653 Asset and (iii) necessary to Manufacture any TAK-653 Product in the Field in the Neurocrine Territory. 1.98. “Neurocrine Prosecuted Patent Rights” has the meaning set forth in Section 12.2.1(a) (Neurocrine’s Right). 1.99. “Neurocrine Sole Program Patent Rights” means Program Patent Rights Covering inventions within the Program Know-How made solely by or on behalf of Neurocrine or its Affiliates. 1.100. “Neurocrine Technology” means Neurocrine’s interest in (a) the Program Know-How and (b) the Program Patent Rights in Japan, in each case (a) and (b) that are (i) Controlled by Neurocrine or its Affiliates during the period starting on the Effective Date and ending on the last day of the Term, (ii) related to the TAK-653, and (iii) necessary to Exploit any TAK-653 Product in the Field in Japan, including any data provided pursuant to Section 4.4 (TAK-653 Product Data Sharing). 1.101. “Neurocrine Territory” has the meaning set forth in Section 1.160 (Territory). 1.102. “New License Agreement” has the meaning set forth in Section 13.4.5 (New License Agreements). 1.103. “Nonclinical Asset” means: 15 (a) (i) any Nonclinical Asset listed on Schedule 1.80 (Licensed Assets), (ii) any salt, hydrate, isotope, solvate, ester, free acid or base, polymorph, enantiomer, metabolite or prodrug of any compound in the preceding clause (i), and (iii) any isotope, ester, enantiomer, metabolite or prodrug of the TAK-653 Asset, (b) (i) [***], and (c) [***] (i) is a [***] and (ii) [***]. 1.104. “Other Component” has the meaning set forth in Section 1.18 (Combination Product). 1.105. “Party” or “Parties” has the meaning set forth in the preamble. 1.106. “Patent Challenge” means any challenge to the validity or enforceability of a Patent Right by commencing any opposition proceeding, post-grant review, inter partes review, or declaratory action, or any foreign equivalent thereof, in any court, arbitration proceeding, or other tribunal, including any Patent Office, but excluding (a) any reexamination, reissue or similar proceeding intended to improve the validity, enforceability or scope of a Patent Right, or (b) complying with any applicable Laws (including court order), including responding to compulsory discovery, subpoenas, or other requests for information in a judicial or arbitration proceeding. 1.107. “Patent Costs” means [***]. 1.108. “Patent Offices” has the meaning set forth in Section 10.2.5 (Validity and Enforceability).
16 1.109. “Patent Right” means any patent (including any utility or design patent) or patent application (including any provisional, utility, continued prosecution, continuation, continuations-in-part, divisional, or substitution application), or other filing claiming priority thereto or sharing any common priority therewith, whether directly or indirectly, as well as any patent that issues or has issued with respect to any such patent application, reissue, re-examination, renewal, or extension (including any patent term adjustment, patent term extension, or supplemental protection certificate, or the equivalent thereof), registration or confirmation patent, patent resulting from a post-grant proceeding, patent of addition, revalidation, restoration or extension thereof, or any inventor’s certificate, utility model (including any petty patent, innovation patent, utility certificate, functional design, short-term patent, minor patent, or small patent), or any equivalent or counterpart thereof in any country or jurisdiction. For clarity, a patent filing (a patent or a patent application) is considered to have been made (or to be pending or in force) within a selected time period if the filing itself, or any other filing to which it claims priority or with which it shares any common priority, was made, within (or was pending, or in force within) the time period. 1.110. “Payments” has the meaning set forth in Section 8.3.5(b) (Withholding Taxes). 1.111. “Person” means any natural person, corporation, unincorporated organization, partnership, association, sole proprietorship, joint stock company, joint venture, limited liability company, trust or government, Governmental Authority, or any other similar entity. 1.112. “Pharmacovigilance Agreement” has the meaning set forth in Section 4.7.1 (Adverse Events Reporting). 1.113. “Phase I Clinical Trial” means a Clinical Trial (or any arm thereof) of an investigational product in subjects that satisfies the requirements of U.S. regulation 21 C.F.R. 312.21(a) and its successor regulation, or an equivalent Clinical Trial prescribed by the relevant Regulatory Authority in a country other than the United States. 1.114. “Phase II Clinical Trial” means a Clinical Trial (or any arm thereof) of an investigational product that satisfies the requirements of U.S. federal regulation 21 C.F.R. § 312.21(b) and its successor regulation, or an equivalent Clinical Trial prescribed by the relevant Regulatory Authority in a country other than the United States. 1.115. “Phase III Clinical Trial” means a Clinical Trial (or any arm thereof) of an investigational product on a sufficient number of patients that satisfies the requirements of U.S. federal regulation 21 C.F.R. § 312.21(c) and its successor regulation or an equivalent Clinical Trial prescribed by the relevant Regulatory Authority in a country other than the United States. 1.116. “PMDA” means the Japanese Pharmaceuticals and Medical Devices Agency or any successor Governmental Authority having substantially the same function. 1.117. “Pricing Approval” means, in any country where a Governmental Authority authorizes reimbursement for, or approves or determines pricing for, pharmaceutical or biologic products, receipt (or, if required to make such authorization, approval or determination effective, publication) of such reimbursement authorization or pricing approval or determination (as the case may be). 1.118. “Program Know-How” means any Know-How generated during the period starting on the Effective Date and ending on the last day of the Term by or on behalf of a Party, any of its Affiliates or Sublicensees, either alone or jointly, in the performance of activities relating to the Exploitation of Licensed Products under the Original Agreement or this Agreement. 17 1.119. “Program Patent Rights” means any Patent Right that (a) has a priority date after the Effective Date, and (b) Covers any Program Know-How. 1.120. “Prosecution and Maintenance” or “Prosecute and Maintain” means, with regard to a particular Patent Right, the preparation, filing, prosecution (including any oppositions, interferences, reissue proceedings, reexaminations, post-grant proceedings, supplemental examinations, post grant review proceedings, inter partes review proceedings, patent interference proceedings, opposition proceedings, derivation proceedings, reissue and reexamination, maintenance (including paying maintenance fees and annuities) and defense) of such Patent Right. 1.121. “Redacted Agreement” has the meaning set forth in Section 9.1.3(b) (Confidential Treatment). 1.122. “Regulatory Approval” means, with respect to a particular country or other regulatory jurisdiction, any approval of a MAA or other approval, product, or establishment license, registration, or authorization of any Regulatory Authority necessary for the commercial marketing or sale of a pharmaceutical or biologic product in such country or other regulatory jurisdiction, excluding, in each case, Pricing Approval. 1.123. “Regulatory Authority” means any Governmental Authority responsible for granting Regulatory Approvals of pharmaceutical or biologic products. 1.124. “Regulatory Exclusivity” means any exclusive marketing rights or data exclusivity rights conferred by any Regulatory Authority with respect to a Licensed Other Product or TAK-653 Product in a country or jurisdiction, other than a Patent Right, that prohibits a Person from (a) relying on safety or efficacy data generated by or on behalf of a Party with respect to such Licensed Other Product or TAK-653 Product in an application for Regulatory Approval of a Generic Product, or (b) Commercializing a Licensed Other Product, TAK-653 Product, or a Generic Product, including pediatric exclusivity (as set forth in Section 505(A) of the FD&C Act), orphan drug exclusivity, rights conferred in the U.S. under the Hatch-Waxman Act, or rights similar thereto in other countries or regulatory jurisdictions. 1.125. “Regulatory Lead” means: (a) Takeda, for TAK-653 Products in Japan; and (b) Neurocrine, for all Licensed Other Products worldwide, and all TAK-653 Products in the Neurocrine Territory. 1.126. “Regulatory Submissions” means any regulatory application, submission, notification, communication, correspondence, registration, Regulatory Approval, or other filing made to, received from or otherwise conducted with a Regulatory Authority related to Developing, Manufacturing, or obtaining marketing authorization for a pharmaceutical or biologic product in a particular country or jurisdiction. 1.127. [***]. 1.128. [***]. 1.129. [***]. 18 1.130. [***]. 1.131. [***]. 1.132. “Royalty” means any US Royalty, any Ex-US Royalty, and any Japan Royalty. 1.133. “Royalty Patent Rights” means (a) with respect to a Licensed Product in the Territory, collectively, any and all Takeda Patent Rights, Defensive Patent Rights, or Joint Program Patent Rights that have any Valid Claim(s) Covering such Licensed Product, and (b) with respect to a TAK-653 Product in Japan, collectively, any and all Takeda Patent Rights, Defensive Patent Rights or Program Patent Rights that have any Valid Claim(s) Covering such TAK-653 Product. 1.134. “Royalty Rates” means the applicable royalty rate set forth in Table 8.1.2(a) (Royalty Payments (US)) or Table 8.1.2(b) (Royalty Payments (Ex-US)). 1.135. “Royalty Report” has the meaning set forth in Section 8.3.2 (Reports and Royalty Payments). 1.136. “Royalty Term” means, with respect to a Licensed Product, a country and a Party, the period extending from the First Commercial Sale of such Licensed Product in such country by such Party or its Affiliate or Sublicensee until the latest of (a) expiration of the last Valid Claim of the last-to- expire Royalty Patent Right Covering such Licensed Product in such country, (b) [***] years after the First Commercial Sale of such Licensed Product in such country, or (c) expiration of all Regulatory Exclusivities for such Licensed Product in such country. 1.137. “Safety Concern” means, with respect to any Licensed Product, (a) any safety concern required to be reported under 21 C.F.R. § 312.32 (“IND Safety Reporting”) if an IND with respect to such Licensed Product was open at the time of the observation (or that would be so reportable if an IND was not open at such time), or (b) a toxicity or drug safety issue or a Serious Adverse Event reasonably related to or observed in connection with Development or Commercialization activities with respect to a Licensed Product. 1.138. “SEC” has the meaning set forth in Section 9.1.2 (Permitted Disclosures). 1.139. “Selling Party” has the meaning set forth in Section 1.96 (Net Sales). 1.140. “Serious Adverse Event” means an adverse drug experience or circumstance, whether or not considered drug related, that results in any of the following outcomes: (a) death, (b) life threatening condition, (c) inpatient hospitalization or a prolongation of existing hospitalization, (d) persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions, (e) a congenital anomaly/birth defect, (f) significant intervention required to prevent permanent impairment or damage, or (g) a medical event that may not result in death, be life threatening, or require hospitalization but, based on appropriate medical judgment, that may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes described in clauses (a) through (f). 1.141. “Subcontractor” means a Third Party contractor engaged by a Party or its Affiliate to perform certain obligations or exercise certain rights of such Party under this Agreement (including all Third Party Distributors, contract research organizations, clinical research organizations or CMOs), but excluding all Sublicensees. 19 1.142. “Sublicensee” means a Third Party to which a Party or its Affiliate has granted or grants a license, sublicense, option to license or sublicense or similar right under the Takeda Technology or the Neurocrine Technology to Exploit any Licensed Product, or any further sublicensee of such rights (regardless of the number of tiers, layers or levels of sublicenses of such rights), beyond the mere right to purchase any Licensed Product from or to provide services on behalf of such Party or its Affiliates, but expressly excluding CMOs, CROs, and contract sales forces. 1.143. “Supply Agreement” has the meaning set forth in Section 3.5 (Supply of TAK-653 Products for Development in Japan). 1.144. “TAK-653 Asset” means (a) the TAK-653 Asset listed on Schedule 1.80 (Licensed Assets), and (b) [***]. 1.145. “TAK-653 Competitive Infringement” means the making, using, selling, or offering for sale in Japan, importing into Japan, or exporting from Japan by a Third Party of a pharmaceutical or biologic product that is an AMPA potentiator, which activity actually or potentially infringes a Valid Claim of a Takeda Patent Right or Defensive Patent Right in Japan or a Program Patent Right to the extent included in the Neurocrine Technology. 1.146. “TAK-653 IP Agreement” has the meaning set forth in Section 2.6.3 (TAK-653 IP Agreements). 1.147. “TAK-653 Product” means any pharmaceutical or biologic product comprising a TAK-653 Asset, either alone or as a Combination Product, provided that, with respect to the licenses granted to Takeda and the definition of Neurocrine Technology and Neurocrine Manufacturing Technology, TAK-653 Product excludes any Combination Product in which the Other Component is controlled by Neurocrine or any of its Affiliates, unless otherwise agreed by the Parties in writing. 1.148. “Takeda” has the meaning set forth in the preamble. 1.149. “Takeda Indemnitees” has the meaning set forth in Section 11.2 (Indemnification by Neurocrine). 1.150. “Takeda Know-How” means Know-How, other than Joint Program Know-How, Controlled by Takeda or its Affiliates during the period starting on the Effective Date and ending on the last day of the Term that (a) is necessary to Exploit any Licensed Product (excluding any active pharmaceutical ingredient therein that is not a Licensed Asset) in the Field, (b) is reasonably useful to Exploit one or more Licensed Products in the Field, but, in the case of this clause (b), excluding any Know-How that was [***], or (ii) to the extent related to any active pharmaceutical ingredient Controlled by Takeda or any of its Affiliates that is not a Licensed Asset, or (c) is described on Schedule 1.150 (Takeda Know-How). For clarity, Takeda Know-How includes Program Know- How owned solely by Takeda. 1.151. “Takeda Patent Right” means any Patent Right, other than any Joint Program Patent Right or Defensive Patent Right, Controlled by Takeda or its Affiliates during the period starting on the Effective Date and ending on the last day of the Term that (a) is necessary to Exploit any Licensed Product (excluding any active pharmaceutical ingredient therein that is not a Licensed Asset) in the Field in the Territory, the Neurocrine Territory or Japan, or (b) is reasonably useful to Exploit one or more Licensed Products in the Field in the Territory, the Neurocrine Territory or Japan, but, in
20 the case of this clause (b), [***], or (ii) to the extent related to any active pharmaceutical ingredient Controlled by Takeda or any of its Affiliates that is not a Licensed Asset. The Takeda Patent Rights as of the Execution Date are set forth on Schedule 10.2.1 (Takeda Patent Rights). For clarity, Takeda Patent Rights includes Program Patent Rights owned solely by Takeda. 1.152. “Takeda Request Date” has the meaning set forth in Section 2.7 (Knowledge and Technology Transfer). 1.153. “Takeda Technology” means, collectively, (a) the Takeda Patent Rights, (b) the Defensive Patent Rights, (c) the Takeda Know-How, and (d) Takeda’s interest in the Joint Program Technology. 1.154. “Target Class” means the group of all Licensed Products the mechanism of action of which is one of the following (in the case of Licensed Assets identified on Schedule 1.80 (Licensed Assets), as identified on such schedule): (a) an AMPA potentiator, (b) a [***], or (c) an [***]. 1.155. “Tax” and “Taxation” means any U.S. and non-U.S. federal, state, local, regional, municipal, or other tax or taxation, levy, duty, charge, withholding, or other assessment of any kind (including any related fine, penalty, addition to tax, surcharge, or interest) imposed by, or payable to, a Governmental Authority, including VAT, excise, stamp, transfer, property, and franchise taxes. 1.156. “Term” has the meaning set forth in Section 13.1 (Term). 1.157. “Terminated Product” means any Licensed Product for which this Agreement has been terminated in accordance with Article 13 (Term and Termination), in the form that each such Licensed Product exists as of the date of notice of such termination, and any improvements, modifications, or enhancements thereof. All Licensed Products in the same Target Class will be deemed Terminated Products if this Agreement is terminated with respect to such Target Class. All Licensed Products will be deemed Terminated Products if this Agreement is terminated in its entirety. 1.158. “Terminated Target Class” means any Target Class for which this Agreement has been terminated in accordance with Article 13 (Term and Termination). All Target Classes will be deemed Terminated Target Classes if this Agreement is terminated in its entirety. 1.159. “Terminated Territory” means, on a Target Class-by-Target Class basis, those countries with respect to which this Agreement has been terminated in accordance with Article 13 (Term and Termination) in relation to such Target Class. The Terminated Territory will be: (a) worldwide with respect to Licensed Other Products, if this Agreement is terminated in its entirety with respect to Licensed Other Products, and (b) worldwide excluding Japan with respect to TAK-653 Products, if this Agreement is terminated in its entirety with respect to TAK-653 Products. 1.160. “Territory” means (a) with respect to any TAK-653 Asset and TAK-653 Product, worldwide excluding Japan (the “Neurocrine Territory”), and (b) with respect to all Nonclinical Assets and Licensed Other Products, worldwide, but excluding, in each case (a) and (b), with respect to any Licensed Product, any then-current Terminated Territory for such Licensed Product. 21 1.161. “Third Party” means any Person other than Takeda, Neurocrine, or their respective Affiliates. 1.162. “Third Party Distributor” means, with respect to a country, any Third Party that purchases Licensed Products in such country from the Selling Party or its Affiliates and is appointed as a distributor to distribute, market, and resell such Licensed Product in such country, even if such Third Party is granted ancillary sublicensed or licensed rights under the Takeda Technology to package, distribute, market, or sell such Licensed Product in such country. 1.163. “Trademark” means any trademark, trade name, service mark, service name, brand, domain name, trade dress, logo, slogan, or other indicia of origin or ownership, including the goodwill and activities associated with each of the foregoing. 1.164. “United States” or “U.S.” means the United States and its territories, possessions and commonwealths. 1.165. “US Royalty” has the meaning set forth in Section 8.1.2 (Royalties). 1.166. “Valid Claim” means: (a) a claim of an issued and unexpired patent (as may be extended through supplementary protection certificate or patent term extension or the like) that has not been revoked, held invalid, or unenforceable by a Patent Office or other Governmental Authority of competent jurisdiction in a final and non-appealable judgment (or judgment from which no appeal was taken within the allowable time period) and which claim has not been disclaimed, denied, or admitted to be invalid or unenforceable through reissue, re-examination, or disclaimer or otherwise; or (b) a pending claim of an unissued, pending patent application, which application has not been pending for the longer of (i) [***] since [***] or (ii) [***] from the date of [***]. 1.167. “VAT” means any value added, consumption, goods services, sales, use, turnover or similar tax. 2. LICENSE GRANT 2.1. License Grant to Neurocrine. Subject to the terms and conditions of this Agreement, during the Term, Takeda hereby grants to Neurocrine an exclusive (even as to Takeda and its Affiliates), non-transferable (except as provided in Section 14.1 (Assignment)), sublicensable (solely as provided in Section 2.3 (Sublicensing Terms)) license in the Field under the Licensed Takeda Technology to Exploit (a) Licensed Other Products in the Territory and (b) TAK-653 Products in the Neurocrine Territory. 2.2. License Grant to Takeda. Subject to the terms and conditions of this Agreement, Neurocrine hereby grants to Takeda: (a) an exclusive (even as to Neurocrine and its Affiliates), perpetual and irrevocable (except as provided in Section 13.3.2(b) (Termination for Patent Challenge), non-transferable (except as provided in Section 14.1 (Assignment)), sublicensable (solely as provided in Section 2.3 (Sublicensing Terms)) license under the Neurocrine Technology to Exploit the TAK-653 Products in the Field in Japan and (b) a non-exclusive, perpetual and irrevocable (except as provided in Section 13.3.2(b) (Termination for Patent Challenge), non-transferable (except as provided in Section 14.1 (Assignment)), sublicensable (solely as provided in Section 2.3 (Sublicensing Terms)), license in the Field in the Neurocrine Territory under the Neurocrine Manufacturing Technology and the Licensed Takeda Technology to Manufacture the TAK-653 22 Products in the Neurocrine Territory solely for the purpose of Exploiting the TAK-653 Products in Japan under the preceding clause (a). 2.3. Sublicensing Terms. Subject to the terms and conditions of [***], each Party may grant sublicenses (through multiple tiers of sublicense) in accordance with the terms of this Section 2.3 (Sublicensing Terms). 2.3.1. Sublicensing Rights. (a) Neurocrine. Subject to the requirements of this Section 2.3 (Sublicensing Terms), Section 2.4 (Subcontractors), [***], and Section 2.5.1 (Neurocrine Grant to Takeda), Neurocrine will have the right to grant sublicenses under the rights granted to it under Section 2.1 (License Grant to Neurocrine) [***]. (b) Takeda. Subject to the requirements of this Section 2.3 (Sublicensing Terms), Section 2.4 (Subcontractors), and Section 2.5.2 (Takeda Grant to Neurocrine), Takeda will have the right to grant sublicenses under the rights granted to it under Section 2.2 (License Grant to Takeda) [***]. 2.3.2. Sublicensing Agreements. Each sublicense granted by a Party pursuant to this Section 2.3 (Sublicensing Terms) will be subject and subordinate to the applicable terms of this Agreement. Any such sublicense (a) will be consistent with the terms of this Agreement, including intellectual property terms and confidentiality, non-disclosure, and non-use provisions at least as restrictive or protective of the Parties as those set forth in this Agreement, and (b) to the extent a Party engages a Sublicensee to Commercialize a Licensed Product, include an obligation of such Sublicensee to account for and report its Net Sales (in local currency and Dollars) on a country-by-country and Licensed Product- by-Licensed Product basis and any other information necessary for such Party to comply with its obligation to provide Royalty Reports in accordance with Section 8.3.2 (Reports and Royalty Payments). In addition, unless agreed otherwise by the JSC, each Party will include in each agreement under which it grants a sublicense an obligation of the Sublicensee to assign or grant a sublicensable license to such Party, upon termination of such agreement or with respect to any territory that is not within the scope of the sublicense, of all Know-How generated by the Sublicensee and all Patent Rights owned or controlled by such Sublicensee Covering any such Know-How, in each case, that are necessary to Exploit any Licensed Product subject to such agreement. Each Party will provide the other Party with a written notice of any sublicense granted by such Party or its Affiliates pursuant to this Section 2.3 (Sublicensing Terms) to any Third Party no later than [***] after the effective date thereof and will provide such other Party with a copy of each Third Party sublicense agreement (excluding sublicenses to subcontractors engaged pursuant to Section 2.4 (Subcontractors)), from which copy such Party may redact any confidential information that is not necessary for such other Party to confirm compliance with the terms of this Agreement. 2.3.3. Liability. Notwithstanding any sublicense, each Party will remain primarily liable to the other Party for the performance of all of such Party’s obligations under, and such Party’s compliance with all provisions of, this Agreement, and for the performance of all obligations of its Affiliates and Sublicensees as required under this Agreement. 23 2.4. Subcontractors. Each Party may perform any of its obligations under this Agreement through one or more subcontractors, provided that: (a) neither Party will engage any subcontractor that has been debarred by any Regulatory Authority, (b) each Party remains fully responsible for the work allocated to, and payment to, its subcontractors to the same extent it would be if such Party had done such work itself, (c) the subcontractor undertakes in writing obligations of confidentiality and non-use applicable to the Confidential Information that are at least as stringent as those set forth in Article 9 (Confidentiality and Publication), (d) unless otherwise agreed by the JSC, the subcontractor agrees in writing to assign or grant a sublicensable license (or in the case of a subcontractor that is an academic, government or nonprofit institution or employee thereof, a right to negotiate a license) to such Party to all Know-How generated by the subcontractor and all Patent Rights owned or controlled by the subcontractor Covering any such Know-How, in each case, that are necessary to Exploit any Licensed Product, but excluding [***], and (e) each Party will be liable for any act or omission of any subcontractor that is a breach of any of such Party’s obligations under this Agreement as though the same were a breach by such Party, and the other Party will have the right to proceed directly against such Party without any obligation to first proceed against such subcontractor. Each Party will be solely responsible for the direction of and communications with each such subcontractor engaged by such Party. 2.5. [***]. 2.5.1. [***]. 2.5.2. [***]. 2.5.3. [***]
