リープセラピューティクスの適時開示・決算・その他

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(D)

of the Securities Exchange Act of 1934

Date of report (Date of earliest event reported): March 26, 2025

Leap Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

Delaware		001-37990		27-4412575
(State or other jurisdiction of incorporation)		(Commission File Number)		(IRS Employer Identification No.)

47 Thorndike Street, Suite B1-1 Cambridge, MA	02141
(Address of principal executive offices)	(Zip Code)

Registrant’s telephone number, including area code: (617) 714-0360

N/A

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425).

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12).

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)).

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)).

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, par value $0.001	LPTX	Nasdaq Capital Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter)

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. ¨

Item 2.02. Results of Operations and Financial Condition

On March 26, 2025, Leap Therapeutics, Inc. (the “Company”) announced its financial results for the fourth quarter and year ended December 31, 2024. The full text of the press release issued by the Company in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

The information contained in this Item 2.02 and in the accompanying exhibit shall not be incorporated by reference into any filing of the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing, unless expressly incorporated by specific reference to such filing. The information set forth under this Item 2.02 and the press release furnished by the Company as Exhibit 99.1 hereto shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended.

Item 8.01. Other Events

On March 26, 2025, the Company issued a press release entitled “Leap Therapeutics Reports Positive Updated Data from Sirexatamab Colorectal Cancer Study.” The full text of the press release is filed as Exhibit 99.2 to this Current Report on Form 8-K and incorporated herein by reference; provided, however that information on or connected to our website referenced in the Company’s press release is expressly not incorporated by reference into or intended to be filed as a part of this Current Report on Form 8-K.

Also on March 26, 2025, the Company posted an updated corporate presentation on its website, www.leaptx.com. A copy of the presentation is filed as Exhibit 99.3 to this Current Report on Form 8-K and incorporated herein by reference. Except for such updated corporate presentation, the information contained on, or that can be accessed from, the Company’s website is not incorporated into, and does not constitute a part of, this Current Report on Form 8-K.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits.

Exhibit Number		Description
99.1		Press Release, dated March 26, 2025
99.2		Press Release, dated March 26, 2025
99.3		Leap Corporate Presentation
104		Cover Page Interactive Data File. (Embedded within the Inline XBRL document.)

- 2 -

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 hereunto duly authorized.

	LEAP THERAPEUTICS, INC.

Dated: March 26, 2025	By:	/s/ Douglas E. Onsi
	Name:	Douglas E. Onsi
	Title:	Chief Executive Officer and President

EX-99.1 2 tm2510101d2_ex99-1.htm EXHIBIT 99.1

Exhibit 99.1

Leap Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results

Leap to host a conference call to present updated CRC clinical data today, March 26, 2025, at 8:00 a.m. ET

Cambridge, MA – March 26, 2025 – Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today reported financial results for the fourth quarter and year ended December 31, 2024.

Leap Highlights:

Reported positive updated data from Part B of the Phase 2 DeFianCe study of sirexatamab (DKN-01) in second-line patients with advanced microsatellite stable (MSS) colorectal cancer (CRC) confirming:

Statistically significant 32% higher overall response rate (ORR), 3.5 month longer progression-free survival (PFS), and longer overall survival (OS) in patients with high DKK1 levels

Statistically significant 22% higher ORR and 2.6 month longer PFS in patients who had not had prior anti-VEGF therapy

FL-501 abstract accepted for poster presentation at the 2025 American Association for Cancer Research (AACR) Annual Meeting.

"In 2024, we continued to advance sirexatamab, our anti-DKK1 antibody, through Phase 2 randomized controlled clinical trials as part of our mission to bring personalized medicines to patients fighting against cancer. In particular, the updated data from Part B of the DeFianCe study that we announced today demonstrated significantly higher ORR and longer PFS for sirexatamab in patients who have high levels of DKK1 or who have not had prior anti-VEGF therapy, two exploratory populations with strong scientific rationale that each represent 25-50% of the second-line CRC market,” said Douglas E. Onsi, President and Chief Executive Officer of Leap. “We believe that there is a compelling opportunity to move forward with a registrational study for sirexatamab in patients with CRC and to advance FL-501 towards clinical trials.”