24 2.6. Third Party IP for TAK-653 Products. 2.6.1. Notice. If, after the Restatement Date during the Term, either Party or its Affiliate identifies any Know-How or Patent Rights from a Third Party that may be necessary or reasonably useful to Exploit any TAK-653 Product (such Know-How or Patent Rights, “Identified TAK-653 Rights”), then such Party will notify the other Party in writing of such Identified TAK-653 Rights and Section 2.6.2 (Neurocrine’s Right) will apply. Within [***] after receipt or delivery of such notice, Takeda will notify Neurocrine in writing if Takeda wishes to obtain rights, as a licensee or sublicensee of Neurocrine, to any such Identified TAK-653 Rights that would be included in the Neurocrine Technology or Neurocrine Manufacturing Technology if they were Controlled by Neurocrine. 2.6.2. Neurocrine’s Right. Neurocrine will have the first right to acquire rights to any Identified TAK-653 Rights, provided that if Takeda does not timely notify Neurocrine pursuant to the last sentence of Section 2.6.1 (Notice) that it wishes to be granted rights under such 25 Identified TAK-653 Rights or if Takeda exercises its opt-out right in accordance with Section 2.6.3 (TAK-653 IP Agreements), then (i) such Identified TAK-653 Rights will be deemed to not be Controlled by Neurocrine, (ii) Neurocrine will either obtain only non- exclusive rights under the applicable Identified TAK-653 Rights in Japan or exclude Japan entirely, in each case, in its agreement for such rights, and (iii) Takeda may, in its discretion and at its sole cost and expense, obtain rights to such Identified TAK-653 Rights solely in Japan. If Neurocrine notifies Takeda in writing that Neurocrine does not intend to obtain rights to such Identified TAK-653 Rights, or does not use reasonable efforts to obtain such Identified TAK-653 Rights within [***] after becoming aware of such Identified TAK- 653 Rights, then Takeda may obtain rights to such Identified TAK-653 Rights solely in Japan. Notwithstanding any provision to the contrary set forth in this Section 2.6 (Third Party IP for TAK-653 Products), Neurocrine will not enter into any agreement for Identified TAK-653 Rights during the Term that would impose disproportionately high (with respect to the relative value of such Identified TAK-653 Rights in each territory) payment terms to Japan in comparison to the Neurocrine Territory. 2.6.3. TAK-653 IP Agreements. If Takeda timely notifies Neurocrine pursuant to the last sentence of Section 2.6.1 (Notice) that it wishes to obtain rights to any particular Identified TAK-653 Rights that would be licensed to Takeda hereunder if Controlled by Neurocrine or its Affiliates, then prior to Neurocrine’s or its Affiliate’s execution of an agreement with a Third Party to acquire or license such Identified TAK-653 Rights (any such agreement, a “TAK-653 IP Agreement”), Neurocrine will (a) provide Takeda an opportunity to review and comment on the terms of the proposed TAK-653 IP Agreement that are applicable to Japan, including any payments that Neurocrine or its Affiliates would be obligated to pay in connection with the grant, maintenance, or exercise of a license or sublicense thereunder, as applicable, (b) use reasonable efforts to incorporate Takeda’s reasonable comments that relate solely to Japan and reasonably attempt to incorporate Takeda’s comments otherwise, and (c) unless Takeda opts out pursuant to the remainder of this sentence, ensure that such TAK-653 IP Agreement includes the right to grant a license or sublicense to Takeda in the Field in Japan under the applicable Identified TAK- 653 Rights, provided that if at any time prior to the execution of the applicable TAK-653 IP Agreement the economic terms of such TAK-653 IP Agreement that apply to Japan have materially deviated from the corresponding economic terms requested in Takeda’s comments provided pursuant to Section 2.6.3(a) (TAK-653 IP Agreements), then Neurocrine will notify Takeda no later than [***] after receiving such terms, and Takeda will have the right, exercisable by Takeda by providing written notice of opt- out to Neurocrine within [***] after receipt of such notice from Neurocrine, to opt-out of such TAK-653 IP Agreement, in which case (i) such TAK-653 Rights will not be deemed Controlled by Neurocrine hereunder, and (ii) Neurocrine will only obtain rights under such TAK-653 Rights in accordance with Section 2.6.2(ii) (Neurocrine’s Right). 2.6.4. Responsibility for Costs. If a TAK-653 IP Agreement includes exclusive rights in Japan in accordance with Sections 2.6.2 (Neurocrine’s Right) and 2.6.3 (TAK-653 IP Agreements), then (a) the applicable Identified TAK-653 Rights will be deemed Controlled by Neurocrine and licensed or sublicensed (as applicable) to Takeda under the licenses granted in Section 2.2 (License Grant to Takeda), subject to the terms of this Agreement and the applicable TAK-653 IP Agreement, and (b) [***] and (ii) [***]. If Takeda itself acquires (not through Neurocrine) any rights to any Identified TAK-653 Rights, then Takeda will [***]. 26 2.7. Knowledge and Technology Transfer. If requested by Neurocrine in writing during the Term, Takeda will promptly disclose to Neurocrine all Takeda Know-How in existence as of the Effective Date or that comes into existence as a result of performance by or behalf of Takeda of activities under the Original Agreement or this Agreement and not previously transferred to Neurocrine. Takeda will provide any assistance as reasonably requested by Neurocrine in connection with Neurocrine’s Exploitation of any particular Takeda Know-How in accordance with this Agreement for a period of up to [***] after the date on which Takeda delivers to Neurocrine such Takeda Know-How. [***]. Notwithstanding any provision to the contrary set forth in this Agreement, Takeda will not be obligated to provide any additional assistance under this Section 2.7 (Knowledge and Technology Transfer) beyond that which can be provided in accordance with the amounts included in the budget agreed by the Parties (as such budget may be updated from time to time by agreement of the Parties). No earlier than [***] after the Restatement Date, Takeda may provide Neurocrine with written notice that Takeda intends in good faith based on approval from its internal governance process to Develop TAK-653 Products in Japan (the date of such notice, the “Takeda Request Date”). Within [***] after the Takeda Request Date, Neurocrine will transfer to Takeda all Program Know-How generated by or on behalf of Neurocrine and not previously provided to Takeda that is included in the Neurocrine Technology. Thereafter, Neurocrine will promptly disclose to Takeda all additional Program Know-How in the Neurocrine Technology that comes into existence as a result of performance by or behalf of Neurocrine of activities under this Agreement and not previously transferred to Takeda. 2.8. No Other Rights and Retained Rights. Except as otherwise expressly provided in this Agreement, under no circumstances will a Party or any of its Affiliates, as a result of this Agreement, obtain any ownership interest, license, or other right in or to any Know-How, Patent Rights, or other intellectual property of the other Party, including tangible or intangible items owned, controlled, or developed by the other Party, or provided by the other Party to the receiving Party at any time, pursuant to this Agreement. Neurocrine will not, and will cause its Affiliates and Sublicensee to not, use or practice any Licensed Takeda Technology outside the scope of or otherwise not in compliance with the rights and licenses granted to Neurocrine under this Agreement. Takeda will not, and will cause its Affiliates and licensees to not, use or practice any Neurocrine Technology or Grantback IP outside the scope of or otherwise not in compliance with the rights and licenses granted to Takeda under this Agreement. Any rights not expressly granted by a Party under this Agreement are hereby retained by such Party. 27 3. DEVELOPMENT 3.1. Development Responsibilities. 3.1.1. Neurocrine. As between the Parties, Neurocrine will be solely responsible for, at its sole expense, all Development of Licensed Products in the Territory and all Manufacturing activities in connection therewith, including preparing Clinical Trial designs and protocols, sponsoring Clinical Trials, engaging CROs, and being responsible for managing activities at Clinical Trial sites. 3.1.2. Takeda. As between the Parties, Takeda will be solely responsible for, at its sole expense, all Development of TAK-653 Products in Japan and, except as expressly set forth herein or otherwise agreed by the Parties in writing, all Manufacturing activities in connection therewith, including preparing Clinical Trial designs and protocols, sponsoring Clinical Trials, engaging CROs, and being responsible for managing activities at Clinical Trial sites. [***]. 3.1.3. Commencing no later than [***] after the Effective Date, and no less than [***] thereafter, each Party will submit a written plan for the Development activities planned to be conducted for TAK-653 Assets and TAK-653 Products, with respect to Takeda, in Japan, and with respect to Neurocrine, in the Neurocrine Territory, including (a) a high-level description of material pre-clinical, clinical, regulatory and other Development activities to be conducted and (b) an estimated timeline of all such Development activities (each Party’s plan, a “Development Plan”). Each Party will submit their initial proposed Development Plans, and each [***] update thereto, to the JSC for review and discussion and, [***]. 3.2. Neurocrine Development Diligence Obligations. Neurocrine will use Commercially Reasonable Efforts to Develop and seek Regulatory Approval and, as applicable, Pricing Approval for (a) at least one TAK-653 Product in each of the Major Markets other than Japan and (b) at least one Licensed Product that comprises a Nonclinical Asset in the [***] Target Class and at least one Licensed Product that comprises a Nonclinical Asset in the [***] Target Class, in each case, in at least one Major Market. 3.3. Licensed Products Development Reports. Neurocrine will keep Takeda informed regarding the progress of the Development of the Licensed Products in the Territory, and Takeda will keep Neurocrine informed regarding the progress of the Development of TAK-653 Products in Japan. Each Party will report to the other Party material developments and information that it comes to possess relating to the Development of the Licensed Products, including any material information regarding the Development of the Licensed Products reasonably requested by such other Party from time to time to the extent and in the form readily available to such Party and able to be disclosed to such other Party (each such report, a “LP Development Report”). All reports and information provided under this Section 3.3 (Licensed Products Development Reports) will be the Confidential Information of the providing Party, and subject to the terms of Article 9 (Confidentiality and Publication).
28 3.4. Scientific Records. Each Party will maintain scientific records of its Development activities hereunder in sufficient detail and in good scientific manner appropriate for patent and regulatory purposes, and in compliance with GLP, cGMP, and GCP with respect to activities intended to be submitted in regulatory filings (including INDs), all of which records will fully and accurately reflect all work done and results achieved in the performance of the Development activities and Clinical Trials by or on behalf of such Party with respect to Licensed Products. 3.5. Supply of TAK-653 Products for Development in Japan. Upon Takeda’s written request at any time after the Takeda Request Date, the Parties will negotiate in good faith and enter into a supply agreement pursuant to which Neurocrine will supply TAK-653 Products (a “Supply Agreement”), in the form then Manufactured by Neurocrine for its own use and according to the Manufacturing process and specifications then used by Neurocrine, to Takeda for use in connection with Takeda’s Development activities; provided that Neurocrine will have no obligation under this Agreement or any supply agreement between the Parties (or their respective Affiliates) to make any changes to its then-current Manufacturing process or specifications in connection with its supply to Takeda. The price for any TAK-653 Product supplied by Neurocrine to Takeda for Development purposes will be [***]. If the Parties fail to enter a Supply Agreement within [***] after Takeda’s request despite the good faith efforts of the Parties, then either Party may refer the outstanding issues in the Supply Agreement for attempted resolution in good faith by the Parties’ Executive Officers by providing written notice to the other Party. After receipt of such written notice, the Executive Officers of each Party will attempt to resolve the outstanding issues in the Supply Agreement in good faith within [***] after such notice is received. If, within [***] after such notice is received, despite such Executive Officers’ good faith efforts, the outstanding issues have not been resolved, then either Party may refer the determination of the final form of the Supply Agreement to [***]. 3.6. Development Costs. 3.6.1. After the Restatement Date, Neurocrine may invoice Takeda for the costs incurred by Neurocrine to Develop the TAK-653 Product prior to the Restatement Date and owed but not previously paid by Takeda under the Original Agreement, provided that such costs are consistent with the Co-Funded Development Budgets (as such term is defined under the Original Agreement) provided by NBI to Takeda under the Original Agreement for the applicable activities. Takeda will pay each such invoice no later than [***] after receipt thereof. 3.6.2. As of the Restatement Date, except as provided herein or in any Supply Agreement between the Parties, (i) Neurocrine will be solely responsible for any and all costs and expenses incurred by Neurocrine after the Restatement Date in connection with the Development and Manufacturing of the TAK-653 Product in the Neurocrine Territory and (ii) Takeda will be solely responsible for any and all costs and expenses incurred by Takeda after the Restatement Date in connection with the Development and Manufacture of the TAK-653 Product in Japan. 4. REGULATORY MATTERS 4.1. Regulatory Responsibilities. 4.1.1. Neurocrine. Neurocrine (itself or through its Affiliate or Sublicensee) will be solely responsible as the Regulatory Lead for all regulatory matters in the Territory relating to the 29 Licensed Products. Neurocrine (itself or through its Affiliate or Sublicensee) will own all INDs, MAA, Regulatory Approvals, other Regulatory Submissions, and related regulatory documents in the Territory with respect to such Licensed Products (in each case, as applicable). Takeda will provide all assistance reasonably requested by Neurocrine in connection with Neurocrine’s preparation and submission of any MAA for a Licensed Product and obtaining Regulatory Approval for Licensed Products, and Neurocrine will reimburse Takeda for all documented FTE Costs at the FTE Rate and external expenses associated with such assistance, within [***] after receipt of an undisputed invoice therefor. 4.1.2. Takeda. Takeda (itself or through its Affiliate or Sublicensee) will be solely responsible as the Regulatory Lead for all regulatory matters in Japan relating to the TAK-653 Products. Takeda (itself or through its Affiliate or Sublicensee) will own all INDs, MAA, Regulatory Approvals, other Regulatory Submissions, and related regulatory documents in Japan with respect to TAK-653 Products (in each case, as applicable). Neurocrine will provide all assistance reasonably requested by Takeda in connection with the preparation and submission of any CTA or MAA for a TAK-653 Product, or obtaining Regulatory Approval, in each case, by or on behalf of Takeda, for TAK-653 Products in Japan, and Takeda will reimburse Neurocrine for all documented FTE Costs at the FTE Rate and external expenses associated with such assistance, within [***] after receipt of an undisputed invoice therefor. 4.2. Regulatory Submissions, Study Reports and Data not Controlled by Takeda. [***]. 4.3. Regulatory Information Obligations. Each Party will provide the other Party, through the JSC at least once every [***] Calendar Quarters, with written notice of each of the following events with regard to each Licensed Product in the Territory with respect to Neurocrine, and each TAK- 653 Product in Japan with respect to Takeda: (a) to the extent notice was not previously provided, notice of the submission of any filings or applications for Regulatory Approval of such Licensed Products to any Regulatory Authority; and (b) a summary of all Regulatory Submissions anticipated to be filed for any Licensed Products within the upcoming [***] Calendar Quarters; provided that each Party will use reasonable efforts to inform the other Party of such events under (a) or (b) prior to public disclosure of such event by such Party. 4.4. TAK-653 Product Data Sharing. On and after the Restatement Date with respect to Takeda as the providing Party, and on and after the Takeda Request Date with respect to Neurocrine as the providing Party, to the extent not previously provided, each Party will promptly provide the other Party with copies (along with an English translation thereof, if applicable) of all data, results and 30 all supporting documentation (e.g., protocols, investigator’s brochures, and analysis plans) Controlled by such Party that is (a) generated by or on behalf of such Party in the performance of Development activities for the TAK-653 Product and (b) licensed to the other Party hereunder. Such copies will be provided upon availability after the conclusion of the applicable study or Clinical Trial. Such data, results, and supporting documentation provided by a Party pursuant to this Section 4.4 (TAK-653 Product Data Sharing) will be the Confidential Information of such Party, and such Party will be the disclosing Party with respect thereto, in each case, subject to the terms of Article 9 (Confidentiality and Publication). Each Party will bear its own costs and expenses of providing data, results, and supporting documentation to the other Party in accordance with this Agreement. If either Party believes that the other Party’s requests under this Section 4.4 (TAK-653 Product Data Sharing) are overly burdensome, then the JSC will discuss such requests and a reasonable schedule for sharing of such data, results, and supporting documentation. 4.5. Costs of Regulatory Affairs. Each Party will be solely responsible for all costs and expenses it incurs in connection with regulatory activities for Licensed Products. 4.6. No Harmful Actions. If Neurocrine believes that Takeda is taking or intends to take any action with respect to a TAK-653 Product that is reasonably likely to have an adverse impact upon the regulatory status of such TAK-653 Product in the Territory, then at Neurocrine’s request, the Parties will discuss in good faith strategies to minimize any such impact (if any). 4.7. Adverse Events Reporting. 4.7.1. If Takeda commences clinical development of any TAK-653 Product, Neurocrine and Takeda will enter into a written agreement (the “Pharmacovigilance Agreement”) that establishes worldwide safety and pharmacovigilance procedures for the Parties with respect to the TAK-653 Products, such as safety data sharing and exchange, Adverse Events reporting and prescription events monitoring. The Pharmacovigilance Agreement will describe the coordination of collection, investigation, reporting, and exchange of information concerning Adverse Events or any other safety problem of any significance, and product quality and product complaints involving Adverse Events, related to TAK-653 Products, sufficient to permit each Party, its Affiliates, and its Sublicensees to comply with its legal obligations. The Pharmacovigilance Agreement will be promptly updated if required by changes in legal requirements. Each Party hereby agrees to comply with its respective obligations under the Pharmacovigilance Agreement and to cause its Affiliates and require its Sublicensees to comply with such obligations. 4.7.2. Each Party will be responsible for complying with all Laws governing Adverse Events for all Clinical Trials of any TAK-653 Product performed by such Party. 4.7.3. Neurocrine will hold and control the global safety database for each TAK-653 Product for the exchange by the Parties, in English, of any information of which a Party becomes aware concerning any Adverse Event experienced by a subject or patient being administered the applicable TAK-653 Product, including any such information received by either Party from any Third Party (subject to receipt of any required consents from such Third Party). [***]. It is understood that each Party and its Affiliates and Sublicensees has the right to disclose such information if disclosure is reasonably necessary to comply with Laws or requirements of any applicable Regulatory Authority. 31 4.8. Data Privacy. The Parties will enter into any necessary agreement(s) under applicable data security and protection Laws (such as a data transfer agreement) when required by applicable Laws. The terms of each such agreement will be agreed by the Parties when the requirement to enter into such agreement has been confirmed by the Parties. 5. COMMERCIALIZATION 5.1. Commercialization of the Licensed Products. Neurocrine (itself or through its Affiliates or Sublicensees) will have the sole right and responsibility for the Commercialization of Licensed Products in the Territory, at its sole expense. Takeda (itself or through its Affiliates or Sublicensees) will have the sole right and responsibility for the Commercialization of TAK-653 Products in Japan, at its sole expense (except if the Parties agree that Neurocrine will supply TAK- 653 Products for Commercial use pursuant to Section 5.7 (Supply of TAK-653 Products for Japan)). 5.2. Commercialization Diligence Obligations. Neurocrine will use Commercially Reasonable Efforts to Commercialize each Licensed Product in each jurisdiction in which such Licensed Product receives Regulatory Approval and, if applicable, Pricing Approval. 5.3. Licensed Products Commercialization Reporting. Each Party will share with the other Party material developments and information that it comes to possess relating to the Commercialization of the Licensed Products, including any material information regarding the Commercialization of the Licensed Products reasonably requested by such other Party from time to time to the extent and in the form readily available to such Party and able to be disclosed to such other Party. In addition, each Party will provide to the JCC (or if the JCC has not been formed, to the JSC, or if the JCC and JSC have disbanded, to the other Party), at least [***] every Calendar Year and reasonably in advance of each meeting of the JCC or JSC (as applicable), a report (by means of a slide presentation or otherwise) summarizing results and key Commercialization activities undertaken and planned to be undertaken for TAK-653 Products in Japan (with respect to Takeda) or in the Neurocrine Territory (with respect to Neurocrine) (including, for example, updates regarding regulatory matters and Commercialization activities for the next Calendar Year) (each such report, a “LP Commercialization Report”). 5.4. Commercialization Information Sharing. Commencing no later than [***] before the expected launch of a TAK-653 Product anywhere in the world and continuing on [***] basis thereafter during the Term, the JCC will review and discuss the efforts each Party will undertake in its territory with respect to (a) [***], (b) [***], (c) [***], and (d) [***]. Each Party will also present updates at each meeting of the JCC regarding any [***]. 5.5. Recalls, Market Withdrawals, or Corrective Actions. Each Party will notify the other Party immediately if it obtains information indicating that any TAK-653 Product may be subject to any recall or other similar market withdrawal or other action. Neurocrine will have the sole right to decide whether to conduct, at its sole cost and expense, any recall or other similar market withdrawal or other action for any Licensed Product in the Territory, and the manner in which any such recall will be conducted (including any such recall requested by a Regulatory Authority). Takeda will have the sole right to decide whether to conduct, at its sole cost and expense, any recall or other similar market withdrawal or other action for any TAK-653 Product in Japan, and the manner in which any such recall will be conducted (including any such recall requested by a Regulatory Authority).
32 5.6. Cross-Territorial Restrictions. Except for Manufacturing and supply of TAK-653 Products in accordance with this Agreement, each Party hereby covenants and agrees that it shall not, and shall ensure that its Affiliates and require that its Sublicensees shall not, either directly or indirectly, promote, market, distribute, import, sell or have sold or otherwise Exploit any TAK-653 Product for Commercial purposes, including via the Internet or mail order, to any Third Party or to any address or Internet Protocol address or the like (a) outside of Japan, with respect to Takeda or (b) in Japan, with respect to Neurocrine, including in each case (a) or (b), to any Third Party that such Party knows (or reasonably should know after due inquiry) has previously exported or is likely to export the TAK-653 Product outside Japan (with respect to Takeda) or into Japan (with respect to Neurocrine). Neither Party shall engage, nor permit its Affiliates and Sublicensees to engage, in any advertising or promotional activities relating to any TAK-653 Product for use directed primarily to customers or other buyers or users of the TAK-653 Product located in any country or jurisdiction outside Japan (with respect to Takeda) or in Japan (with respect to Neurocrine), or solicit orders from any prospective purchaser located in any country or jurisdiction outside Japan (with respect to Takeda) or in Japan (with respect to Neurocrine). If a Party or its Affiliates or Sublicensees receive any order for the TAK-653 Product from a prospective purchaser located in a country or jurisdiction outside Japan (with respect to Takeda) or in Japan (with respect to Neurocrine), then such Party shall immediately refer that order to such other Party and shall not accept any such orders. Neither Party shall, nor permit its Affiliates or Sublicensees to, deliver or tender (or cause to be delivered or tendered) any TAK-653 Product to any Third Party for use in or distribution into any country or jurisdiction outside Japan (with respect to Takeda) or in Japan (with respect to Neurocrine). 5.7. Supply of TAK-653 Products for Japan. Upon Takeda’s reasonable request following Takeda’s Initiation of a Phase III Clinical Trial of a TAK-653 Product in Japan, the Parties will negotiate in good faith and enter into, as applicable, an amendment to the Supply Agreement (if the Parties have agreed to a Supply Agreement for Development supply) or a new Supply Agreement, pursuant to which Neurocrine will supply TAK-653 Products, in the form then Manufactured by Neurocrine for its own use and according to the Manufacturing process and specifications then used by Neurocrine, to Takeda for Commercial use in Japan; provided that Neurocrine will have no obligation under this Agreement or any Supply Agreement between the Parties (or their respective Affiliates) to make any changes to its then-current Manufacturing process or specifications in connection with its supply to Takeda. The price for any TAK-653 Product supplied by Neurocrine to Takeda will be [***]. If the Parties fail to enter a Supply Agreement within [***] after Takeda’s request despite the good faith efforts of the Parties, then either Party may refer the outstanding issues in the Supply Agreement for attempted resolution in good faith by the Parties’ Executive Officers by providing written notice to the other Party. After receipt of such written notice, the Executive Officers of each Party will attempt to resolve the outstanding issues in the Supply Agreement in good faith within [***] after such notice is received. If, within [***] after such notice is received, despite such Executive Officers’ good faith efforts, the outstanding issues have not been resolved, then either Party may refer the determination of the final form of the Supply Agreement to [***]. 6. MEDICAL AFFAIRS 6.1. Responsibilities. Neurocrine will be solely responsible, at its sole expense, for all Medical Affairs activities for Licensed Products in the Territory. Takeda will be solely responsible, at its sole expense, for all Medical Affairs activities for TAK-653 Products in Japan. Each Party will keep the other Party informed regarding its Medical Affairs activities for TAK-653 Products. The Parties 33 will review and discuss at the JSC each Party’s [***]. 7. GOVERNANCE 7.1. Alliance Manager. Under the Original Agreement, each Party designated an individual to facilitate communication and coordination of the Parties’ activities under this Agreement relating to the Licensed Products and to provide support and guidance to the JSC, including preparing agendas, meeting materials, and meeting minutes for JSC meetings (each, an “Alliance Manager”). Each Alliance Manager may, but is not required to, serve as a representative of its respective Party on the JSC, but the Alliance Managers or suitable designees will attend all meetings of the JSC. The Alliance Managers may bring to the attention of the JSC any matters or issues either of them reasonably believes should be discussed by the JSC. Each Party may replace its Alliance Manager at any time by written notice to the other Party. The Alliance Managers will be responsible for creating and maintaining a constructive work environment between the Parties. Without limiting the generality of the foregoing, the Alliance Managers will: (a) identify and timely bring to the attention of their respective managements any disputes arising between the Parties related to this Agreement; (b) provide a single point of communication between the Parties with respect to this Agreement and the Parties’ respective activities hereunder; (c) ensure that meetings of the JSC occur as set forth in this Agreement, that procedures are followed with respect to such meetings (including the giving of proper notice and the preparation and approval of minutes) and that relevant action items resulting from such meetings are appropriately carried out or otherwise addressed; and (d) undertake such other responsibilities as the Parties may mutually agree in writing. 7.2. Joint Steering Committee. 7.2.1. Purpose; Formation. Under the Original Agreement, the Parties established a joint steering committee (the “JSC”) that will monitor and provide strategic oversight of the activities under this Agreement and facilitate communication between the Parties, in each case, with respect to the Development of all Licensed Products, all in accordance with the terms of this Agreement. The JSC will disband upon [***]; provided that if, following the disbandment of the JSC pursuant to this Section 7.2.1 (Purpose; Formation), either Party or its Affiliate or Sublicensee thereafter commences any additional Development of any Licensed Product, then the JSC will be reinstated. 7.2.2. Composition. Each Party’s representatives to the JSC will have knowledge and expertise in the Exploitation of assets and products similar to the Licensed Products, and will have sufficient seniority within the applicable Party to provide meaningful input and make decisions arising within the scope of the JSC’s responsibilities. The JSC may change its size from time to time by unanimous consent of the Parties, provided that, unless otherwise agreed by the Parties in writing, the JSC will consist at all times of an equal number of representatives of each Party. Each Party may replace its JSC representatives at any time upon written notice to the other Party. The JSC may invite non-members to participate in the discussions and meetings of the JSC, but such participants will have no voting authority at the JSC and must be bound under written obligations of confidentiality no less protective of the Parties’ Confidential Information than those set forth in this Agreement. The Alliance Managers will prepare and circulate agendas and ensure the preparation and approval of minutes. 34 7.2.3. Responsibilities of JSC. In addition to its overall responsibility for monitoring and providing strategic oversight with respect to the Parties’ activities with respect to the Development of all Licensed Products under this Agreement, the JSC will have the following responsibilities: (a) review and discuss each Party’s Development Plan, and approve Takeda’s Development Plan, in each case, including any updates and amendments thereto, and review, discuss and approve the design and protocol of each Clinical Trial of a TAK-653 Product in Japan; (b) determine whether to approve any sublicense agreement in which the potential Sublicensee does not agree to assign or grant a sublicensable license to a Party upon termination of such agreement or with respect to any territory that is not within the scope of the sublicense of all Know-How generated by the Sublicensee and all Patent Rights owned or controlled by such Sublicensee Covering any such Know-How, in each case, that are necessary to Exploit any Licensed Product subject to such agreement, as described in Section 2.3.2 (Sublicensing Agreements); (c) determine whether to approve the engagement of any potential subcontractor that does not agree to assign or grant a sublicensable license (or in the case of a subcontractor that is an academic, government or nonprofit institution, or any employee thereof, a right to negotiate a license) to a Party to all Know-How generated by the subcontractor and all Patent Rights owned or controlled by the subcontractor Covering any such Know-How, in each case, that are necessary to Exploit any Licensed Product, as described in Section 2.4 (Subcontractors); (d) review and discuss [***]; (e) review and discuss any proposed publication by either Party, as described in Section 9.2 (Publication and Publicity); (f) serve as a forum for exchange of information for the Parties in relation to the Licensed Products, or any activities undertaken by or on behalf of either Party under this Agreement; (g) review and discuss LP Development Reports, as described in Section 3.3 (Licensed Products Development Reports), LP Commercialization Reports, if applicable as described in Section 5.3 (Licensed Products Commercialization Reporting), and notices and summaries of Regulatory Submissions, as described in Section 4.3 (Regulatory Information Obligations), in each case that are provided by either Party; (h) if requested by either Party, discuss each Party’s requests and a reasonable schedule for sharing of data, results, and supporting documentation under Section 4.4 (TAK-653 Product Data Sharing); 35 (i) attempt to resolve any disputes on matters within the JSC’s authority on an informal basis and in good faith prior to the institution of escalation or other formal dispute resolution mechanisms hereunder; and (j) perform such other functions expressly allocated to the JSC in this Agreement or by the written agreement of the Parties. 7.2.4. JSC Meetings. The JSC will meet at least semi-annually unless the Parties mutually agree in writing to a different frequency. No later than [***] prior to any meeting of the JSC (or such shorter time period as the Parties may agree), the Alliance Managers will prepare and circulate an agenda for such meeting; provided, however, that either Party may propose additional topics to be included on such agenda, either prior to or in the course of such meeting. Either Party may also call a special meeting of the JSC (by videoconference, teleconference, or in person) by providing at least [***] prior written notice to the other Party if such Party reasonably believes that a significant matter must be addressed prior to the next scheduled meeting, in which event such Party will work with the Alliance Managers to provide the members of the JSC, no later than [***] prior to the special meeting, with an agenda for the meeting and materials reasonably adequate to enable an informed decision on the matters to be considered. In addition to any items set forth on the agenda for a meeting of the JSC, at each meeting of the JSC, each Party will provide a high-level update on all activities performed by or on behalf of such Party in connection with the Exploitation of the Licensed Products since the last meeting of the JSC. The JSC may meet in person, by videoconference or by teleconference. Notwithstanding the foregoing, at least one meeting per Calendar Year will be in person unless the Parties agree in writing to waive such requirement. In-person JSC meetings will be held at locations alternately selected by each Party. Each Party will bear the expense of its respective JSC members’ participation in JSC meetings. Meetings of the JSC will be effective only if at least one representative of each Party (which representative is not such Party’s Alliance Manager) is present or participating in such meeting. The Alliance Managers will be responsible for preparing reasonably detailed written minutes of all JSC meetings that reflect material decisions made and action items identified at such meetings. The Alliance Managers will send draft meeting minutes to each member of the JSC for review and approval within [***] after each JSC meeting. Such minutes will be deemed approved unless one or more members of the JSC object to the accuracy of such minutes within [***] of receipt. 7.3. Decisions of the JSC. The JSC has the authority (a) for matters specifically delegated to it or expressly specified in this Agreement and (b) with respect to any other matter agreed to by the Parties in writing. For clarity, the JSC will not have any power to amend, modify, or waive compliance with this Agreement. The JSC has no other authority under this Agreement than what is expressly granted under this Agreement. The JSC will use good faith, commercially reasonable efforts in compliance with this Section 7.3 (Decisions of the JSC) to promptly resolve any such matter for which it has authority. If the JSC is unable to reach consensus with respect to any such matter for which it is responsible within [***] after a Party affirmatively states to the other Party that a decision needs to be made, then such matter will be subject to Section 7.4 (Resolution of JSC Disputes). 7.4. Resolution of JSC Disputes. 7.4.1. Referral to Executive Officers. Either Party may make an election under Section 7.3 (Decisions of the JSC) to refer a matter as to which the JSC cannot reach a consensus
36 decision to the Executive Officers, following which the JSC will promptly submit in writing the respective positions of the Parties to their respective Executive Officers. Such Executive Officers will use good faith efforts, in compliance with this Section 7.4.1 (Referral to Executive Officers), to resolve promptly such matter within [***] after the JSC’s submission of such matter to such Executive Officers, which good faith efforts will include at least one in-person or telephonic meeting between such Executive Officers within such [***] period. 7.4.2. Final Decision-Making Authority. If the Executive Officers are unable to reach agreement on any such matter referred to them under Section 7.4.1 (Referral to Executive Officers) within the applicable [***] period, then: (a) Takeda will have final decision- making authority with respect to [***], and (b) Neurocrine will have final decision- making authority with respect to [***]. 7.4.3. Limitations on Decisions. Notwithstanding any provision to the contrary set forth in this Agreement, without the other Party’s prior written consent, no exercise of a Party’s decision-making authority on any such matters may, without the other Party’s prior written consent, (a) result in an increase in the other Party’s or its Affiliates’ obligations under this Agreement, (b) impose any requirements that the other Party take or decline to take any action that would result in a violation of any Law, ethical requirement, or any agreement with any Third Party or the infringement of intellectual property rights of any Third Party, or (c) otherwise conflict with, or constitute a modification of or waiver under, this Agreement. 7.4.4. Good Faith. In conducting themselves on committees, and in exercising their rights under this Section 7.4 (Resolution of JSC Disputes), all representatives of both Parties will consider diligently, reasonably, and in good faith all input received from the other Party, and will use reasonable efforts to reach consensus on all matters before them. In exercising any decision-making authority granted to it under this Section 7.4 (Resolution of JSC Disputes), each Party will act based on its reasonable and good faith judgment taking into consideration Neurocrine’s obligations to use Commercially Reasonable Efforts with respect to Exploitation of the Licensed Products as set forth in this Agreement. 7.5. JSC Disbandment. After the disbandment of the JSC under this Article 7 (Governance), the JSC will have no further obligations under this Agreement, and thereafter each Party will designate a contact person for the exchange of information under this Agreement or such exchange of information will be made through the Alliance Managers, and decisions of the disbanded JSC will be decisions as between the Parties, subject to the other terms and conditions of this Agreement. 7.6. Joint Commercialization Committee. 37 7.6.1. Formation; Authority. No later than [***] prior to the expected Regulatory Approval of a TAK-653 Product in Japan, the JSC will establish and delegate specifically- defined duties to a joint commercialization committee that will oversee worldwide Commercialization of TAK-653 Products (the “JCC”). The JCC and its activities will be subject to the oversight of, and will report to, the JSC. The JCC may not exceed its authorities specified for the JSC in this Article 7 (Governance). Any disagreement between the representatives of the Parties on the JCC will be referred to the JSC for resolution in accordance with Section 7.4 (Resolution of JSC Disputes). The JCC will dissolve upon the expiration of the final Royalty Term for a TAK-653 Product. 7.6.2. Membership of the JCC. Each Party will designate up to [***] representatives with appropriate knowledge, expertise, and decision-making authority to serve as members of the JCC; provided that each Party shall have the same number of representatives as the other Party. Each Party may replace its JCC representatives at any time upon written notice to the other Party. The Alliance Manager of each Party (or his or her designee) may attend meetings of the JCC as a non-voting participant. 7.6.3. JCC Leadership and Meetings. The JCC members will designate a chairperson of the JCC, who will be responsible (or his or her designee) for calling meetings, preparing and circulating an agenda in advance of each meeting, and preparing and issuing minutes of each meeting within [***] thereafter. Such minutes will be finalized upon endorsement of all JCC members. The JCC will hold meetings at such times as it elects to do so and at such locations as the Parties may agree upon or, if agreed by the Parties, by audio or video teleconference. Each Party will be responsible for all of its own expenses of participating in any JCC meeting. 7.6.4. Specific Responsibilities of the JCC. The responsibilities of the JCC will be to: (a) serve as a forum for exchange of information with respect to the Commercialization of TAK-653 Products worldwide; (b) review and discuss LP Commercialization Reports provided by either Party, as described in Section 5.3 (Licensed Products Commercialization Reporting); and (c) review and discuss the (i) [***], (ii) [***], (iii) [***], and (iv) [***], in each case (i)-(iv), with respect to TAK-653 Products as described in Section 5.4 (Commercialization Information Sharing). 8. PAYMENTS 8.1. Payments for the Licensed Assets and Licensed Products. 8.1.1. Milestone Payments. (a) Development Milestones. Subject to this Section 8.1.1(a) (Development Milestones), unless paid under the Original Agreement, Neurocrine will make [***] milestone payments (each, a “Development Milestone Payment”) on a Licensed Product-by-Licensed Product basis to Takeda upon the first achievement by Neurocrine or its Affiliates or Sublicensees of each of the development 38 milestone events set forth in Table 8.1.1(a) (Development Milestones) below (each, a “Development Milestone Event”) for each Licensed Product to achieve the applicable Development Milestone Event. Neurocrine will notify Takeda in writing of the achievement of a Development Milestone Event by Neurocrine or its Affiliates or Sublicensees no later than [***] after the achievement thereof. Thereafter, Takeda will provide Neurocrine with an invoice for the corresponding Development Milestone Payment, and Neurocrine will pay to Takeda such Development Milestone Payment no later than [***] after its receipt of an invoice for such Development Milestone Payment. [***]. Table 8.1.1(a) – Development Milestones Development Milestone Event TAK-653 Product Milestone Payment Nonclinical Asset Milestone Payment (1) [***] [***] $[***] (2) [***] [***] $[***] (3) [***] $[***] $[***] (4) [***] $[***] $[***] For clarity, for a particular Licensed Product, Milestone #1 will be deemed achieved and payable, if not already achieved, upon achievement of any of Milestone #2 or Milestone #3 for such Licensed Product; Milestone #2 will be deemed achieved and payable, if not already achieved, upon achievement of Milestone #3 or Milestone #4 for such Licensed Product; and Milestone #3 will be deemed achieved and payable, if not already achieved, upon achievement of Milestone #4 for such Licensed Product. [***]. (b) Commercial Milestones. Subject to this Section 8.1.1(b) (Commercial Milestones), on a Licensed Asset-by-Licensed Asset basis, Neurocrine will make [***] commercial milestone payments (each, a “Commercial Milestone Payment” and together with the Development Milestone Payments, the “Milestone Payments”) to Takeda upon the achievement by Neurocrine or its Affiliates or Sublicensees of each of the sales-based milestones events set forth in Table 8.1.1(b) (Commercial Milestones) below (each, a “Commercial Milestone Event” and together with the Development Milestone Events, the “Milestone Events”) with respect to aggregate Annual Net Sales in the Territory of all 39 Licensed Products that contain the same Licensed Asset, provided that Net Sales of any Licensed Product in any country will not be included after the Royalty Term for such Licensed Product and country has ended. For clarity, for purposes of Commercial Milestone Events for TAK-653 Products, only Annual Net Sales worldwide outside of Japan will be included. Neurocrine will notify Takeda in writing of the achievement of a Commercial Milestone Event by Neurocrine or its Affiliates or Sublicensees no later than [***] after the end of the Calendar Quarter in which such Commercial Milestone Payment is payable pursuant to the preceding sentence. Thereafter, Takeda will provide Neurocrine with an invoice for the corresponding Commercial Milestone Payment, and Neurocrine will pay to Takeda such Commercial Milestone Payment no later than [***] after receipt of the applicable invoice from Takeda. If, during any Calendar Quarter, Neurocrine or its Affiliates or Sublicensees achieves more than one Commercial Milestone Event, then Neurocrine will make payment with respect to both such achieved Commercial Milestone Events according to the foregoing payment timeline in such Calendar Quarter. Table 8.1.1(b) – Commercial Milestones Commercial Milestone Event Commercial Milestone Payment First Calendar Year in which aggregate Annual Net Sales in the Territory of all Licensed Products that contain the same Licensed Asset exceed $[***] $[***] First Calendar Year in which aggregate Annual Net Sales in the Territory of all Licensed Products that contain the same Licensed Asset exceed $[***] $[***] First Calendar Year in which aggregate Annual Net Sales in the Territory of all Licensed Products that contain the same Licensed Asset exceed $[***] $[***] 8.1.2. Royalties. (a) Payable by Neurocrine. Until the expiration of the Royalty Term for each Licensed Product in each country in the Territory and subject to the provisions of Section 8.1.3 (Royalty Reductions), Neurocrine will pay to Takeda royalties in the amount of (a) the marginal Royalty Rates set forth in Table 8.1.2(a) (Royalty Payments (US)) below, based on the aggregate Net Sales resulting from the sale of all Licensed Products that contain the same Licensed Asset in the United States during each Calendar Year until the expiration of the applicable Royalty Term (for each Licensed Product, the “Annual US Net Sales,” and such payments, “US Royalties”), and (b) the marginal Royalty Rates set forth in Table 8.1.2(b) (Royalty Payments (Ex-US)) below, based on the aggregate Net Sales resulting from the sale of all Licensed Products that contain the same Licensed Asset in the Territory other than in the United States during each Calendar Year until the expiration of the applicable Royalty Term (for each Licensed Product, the “Annual Ex-US Net Sales,” and such payments, “Ex-US Royalties”). For clarity, Annual Ex-US Net Sales for TAK-653 Products do not include Net Sales in Japan. TABLE 8.1.2(a) –Royalty Payments (US) Annual US Net Sales TAK-653 Product Nonclinical Asset