DKN-01 Development Update

Reported updated clinical data from Part B of the DeFianCe Study of sirexatamab plus bevacizumab and chemotherapy in CRC patients. Today, the Company announced updated preliminary data from Part B of the DeFianCe study (NCT05480306), a Phase 2, open-label, global study of sirexatamab in combination with bevacizumab and chemotherapy (Experimental Arm) compared to bevacizumab and chemotherapy (Control Arm) in patients with MSS CRC who have received one prior systemic therapy for advanced disease. In the updated data announced today,

Patients with high DKK1 levels, either at the upper quartile or above the median, treated in the sirexatamab Experimental Arm had significantly improved ORR, PFS, and OS compared to the Control Arm.

In patients who had not received prior anti-VEGF therapy, the sirexatamab Experimental Arm had significantly improved ORR and PFS compared to the Control Arm, with an early advantage in OS.

Across the intent-to-treat population, the sirexatamab Experimental Arm had improved ORR compared to the Control Arm, with PFS and OS maturing with a higher number of patients continuing to benefit on the sirexatamab Experimental Arm.

The strong signal from the DeFianCe study supports a registrational Phase 3 clinical trial to evaluate sirexatamab plus bevacizumab and chemotherapy in second-line MSS CRC patients with high DKK1 levels or in patients who have not received prior anti-VEGF therapy.

With approximately 30,000 second-line treated CRC patients in the US and 160,000 in the next 7 largest markets, sirexatamab has a large market opportunity in the 25-50% of patients who have high DKK1 levels or in the approximately 50% of patients who did not receive prior anti-VEGF therapy. In addition, the outcomes in patients with no prior anti-VEGF therapy provides an opportunity to move into treating first-line CRC patients, where there are an estimated 45,000 patients in the US and 265,000 in the next 7 largest markets who receive therapy for their advanced disease.

Leap has engaged a leading financial advisor to explore business development opportunities to further the development of sirexatamab.

Pipeline Update

Presenting preclinical FL-501 data at the 2025 American Association for Cancer Research (AACR) Annual Meeting. Preclinical data from FL-501, a potential best-in-class monoclonal antibody designed to neutralize GDF-15 to treat patients with cachexia and other GDF-15-driven diseases, will be featured during a poster session at the 2025 AACR Annual Meeting taking place April 25-30 in Chicago. In addition, manufacturing and non-clinical development continues with the goal of beginning a clinical trial in 2026.

Conference Call

Leap’s management team will host a conference call today, March 26, 2025 at 8:00 a.m. Eastern Time to further discuss the data. The conference call will be broadcast live in listen-only mode and can be accessed via the webcast URL: https://edge.media-server.com/mmc/p/t6576mgc. A replay of the event will be available for a limited time on the Investors page of the Company’s website at https://investors.leaptx.com/.

Selected Year-End and Fourth Quarter 2024 Financial Results

Net Loss was $67.6 million for the year ended December 31, 2024, compared to $81.4 million for the year ended December 31, 2023. The decrease was primarily due to a decrease in research and development expenses.

Research and development expenses were $57.2 million for the full year 2024, compared to $73.2 million for the same period in 2023. Research and development expenses were $13.1 million for the fourth quarter ended 2024, compared to $11.7 million for the same period in 2023. The decreases for the full year 2024 were primarily due to in-process research and development acquired in the Flame merger which were expensed in the year ended December 31, 2023.

General and administrative expenses were $12.8 million for the full year 2024, compared to $13.8 million for the same period in 2023. General and administrative expenses were $3.0 million for the fourth quarter ended 2024, compared to $3.1 million for the same period in 2023. The decreases for the full year 2024 were primarily due to a decrease in professional fees due to lower finance and legal costs.

Cash and cash equivalents totaled $47.2 million at December 31, 2024.

About Leap Therapeutics

Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, sirexatamab (DKN-01), is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. Sirexatamab is being studied in patients with colorectal cancer. Leap's pipeline also includes FL-501, a humanized monoclonal antibody targeting the growth and differentiation factor 15 (GDF-15) protein, in preclinical development. For more information about Leap Therapeutics, visit http://www.leaptx.com or view our public filings with the SEC that are available via EDGAR at http://www.sec.gov or via https://investors.leaptx.com/.

FORWARD-LOOKING STATEMENTS

This press release contains forward-looking statements within the meaning of the federal securities laws. Such statements are based upon current plans, estimates and expectations of the management of Leap that are subject to various risks and uncertainties that could cause actual results to differ materially from such statements. The inclusion of forward-looking statements should not be regarded as a representation that such plans, estimates and expectations will be achieved. Words such as "anticipate," "expect," "project," "intend," "believe," "may," "will," "should," "plan," "could," "continue," "target," "contemplate," "estimate," "forecast," "guidance," "predict," "possible," "potential," "pursue," "likely," and words and terms of similar substance used in connection with any discussion of future plans, actions or events identify forward-looking statements.