40 Marginal Royalty Rate (% of Annual US Net Sales) Marginal Royalty Rate (% of Annual US Net Sales) The portion of Annual US Net Sales less than $[***] [***]% [***]% The portion of Annual US Net Sales greater than or equal to $[***]and less than $[***] [***]% [***]% The portion of Annual US Net Sales greater than or equal to $[***]and less than $[***] [***]% [***]% The portion of Annual US Net Sales greater than or equal to $[***] [***]% [***]% TABLE 8.1.2(b) – Royalty Payments (Ex-US) Annual Ex-US Net Sales TAK-653 Product Marginal Royalty Rate (% of Annual Ex-US Net Sales) Nonclinical Asset Marginal Royalty Rate (% of Annual Ex-US Net Sales) The portion of Annual Ex-US Net Sales less than $[***] [***]% [***]% The portion of Annual Ex-US Net Sales greater than or equal to $[***] and less than $[***] [***]% [***]% The portion of Annual Ex-US Net Sales greater than or equal to $[***]and less than $[***] [***]% [***]% The portion of Annual Ex-US Net Sales greater than or equal to $[***] [***]% [***]% (b) Payable by Takeda. Until the expiration of the Royalty Term for each TAK-653 Product in Japan and subject to the provisions of Section 8.1.3 (Royalty Reductions), Takeda will pay to Neurocrine royalties in the amount of the marginal royalty rates set forth in Table 8.1.2(b) (Royalty Payments (Japan) for TAK-653 Products) below, based on the aggregate Net Sales resulting from the sale of all TAK-653 Products that contain the same TAK-653 Asset in Japan during each Calendar Year until the expiration of the applicable Royalty Term (for each TAK- 653 Product, the “Annual Japan Net Sales,” and such payments, “Japan Royalties”). TABLE 8.1.2(b) – Royalty Payments (Japan) for TAK-653 Products Annual Japan Net Sales TAK-653 Product Marginal Royalty Rate (% of Annual Japan Net Sales) The portion of Annual Japan Net Sales less than $[***] [***]% The portion of Annual Japan Net Sales greater than or equal to $[***]and less than $[***] [***]% 41 The portion of Annual Japan Net Sales greater than or equal to $[***]and less than $[***] [***]% The portion of Annual Japan Net Sales greater than or equal to $[***] [***]% 8.1.3. Royalty Reductions. (a) Royalty Reduction for [***]. Subject to Section 8.1.3(d) (Cumulative Reductions Floor), on a Licensed Product-by-Licensed Product and country-by- country basis, if, during any Calendar Quarter prior to the expiration of the Royalty Term for a given Licensed Product in any country, [***], then, for each such Calendar Quarter for which this Section 8.1.3(a) (Royalty Reduction for [***]) applies, the Net Sales of such Licensed Product used for calculation of royalties pursuant to Section 8.1.2 (Royalties) will be reduced by [***]%. (b) Reduction for [***]. Subject to Section 8.1.3(d) (Cumulative Reductions Floor), on a Licensed Product-by-Licensed Product and country-by- country basis, in the event of [***] with respect to such Licensed Product in such country, commencing in the first Calendar Quarter after which this Section 8.1.3(b) (Reduction for [***]) applies (and in each Calendar Quarter thereafter in which it continues to apply), the applicable annual Net Sales of such Licensed Product in such country used for calculation of royalties pursuant to Section 8.1.2 (Royalties) will be reduced by [***]% where the [***] percentage is at least [***]% for such Licensed Product in such Calendar Quarter in such country. (c) Third Party Payments. (i) Subject to Section 8.1.3(d) (Cumulative Reductions Floor), for any agreement with a Third Party pursuant to which Neurocrine is granted rights (whether by acquisition or license) under any Patent Rights that are necessary for the Commercialization of a Licensed Other Product in a country in the Territory or TAK-653 Product in the Neurocrine Territory (other than any Patent Rights that Cover only an Other Component), Neurocrine may credit [***]% of any royalty or profit- or revenue-share payment made by Neurocrine under such agreement as a result of sales of such Licensed Product in such country in a given Calendar Quarter against any Royalties payable by Neurocrine to Takeda in such Calendar Quarter in such country. (ii) Subject to Section 8.1.3(d) (Cumulative Reductions Floor), for any agreement with a Third Party pursuant to which Takeda is granted rights (whether by acquisition or license) under any Patent Rights that are necessary for the Commercialization of a TAK-653 Product in Japan (other than any Patent Rights that Cover only an Other Component), Takeda may credit [***]% of any royalty or profit- or revenue-share payment made by Takeda under such agreement as a result of sales of such TAK- 653 Product in Japan in a given Calendar Quarter against any Japan Royalties payable by Takeda to Neurocrine in such Calendar Quarter. 42 (d) Cumulative Reductions Floor. In no event will the royalties otherwise due (i) from Takeda to Neurocrine with respect to a TAK-653 Product, or (ii) from Neurocrine to Takeda for any Licensed Product, in each case (i) and (ii), in a Calendar Quarter during the applicable Royalty Term for such Licensed Product be reduced by more than [***]% of the amount that would otherwise be due in such Calendar Quarter for such Licensed Product but for the reductions set forth in Section 8.1.3(a) (Royalty Reduction for [***]), Section 8.1.3(b) (Reduction for [***]), or Section 8.1.3(c) (Third Party Payments). A Party may, on a Licensed Product-by-Licensed Product basis, carry forward to subsequent Calendar Quarters any amounts it could not deduct as a result of such floor. 8.2. Other Amounts Payable. With respect to any amounts owed under this Agreement by one Party to the other for which no other invoicing and payment procedure is specified in this Agreement, within [***] after the end of each Calendar Quarter each Party will provide an invoice, together with reasonable supporting documentation, to the other Party for such amounts owed in respect of such Calendar Quarter. The owing Party will pay any undisputed amounts within [***] after receipt of the invoice, and will pay any disputed amounts owed by such Party within [***] of resolution of the Dispute. 8.3. Payment Terms. 8.3.1. Manner of Payment. All payments to be made between the Parties under this Agreement will be made in Dollars and may be paid by wire transfer in immediately available funds in accordance with the instructions provided by the payee. 8.3.2. Reports and Royalty Payments. Commencing upon the First Commercial Sale of a Licensed Product by a Party or its Affiliate or Sublicensee and continuing for as long as any Royalties are due by such Party under Section 8.1.2 (Royalties), such Party will deliver to the other Party (a) within [***] after the end of a Calendar Quarter, a written preliminary report setting forth [***] and (b) within [***] after the end of each Calendar Quarter, a written report setting forth [***] (each, a “Royalty Report”). Upon receipt of such Royalty Report, the receiving Party will issue an invoice to the paying Party for the amount of the royalties set forth in such Royalty Report, which invoice will specify the amount of the Royalties that should be paid. The paying Party will pay all Royalties it owes for a Calendar Quarter set forth in any such invoice within [***] after receipt of such invoice. 8.3.3. Records and Audits. Each Party will keep complete, true, and accurate books and records in accordance with the applicable Accounting Standards in relation to this Agreement, including in relation to all Net Sales and Royalties. Each Party will keep such books and records for three years following the Calendar Year to which they pertain. Each Party may, 43 upon written request, cause an internationally-recognized independent accounting firm (the “Auditor”) that is reasonably acceptable to the audited Party to inspect the relevant records of the audited Party and its Affiliates to verify the payments made by the audited Party and the related reports, statements and books of accounts, as applicable. Before beginning its audit, the Auditor will execute an undertaking acceptable to the audited Party by which the Auditor agrees to keep confidential all information reviewed during the audit. The audited Party and its Affiliates will make their records available for inspection by the Auditor during regular business hours at such place or places where such records are customarily kept, upon receipt of reasonable advance notice from the auditing Party. The Auditor will review the records solely to verify the accuracy of the audited Party’s Net Sales and Royalties. Such inspection right will not be exercised more than once in any Calendar Year and not more frequently than once with respect to records covering any specific period of time. In addition, the auditing Party will only be entitled to audit the books and records of the audited Party from the three Calendar Years prior to the Calendar Year in which the audit request is made. The auditing Party agrees to hold in strict confidence all information received and all information learned in the course of any audit or inspection, except to the extent necessary to enforce its rights under this Agreement or to the extent required to comply with any law, regulation or judicial order. The Auditor will provide its audit report and basis for any determination to the audited Party at the time such report is provided to the auditing Party. In the event that the final result of the inspection reveals an undisputed underpayment or overpayment by the audited Party, the underpaid or overpaid amount will be settled promptly. The auditing Party will pay for such inspections, as well as its expenses associated with enforcing its rights with respect to any payments hereunder; provided, however, that in the event of an underpayment of more than [***]% of the total payments due hereunder for the audited period, then the fees and expenses charged by the Auditor will be paid the audited Party. 8.3.4. Currency Exchange. All amounts due to either Party hereunder will be expressed in Dollars. The rate of exchange to be used in computing the amount of currency equivalent in Dollars owed to a Party under this Agreement will be the exchange rate used by such Party in its financial reporting in accordance with its Accounting Standards. 8.3.5. Taxes. (a) VAT. (i) All payments or amounts due under this Agreement, whether monetary or non-monetary, are stated exclusive of VAT. Except where a VAT reverse charge applies, a Party receiving a supply under this Agreement in respect of which VAT is chargeable hereby covenants that it will pay an amount equal to any such VAT in addition to any amounts due under this Agreement provided that such VAT is correctly charged and has been duly invoiced in accordance with applicable Laws. If applicable Law requires a VAT reverse charge, then the receiving Party covenants that it shall correctly account for VAT in respect of the services received. The Party making a supply agrees that it will raise and provide to the receiving Party a valid tax invoice, compliant with relevant Law and fiscal regulations to support the VAT charge (or the VAT reverse charge, as the case may be). (ii) In the event that any amount in respect of VAT originally paid by a Party receiving a supply under this Agreement is subsequently determined by
44 the relevant Tax authority not to have been chargeable under applicable Law, in the first instance, the supplying Party shall consider in good faith such determination and if, in the reasonable opinion of the supplying Party, there are reasonable grounds for contesting such determination, undertake in reasonable cooperation with the receiving Party reasonable steps to contest any such determination by the relevant Tax authority. Only once this process is completed, the Party that made the relevant supply will, within [***], issue, as applicable, an invoice or credit note (as might be required) and refund the relevant amount to the Party that received the relevant supply. In the event that relevant Tax authorities determine that VAT should have been paid by the Party receiving a supply under this Agreement, in the first instance, the supplying Party shall consider in good faith such determination and if, in the reasonable opinion of the supplying Party, there are reasonable grounds for contesting such determination, undertake in reasonable cooperation with the receiving Party reasonable steps to contest any such determination by the relevant Tax authority. Only once this process is completed, the Party that made the relevant supply will, within [***] issue, as applicable an invoice or debit note (as required by applicable Law) for the additional VAT amount, and receiving Party will pay the relevant VAT amount within [***] of receipt of the VAT invoice. For the avoidance of doubt, notwithstanding the preceding provisions, the supplying Party shall not be required to make a formal appeal to any tribunal, court, appellate body or judicial authority. The Parties shall issue invoices and credit notes in accordance with applicable Law consistent with VAT requirements and irrespective of whether amounts or other consideration may be netted for settlement purposes. (iii) Any costs or expenses of a Party that are required under this Agreement to be reimbursed, indemnified or otherwise paid by the other Party shall exclude such part thereof (if any) as represents VAT (and such amount shall accordingly not be required to be reimbursed, indemnified or paid by the other Party) to the extent that such VAT is recoverable (whether by way of repayment, credit or set-off) by the payee (or any Affiliate thereof) from relevant Tax authorities. Neither Party shall be responsible for, or bear the cost of, any VAT that results from the other Party’s non- compliance with applicable Laws. (b) Withholding Taxes. The amounts payable pursuant to this Agreement (“Payments”) will not be reduced on account of any Taxes unless required by applicable Law. Each Party (the “Payor”) will deduct and withhold from the Payments made to the other Party (the “Payee”) any Taxes that it is required by applicable Law to deduct or withhold (“Withholding Taxes”), and any such amounts deducted or withheld by the Payor will be treated as having been paid to the Payee for purposes of this Agreement. Any such Withholding Taxes will be an expense of and borne by the Payee. If any such Withholding Tax is assessed against, or paid (but in each case not withheld) by the Payor, then the Payee will pay the relevant amount of such Withholding Tax to the Payor. In the event that a Governmental Authority retroactively determines that a payment made under this Agreement should have been subject to Withholding Taxes (or to additional Withholding Taxes), and the Payor remits such Withholding Taxes to the 45 Governmental Authority, including any interest and penalties that may be imposed thereon, at the option of the Payor, then the Payee will pay the relevant amount of any Withholding Tax (including any interest and penalties thereon) to the Payor. Notwithstanding the foregoing, if the Payee is entitled under any applicable tax treaty to a reduction of rate of, or the elimination of, or recovery of, applicable Withholding Tax, then it may deliver to the Payor or the appropriate Governmental Authority the prescribed forms necessary to reduce the applicable rate of withholding or to relieve the Payor of its obligation to withhold tax. If the Payee timely delivers to the Payor a validly executed form establishing a reduced rate or exemption from withholding, the Payor shall apply the reduced rate of withholding, or not withhold, as the case may be, provided that the Payor is in receipt of evidence, in a form reasonably satisfactory to the Payor, for example delivery of all applicable documentation at least two weeks prior to the time that the Payments are due. If, in accordance with the foregoing, the Payor withholds any amount, then it will pay to the Payee the balance when due, make timely payment (or cause its agent to make timely payment) to the proper taxing authority of the withheld amount, and send the Payee proof of such payment within [***] following that payment. On or before the Effective Date, Takeda shall deliver to Neurocrine a properly completed Internal Revenue Service (“IRS”) Form W- 8BEN-E or other applicable IRS Form W-8. (c) Tax Cooperation. Each Party will provide the other with reasonable assistance to enable the recovery, as permitted by Law, of Withholding Taxes, VAT, or similar obligations resulting from payments made under this Agreement, such recovery to be for the benefit of the Party bearing such Withholding Tax or VAT. (d) No Other Reductions. Except as provided in this Section 8.3 (Payment Terms) and those deductions expressly included in the definition of Net Sales, the amounts payable hereunder will not be reduced on account of any Taxes, unless required by applicable Law. (e) Tax Exemptions and Credits. The Parties will reasonably cooperate with each other in seeking any tax exemption or credits that may be available with respect to any Licensed Product, including the tax credit available under Section 45C of the Code by reason of a Party’s research and Development expenditures contributing to the Licensed Product being granted orphan drug status by the FDA, or equivalent Law of any other country. (f) Withholding Reimbursement. Notwithstanding anything in this Agreement to the contrary, the Parties acknowledge and agree that if either Party redomiciles, or assigns or sublicenses its rights or obligations under this Agreement (including an assignment of this Agreement as permitted under Section 16.1 (Assignment) of this Agreement), and such action leads to the imposition of withholding Tax liability on the other Party that would not have been imposed in the absence of such action or in an increase in such liability above the liability that would have been imposed in the absence of such action, then such Party will, if it is the Payor, increase the applicable payment to the Payee by the amount necessary to ensure that the Payee receives an amount equal to the amount it would have received had no such action occurred. 46 8.3.6. Blocked Payments. In the event that, by reason of applicable Law in any country, it becomes impossible or illegal for a Party to transfer, or have transferred on its behalf, payments owed the other Party hereunder, such Party will promptly notify the other Party of the conditions preventing such transfer and such payments will be deposited in local currency in the relevant country to the credit of the other Party in a recognized banking institution designated by the other Party or, if none is designated by the other Party within a period of [***], in a recognized banking institution selected by the transferring Party, as the case may be, and identified in a written notice given to the other Party. 8.3.7. Interest Due. Each paying Party will pay the other Party interest on any undisputed payments that are not paid on or before the date such payments are due under this Agreement at the per [***]. 9. CONFIDENTIALITY AND PUBLICATION 9.1. Nondisclosure and Non-Use Obligations. 9.1.1. Confidential Information. All Confidential Information disclosed by one Party to the other Party under the Original Agreement or this Agreement will, during the Term and for a period of [***] thereafter, be maintained in confidence by the receiving Party and will not be disclosed to a Third Party or used for any purpose except to exercise its licenses and other rights, to perform its obligations, or as otherwise set forth herein, without the prior written consent of the disclosing Party. The existence and terms of the Original Agreement and this Agreement are the Confidential Information of each Party, and each Party will be deemed a receiving Party with respect thereto. Unpublished patent applications or Know- How solely owned by a Party are such Party’s Confidential Information, and Patent Rights and Know-How jointly owned by the Parties will be deemed both Parties’ Confidential Information, in each case, regardless of which Party is the disclosing Party. All information exchanged between the Parties regarding the Prosecution and Maintenance, defense, and enforcement of the Patent Rights under Article 12 (Intellectual Property) will be the Confidential Information of the prosecuting Party. All data, results, and reports pertaining to any Licensed Product (a) generated by Neurocrine under the Original Agreement or this Agreement will be the Confidential Information of Neurocrine and (b) generated by Takeda under the Original Agreement or this Agreement will be the Confidential Information of Takeda; provided that Takeda will maintain such data, results, and reports described in the foregoing clause (b) in confidence and not disclose them to any Third Party for so long as they remain Confidential Information of Takeda, except as permitted under Section 9.1.2 (Permitted Disclosures), Section 9.2 (Publication and Publicity), or Section 12.2.1(b) (Takeda’s Right). The Takeda Know-How will be the Confidential Information of Takeda. All information disclosed by a Party pursuant to that certain Confidentiality Agreement between the Parties dated January 31, 2020 is deemed the Confidential Information of such Party pursuant to this Agreement. During the Term, the receiving Party will use at least the same degree of care to protect the secrecy of the Confidential Information of the disclosing Party that it uses to prevent the disclosure of its own other confidential information of similar importance and in any event no less than a reasonable duty of care. 9.1.2. Permitted Disclosures. Notwithstanding the obligations of confidentiality and non-use set forth above, a receiving Party may provide Confidential Information disclosed to it, and disclose the existence and terms of the Original Agreement and this Agreement to: 47 (a) its Affiliates or, in the case of Neurocrine, actual or potential Sublicensees, and its and their respective employees, directors, agents, consultants, or advisors to the extent necessary for the potential or actual performance of its obligations or exercise of its licenses and other rights under this Agreement, in each case, who are under an obligation of confidentiality with respect to such information that is no less stringent than the terms of this Section 9.1.2 (Permitted Disclosures); (b) Governmental Authorities or other Regulatory Authorities (i) in connection with regulatory filings for Licensed Products as permitted hereunder and (ii) in order to obtain Patent Rights or otherwise perform its obligations or exploit its rights with respect to any Patent Right under this Agreement to the extent permitted; (c) the extent, based on the advice of outside counsel, required by Law or any Governmental Authorities, including by the rules or regulations of the United States Securities and Exchange Commission (“SEC”) or similar regulatory agency in a country other than the United States or of any stock exchange or listing entity; and (d) with respect to the terms of the Original Agreement and this Agreement and, in the case of Neurocrine, all Licensed Takeda Technology or, in the case of Takeda, information, data, and results related to any Licensed Product or to any Terminated Product as defined in the Original Agreement and the Grantback IP as defined in the Original Agreement or, after termination of this Agreement with respect to any Terminated Product, the Grantback IP, any actual or bona fide prospective acquirers, underwriters, investors, lenders, or other financing sources, in each case, who are under obligations of confidentiality and non-use with respect to such information that is no less stringent than the terms of this Section 9.1.2 (Permitted Disclosures) (except that the term of such obligations may be shorter, but no less than [***]). 9.1.3. Confidential Treatment. (a) Notwithstanding any provision to the contrary set forth in this Agreement, if a Party is required to make a disclosure of the other Party’s Confidential Information pursuant to Section 9.1.2(c) (Permitted Disclosure), then it will, to the extent not prohibited by applicable Law or judicial or administrative process, give reasonable advance notice to the other Party of such proposed disclosure and use reasonable efforts to secure confidential treatment of such information and will only disclose that portion of Confidential Information that is legally required to be disclosed as advised by its legal counsel. In any event, each Party agrees to take reasonable action to avoid any disclosure of Confidential Information of the other Party hereunder. (b) In addition, the Parties acknowledge that either or both Parties may be obligated to file a copy of this Agreement (or portions of this Agreement or an abstract of the terms of this Agreement) with the SEC or other Governmental Authorities. Each Party will be entitled to make such a required filing, provided that it initially files a redacted copy of this Agreement (or portions of this Agreement or an abstract of the terms of this Agreement) reviewed by each Party (“Redacted Agreement”) and requests confidential treatment of the terms redacted from this Agreement for a reasonable period of time, in each case, pursuant to the following
48 procedure. In the event of any such filing, each Party will (i) permit the other Party to review and comment upon a Redacted Agreement at least [***] in advance of its submission to the SEC or such other Governmental Authorities, (ii) cooperate in good faith with and reasonably consider and incorporate the other Party’s reasonable comments thereon to seek confidential treatment of the terms and conditions of this Agreement that such other Party requests to be kept confidential or otherwise afforded confidential treatment, to the extent consistent with the then-current legal requirements governing redaction of information from material agreements (as determined based on the advice of such Party’s outside counsel) that must be publicly filed in the applicable country, (iii) only disclose Confidential Information that counsel reasonably advises is legally required to be disclosed, (iv) promptly advise the other Party of any other substantive communications between it or its representatives with such Governmental Authority with respect to such confidential treatment request, (v) upon the written request of the other Party, request an appropriate extension of the term of the confidential treatment period upon the expiration thereof, where available, and (vi) if such Governmental Authority requests any changes to the redactions set forth in the Redacted Agreement, use Commercially Reasonable Efforts to reach a reasonable resolution in light of the redactions in the Redacted Agreement as originally filed and taking into account the then-current legal requirements governing redaction of information from material agreements that must be publicly filed, as determined based on the advice of such Party’s outside counsel, and, to the extent reasonably practicable, review with the other Party any changes to the redactions in the Redacted Agreement before making such changes; provided, however, that each Party will have the right to make any such filing or disclosure as it reasonably determines to make, based on the advice of outside counsel, under applicable Laws. Each Party will be responsible for its own legal and other external costs in connection with any such filing, registration, or notification. 9.2. Publication and Publicity. 9.2.1. Publication. Except for disclosures permitted in accordance with Section 9.1.2 (Permitted Disclosures), either Party wishing to make a publication or public presentation that contains the Confidential Information of the other Party or any Takeda Know-How will deliver to the other Party and the JSC a copy of the proposed written publication or presentation at least [***] prior to submission for publication or presentation. The reviewing Party, through the JSC, will have the right to (a) propose modifications to the publication or presentation for patent reasons or trade secret reasons or to remove Confidential Information of the reviewing Party or its Affiliates, and the publishing Party will remove all Confidential Information of the reviewing Party if requested by the reviewing Party and otherwise use good faith efforts to reflect such Party’s reasonable comments, or (b) request a reasonable delay in publication or presentation in order to protect patentable information. If the reviewing Party requests a delay to enable the reviewing Party to file patent applications as permitted under Article 12 (Intellectual Property) protecting such Party’s right in such information, then the publishing Party will delay such submission or presentation for a period of [***] (or such shorter period as may be agreed by the Parties). With respect to any proposed publications or disclosures by investigators or academic or non-profit collaborators, such materials will be subject to review under this Section 9.2 (Publication and Publicity) to the extent that Takeda or Neurocrine, as the case may be, has the right and ability to do so (after using Commercially Reasonable Efforts to obtain such 49 right and ability). All publications relating to any Licensed Product will be prepared, presented, and published in accordance with pharmaceutical industry accepted guidelines including: (i) International Committee of Medical Journal Editors (ICMJE) guidelines, (ii) Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication, (iii) Pharmaceutical Research and Manufacturers of America (PhRMA) guidelines, and (iv) Principles on Conduct of Clinical Trials. 9.2.2. Publicity. Except as set forth in Section 9.1 (Nondisclosure and Non-Use Obligations), Section 9.2 (Publication and Publicity) or Section 9.2.3 (Press Release), the terms of the Original Agreement or this Agreement may not be disclosed by either Party. Neither Party will use the name, Trademark, trade name or logo of the other Party or its employees in any publicity, news release or disclosure relating to this Agreement, its subject matter, or the activities of the Parties hereunder, in each case, without the prior express written permission of the other Party, except (a) as may be required by applicable Law (as determined based on the advice of outside counsel), including by the rules or regulations of the United States Securities and Exchange Commission or similar regulatory agency in any country other than the United States or of any stock exchange or listing entity, provided that the Party making such disclosure or use of the name, Trademark, trade name, or logo of the other Party or its employees gives the other Party reasonable prior written notice of such disclosure and otherwise complies with Section 9.1.2 (Permitted Disclosures), or (b) as expressly permitted by the terms hereof. 9.2.3. Press Release. The Parties have agreed on the contents of a press release, in substantially the form attached hereto as Schedule 9.2.3 (Press Release), which may be issued by Neurocrine on or after the Restatement Date. Except for such press release or as provided in Section 9.2.1 (Publicity) or this Section 9.2.3 (Press Release), neither Party will issue any press release or public announcement relating to this Agreement without the prior written approval of the other Party (such approval not to be unreasonably withheld), except that a Party may (a) once a press release or other public statement is approved in writing by both Parties, make subsequent public disclosure of the information contained in such press release or other written statement without the further approval of the other Party (so long as such information remains true and correct), and (b) issue a press release or public announcement as required by applicable Law (including a press release corresponding to any securities disclosure, such as pursuant to a Form 8-K, or any earnings or financial press release), including by the rules or regulations of the United States Securities and Exchange Commission or similar regulatory agency in a country other than the United States or of any stock exchange or listing entity, provided that the Party issuing such press release gives reasonable prior notice to the other Party of and the opportunity to comment on the press release or public announcement, and otherwise complies with this Article 9 (Confidentiality and Publication). 10. REPRESENTATIONS, WARRANTIES AND COVENANTS 10.1. Mutual Representations and Warranties as of the Restatement Date. Each Party represents and warrants to the other Party, as of the Restatement Date, that: 10.1.1. such Party is a corporation duly organized, validly existing, and in good standing under the Laws of its jurisdiction of incorporation or formation; 10.1.2. such Party has all requisite corporate power and corporate authority to enter into this Agreement and to carry out its obligations under this Agreement; 50 10.1.3. all requisite corporate action on the part of such Party, its directors and stockholders required by applicable Law for the authorization, execution, and delivery by such Party of this Agreement, and the performance of all obligations of such Party under this Agreement, has been taken; 10.1.4. the execution, delivery, and performance of this Agreement, and compliance with the provisions of this Agreement, by such Party do not and will not: (a) violate any provision of applicable Law or any ruling, writ, injunction, order, permit, judgment, or decree of any Governmental Authority, (b) constitute a breach of, or default under (or an event that, with notice or lapse of time or both, would become a default under) or conflict with, or give rise to any right of termination, cancellation or acceleration of, any agreement, arrangement or instrument, whether written or oral, by which such Party or any of its assets are bound, or (c) violate or conflict with any of the provisions of such Party’s organizational documents (including any articles or memoranda of organization or association, charter, bylaws, or similar documents); and 10.1.5. no consent, approval, authorization, or other order of, or filing with, or notice to, any Governmental Authority or other Third Party is required to be obtained or made by such Party in connection with the authorization, execution, and delivery by such Party of this Agreement. 10.2. Representations and Warranties by Takeda. Takeda represents and warrants to Neurocrine, as of the Execution Date that: 10.2.1. Takeda Patent Rights. Schedule 10.2.1 (Takeda Patent Rights) to the Original Agreement sets forth a complete and accurate list of all Takeda Patent Rights issued or pending as of the Execution Date. 10.2.2. Takeda Technology. Except as otherwise set forth on Schedule 10.2.2 (Takeda Technology), Takeda has (a) legal or beneficial title and sole ownership of all Takeda Technology, free and clear of all mortgages, pledges, liens, encumbrances or claims of any kind, including claims by any Governmental Authority or academic or non-profit institution; and (b) authority to grant to Neurocrine and its Affiliates the licenses set forth in this Agreement under the Takeda Technology. Takeda is not a party to any agreement with a Third Party under which Takeda has obligations to such Third Party with respect to (i) the grant of a license to Neurocrine under any Takeda Technology or (ii) Neurocrine’s practice thereunder or Exploitation of Licensed Products. 10.2.3. Control. Takeda or its Affiliates Controls all Patent Rights and Know-How owned, invented or licensed by Takeda as of the Execution Date that are necessary or actually used as of the Execution Date to Exploit Licensed Products. 10.2.4. Ownership of Takeda Technology. With respect to any Takeda Technology owned or purported to be owned by Takeda, (a) to Takeda’s Knowledge, Takeda and its Affiliates have obtained from all employees and independent contractors who participated in the invention or authorship thereof, assignments of all ownership rights of such employees and independent contractors in such Takeda Technology, either pursuant to written agreement or by operation of Law; (b) except as otherwise set forth on Schedule 10.2.4 (Ownership of Takeda Technology), all of its employees, officers, contractors, and consultants have executed agreements or have existing obligations under applicable Law requiring assignment to Takeda or its Affiliate, as applicable, of all rights, title, and interests in and 51 to inventions made during the course of and as the result of this Agreement; and (c) to Takeda’s Knowledge, no officer or employee of Takeda or its Affiliate is subject to any agreement with any other Third Party that requires such officer or employee to assign any interest in any Takeda Technology to any Third Party. 10.2.5. Validity and Enforceability. With respect to Takeda Patent Rights, there are no oppositions, nullity actions, interferences, inter partes reexaminations, inter partes reviews, post-grant reviews, derivation proceedings, or other proceedings pending or, to Takeda’s Knowledge, threatened in writing (but excluding office actions or similar communications issued by the United States Patent and Trademark Office or any analogous foreign Governmental Authority (collectively, “Patent Offices”) in the ordinary course of Prosecution and Maintenance of any patent application) that challenge the scope, validity, or enforceability of the Takeda Patent Rights owned or purported to be owned by Takeda. Takeda does not have Knowledge of any fact or circumstance that would cause Takeda to reasonably conclude that any of the Takeda Patent Rights is, or will be upon issuance, invalid or unenforceable. 10.2.6. Inventorship. To Takeda’s Knowledge, inventorship of each Takeda Patent Right is properly identified on each patent and patent application. Takeda has no Knowledge of any disputes with respect to inventorship of any Takeda Patent Rights. 10.2.7. Good Standing. All official fees, maintenance fees and annuities for any pending or issued Takeda Patent Rights have been paid when due, and all administrative procedures with Governmental Authorities have been completed for such Takeda Patent Rights such that such Patent Rights are subsisting and in good standing. 10.2.8. Duty of Disclosure. To Takeda’s Knowledge, all Takeda Patent Rights have been duly and properly filed and maintained and the inventors thereof and parties prosecuting such applications have complied in all material respects with their duty of candor and disclosure to the U.S. Patent and Trademark Office and other foreign patent offices in connection with such applications. 10.2.9. Disclosure to Neurocrine. To Takeda’s Knowledge, Takeda has disclosed to Neurocrine in writing (a) all information that is (i) known to any individual associated with the filing or prosecution (as defined in 37 C.F.R. § 1.56(c)) of the Takeda Patent Rights and (ii) material to patentability of the Takeda Patent Rights (as defined in 37 C.F.R. § 1.56(b)), or that would be considered material to patentability as defined in 37 C.F.R. § 1.56(b) but for an exception under 35 U.S.C. § 102(b), and (b) an indication to which Takeda Patent Rights each piece of such information relates. 10.2.10. Prior Art. To Takeda’s Knowledge, there is not any reference or prior art that would anticipate the issuance of any claim as pending as of the Execution Date in any Takeda Patent Rights. 10.2.11. Government Funding. No government funding, facilities of a university, college, or other educational institution or research center was used in the development of any Takeda Patent Rights. No Person who was involved in, or who contributed to, the creation or development of any Takeda Patent Rights has performed services for the government, university, college, or other educational institution or research center in a manner that would affect Takeda’s rights in the Takeda Patent Rights.
52 10.2.12. No Claims. There are (a) no claims, judgments or settlements against or owed by Takeda or its Affiliates and (b) no pending or, to Takeda’s Knowledge, threatened claims or litigation, in each case ((a) and (b)), related to the Takeda Technology or the Licensed Assets. 10.2.13. Notice of Infringement or Misappropriation. Neither Takeda nor its Affiliates have received any written notice or, to Takeda’s Knowledge, threat in writing from any Third Party asserting or alleging that any Development or Manufacture of the Licensed Assets by Takeda or its Affiliates prior to the Execution Date infringed or misappropriated any intellectual property rights of such Third Party. 10.2.14. No Conflicts. Takeda has not entered into any agreement with any Third Party that is in conflict with the rights granted to Neurocrine under this Agreement, and has not taken any action that would prevent it from granting the rights granted to Neurocrine under this Agreement, or that would otherwise materially conflict with or adversely affect Neurocrine’s rights under this Agreement. 10.2.15. Third Party Technology. To Takeda’s Knowledge (a) the Development, Manufacture and Commercialization of Licensed Assets and Licensed Products in the form such Licensed Assets and Licensed Products exist as of the Effective Date does not and will not infringe any issued patents of a Third Party, (b) Takeda has disclosed to Neurocrine any pending Third Party patent applications that, if issued with the published or currently pending claims, would be infringed by any such activities, and (c) except for those disclosed by Takeda as described in clause (b), there are no pending Third Party patent applications that, if issued with the published or currently pending claims, would be infringed by any such activities. 10.2.16. Third Party Infringement. To Takeda’s Knowledge, no Third Party is infringing or has infringed any Takeda Patent Rights or has misappropriated any Takeda Know-How. 10.2.17. Compliance with Laws. Takeda and its Affiliates have conducted the Exploitation of the Licensed Assets in material compliance with all applicable Laws, including as applicable GLP, GCP, and cGMP and any applicable anti-corruption or anti-bribery laws or regulations of any Governmental Authority with jurisdiction over such Exploitation. Takeda and its Affiliates did not use in any capacity in connection with the Exploitation of any Licensed Asset any Person that had been debarred pursuant to Section 306 of the FD&C Act, as amended, or that was the subject of a conviction described in such section. 10.2.18. Regulatory Submissions and Study Reports. Takeda or its Affiliates Control all Regulatory Submissions in the Territory related to the Licensed Assets, and to Takeda’s Knowledge, Takeda or its Affiliates Control all study reports and underlying data from the Phase II Ongoing Activities or any other Clinical Trials of any Licensed Asset conducted before the Effective Date. 10.2.19. No Fraudulent Statements. Neither Takeda nor its Affiliates, nor, to Takeda’s Knowledge, any of its or their respective directors, officers, employees or agents has (a) committed an act, (b) made a statement or (c) failed to act or make statement, in any case ((a), (b) or (c)), that (i) would be or create an untrue statement of material fact or fraudulent statement to the FDA or any other Regulatory Authority with respect to the Development and Manufacture of any Licensed Asset or Licensed Product or (y) could reasonably be expected to provide a basis for the FDA or any other Regulatory Authority to invoke its 53 policy respecting “Fraud, Untrue Statements of Material Facts, Bribery and Illegal Gratuities”, set forth in 56 Fed. Reg. 46191 (September 10, 1991) and any amendments thereto or any analogous laws or policies, with respect to the Development and Manufacture of any Licensed Asset or Licensed Product. 10.2.20. Disclosure. Takeda has not withheld material information related to the Takeda Technology, Licensed Assets, or Licensed Products, in each case, that was requested by Neurocrine in writing. 10.3. Warranty Disclaimer. EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THIS AGREEMENT, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY PATENTS, KNOW-HOW, MATERIALS, COMPOUND, PRODUCT, LICENSED ASSET, LICENSED PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER SUBJECT MATTER OF THIS AGREEMENT AND HEREBY DISCLAIMS ALL IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, TITLE OR NONINFRINGEMENT WITH RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS ANY REPRESENTATION OR WARRANTY THAT THE EXPLOITATION OF ANY LICENSED ASSET OR LICENSED PRODUCT PURSUANT TO THIS AGREEMENT WILL BE SUCCESSFUL. 10.4. Certain Covenants. 10.4.1. Compliance. Each Party and its respective Affiliates and Sublicensees will conduct the Exploitation of the Licensed Products in a good scientific manner [***] in accordance with all applicable Laws, including, as applicable, GLP, GCP, and cGMP or regulations of any Governmental Authority with jurisdiction over the activities performed by or on behalf of such Party or its Affiliates or Sublicensees in furtherance of such obligations. In addition, if Neurocrine is or becomes subject to a legal obligation to a Governmental Authority (such as a corporate integrity agreement or settlement agreement with a Governmental Authority), then Takeda will perform such activities as may be reasonably requested by Neurocrine to enable Neurocrine to comply with its legal obligation to such Governmental Authority with respect to the Licensed Products. Before entering into a sublicense agreement with any potential Sublicensee, each Party will conduct appropriate due diligence regarding such potential Sublicensee’s compliance programs to assess the Sublicensee’s ability to comply with the requirements of this provision and will not grant rights to any potential Sublicensee that such Party reasonably determines does not have a compliance program sufficient to ensure such potential Sublicensee’s compliance with this provision. 10.4.2. No Debarment. Neither Party will use or permit its Affiliates or Sublicensees to use, in any capacity in connection with the performance of its obligations under this Agreement, any Person that has been debarred pursuant to Section 306 of the FD&C Act, as amended, or that is the subject of a conviction described in such section. Each Party agrees to inform the other Party in writing immediately if it or any Person that is performing activities under this Agreement on its behalf is debarred or is subject to debarment or is the subject of a conviction described in Section 306 of the FD&C Act, or if any action, suit, claim, investigation, or legal or administrative proceeding (a) has been filed and is pending or (b) is threatened in writing relating to the debarment or conviction of such Party or, to such Party’s knowledge, any Person or entity used in any capacity by such Party or any of its Affiliates with respect to this Agreement or the performance of its other obligations under 54 this Agreement. Each Party will use commercially reasonable efforts to include in any agreement with any Person or entity used in any capacity by such Party or any of its Affiliates with respect to this Agreement or the performance of its other obligations under this Agreement an obligation to provide notice to such Party of the matters described in this Section 10.4.2 (No Debarment). 10.4.3. Control. Takeda or its Affiliates will retain Control during the Term of all Patent Rights and Know-How owned by Takeda or its Affiliates as of the Effective Date that are (a) necessary to Exploit any Licensed Products (excluding any active pharmaceutical ingredient therein that is not a Licensed Asset) in the Field in the Territory or (b) reasonably useful to Exploit one or more Licensed Products in the Field in the Territory, but, in the case of this clause (b), excluding any Patent Rights or Know-How that were not practiced or used by Takeda or its Affiliates in connection with the Exploitation of the applicable Licensed Products as of the Effective Date and (i) that Covers (in the case of Patent Rights) or relates to (in the case of Know-How) manufacturing, formulation or other technology that is generally applicable to other products, as well as one or more Licensed Products, or (ii) to the extent related to any active pharmaceutical ingredient Controlled by Takeda or any of its Affiliates that is not a Licensed Asset. 10.4.4. No Conflicts. Takeda will not enter into any agreement with any Third Party that is in conflict with the rights granted to Neurocrine under this Agreement and will not take any action that would prevent it from granting the rights granted to Neurocrine under this Agreement or that would otherwise materially conflict with or adversely affect the rights granted to Neurocrine under this Agreement. 10.4.5. Assignment. Upon Neurocrine’s request, Takeda or its Affiliates will obtain, unless impracticable, from each employee and independent contractor who participated in the invention or authorship of any Takeda Technology, assignments of all ownership rights of such employees and independent contractors in such Takeda Technology pursuant to written agreement. 11. INDEMNIFICATION; LIMITATION OF LIABILITY; INSURANCE 11.1. Indemnification by Takeda. Takeda will indemnify, hold harmless, and defend Neurocrine, its Affiliates, and their respective directors, officers, employees, and agents (“Neurocrine Indemnitees”) from and against any and all losses, liabilities, damages, costs, taxes (including penalties and interest) fees, and expenses (including reasonable attorneys’ fees and litigation expenses) (collectively, “Losses”) resulting from any claims, suits, proceedings or causes of action brought by a Third Party (collectively, “Claims”) against such Neurocrine Indemnitees to the extent arising out of or resulting from: 11.1.1. any breach of, or inaccuracy in, any representation or warranty made by Takeda, or any breach or violation of any covenant or agreement of Takeda, in each case (a) in this Agreement on or after the Restatement Date or (b) in the Original Agreement from the Effective Date until the Restatement Date, 11.1.2. the negligence or willful misconduct by or of Takeda or any of its Affiliates, or any of their respective directors, officers, employees, or agents in the performance of Takeda’s obligations or exercise of its rights under this Agreement from and after the Restatement Date or under the Original Agreement from the Effective Date until the Restatement Date, or 55 11.1.3. the Exploitation of any Licensed Product or of any Terminated Product or any Terminated Product as defined in the Original Agreement, in each case, by or on behalf of Takeda or any of its Affiliates or Sublicensees or other licensees, including the infringement of any Third Party Patent Right in the course of such Exploitation. Notwithstanding the foregoing, Takeda will have no obligation to indemnify the Neurocrine Indemnitees to the extent that the Losses arise out of or result from matters described under Section 11.2.1 or 11.2.2 (Indemnification by Neurocrine). 11.2. Indemnification by Neurocrine. Neurocrine will indemnify, hold harmless, and defend Takeda, its Affiliates and licensees and their respective directors, officers, employees, and agents (“Takeda Indemnitees”) from and against any and all Losses resulting from any Claims against such Takeda Indemnitees to the extent arising out of or resulting from: 11.2.1. any breach of, or inaccuracy in, any representation or warranty made by Neurocrine, or any breach or violation of any covenant or agreement of Neurocrine, in each case (a) in this Agreement on or after the Restatement Date or (b) in the Original Agreement from the Effective Date until the Restatement Date, 11.2.2. the negligence or willful misconduct by or of Neurocrine or any of its Affiliates or Sublicensees, or any of their respective directors, officers, employees, or agents in the performance of Neurocrine’s obligations or exercise of its rights under this Agreement from and after the Restatement Date or under the Original Agreement from the Effective Date until the Restatement Date, and 11.2.3. the Exploitation of any Licensed Product by or on behalf of Neurocrine or any of its Affiliates or Sublicensees, including the infringement of any Third Party Patent Right in the course of such Exploitation. Notwithstanding the foregoing, Neurocrine will have no obligation to indemnify the Takeda Indemnitees to the extent that the Losses arise out of or result from matters described under Section 11.1.1 or 11.1.2 (Indemnification by Takeda). 11.3. Indemnification Procedure. 11.3.1. Notice. The Party entitled to indemnification under this Article 11 (Indemnification; Limitation of Liability; Insurance) (an “Indemnified Party”) will notify the Party responsible for such indemnification (the “Indemnifying Party”) in writing promptly upon being notified of or having knowledge of any claim or claims asserted or threatened against the Indemnified Party that could give rise to a right of indemnification under this Agreement; provided that the failure to give such notice will not relieve the Indemnifying Party of its indemnity obligation hereunder except to the extent that such failure materially prejudices the Indemnifying Party. 11.3.2. Indemnifying Party’s Right to Defend. The Indemnifying Party will have the right to defend, at its sole cost and expense, any such claim by all appropriate proceedings; provided that the Indemnifying Party may not enter into any compromise or settlement unless (a) such compromise or settlement imposes only a monetary obligation on the Indemnifying Party and which includes as an unconditional term thereof the giving by each claimant or plaintiff of the Indemnified Party a release from all liability in respect of such claim; or (b) the Indemnified Party consents to such compromise or settlement, which