All statements, other than historical facts, including statements regarding the potential safety, efficacy, and regulatory and clinical progress of Leap's product candidates; the size of the potential addressable market for sirexatamab, including the number or percentage of patients with advanced CRC that have or are likely to have high levels of DKK1 or that have not had or are likely not to have prior anti-VEGF therapy; the anticipated timing for initiation or completion of clinical trials and release of clinical trial data and the expectations surrounding the outcomes thereof; Leap's future clinical or preclinical product development plans for any of Leap's product candidates; Leap's estimations of projected cash runway; and any assumptions underlying any of the foregoing, are forward-looking statements. Important factors that could cause actual results to differ materially from Leap's plans, estimates or expectations could include, but are not limited to: (i) the results of Leap's clinical trials and pre-clinical studies, including whether the final data from Part B of the DeFianCe study or Part C of the DisTinGuish study are the same as the initial data reported, (ii) the actual size of the potential addressable market for sirexatamab, including the number or percentage of patients with advanced CRC that have or are likely to have high levels of DKK1 or that have not had or are likely not to have prior anti-VEGF therapy, may be smaller than estimated, (iii) Leap's ability to successfully finance or enter into new strategic partnerships for sirexatamab or any of its other programs; (iv) any regulatory feedback that Leap may receive from U.S. Food and Drug Administration (FDA) or equivalent foreign regulatory agency with respect to the registrational Phase III clinical trials that Leap proposes to conduct using sirexatamab for the treatment of patients with second-line CRC or with respect to any other pre-clinical or clinical development activities that Leap will be required to conduct in order to obtain regulatory approval of sirexatamab for the treatment of second-line CRC; (v) whether any Leap products will receive approval from the FDA or equivalent foreign regulatory agencies; and (vi) exposure to inflation and interest rate fluctuations, as well as fluctuations in the market price of Leap's traded securities. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Leap may not actually achieve the forecasts disclosed in such forward-looking statements, and you should not place undue reliance on such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Leap's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither Leap, nor any of its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing Leap's views as of any date subsequent to the date hereof.

CONTACT:

Douglas E. Onsi

President & Chief Executive Officer

Leap Therapeutics, Inc.

617-714-0360

donsi@leaptx.com

Matthew DeYoung

Investor Relations

Argot Partners

212-600-1902

leap@argotpartners.com

Leap Therapeutics, Inc

Consolidated Statement of Operations

Leap Therapeutics, Inc.

Consolidated Statements of Operations

(in thousands, except share and per share amounts)

							(Unaudited)
	Year Ended December 31						Three Months Ended December 31
	2024			2023			2024			2023
Operating expenses:
Research and development	$	57,211		$	73,234		$	13,112		$	11,685
General and administrative		12,846			13,807			3,013			3,135
Total operating expenses		70,057			87,041			16,125			14,820
Loss from operations		(70,057	)		(87,041	)		(16,125	)		(14,820	)
Interest income		3,129			4,027			595			938
Australian research and development incentives		-			1,101			-			(23	)
Other income		-			500			-			500
Foreign currency gain (loss)		(42	)		(13	)		(24	)		940
Change in fair value of Series X preferred stock warrant liability		-			12			-			-
Loss before income taxes		(66,970	)		(81,414	)		(15,554	)		(12,465	)
Provision for (benefit from) income taxes		(585	)		-			123			-
Net loss		(67,555	)		(81,414	)		(15,431	)		(12,465	)
Dividend attributable to common stockholders		(234	)		-			-			-
Net loss attributable to common stockholders	$	(67,789	)	$	(81,414	)	$	(15,431	)	$	(12,465	)

Net loss per share
Basic and Diluted	$	(1.81	)	$	(3.98	)	$	(0.37	)	$	(0.46	)

Weighted average common shares outstanding
Basic and diluted		37,550,677			20,445,109			41,252,022			26,987,182

Leap Therapeutics, Inc

Consolidated Balance Sheet

Leap Therapeutics, Inc.