56 consent will not be unreasonably withheld unless such compromise or settlement involves (i) any admission of legal wrongdoing by the Indemnified Party, (ii) any payment by the Indemnified Party that is not indemnified under this Agreement, or (iii) the imposition of any equitable relief against the Indemnified Party (in which case, (i) through (iii), the Indemnified Party may withhold its consent to such settlement in its sole discretion). 11.3.3. Indemnified Party’s Right to Defend. If the Indemnifying Party does not elect to assume control of the defense of a claim, then the Indemnified Party will have the right, at the expense of the Indemnifying Party, upon at least [***] prior written notice to the Indemnifying Party of its intent to do so, to undertake the defense of such claim for the account of the Indemnifying Party (with counsel reasonably selected by the Indemnified Party); provided that the Indemnified Party will keep the Indemnifying Party apprised of all material developments with respect to such claim. The Indemnified Party may not enter into any compromise or settlement without the prior written consent of the Indemnifying Party, such consent not to be unreasonably withheld. 11.3.4. Cooperation. The Indemnified Party will cooperate with the Indemnifying Party and may participate in, but not control, any defense or settlement of any claim controlled by the Indemnifying Party pursuant to this Section 11.3 (Indemnification Procedure) and will bear its own costs and expenses with respect to such participation; provided that the Indemnifying Party will bear such costs and expenses if counsel for the Indemnifying Party reasonably determines that such counsel may not properly represent both the Indemnifying Party and the Indemnified Party. 11.4. Limitation of Liability. NEITHER PARTY WILL BE LIABLE FOR SPECIAL, INCIDENTAL, CONSEQUENTIAL, OR PUNITIVE DAMAGES ARISING OUT OF THIS AGREEMENT, OR THE EXERCISE OF ITS RIGHTS OR THE PERFORMANCE OF ITS OBLIGATIONS HEREUNDER, OR ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT, INCLUDING LOST PROFITS, REGARDLESS OF ANY NOTICE OF THE POSSIBILITY OF SUCH DAMAGES, EXCEPT FOR DAMAGES THAT ARISE AS A RESULT OF (A) A PARTY’S GROSS NEGLIGENCE OR WILLFUL MISCONDUCT, (B) A BREACH OF ARTICLE 9 (CONFIDENTIALITY AND PUBLICATION), OR (C) INFRINGEMENT, MISAPPROPRIATION, OR OTHER VIOLATION OF ANY TAKEDA TECHNOLOGY, NEUROCRINE TECHNOLOGY OR GRANTBACK IP (AS APPLICABLE). NOTHING IN THIS SECTION 11.4 (LIMITATION OF LIABILITY) IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY UNDER THIS AGREEMENT. 11.5. Insurance. Neurocrine will obtain and maintain insurance during the Term and for a period of at least [***] after the last commercial sale of any Licensed Product for any claims made policies, in an amount appropriate for its business and products of the type that are the subject of this Agreement and for its obligations under this Agreement. Specifically, Neurocrine will maintain (a) worker’s compensation insurance with statutory limits in compliance with the worker’s compensation laws of the state or states in which Neurocrine has employees in the United States (excluding Puerto Rico), (b) employer’s liability coverage with a minimum limit of $[***] per occurrence; provided that Neurocrine has employees in the United States (excluding Puerto Rico), (c) [***] with a minimum limit of $[***], and (d) [***] with a minimum limit of [***]. Beginning at least [***] prior to the Initiation of a Clinical Trial, Neurocrine will obtain and maintain clinical trial insurance (either separately or as part of the general or product liability insurance). Beginning at least [***] prior to the First 57 Commercial Sale of Licensed Product, Neurocrine will obtain and maintain product liability insurance of $[***]. Upon request, Neurocrine will provide Takeda with evidence of the existence and maintenance of such insurance coverage. Neurocrine will notify Takeda [***] in advance of cancelation of any such insurance. All such insurances under this Section 11.5 (Insurance) will be provided by a company or companies licensed to do business in United States having a financial rating of not less than A- Viii in the most current edition of Best’s Key Rating Guide. Takeda will maintain, during the Term and for [***] thereafter, at its own expense, insurance or self-insurance, as reasonably necessary to cover its own product liability and its obligations under this Agreement. 12. INTELLECTUAL PROPERTY 12.1. Inventions. 12.1.1. Inventorship. Ownership of Program Know-How and Program Patent Rights will be determined in accordance with United States patent Laws for determining inventorship. The Parties will jointly own any and all Joint Program Technology. Except to the extent either Party is restricted by the licenses granted to the other Party under this Agreement, each Party will be entitled to practice, license, assign, and otherwise practice under the Joint Program Technology without the duty of accounting or seeking consent from the other Party, and where consent is required, such consent is hereby given. 12.1.2. Disclosure. Each Party will promptly disclose to the other Party all invention disclosures or other similar documents relating to Program Know-How made by or on behalf of such Party hereunder during the Term, in the case of Neurocrine as the disclosing Party, only for Program Know-How that Takeda requires to practice the license granted pursuant to Section 2.2 (License Grant to Takeda), and all invention disclosures or other similar documents submitted to such Party by its or its Affiliates’ employees, agents or independent contractors relating to such Program Know-How, and shall also respond promptly to reasonable requests from the other Party for additional information relating to such disclosures, documents or applications. 12.1.3. Personnel Obligations. Each employee, agent, or independent contractor of a Party or its respective Affiliates performing work under this Agreement will, prior to commencing such work, be bound by written invention assignment obligations, including: (a) promptly reporting any invention, discovery, or other intellectual property right; (b) presently assigning to the applicable Party or Affiliate all of his or her right, title, and interest in and to any invention, discovery, or other intellectual property; (c) cooperating in the preparation, filing, prosecution, maintenance and enforcement of any patent and patent application; and (d) performing all acts and signing, executing, acknowledging, and delivering any and all documents required for effecting the obligations and purposes of this Agreement. It is understood and agreed that such invention assignment agreement need not reference or be specific to this Agreement. Each Party will be solely responsible for any payments to inventors with an obligation to assign, or who do assign, their rights, title, and interests in and to any Program Know-How and Program Patent Rights to such Party. Takeda will be solely responsible for payments to inventors of any other Takeda Patent Rights. 12.1.4. Joint Research Agreement. This Agreement is a joint research agreement within the meaning of pre-AIA 35 U.S.C. § 103(c) and AIA 35 U.S.C. § 102(c). 58 12.2. Prosecution and Maintenance of Patent Rights. The Parties will conduct the Prosecution and Maintenance of the applicable Patent Rights in accordance with this Section 12.2 (Prosecution and Maintenance of Patent Rights). 12.2.1. Right to Prosecute Patent Rights. (a) Neurocrine’s Right. Beginning on the Effective Date, as between the Parties, Neurocrine will have the (i) sole right to Prosecute and Maintain the Neurocrine Sole Program Patent Rights worldwide (except Japan) and (ii) first right (but not the obligation) to Prosecute and Maintain all (A) Takeda Patent Rights, (B) Defensive Patent Rights, (C) Joint Program Patent Rights worldwide, and (D) Neurocrine Sole Program Patent Rights in Japan (such Patent Rights in clauses (i)- (ii), collectively, the “Neurocrine Prosecuted Patent Rights”), in each case (clauses (i)-(ii)), using outside patent counsel agreed to by Takeda (such agreement not to be unreasonably withheld). Neurocrine will bear all Patent Costs it incurs for such Prosecution and Maintenance. Neurocrine will bear the costs and expenses of all annuities and maintenance fees for Takeda Patent Rights and Defensive Patent Rights from and after the Effective Date, including the near-term annuities and maintenance fees set forth on Schedule 12.2.1(a) (Annuities and Maintenance Fees). Neurocrine will provide Takeda a reasonable opportunity to review and comment on material communications from any patent authority regarding the Neurocrine Prosecuted Patent Rights, as well as drafts of any material filings or responses to be made to such patent authorities in advance of submitting such filings or responses. Neurocrine will consider Takeda’s comments regarding such communications and drafts in good faith. In addition, Neurocrine will provide Takeda with (A) copies of all final material filings and responses made to any Patent Office with respect to the Neurocrine Prosecuted Patent Rights in a timely manner following submission thereof, and (B) a report each Calendar Year detailing the status of all Neurocrine Prosecuted Patent Rights. Takeda will (1) promptly after the Effective Date provide to Neurocrine or counsel designated by Neurocrine the file histories for, and correspondence with foreign patent counsel related to, the Takeda Patent Rights and Defensive Patent Rights, (2) provide to Neurocrine promptly after the Effective Date a report detailing the status of the Takeda Patent Rights and Defensive Patent Rights, and (3) provide all assistance reasonably requested by Neurocrine in Neurocrine’s Prosecution and Maintenance of the Takeda Patent Rights, Defensive Patent Rights, and Program Patent Rights (including by executing all requested documents and providing additional information with respect to the applicable Patent Rights), provided that Neurocrine will be responsible for any reasonable costs and expenses paid to a Third Party relating to such assistance and transition of the Prosecution and Maintenance to Neurocrine of the Takeda Patent Rights and Defensive Patent Rights, and accordingly, Takeda will submit a reasonably detailed invoice to Neurocrine for any such costs and expenses incurred by Takeda in connection with such transition, along with reasonable documentation therefor, which undisputed invoiced amounts Neurocrine will pay no later than [***] after its receipt of such invoice. (b) Takeda’s Right. If Neurocrine determines in its sole discretion to abandon, not to Maintain, or not to pursue the Prosecution of any Takeda Patent Right, Defensive Patent Right, Joint Program Patent Right, or Neurocrine Sole Program Patent Right in Japan, then (i) Neurocrine will provide Takeda with written notice promptly after such determination to allow Takeda a reasonable period of time to 59 determine, on a country-by-country basis, in its sole discretion, its interest in Prosecuting or Maintaining such Patent Rights (which notice by Neurocrine will be given no later than [***] prior to the final deadline for any pending action or response that may be due with respect to such Patent Right with the applicable Patent Office), and (ii) only in the event that such abandonment or decision not to Maintain or pursue the Prosecution of such Patent Rights (A) is not done for strategic reasons to improve the exclusivity position for, or revenue from, a Licensed Product and (B) applies with respect to all applications within a particular patent family in a particular country or jurisdiction, then such Patent Rights will no longer be included in the Licensed Takeda Technology subject to the licenses granted by Takeda to Neurocrine in Section 2.1 (License Grant to Neurocrine) in such country or jurisdiction. If Takeda provides written notice to Neurocrine expressing its interest in Maintaining such Patent Right, then, with respect to such Patent Right in such country, (A) Takeda may, in its sole discretion and at Takeda’s cost and expense, Prosecute and Maintain or abandon such Patent Right, and (B) Neurocrine will promptly: (1) provide to Takeda or counsel designated by Takeda the file histories for, and correspondence with foreign patent counsel related to, such Patent Right, (2) provide to Takeda a report detailing the status of such Patent Right as of the applicable date of such notice by Neurocrine, and (3) provide all assistance reasonably requested by Takeda in Takeda’s Prosecution and Maintenance of the applicable Patent Rights (including by executing all requested documents and providing additional information with respect to the applicable Patent Rights). 12.3. Third Party Infringement and Defense. The Parties will conduct the enforcement and defense of the applicable Patent Rights in accordance with this Section 12.3 (Third Party Infringement and Defense). 12.3.1. Notices. Each Party will promptly report in writing to the other Party any Competitive Infringement or TAK-653 Competitive Infringement of which such Party (or any of its Affiliates or Sublicensees) becomes aware, and will provide the other Party with all available evidence of such Competitive Infringement or TAK-653 Competitive Infringement in such Party’s control. 12.3.2. Infringement Actions. (a) Neurocrine’s Right in the Territory. As between the Parties, Neurocrine will have (i) the first right, but not the obligation, to bring an appropriate suit or other action to abate any existing, alleged, or threatened Competitive Infringement in the Territory involving the Takeda Patent Rights, Defensive Patent Rights, or Joint Program Patent Rights, and (ii) the sole right, but not the obligation, to bring an appropriate suit or other action to abate any existing, alleged, or threatened Competitive Infringement in the Territory involving the Neurocrine Sole Program Patent Rights. (b) Takeda’s Right in the Territory. Neurocrine will notify Takeda of its decision as to whether to take any action in accordance with Section 12.3.2(a) (Neurocrine’s Right in the Territory) at least [***] before any time limit set forth in an applicable Law or regulation, or within [***] after being notified of such Competitive Infringement, whichever is shorter. If Neurocrine decides not to take such action with respect to any Takeda Patent Right, Defensive Patent Right, or
60 Joint Program Patent Right, then Neurocrine will so notify Takeda in writing, and following discussion with Neurocrine and consideration in good faith of any rationale provided by Neurocrine as to why Neurocrine elected not to take such action, and Neurocrine’s written consent (not to be unreasonably withheld) following consideration in good faith of any rationale provided by Takeda, Takeda will have the right, but not the obligation, to commence a suit or take action to enforce the applicable Takeda Patent Right, Defensive Patent Right, or Joint Program Patent Right to abate such Competitive Infringement in the Territory, by counsel of its own choice and at its own expense. (c) TAK-653 Products in Japan. If there is an existing, alleged, or threatened TAK- 653 Competitive Infringement, then Takeda will have the (i) sole right to bring an appropriate suit or other action to enforce the Takeda Patent Rights and Defensive Patent Rights and (ii) first right to bring an appropriate suit or other action to enforce the Patent Rights in the Neurocrine Technology, in each case (i) and (ii), against such TAK-653 Competitive Infringement, provided that prior to Takeda initiating any such suit or other action, Takeda will provide written notice [***] to Neurocrine [***]. [***]. Takeda will notify Neurocrine of its decision as to whether to take any action in accordance with this Section 12.3.2(c) (TAK-653 Products in Japan) at least [***] before any time limit set forth in an applicable Law, or within [***] after being notified of such TAK-653 Competitive Infringement, whichever is shorter. If Takeda decides not to take such action with respect to any TAK-653 Competitive Infringement of a Program Patent Right included in the Neurocrine Technology, then Takeda will so notify Neurocrine in writing, and Neurocrine will have the right, but not the obligation, to commence a suit or take action to abate such TAK-653 Competitive Infringement, by counsel of its own choice and at its own expense. (d) Hatch-Waxman. Notwithstanding any provision to the contrary in this Agreement, should a Party receive a certification for a Licensed Product pursuant to the Hatch-Waxman Act, or its equivalent in a country other than the U.S., with respect to any activities under this Agreement in the Field, then such Party will immediately provide the other Party with a copy of such certification. For each Licensed Product, Neurocrine will have [***] from the date on which it receives or provides a copy of such certification to provide written notice to Takeda (“H- W Suit Notice”) whether Neurocrine will bring suit, at its expense, within a [***] period from the date of such certification. Should such [***] period expire 61 without Neurocrine bringing suit or providing such H-W Suit Notice, then Takeda will be free to bring suit in its name (i) if such certification is with respect to U.S. patents or (ii) upon Neurocrine’s written consent, not to be unreasonably withheld, if such certification is with respect to patents for any country other than the U.S. and there is at such time an ongoing suit or there may be in the future a suit regarding a certification for a Licensed Product pursuant to the Hatch-Waxman Act in the U.S. (e) Cooperation. Each Party will provide to the Party enforcing any such rights under this Section 12.3.2 (Infringement Actions) reasonable assistance in such enforcement, at such enforcing Party’s request and expense, including joining such action as a party plaintiff if required by applicable Law to pursue such action or providing the enforcing Party any reasonably requested documentation or other materials. The enforcing Party will keep the other Party regularly informed of the status and progress of such enforcement efforts, including providing the other Party a reasonable opportunity to comment on the enforcing Party’s determination of litigation strategy and the filing of important papers to the competent court and the enforcing Party will consider such comments in good faith. If one Party elects to bring suit or take action against any Competitive Infringement or TAK-653 Competitive Infringement, then the other Party will have the right (if allowed under applicable Law), during or prior to commencement of the trial, suit, or action, to join any such suit or action at such other Party’s own expense by counsel of its own choice, but such other Party will at all times reasonably cooperate with the Party bringing such action. In addition, if Takeda is enforcing Patent Rights against TAK-653 Competitive Infringement, and NBI is enforcing Patent Rights in the Neurocrine Territory against the same or a related Third Party, then the Parties will discuss and reasonably coordinate enforcement strategies. (f) Expenses. Subject to this Section 12.3.2(f) (Expenses) and Section 12.3.2(h) (Allocation of Proceeds), the enforcing Party will be responsible for all expenses arising from a suit or action against a Competitive Infringement or TAK-653 Competitive Infringement, except as otherwise set forth in this Section 12.3.2 (Infringement Actions). For the avoidance of doubt, the enforcing Party will not be responsible for the other Party’s internal expenses (e.g., FTEs) incurred as a result of the other Party’s cooperation with the enforcement action as provided in this Section 12.3.2 (Infringement Actions). (g) Settlement. Neither Party will settle any claim, suit, or action that it brought under this Section 12.3.2 (Infringement Actions) in a manner that could reasonably be expected to affect the other Party’s rights or interests without the prior written consent of the other Party, which consent will not be unreasonably withheld. (h) Allocation of Proceeds. If either Party recovers monetary damages from any Third Party in a suit in the Territory pursuant to this Section 12.3.2 (Infringement Actions) or any royalties from a license agreement with a Third Party related to any alleged Competitive Infringement or TAK-653 Competitive Infringement, whether or not such damages or royalties result from the infringement of Neurocrine Prosecuted Patent Rights, such recovery will be allocated first to the reimbursement of any expenses incurred by each Party in such litigation, action, or license, and any remaining amounts will be split as follows: (i) with respect to a Competitive Infringement, (A) if Neurocrine brings the action, then [***], and (B) if Takeda brings the action, [***], and (ii) with respect to a TAK-653 62 Competitive Infringement, (A) if Takeda brings the action, then [***], and (B) if Neurocrine brings the action, [***]. 12.3.3. Defense. As between the Parties, the Party controlling the Prosecution and Maintenance of any Patent Right under Section 12.2 (Prosecution and Maintenance of Patent Rights), will have the right (but not the obligation), at its sole discretion, to defend against a declaratory judgment action, inter partes review, opposition proceeding, interference, or other legal or administration action challenging any such Patent Right. If the Party controlling such Prosecution and Maintenance of Takeda Patent Rights, Defensive Patent Rights, or Joint Program Patent Rights under Section 12.2 (Prosecution and Maintenance of Patent Rights) does not defend such Patent Right under this Section 12.3.3 (Defense) within [***], or elects not to continue any such defense (in which case it will promptly provide notice thereof to the other Party), then the other Party will have the right (but not the obligation), at its sole discretion, to defend any such Patent Right. Any awards or amounts received in defending any such action will be allocated between the Parties as provided in 12.3.2(h) (Allocation of Proceeds). 12.4. Patent Right Extensions. 12.4.1. By Neurocrine. Neurocrine will have the right to elect and file for patent term restoration or extension, supplemental protection certificate, or any of their equivalents with respect to Neurocrine Prosecuted Patent Rights worldwide for Licensed Other Products and in the Neurocrine Territory for TAK-653 Products. Neurocrine will inform Takeda of any such decision. Neurocrine will be responsible for applying for any such patent term extension. Upon the request by Neurocrine, Takeda will reasonably cooperate in the implementation of Neurocrine’s decisions made pursuant to this Section 12.4 (Patent Right Extensions). Neurocrine will bear the applicable Patent Costs incurred by Neurocrine in furtherance of such filing for any Licensed Product in the Territory. 12.4.2. By Takeda. Takeda will have the right to elect and file for patent term restoration or extension, supplemental protection certificate, or any of their equivalents with respect to Neurocrine Prosecuted Patent Rights that Cover any TAK-653 Product in Japan. Takeda will inform Neurocrine of any such decision. Takeda will be responsible for applying for any such patent term extension. Upon the request by Takeda, Neurocrine will reasonably cooperate in the implementation of Takeda’s decisions made pursuant to this Section 12.4 (Patent Right Extensions). 12.5. Third Party Rights. Notwithstanding anything in this Article 12 (Intellectual Property) to the contrary, the Parties’ rights and obligations with respect to any Patent Right Controlled pursuant to a license agreement with a Third Party will be subject to the Third Party rights and obligations under any such applicable license agreement. 12.6. Orange Book Listing. Neurocrine and Takeda will discuss in good faith the Takeda Patent Rights, Defensive Patent Rights, or Program Patent Rights that will be included in the Orange Book maintained by the FDA or similar or equivalent patent listing source, if any, in other countries for Licensed Products. After considering Takeda’s comments in good faith, Neurocrine will have the sole right to determine which Patent Rights will be included for Licensed Products in the Territory. 63 After considering Neurocrine’s comments in good faith, Takeda will have the sole right to determine which Patent Rights will be included for TAK-653 Products in Japan. Each Party will provide such assistance as may be reasonably requested by the other Party in connection with any such listing. 12.7. Trademarks. Neurocrine will have the right to brand Licensed Products in the Territory using Neurocrine-related Trademarks and any other Trademarks it determines appropriate, which may vary by country or within a country. Neurocrine will own all rights in such Trademarks and shall have the sole right to register and maintain such Trademarks in the countries and regions that it determines, at Neurocrine’s cost and expense. Takeda will have the right to brand TAK-653 Products in Japan using Takeda-related Trademarks and any other Trademarks it determines appropriate. Takeda will own all rights in such Trademarks and shall have the sole right to register and maintain such Trademarks in Japan, at Takeda’s cost and expense. Notwithstanding the foregoing, Takeda will not use, register or attempt to register (a) any Trademark for a TAK-653 Product in Japan or in the Territory that is confusingly similar to any Trademark used by Neurocrine for TAK-653 Products, or (ii) any Trademark that is confusingly similar to any USAN, INN, or other generic name for any TAK-653 Product in the Territory, in each case ((a) and (b)), without the prior written consent of Neurocrine. If Takeda desires to use Neurocrine’s global Trademark for TAK-653 Products in Japan, then at Takeda’s written request, the Parties will negotiate the terms under which Neurocrine would grant Takeda a license to use such Trademark. 12.8. Common Interest. All information exchanged between the Parties regarding the Prosecution and Maintenance, defense, and enforcement, of the Patent Rights under this Article 12 (Intellectual Property) will be deemed Confidential Information of the disclosing Party. In addition, the Parties acknowledge and agree that, with regard to such Prosecution and Maintenance, defense, and enforcement of the Patent Rights under this Article 12 (Intellectual Property), the interests of the Parties as licensor and licensee are to obtain the strongest patent protection possible, and as such, are aligned and are legal in nature. The Parties agree and acknowledge that they have not waived, and nothing in this Agreement constitutes a waiver of, any legal privilege concerning the Patent Rights under this Article 12 (Intellectual Property), including privilege under the common interest doctrine and similar or related doctrines. Notwithstanding any provision to the contrary contained herein, to the extent a Party has a good faith belief that any information required to be disclosed by such Party to the other Party under this Article 12 (Intellectual Property) is protected by attorney-client privilege or any other applicable legal privilege or immunity, such Party will not be required to disclose such information and the Parties will in good faith cooperate to agree upon a procedure (including entering into a specific common interest agreement, disclosing such information on a “for counsel eyes only” basis or similar procedure) under which such information may be disclosed without waiving or breaching such privilege or immunity. 13. TERM AND TERMINATION 13.1. Term. This Agreement will be effective as of the Restatement Date and, unless terminated earlier, will continue on a Licensed Product-by-Licensed Product and country-by-country basis until the date on which the Royalty Term has expired in such country in the Territory (collectively, the “Term”). Upon expiration of the Royalty Term for a Licensed Product in any country in the Territory, the licenses granted from Takeda to Neurocrine in Section 2.1 (License Grant to Neurocrine) with respect to such Licensed Product in such country will become fully paid, irrevocable, and perpetual.
64 13.2. Termination for Convenience. 13.2.1. Prior to First Commercial Sale. Neurocrine may terminate this Agreement for convenience in its entirety or in one or more (but not all) of the Major Markets, provided that for purposes of this Section 13.2 (Termination for Convenience), [***], on six months’ written notice to Takeda (a) with respect to all Licensed Products prior to the First Commercial Sale of the first Licensed Product for which First Commercial Sale occurs in the Territory or the applicable Major Market(s), or (b) with respect to all Licensed Products in one or more given Target Classes prior to the First Commercial Sale of the first Licensed Product in such Target Class(es) for which First Commercial Sale occurs in the Territory or the applicable Major Market(s), in each ((a) and (b)), excluding TAK-653 Products in Japan. 13.2.2. After First Commercial Sale. Neurocrine may terminate this Agreement for convenience in its entirety or in one or more (but not all) of the Major Markets on 12 months’ written notice to Takeda (a) with respect to all Licensed Products following the First Commercial Sale of the first Licensed Product for which First Commercial Sale occurs in the Territory or the applicable Major Market(s), or (b) with respect to all Licensed Products in one or more given Target Classes following the First Commercial Sale of the first Licensed Product in such Target Class(es) for which First Commercial Sale occurs in the Territory or the applicable Major Market(s), in each ((a) and (b)), excluding TAK-653 Products in Japan. 13.3. Termination for Cause. 13.3.1. Termination by Takeda. (a) Termination for Material Breach. Takeda will have the right to terminate this Agreement upon delivery of written notice to Neurocrine in the event of any material breach of this Agreement by Neurocrine, solely with respect to the Target Class of a Licensed Product to which such material breach relates, or in its entirety in the event of any material breach of this Agreement by Neurocrine that relates to all Licensed Products, provided that such termination will not be effective if such breach has been cured within [***] after written notice thereof is given by Takeda to Neurocrine specifying the nature of the alleged breach; provided, however, that (i) to the extent such material breach involves the failure to make a payment when due, such breach must be cured within [***] after written notice thereof is given by Takeda to Neurocrine, and (ii) if such breach (other than a failure to make a payment when due) is capable of cure but is not reasonably capable of cure within such [***] period, then Neurocrine may submit a reasonable cure plan prior to the end of such time period, in which case Takeda will not have the right to terminate this Agreement for so long as Neurocrine is using reasonable efforts to implement such cure, for a period not to exceed an additional [***] from the end of the initial [***] cure period. (b) Termination for Patent Challenge. If Neurocrine or any of its Affiliates files, assists a Third Party in filing, or joins a Third Party in filing or maintaining, a Patent Challenge of any Patent Right Controlled by Takeda that Covers any Licensed Product, then Takeda may terminate this Agreement with respect to the Target Classes for all Licensed Products Covered by such Patent Right by providing written notice of such termination to Neurocrine. This Section 13.3.1(b) 65 (Termination for Patent Challenge) will not apply to any such Patent Challenge that is first made by Neurocrine or any of its Affiliates in defense of a claim of patent infringement brought by Takeda under the applicable Patent Right, and with respect to any Sublicensee, Takeda will not have the right to terminate this Agreement under this Section 13.3.1(b) (Termination for Patent Challenge) with respect to any Licensed Product if Neurocrine (i) causes such Patent Challenge to be terminated or dismissed (or in the case of ex parte proceedings, multi-party proceedings, or other Patent Challenges in which Neurocrine does not have the power to unilaterally cause the Patent Challenge to be withdrawn, causes such Sublicensee to withdraw as a party from such Patent Challenge and to cease actively assisting any other party to such Patent Challenge) or (ii) terminates such Sublicensee’s sublicense to the Patent Rights being challenged by the Sublicensee, in each case, within [***] of Takeda’s notice to Neurocrine under this Section 13.3.1(b) (Termination for Patent Challenge). (c) Termination for Cessation of Development or Commercialization. On a Target Class-by-Target Class basis, Takeda may, at its election, terminate this Agreement with respect to a Target Class upon [***] prior written notice to Neurocrine in the event that Neurocrine, itself or together with or through any of its Affiliates or Sublicensees, does not conduct any Development or Commercialization activities with respect to any Licensed Product within such Target Class for a continuous period of more than [***]. Notwithstanding any provision to the contrary set forth in this Section 13.3.1(c) (Termination for Cessation of Development or Commercialization), [***]. 13.3.2. Termination by Neurocrine. (a) Termination for Material Breach. Neurocrine will have the right to terminate this Agreement upon delivery of written notice to Takeda in the event of any material breach of this Agreement by Takeda solely with respect to the Target Class of a Licensed Product to which such material breach relates, or in its entirety in the event of any material breach of this Agreement by Takeda that relates to all Licensed Products, provided that such termination will not be effective if such breach has been cured within [***] after written notice thereof is given by Neurocrine to Takeda specifying the nature of the alleged breach; provided, however, that (i) to the extent such material breach involves the failure to make a payment when due, such breach must be cured within [***] after written notice thereof is given by Neurocrine to Takeda, and (ii) if such breach (other than a failure to make a payment when due) is capable of cure but is not reasonably capable of cure within such [***] period, then Takeda may submit a reasonable cure plan prior to the end of such time period, in which case Neurocrine will not have the right to terminate this Agreement for so long as Takeda is using 66 reasonable efforts to implement such cure, for a period not to exceed an additional [***] from the end of the initial [***] cure period. (b) Termination for Patent Challenge. If Takeda or any of its Affiliates files, assists a Third Party in filing, or joins a Third Party in filing or maintaining, a Patent Challenge of any Patent Right that is pending or granted in Japan, Controlled by Neurocrine, and Covers any TAK-653 Product in Japan, then Neurocrine may terminate (A) the licenses granted to Takeda in Section 2.2 (License Grant to Takeda), (B) Neurocrine’s obligations to disclose Neurocrine Technology to Takeda under Sections 2.7 (Knowledge and Technology Transfer) and 4.4 (TAK- 653 Product Data Sharing) and (C) Takeda’s rights under Article 12 (Intellectual Property) with respect to Patent Rights in the Neurocrine Technology, in each case (A)-(C) immediately upon written notice of such termination to Takeda. If Neurocrine provides such written notice of such termination to Takeda, then Takeda’s obligation to pay royalties to Neurocrine on TAK-653 Products in Japan pursuant to Section 8.1.2(b) (Payable by Takeda) will also terminate as of the date of such written notice (except, for clarity, Takeda will pay royalties to the extent accrued prior to the date of such notice). This Section 13.3.2(b) (Termination for Patent Challenge) will not apply to any such Patent Challenge that is first made by Takeda or any of its Affiliates in defense of a claim of patent infringement brought by Neurocrine under the applicable Patent Right, and with respect to any Patent Challenge by a Sublicensee, Neurocrine will not have the right to terminate such licenses and rights under this Section 13.3.2(b) (Termination for Patent Challenge) if Takeda (i) causes such Patent Challenge to be terminated or dismissed (or in the case of ex parte proceedings, multi-party proceedings, or other Patent Challenges in which Takeda does not have the power to unilaterally cause the Patent Challenge to be withdrawn, causes such Sublicensee to withdraw as a party from such Patent Challenge and to cease actively assisting any other party to such Patent Challenge) or (ii) terminates such Sublicensee’s sublicense to the Patent Rights being challenged by the Sublicensee, in each case, within [***] of Neurocrine’s notice to Takeda under this Section 13.3.2(b) (Termination for Patent Challenge). For clarity, termination under this Section 13.3.2(b) (Termination for Patent Challenge) is not a termination of this Agreement, and Section 13.4 (Effects of Termination) will not apply to such termination. 13.3.3. Disputed Breach. If the alleged breaching Party disputes in good faith the existence or materiality of a breach specified in a notice provided by the other Party in accordance with Section 13.3.1(a) (Termination for Material Breach), Section 13.3.2(a) (Termination for Material Breach), or Section 13.3.1(c) (Termination for Cessation of Development or Commercialization) and such alleged breaching Party provides the other Party notice of such Dispute within such applicable period, then the cure periods set forth in Section 13.3.1(a) (Termination for Material Breach), Section 13.3.2(a) (Termination for Material Breach), or Section 13.3.1(c) (Termination for Cessation of Development or Commercialization), as applicable, will be tolled during the pendency of the dispute resolution process as set forth in Section 14.3 (Dispute Resolution) and the non-breaching Party will not have the right to terminate this Agreement under Section 13.3.1(a) (Termination for Material Breach), Section 13.3.2(a) (Termination for Material Breach), or Section 13.3.1(c) (Termination for Cessation of Development or Commercialization), as applicable, unless and until such dispute resolution process has been completed (including the tolling and cure period set forth therein) and such process results in a determination that the alleged breaching Party has materially breached this Agreement and 67 failed to cure such breach within the applicable time periods. During the pendency of such dispute, all of the terms and conditions of this Agreement will remain in effect and the Parties will continue to perform all of their respective obligations hereunder. 13.4. Effects of Termination. Upon termination (but not expiration) of this Agreement in its entirety or on a Terminated Target Class-by-Terminated Target Class basis, as applicable, in each case, in accordance with Section 13.2 (Termination for Convenience) or Section 13.3 (Termination for Cause), the following will apply with respect to the Terminated Products in the Terminated Territory: 13.4.1. Termination of Licenses. As of the effective date of termination of this Agreement, all licenses granted under Article 2 (License Grant) with respect to the Terminated Products in the Terminated Territory will terminate, and all sublicenses granted by Neurocrine or its Affiliates pursuant to Section 2.3 (Sublicensing Terms) with respect to the Terminated Products in the Terminated Territory will also terminate, unless the applicable Sublicensee is not then in breach of its sublicense agreement or the terms of this Agreement applicable to such Sublicensee and elects in writing prior to such termination to be granted a direct license from Takeda under the terms of Section 13.4.5 (New License Agreements). 13.4.2. Return of Confidential Information. As soon as reasonably practicable after the effective date of termination of this Agreement, each Party will promptly destroy (and certify such destruction in writing) or return to the other Party all of such other Party’s Confidential Information that relates specifically to a Terminated Product or the Terminated Territory, except that such Party will have the right to retain a copy of tangible Confidential Information of such other Party for legal archival purposes. 13.4.3. Intellectual Property License to Takeda. (a) Effective upon any termination of this Agreement other than as provided in the following Section 13.4.3(b) (Intellectual Property License to Takeda), upon Takeda’s request, Neurocrine will grant, and hereby does grant (which license shall be exercisable only upon the date that such termination becomes effective), to Takeda an irrevocable, perpetual license in the Field in the Terminated Territory, with the right to grant sublicenses (through multiple tiers), under [***]: (i) [***]. (ii) [***].
68 (b) Effective upon termination of this Agreement by Neurocrine pursuant to Section 13.3.2(a) (Termination for Material Breach), upon Takeda’s request, Neurocrine will grant, and hereby does grant (which license shall be exercisable only upon the date that such termination becomes effective), to Takeda a [***] license in the Field in the Terminated Territory, with the right to grant sublicenses (through multiple tiers) under the Grantback IP to Exploit the Terminated Product in the form such product exists as of the applicable effective date of termination, [***]. (c) To the extent any such Grantback IP is in-licensed or acquired by Neurocrine from a Third Party, [***]. (d) [***]. (e) The terms of Article 8 (Payments) will apply to the payment and reporting of any royalties described in this Section 13.4.3 (Intellectual Property License to Takeda), mutatis mutandis. 13.4.4. Trademarks for Terminated Products. Effective upon any termination of this Agreement in all countries of the Territory, if, as of the effective date of termination, the Terminated Product has received Regulatory Approval in any country in the Territory, Neurocrine will assign and transfer (and if unable to assign and transfer, exclusively license) to Takeda any trademarks owned or Controlled by Neurocrine that identify such 69 Terminated Product for the purpose of Commercializing such Terminated Product. If this Agreement is terminated with respect to one or more, but not all, countries in the Territory, then Neurocrine will grant an exclusive license to Takeda under any trademarks in the Terminated Territory owned or Controlled by Neurocrine or its Affiliates or terminated Sublicensees that identify such Terminated Product for the purpose of Commercializing such Terminated Product in the Terminated Territory. 13.4.5. New License Agreements. Upon termination of this Agreement for any reason with respect to Terminated Product and the Terminated Territory, [***] (each a “New License Agreement”). Under any such New License Agreement [***]. 13.4.6. Assignment of Agreements. Upon any termination of this Agreement, upon Takeda’s request, Neurocrine will [***] to assign to Takeda any Third Party agreements pursuant to which Neurocrine then Controls any Patent Rights that Cover, or Know-How that relates to, a Terminated Product in the Terminated Territory, [***]. If such a sublicense or other right is granted to Takeda, then Takeda will pay to Neurocrine [***]% of all payments due to the applicable Third Party under any such Third Party agreement in consideration of such sublicense or other rights. [***]. 70 13.4.7. Assignment and Disclosure. Upon termination of this Agreement, to the extent requested by Takeda following the date that a Party provides notice of termination of this Agreement (and in any event, no later than [***] after the effective date of termination), Neurocrine will use reasonable efforts promptly upon request of Takeda to: (a) assign and transfer to Takeda or its designee all of Neurocrine’s rights, title, and interests in and to all (i) clinical trial agreements (subject to Section 13.4.9 (Ongoing Clinical Trials)), manufacturing and supply agreements, distribution agreements, and other agreements to which Neurocrine is a party that relates to the Terminated Product and (ii) data from any applicable Clinical Trials in Neurocrine’s Control, in each case, solely to the extent assignable without consent of, or the provision of consideration (whether monetary or otherwise) to, any Third Party and not cancelled and solely to the extent the foregoing relate exclusively to the Terminated Products in the Terminated Territory and are necessary for the Exploitation of the Terminated Products in the Terminated Territory; and (b) to the extent any agreement or data set forth in the foregoing clause (a) is not assignable to Takeda or does not exclusively relate to the Terminated Products in the Terminated Territory, reasonably cooperate with Takeda to arrange to continue to provide such services for a reasonable time after termination of this Agreement (not to exceed [***]) with respect to such Terminated Products in the Terminated Territory to facilitate the orderly transition of all Development, Commercialization, and other activities then being performed by or on behalf of Neurocrine or its Affiliates or Sublicensees for the Terminated Products in the Terminated Territory to Takeda or its designee. Neurocrine will provide up to an aggregate (including such assistance provided pursuant to this Section 13.4.7(b) (Assignment and Disclosure), Section 13.4.11 (Know-How Transfer Support), and Section 13.4.14 (Transition Assistance)) of [***] FTE hours of transition assistance per Terminated Product from Neurocrine FTEs at no cost to Takeda, up to a maximum of [***] FTE hours in the aggregate for all Terminated Products, provided that Takeda will thereafter be responsible and reimburse Neurocrine for all documented FTE Costs at the FTE Rate and expenses associated with such assistance in accordance with an agreed budget, and accordingly, Neurocrine may invoice Takeda for such FTE Costs and expenses, in each case, incurred in connection with providing such assistance in accordance with such budget, and Takeda will pay the undisputed invoiced amounts within [***] after the date of such invoice. Neurocrine will be responsible for the costs and expenses it incurs associated with the assignments set forth in this Section 13.4.7 (Assignment and Disclosure). 13.4.8. Assignment of Regulatory Documentation; Data. Upon termination of this Agreement in its entirety or with respect to Terminated Products in the Terminated Territory: (a) upon Takeda’s request, (i) Neurocrine will and hereby does, and will cause its Affiliates and applicable terminated Sublicensees to, assign and transfer to Takeda or its designee, at no cost to Takeda, all of Neurocrine’s rights, title, and interest in and to all Regulatory Submissions, Regulatory Approvals, and Pricing Approvals for the Terminated Products in the Terminated Territory then Controlled by Neurocrine or any of its Affiliates or, as 71 applicable, terminated Sublicensees, and (ii) to the extent assignment pursuant to clause (i) is delayed or is not permitted by the applicable Regulatory Authority, permit Takeda to cross-reference and rely upon any Regulatory Submissions, Regulatory Approvals, and Pricing Approvals filed by Neurocrine with respect to such Terminated Products in the Terminated Territory, (b) upon Takeda’s reasonable written request, (i) Neurocrine will execute and deliver, or will cause to be executed and delivered, to Takeda or its designee such endorsements, assignments, commitments, acknowledgements, and other documents as may be necessary to assign, convey, transfer, and deliver to Takeda or its designee all of Neurocrine’s or its applicable Affiliate’s or designee’s rights, title, and interests in and to all such assigned Regulatory Submissions, Regulatory Approvals, and Pricing Approvals, including submitting to each applicable Regulatory Authority or other Governmental Authority in the Terminated Territory a letter or other necessary documentation (with copy to Takeda) notifying such Regulatory Authority or other Governmental Authority of, or otherwise giving effect to, the transfer of ownership to Takeda of all such assigned Regulatory Submissions, Regulatory Approvals, and Pricing Approvals, and (ii) Neurocrine will, (A) at its cost and expense, provide to Takeda copies of all material related documentation, including material non-clinical, preclinical, and clinical data related to the Terminated Products in the Terminated Territory that are then held by or reasonably available to Neurocrine or its Affiliates, provided that Neurocrine will have no obligation to provide copies of any such documentation to the extent previously received by Neurocrine from Takeda or provided from Neurocrine to Takeda or otherwise publicly available, and (B) provide Takeda with reasonable assistance with any inquiries and correspondence with Regulatory Authorities regarding the Terminated Products, and (c) the Parties will discuss and establish appropriate arrangements with respect to safety data exchange. 13.4.9. Ongoing Clinical Trials. (a) Transfer to Takeda. Unless prohibited by any Regulatory Authority or applicable Law, at Takeda’s written request, (i) Neurocrine will transfer control of all Clinical Trials involving any Terminated Products being conducted only in the Terminated Territory by or on behalf of Neurocrine, its Affiliate, or applicable terminated Sublicensees as of the effective date of termination to Takeda or its Affiliates or a Third Party that is designated in writing by Takeda, and (ii) Neurocrine will continue to conduct such Clinical Trials, at Takeda’s cost, to minimize interruption of any such Clinical Trials. Takeda will pay all external expenses incurred by either Party and all internal costs incurred by Neurocrine to complete such Clinical Trials if Takeda requests that such Clinical Trials be completed. (b) Neurocrine Wind-Down. If Takeda does not elect to assume control of any such Clinical Trials, then Neurocrine will, in accordance with accepted pharmaceutical industry norms and ethical practices, wind-down any on-going Clinical Trials of Terminated Products in the Terminated Territory for which it has responsibility hereunder. Neurocrine will be responsible for any external expenses associated with such wind-down. 13.4.10. Appointment as Exclusive Distributor. Upon any termination of this Agreement, if Neurocrine is Commercializing any Terminated Products in the Terminated Territory as of the applicable effective date of termination, then, upon Takeda’s request (in its sole discretion) on a country-by-country basis and at Takeda’s expense, until such time as all Regulatory Approvals with respect to such Terminated Products in such Terminated
72 Territory have been assigned and transferred to Takeda, Neurocrine will appoint Takeda or its designee as its exclusive distributor of such Terminated Products in such Terminated Territory and grant Takeda or its designee the right to appoint sub-distributors, to the extent not prohibited by any written agreement between Neurocrine or any of its Affiliates and a Third Party. 13.4.11. Know-How Transfer Support. Upon any termination of this Agreement, in furtherance of the license of Grantback IP pursuant to Section 13.4.3 (Intellectual Property License to Takeda), Neurocrine will, for a period of [***] from the effective date of such termination, provide a reasonable amount of consultation or other assistance, as Takeda may reasonably request to assist Takeda in becoming familiar with such Grantback IP in order for Takeda to undertake further Exploitation of the Terminated Products in the Terminated Territory. Neurocrine will provide assistance and the Parties will bear costs of such assistance as set forth in Section 13.4.7(b) (Assignment and Disclosure). 13.4.12. Inventory. Upon any termination of this Agreement with respect to the Terminated Products in the Terminated Territory, upon Takeda’s request, Neurocrine will transfer to Takeda or its designee some or all inventory of the Terminated Products (including all final product, bulk drug substance, intermediates, works-in-process, formulation materials, reference standards, drug product clinical reserve samples, packaged retention samples, and the like) then in the possession or Control of Neurocrine or its Affiliates or applicable terminated Sublicensees; provided that Takeda will pay Neurocrine [***]. 13.4.13. Wind-Down. Upon termination of this Agreement, Neurocrine will either, as directed by Takeda, (a) wind-down any ongoing activities with respect to the Terminated Products for the Terminated Territory in an orderly fashion, or (b) transfer such activities to Takeda or its designee in accordance with this Section 13.4 (Effects of Termination) in an orderly fashion and in compliance with all applicable Laws. 13.4.14. Transition Assistance. Upon any termination of this Agreement, upon Takeda’s request, Neurocrine will use reasonable efforts to seek an orderly transition of the Development and Commercialization of the Terminated Products in the Terminated Territory to Takeda or its designee, for so long as is necessary to ensure patient safety, including ensuring continuity of supply to any patients, but in no event for longer than [***] from the effective date of termination. Neurocrine will provide such assistance and the Parties will bear the costs of such assistance as set forth in Section 13.4.7(b) (Assignment and Disclosure). 13.4.15. Obligations re TAK-653. If this Agreement is terminated by either Party with respect to all Target Classes or with respect to the AMPA potentiator Target Class (excluding any termination that is solely with respect to one or more Major Markets outside Japan), then notwithstanding any provision to the contrary set forth herein, Takeda will continue to pay Neurocrine royalties on Net Sales of TAK-653 Products in Japan as set forth in Section 8.1.2(b) (Payable by Takeda) and the applicable terms of Article 8 (Payments). For the avoidance of doubt, on any termination of the Agreement, Takeda will only pay royalties to Neurocrine on TAK-653 Products in Japan pursuant to Section 8.1.2(b) (Payable by Takeda) and will not pay any additional royalties pursuant to Section 13.4.3 (Intellectual Property License to Takeda). 73 13.5. Survival. In addition to the termination consequences set forth in Section 13.4 (Effects of Termination), the following provisions will survive the expiration or termination of this Agreement for any reason: all of Article 1 (Definitions), Section 2.2 (except as provided in Section 13.3.2(b) (Termination for Patent Challenge), Section 2.8 (No Other Rights and Retained Rights), Section 3.4 (Scientific Records) (to the extent consistent with the applicable Party’s record retention policies and applicable Law), Section 5.5 (Recalls, Market Withdrawals, or Corrective Actions), Article 8 (Payments) (solely with respect to amounts accrued prior to termination but not paid and the reporting and information sharing procedures associated therewith and with respect to royalties on Net Sales of TAK-653 Products in Japan after the effective date of termination and the reporting and information sharing procedures associated therewith), Article 9 (Confidentiality and Publication), Article 11 (Indemnification; Limitation of Liability; Insurance), Section 12.1 (Inventions), Section 12.8 (Common Interest), Section 13.1 (Term) (solely in case of expiration), this Section 13.5 (Survival), and Article 14 (Miscellaneous). Expiration or termination of this Agreement for any reason will not relieve the Parties of any liability or obligation which accrued hereunder prior to the effective date of such termination or expiration, nor preclude either Party from pursuing all rights and remedies it may have hereunder or at law or in equity, with respect to any breach of this Agreement. 