Consolidated Balance Sheets

(in thousands, except share and per share amounts)

	December 31,
	2024			2023
Assets
Current assets:
Cash and cash equivalents	$	47,249		$	70,643
Research and development incentive receivable		704			771
Prepaid expenses and other current assets		86			183
Total current assets		48,039			71,597

Property and equipment, net		-			5
Right of use assets, net		262			257
Deposits		823			966
Total assets	$	49,124		$	72,825
Liabilities and Stockholders' Equity
Current liabilities:
Accounts payable	$	4,743		$	6,465
Accrued expenses		8,536			5,957
Income tax payable		531			-
Lease liability - current portion		266			262
Total current liabilities		14,076			12,684

Stockholders' equity:
Preferred stock, $0.001 par value; 10,000,000 shares authorized; 0 shares issued and outstanding		-			-
Common stock, $0.001 par value; 240,000,000 shares authorized; 38,329,894 and 25,565,414 shares issued and outstanding as of December 31, 2024 and 2023, respectively		38			26
Additional paid-in capital		502,501			459,591
Accumulated other comprehensive (loss) income		(120	)		106
Accumulated deficit		(467,371	)		(399,582	)
Total stockholders’ equity		35,048			60,141
Total liabilities and stockholders' equity	$	49,124		$	72,825

Leap Therapeutics, Inc

Consolidated Statement of Cash Flows

Leap Therapeutics, Inc.

Condensed Consolidated Statements of Cash Flows

(in thousands)

							(Unaudited)
	Year Ended December 31,						Three Months Ended December 31,
	2024			2023			2024			2023
Cash used in operating activities	$	(60,299	)	$	(43,753	)	$	(15,512	)	$	(10,380	)
Cash provided by investing activities		-			48,969			-			-
Cash provided by (used in) financing activities		37,184			(30	)		104			-
Effect of exchange rate changes on cash and cash equivalents		(279	)		(43	)		(166	)		280
Net increase (decrease) in cash and cash equivalents	$	(23,394	)	$	5,143			(15,574	)		(10,100	)
Cash and cash equivalents at beginning of period		70,643			65,500			62,823			80,743
Cash and cash equivalents at end of period	$	47,249		$	70,643		$	47,249		$	70,643

EX-99.2 3 tm2510101d2_ex99-2.htm EXHIBIT 99.2

Exhibit 99.2

Leap Therapeutics Reports

Positive Updated Data from Sirexatamab Colorectal Cancer Study

Updated data confirms statistically significant 32% higher ORR and 3.5 month longer PFS

in second-line CRC patients with high DKK1 levels treated with sirexatamab plus bevacizumab and chemotherapy

Statistically significant 22% higher ORR and 2.6 month longer PFS

in patients who had not had prior anti-VEGF therapy

Leap to host a conference call to present clinical data today, March 26, 2025, at 8:00 a.m. ET

Cambridge, MA – March 26, 2025 – Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today presented updated preliminary data from Part B of the DeFianCe study (NCT05480306), a Phase 2, open-label, global study of sirexatamab (DKN-01), an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy (Experimental Arm) compared to bevacizumab and chemotherapy (Control Arm) in patients with advanced microsatellite stable (MSS) colorectal cancer (CRC) who have received one prior systemic therapy for advanced disease. The updated analysis includes overall response rate (ORR), by both investigator-assessment (IA) and blinded independent central review (BICR), an additional two months of patient follow-up for progression-free survival (PFS) that demonstrates a favorable maturation of the data, and initial overall survival (OS) data. As of March 12, 2025, 34 patients remain on study drug in the sirexatamab Experimental Arm compared to 24 patients in the Control Arm.

"The updated data from Part B of the DeFianCe study presented today confirms that sirexatamab can generate significantly higher ORR and longer PFS in CRC patients who have high levels of DKK1 or who have not had prior anti-VEGF therapy, two exploratory populations with strong scientific rationale. In the full intent-to-treat population, sirexatamab demonstrated a higher ORR and a tail population with longer PFS that continues to mature. With more sirexatamab-treated patients currently continuing on study drug than control arm patients, there is potential for the dataset to continue to strengthen over the coming months,” said Cynthia Sirard, MD, Chief Medical Officer of Leap. “We believe that there is a compelling opportunity to move forward with a registrational study for sirexatamab to confirm these results and bring a new therapy to patients with CRC.”