14. MISCELLANEOUS 14.1. Assignment. Except as provided in this Section 14.1 (Assignment), this Agreement may not be assigned or otherwise transferred, nor may any right or obligation hereunder be assigned or transferred, by either Party without the written consent of the other Party. Notwithstanding the foregoing, either Party may, without the other Party’s written consent, assign this Agreement and its rights and obligations hereunder in whole or in part (a) to an Affiliate, provided that if the entity to which this Agreement is assigned ceases to be an Affiliate of the assigning Party, this Agreement will be automatically assigned back to the assigning Party or its successor, or (b) to a party that acquires, by or otherwise in connection with a merger, sale of assets, or otherwise, all or substantially all of the business of the assigning Party to which the subject matter of this Agreement relates. The assigning Party will remain responsible for the performance by its assignee of any obligation hereunder so assigned. Any purported assignment in violation of this Section 14.1 (Assignment) will be null, void, and of no legal effect. 14.2. Governing Law. This Agreement will be construed and the respective rights of the Parties determined in accordance with the substantive Laws of the State of New York, notwithstanding any provisions of New York Laws or any other Laws governing conflicts of laws to the contrary, and the patent Laws of the relevant jurisdiction without reference to any rules of conflicts of laws to the contrary. 14.3. Dispute Resolution. 14.3.1. Exclusive Dispute Resolution Mechanism. The Parties agree that, except as expressly set forth in this Agreement (including under Section 7.4.2 (Final Decision-Making Authority, Section 3.5 (Supply of TAK-653 Products for Development in Japan), Section 5.7 (Supply of TAK-653 Products for Japan)), and Section 13.4.3 (Intellectual Property License to Takeda)), the procedures set forth in this Section 14.3 (Dispute Resolution) will be the exclusive mechanism for resolving any dispute, controversy, or claim between the Parties arising out of or relating to this Agreement (whether based on contract, tort or otherwise) (each, a “Dispute,” and collectively, the “Disputes”). 74 14.3.2. Resolution by Executive Officers. [***]. 14.3.3. Litigation. With the exception of legal actions, proceedings or claims described in Sections 14.3.4 (Preliminary Injunctions) and 14.3.5 (Patent and Trademark Disputes) below, any legal action or proceedings to resolve a Dispute that was subject to and not resolved under Section 14.3.2 (Resolution by Executive Officers) will be brought exclusively in a court of competent jurisdiction, federal or state, located in New York, New York, and in no other jurisdiction. Each Party hereby irrevocably consents to personal jurisdiction and venue in, and irrevocably agrees to service of process issued or authorized by, any such court in any such action or proceeding. The Parties hereby irrevocably waive any objection which they may now have or hereafter have to the laying of venue in the federal or state courts of New York in any such action or proceeding, and hereby irrevocably waive and agree not to plead or claim in any such court that any such action or proceeding brought in any such court has been brought in an inconvenient forum. The Parties hereby agree that any final judgment rendered by any such federal or state court of New York in any action or proceeding involving any Dispute, from which no appeal can be or is taken, may be enforced by the prevailing Party in any court of competent jurisdiction. 14.3.4. Preliminary Injunctions. Notwithstanding any provision to the contrary set forth in this Agreement, in the event of an actual or threatened breach of a Party’s covenants or obligations under this Agreement, a Party may seek a temporary restraining order or a preliminary injunction from any court of competent jurisdiction in order to prevent immediate and irreparable injury, loss, or damage on a provisional basis. 14.3.5. Patent and Trademark Disputes. Notwithstanding anything to the contrary set forth in this Agreement, any and all issues regarding the scope, construction, validity, and enforceability of any Patent Right or Trademark relating to a Licensed Product will be determined in a court or other tribunal, as the case may be, of competent jurisdiction under the applicable patent or trademark laws of the country in which such Patent Rights or Trademarks were granted or arose. 14.3.6. Confidentiality. Any and all activities conducted under this Section 14.3 (Dispute Resolution), including any and all proceedings and decisions hereunder, will be deemed Confidential Information of each of the Parties, and will be subject to Article 9 (Confidentiality and Publication), to the extent permitted in accordance with applicable Law. 14.4. Entire Agreement; Amendments. This Agreement, including its Schedules, contains the entire understanding of the Parties with respect to the subject matter hereof and supersedes all previous arrangements with respect to the subject matter hereof, whether written or oral (other than the Original Agreement, which governs the Parties’ rights and obligations thereunder during the period 75 from the Effective Date until the Restatement Date). This Agreement may be amended, or any term hereof modified or waived, only by a written instrument duly-executed by authorized representatives of both Parties. For clarity, the Schedules attached hereto may be amended, or any term thereof modified, only by a written instrument duly-executed by authorized representatives of both Parties. 14.5. Severability. If any provision hereof is held invalid, illegal, or unenforceable in any respect in any jurisdiction, then the Parties will negotiate in good faith to promptly substitute, by mutual consent, valid provisions for such invalid, illegal or unenforceable provisions, which valid provisions in their economic effect are sufficiently similar to the invalid, illegal or unenforceable provisions that most closely effectuate the original economic intent of the Parties. In case such valid provisions cannot be agreed upon, the invalid, illegal, or unenforceable nature of one or several provisions of this Agreement will not affect the validity of this Agreement as a whole, unless the invalid, illegal or unenforceable provisions are of such essential importance to this Agreement that it is to be reasonably assumed that the Parties would not have entered into this Agreement without the invalid, illegal, or unenforceable provisions. 14.6. Headings. The captions to the Sections hereof are not a part of this Agreement, but are merely for convenience to assist in locating and reading the several Sections hereof. 14.7. Waiver of Rule of Construction. Each Party has had the opportunity to consult with counsel in connection with the review, drafting and negotiation of this Agreement. Accordingly, the rule of construction that any ambiguity in this Agreement will be construed against the drafting Party will not apply. 14.8. Interpretation. Except where the context expressly requires otherwise, (a) the use of any gender herein will be deemed to encompass references to either or both genders, and the use of the singular will be deemed to include the plural (and vice versa); (b) the words “include”, “includes” and “including” will be deemed to be followed by the phrase “without limitation” and will not be interpreted to limit the provision to which it relates; (c) the word “will” will be construed to have the same meaning and effect as the word “shall”; (d) any definition of or reference to any agreement, instrument or other document herein will be construed as referring to such agreement, instrument or other document as from time to time amended, supplemented or otherwise modified (subject to any restrictions on such amendments, supplements or modifications set forth herein); (e) any reference herein to any Person will be construed to include the Person’s successors and assigns; (f) the words “herein,” “hereof,” and “hereunder,” and words of similar import, will be construed to refer to this Agreement in its entirety, as the context requires, and not to any particular provision hereof; (g) all references herein to Sections or Schedules will be construed to refer to sections or schedules of this Agreement, and references to this Agreement include all Schedules hereto; (h) the word “notice” means notice in writing (whether or not specifically stated) and will include notices, consents, approvals and other written communications contemplated under this Agreement; (i) provisions that require that a Party, the Parties, or any committee hereunder “agree,” “consent,” or “approve” or the like will require that such agreement, consent or approval be specific and in writing, whether by written agreement, letter, approved minutes or otherwise (but excluding e-mail and instant messaging); (j) references to any specific law, rule, or regulation, or article, section, or other division thereof, will be deemed to include the then-current amendments thereto or any replacement or successor law, rule, or regulation thereof; (k) the term “or” will be interpreted in the inclusive sense commonly associated with the term “and/or” unless preceded by the word “either” or other language indicating the subjects of the conjunction are, or are intended to be, mutually exclusive; and (l) unless otherwise specified, “day” means a calendar day.
76 14.9. No Implied Waivers; Rights Cumulative. No failure on the part of Neurocrine or Takeda to exercise, and no delay in exercising, any right, power, remedy or privilege under this Agreement, or provided by statute or at Law or in equity or otherwise, will impair, prejudice or constitute a waiver of any such right, power, remedy or privilege, or be construed as a waiver of any breach of this Agreement or as an acquiescence therein, nor will any single or partial exercise of any such right, power, remedy or privilege preclude any other or further exercise thereof or the exercise of any other right, power, remedy or privilege. 14.10. Notices. All notices which are required or permitted hereunder will be in writing and sufficient if delivered personally, sent by email with confirmation of receipt, sent by nationally-recognized overnight courier or sent by registered or certified mail, postage prepaid, return receipt requested, addressed as follows: If to Neurocrine, to: Neurocrine Biosciences, Inc. 12780 El Camino Real San Diego, CA 92130 Attention: Vice President, Business Development Email: [***] With a copy (which will not constitute notice) to: Neurocrine Biosciences, Inc. 12780 El Camino Real San Diego, CA 92130 Attention: Chief Legal Officer Email: [***] and a copy (which will not constitute notice) to: Cooley LLP 4401 Eastgate Mall San Diego, CA 92121 Attention: Jason Kent Email: [***] If to Takeda, to: Takeda Pharmaceutical Company Limited 1-1, Doshomachi 4-Chome, Chuo-ku Osaka 540-8645, Japan Attention: General Manager, Global Business Development With a copy (which will not constitute notice) to: Takeda Pharmaceutical Company Limited 1-1, Doshomachi 4-chome, Chuo-ku, Osaka 540-8645, Japan Attention: Head of IP Licensing & R&D Contract, Japan Legal Takeda Pharmaceuticals U.S.A., Inc. 500 Kendall Street Cambridge, MA 02142 Attention: Regional General Counsel 77 Ropes & Gray LLP Prudential Tower 800 Boylston Street Boston, MA 02199-3600 Attention: Hannah H. England Email: [***] or to such other address as the Party to whom notice is to be given may have furnished to the other Party in writing in accordance herewith. Any such notice will be deemed to have been given: (a) when delivered if personally delivered on a Business Day (or if delivered or sent on a non-Business Day, then on the next Business Day); (b) when sent if sent by email on a Business Day (or if sent on a non-Business Day, then on the next Business Day); (c) on the Business Day of receipt if sent by overnight courier; or (d) on the Business Day of receipt if sent by mail. 14.11. Compliance with Export Regulations. Neither Party will export any technology licensed to it by the other Party under this Agreement except in compliance with U.S. export Laws and regulations. 14.12. Force Majeure. Neither Party will be held liable to the other Party nor be deemed to have defaulted under or breached this Agreement for failure or delay in achieving any objective, satisfying any condition, or performing any obligation under this Agreement to the extent that such failure or delay is caused by or results from acts or events beyond the reasonable control of such Party, including acts of God, embargoes, war, acts of war (whether war be declared or not), terrorism, insurrections, riots, civil commotions, strikes, lockouts, or other labor disturbances (other than strikes, lockouts, or labor disturbances involving a Party’s own employees), government actions, fire, earthquakes, floods, epidemics, pandemics, the spread of infectious diseases, and quarantines (“Force Majeure”). Notwithstanding the foregoing, a Party will not be excused from making payments owed hereunder due to any such Force Majeure circumstances affecting such Party. The affected Party will notify the other Party in writing of any Force Majeure circumstances that may affect its performance under this Agreement as soon as reasonably practical, will provide a good faith estimate of the period for which its failure or delay in performance under the Agreement is expected to continue based on currently available information, and will undertake reasonable efforts necessary to mitigate and overcome such Force Majeure circumstances and resume normal performance of its obligations hereunder as soon a reasonably practicable under the circumstances. If the Force Majeure circumstance continues, then, to the extent reasonably possible under the circumstances, the affected Party will update such written notice to the other Party on a bi-weekly basis, or more frequently if requested by the other Party, to provide updated summaries of its mitigation efforts and its estimates of when normal performance under the Agreement will be able to resume. 14.13. Independent Parties. It is expressly agreed that Neurocrine and Takeda will be independent contractors and that, except as otherwise required by applicable Law, the relationship between Neurocrine and Takeda will not constitute a partnership (including for U.S. federal Tax purposes), joint venture, or agency. Neurocrine will not have the authority to make any statements, representations, or commitments of any kind, or to take any action, that will be binding on Takeda, without the prior written consent of Takeda, and Takeda will not have the authority to make any statements, representations, or commitments of any kind, or to take any action, that will be binding on Neurocrine, without the prior written consent of Neurocrine. The Parties (and any successor, assignee, transferee, or Affiliate of a Party) will not treat or report the relationship between the Parties arising under this Agreement as a partnership for United States tax purposes to the extent reasonably permitted based upon advice of the applicable Party’s tax return preparer. 78 14.14. Further Assurances. The Parties agree to reasonably cooperate with each other in connection with any actions required to be taken as part of their respective obligations under this Agreement, and will (a) furnish to each other such further information; (b) execute and deliver to each other such other documents; and (c) do such other acts and things (including working collaboratively to correct any clerical, typographical, or other similar errors in this Agreement), all as the other Party may reasonably request for the purpose of carrying out the intent of this Agreement. 14.15. Performance by Affiliates. Each Party acknowledges and accepts that the other Party may exercise its rights and perform its obligations (including granting or continuing licenses and other rights) under this Agreement either directly or through one or more of its Affiliates. A Party’s Affiliates will have the benefit of all rights (including all licenses and other rights) of such Party under this Agreement. Accordingly, in this Agreement “Takeda” will be interpreted to mean “Takeda or its Affiliates” and “Neurocrine” will be interpreted to mean “Neurocrine or its Affiliates” where necessary to give each Party’s Affiliates the benefit of the rights provided to such Party in this Agreement and the ability to perform its obligations (including granting or continuing licenses and other rights) under this Agreement; provided, however, that in any event each Party will remain responsible for the acts and omissions, including financial liabilities, of its Affiliates. 14.16. Binding Effect; No Third Party Beneficiaries. As of the Restatement Date, this Agreement will be binding upon and inure to the benefit of the Parties and their respective permitted successors and permitted assigns. Except as expressly set forth in this Agreement, no Person other than the Parties and their respective Affiliates and permitted assignees hereunder will be deemed an intended beneficiary hereunder or have any right to enforce any obligation of this Agreement. 14.17. Counterparts. This Agreement may be executed in two or more counterparts, including by facsimile or PDF signature pages, each of which will be deemed an original, but all of which together will constitute one and the same instrument. [THE REMAINDER OF THIS PAGE HAS BEEN LEFT INTENTIONALLY BLANK] IN WITNESS WHEREOF, the Parties have caused this Amended and Restated Exclusive License Agreement to be executed by their duly authorized representatives as of the Restatement Date. TAKEDA PHARMACEUTICAL COMPANY LIMITED BY: /s/ Rika Kurosaki NAME: Rika Kurosaki TITLE: Lead, Corporate Development, Global Business Development [Signature Page to Amended and Restated Exclusive License Agreement]
IN WITNESS WHEREOF, the Parties have caused this Amended and Restated Exclusive License Agreement to be executed by their duly authorized representatives as of the Restatement Date. NEUROCRINE BIOSCIENCES, INC. BY: /s/ Kyle Gano NAME: Kyle W. Gano, Ph.D. TITLE: Chief Executive Officer [Signature Page to Amended and Restated Exclusive License Agreement] SCHEDULE 1.33 DEFENSIVE PATENT RIGHTS [***] SCHEDULE 1.80 LICENSED ASSETS Licensed Asset Mechanism of Action TAK-653 Asset NBI-1065845 (TAK-653) AMPA potentiator Nonclinical Assets [***] [***] [***] [***] SCHEDULE 1.188 TAKEDA KNOW-HOW Structure-activity relationship data and in vitro and in vivo data for the following chemical series: [***] [***]
SCHEDULE 3.5 [***] DISPUTE RESOLUTION [***] SCHEDULE 9.2.3 PRESS RELEASE Neurocrine Biosciences Announces Amendment to Strategic Collaboration with Takeda to Develop and Commercialize Osavampator (formerly NBI-1065845/TAK-653) - Neurocrine Obtains Exclusive Worldwide Development and Commercialization Rights Excluding Japan and Converts to Royalty-Bearing License for Osavampator - Takeda Reacquires Rights to Osavampator in Japan SAN DIEGO, Jan. 27, 2025 – Neurocrine Biosciences (Nasdaq: NBIX) today announced it has amended its agreement with Takeda to develop and commercialize osavampator (NBI- 1065845/TAK-653). Under the amended agreement, Neurocrine will obtain exclusive rights for all indications to develop and commercialize osavampator, a potential first-in-class AMPA positive allosteric modulator in development for patients with inadequate response to treatment of major depressive disorder (MDD) in all territories worldwide except Japan, where Takeda will reacquire exclusive rights. Under the terms of the updated agreement, each company is responsible for development costs in their respective region, and both companies are eligible to receive royalty payments. “This streamlined collaboration structure allows Neurocrine to focus on bringing this important medicine to patients as quickly as possible,” said Kyle Gano, Ph.D., Chief Executive Officer at Neurocrine Biosciences. “With the recent successful completion of our End-of-Phase 2 meeting with FDA for osavampator, we look forward to beginning the Phase 3 program in the first half of this year.” “With its long-standing expertise developing therapies for serious psychiatric disorders, Neurocrine is the ideal partner to develop osavampator,” said Sarah Sheikh, M.Sc., B.M., B.Ch, MRCP, Head, Neuroscience Therapeutic Area Unit and Head, Global Development at Takeda. “As it continues to progress through clinical development, osavampator has the potential to add a meaningful new treatment option for patients with MDD.” About the Collaboration with Takeda In 2020, Neurocrine Biosciences and Takeda entered into a strategic collaboration to develop and commercialize compounds in depression and schizophrenia, including an exclusive license to both osavampator and NBI-1070770, which are being studied for the treatment of major depressive disorder, as well as a preclinical GPR139 antagonist development program. About Osavampator Osavampator is a potential first-in-class, investigational alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) in development for patients with MDD who have not benefited from treatment with at least one antidepressant in their current episode of depression. In April 2024, Neurocrine announced positive topline data for its Phase 2 SAVITRI™ study in adult subjects with MDD. Neurocrine plans to initiate a Phase 3 program in the first half of this year. About Major Depressive Disorder Major depressive disorder (MDD) is a serious disorder characterized by a persistently depressed mood, loss of interest, poor concentration, and decreased energy, among other symptoms. According to the World Health Organization, MDD is one of the leading causes of disability, is a serious condition that presents an increased risk of suicide and self-harm, and is associated with increased all-cause mortality rates. More than 21 million people in the U.S. live with MDD and it is estimated that roughly a third of those do not respond to available antidepressants. About Neurocrine Biosciences Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA- approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids,* as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (formerly Twitter) and Facebook. (*in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. SAVITRI is a trademark of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements related to the benefits to be derived from transactions with Takeda Pharmaceutical Company Limited; statements regarding the clinical results from, and our future development plans with respect to, osavampator, as well as the therapeutic potential and clinical benefits or safety profile of osavampator. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements include: risks that clinical development activities may not be initiated or completed on time or at all, or may be delayed for regulatory, manufacturing, or other reasons, may not be successful or replicate previous clinical trial results, may fail to demonstrate that our product candidates are safe and effective, or may not be predictive of real-world results or of results in subsequent clinical trials; our future financial and operating performance; risks associated with our dependence on third parties for development, manufacturing, and commercialization activities for our products and product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that the potential benefits of the agreements with our collaboration partners may never be realized; risks that our products, and/or our product candidates may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks associated with U.S. federal or state legislative or regulatory and/or policy efforts which may result in, among other things, an adverse impact on our revenues or potential revenue; risks associated with potential generic entrants for our products; risks that the benefits of the agreements with Takeda may never be realized; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended September 30, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. Neurocrine Biosciences, Inc.: Media: Tony Jewell, 1-609-576-3800, media@neurocrine.com; Investors: Todd Tushla, 1-858-617-7143, ir@neurocrine.com
SCHEDULE 10.2.1 TAKEDA PATENT RIGHTS [***] SCHEDULE 10.2.2 TAKEDA TECHNOLOGY [***] SCHEDULE 10.2.4 OWNERSHIP OF TAKEDA TECHNOLOGY None SCHEDULE 12.2.1(a) ANNUITIES AND MAINTENANCE FEES None
SCHEDULE 13.4.3 [***] DISPUTE RESOLUTION [***]
EX-31.1
4
q1-2025xexhibit311.htm
EX-31.1
Document
CERTIFICATION OF CHIEF EXECUTIVE OFFICER PURSUANT
TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002
I, Kyle W. Gano, Chief Executive Officer of Neurocrine Biosciences, Inc., certify that:
1.I have reviewed this quarterly report on Form 10-Q of Neurocrine Biosciences, Inc.;
2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
4.The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)), for the registrant and have:
a.Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;
b.Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;
c.Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
d.Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
5.The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):
a.All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and
b.Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.
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Dated: May 5, 2025 |
/s/ Kyle W. Gano |
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Kyle W. Gano |
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Chief Executive Officer |
EX-31.2
5
q1-2025xexhibit312.htm
EX-31.2
Document
CERTIFICATION OF CHIEF FINANCIAL OFFICER PURSUANT
TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002
I, Matthew C. Abernethy, Chief Financial Officer of Neurocrine Biosciences, Inc., certify that:
1.I have reviewed this quarterly report on Form 10-Q of Neurocrine Biosciences, Inc.;
2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
4.The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)), for the registrant and have:
a.Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;
b.Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;
c.Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
d.Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
5.The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):
a.All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and
b.Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.
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Dated: May 5, 2025 |
/s/ Matthew C. Abernethy |
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Matthew C. Abernethy |
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Chief Financial Officer |
EX-32
6
q1-2025xexhibit32.htm
EX-32
Document
CERTIFICATIONS OF
CHIEF EXECUTIVE OFFICER AND CHIEF FINANCIAL OFFICER
PURSUANT TO 18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
In connection with the Quarterly Report of Neurocrine Biosciences, Inc. (Company) on Form 10-Q for the period ended March 31, 2025 as filed with the Securities and Exchange Commission on the date hereof (Report), I, Kyle W. Gano, Chief Executive Officer of the Company, certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that to my knowledge:
(1)The Report fully complies with the requirements of Section 13(a) or 15(d), of the Securities Exchange Act of 1934; and
(2)That information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
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May 5, 2025 |
By: |
/s/ Kyle W. Gano |
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Name: |
Kyle W. Gano |
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Title: |
Chief Executive Officer |
In connection with the Quarterly Report of Neurocrine Biosciences, Inc. (Company) on Form 10-Q for the period ended March 31, 2025 as filed with the Securities and Exchange Commission on the date hereof (Report), I, Matthew C. Abernethy, Chief Financial Officer of the Company, certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that to my knowledge:
(1)The Report fully complies with the requirements of Section 13(a) or 15(d), of the Securities Exchange Act of 1934; and
(2)That information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
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May 5, 2025 |
By: |
/s/ Matthew C. Abernethy |
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Name: |
Matthew C. Abernethy |
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Title: |
Chief Financial Officer |