DeFianCe Study Update

In patients with high DKK1 levels (upper quartile, n=44), the sirexatamab Experimental Arm has a statistically significant 32% higher ORR, 3.5 month longer PFS, and OS compared to the Control Arm:

	Sirexatamab Experimental Arm (n=25)	Control Arm (n=19)
ORR by IA	48.0%	15.8%	p = 0.0067
ORR by BICR	40.0%	5.3%	p < 0.001
Median PFS	9.36 months	5.88 months	HR 0.46 95% CI: 0.21, 1.02 p = 0.0248
Median OS	Not Yet Reached	9.49 months	HR 0.09 95% CI: 0.01, 0.69 p = 0.0018
Patients on study drug	10	1

In patients who had not received prior anti-VEGF therapy (n=95), the sirexatamab Experimental Arm has a statisticially significant 22% higher ORR and 2.6 month longer PFS compared to the Control Arm, with OS not mature but favoring the sirexatamab Experimental Arm:

	Sirexatamab Experimental Arm (n=49)	Control Arm (n=46)
ORR by IA	55.1%	32.6%	p = 0.0116
ORR by BICR	44.9%	21.7%	p = 0.0066
Median PFS	10.94 months	8.34 months	HR 0.59 95% CI: 0.32, 1.07 p = 0.0386
Median OS	Not Yet Reached	Not Yet Reached	HR 0.22 95% CI: 0.03, 2.01 p = 0.0719
Patients on study drug	23	8

Across the intent-to-treat population (n=188), the sirexatamab Experimental Arm has improved ORR compared to the Control Arm, with the primary endpoint of PFS still to mature due to the higher number of patients remaining on sirexatamab driving separation after the median:

	Sirexatamab Experimental Arm (n=94)	Control Arm (n=94)
ORR by IA	36.2%	25.5%	p = 0.0536
ORR by BICR	33.0%	16.0%	p = 0.0023
Median PFS	7.82 months	8.31 months	HR 0.83 95% CI: 0.56, 1.24 p = 0.1809
Patients on study drug	34	24

The combination of sirexatamab plus bevacizumab and chemotherapy is well tolerated with a safety profile that is consistent with previous studies.

Leap has engaged a leading financial advisor to explore business development opportunities to further the development of sirexatamab.

Conference Call

About Leap Therapeutics

FORWARD-LOOKING STATEMENTS

CONTACT:

Douglas E. Onsi

President & Chief Executive Officer

Leap Therapeutics, Inc.

617-714-0360

donsi@leaptx.com

Matthew DeYoung

Investor Relations

Argot Partners

212-600-1902

leap@argotpartners.com

EX-99.3 4 tm2510101d2_ex99-3.htm EXHIBIT 99.3

Exhibit 99.3

company presentation LEAP THERAPEUTICS March 26, 2025

Forward looking statements 2 This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, future operations, clinical trials, collaborations and partnerships, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements within the meaning of U.S. securities laws. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. These and other risk factors are listed from time to time in reports filed with the Securities and Exchange Commission, including, but not limited to, our Annual Reports on Form 10-K and our Quarterly Reports on Form 10-Q. We assume no obligation to update any forward-looking statements, except as required by applicable law. This presentation does not constitute an offer to sell, or the solicitation of an offer to buy, any securities.

Developing biomarker-targeted antibody therapies for cancer patients 3 Lead program preparing for Phase 3 CRC clinical trials – sirexatamab (DKN-01) targeting DKK1 Statistically Significant ORR and PFS in 2L CRC patients with high DKK1 levels or are VEGF-naïve Biomarker strategy, focus on CRC $42.7M cash at December 31, 2024

Pipeline 4 Indication: Treatment: Preclinical Phase 1 Phase 2 Phase 3 sirexatamab (DKN-01) Anti-DKK1 antibody bevacizumab + chemotherapy Colorectal cancer FL-501 Anti-GDF-15 antibody

SIREXATAMAB (DKN-01) Anti-DKK1 monoclonal antibody

The role of DKK1 in cancer 6 Tumor CKAP4 Angiogenesis Akt PI3K Cancer cell Cancer cells DKK1 is produced and secreted by cancer cells, and functions on several tumor pathways and nearby immune cells. Enhances the suppressive activity of MDSCs and M2 macrophages. Reduces NK cell activity and T-cell infiltration. Promotes angiogenesis by increasing the number and size of blood vessels. Promotes activation of Akt by direct signaling through CKAP4 and PI3 kinase. Cancer cell DKK1

DKK1 production from multiple sources can drive tumor growth 7 Tumor DKK1 DKK1 Bone DKK1 high DKK1 low Blood vessel ELISA Enzyme-Linked Immunosorbent Assay DKK1 RNA from the tumor is measured by RNAscope DKK1 protein in circulation is measured by ELISA

Activity of sirexatamab (DKN-01) to treat cancer 8 CKAP4 Angiogenesis Akt PI3K Cancer cell Cancer cells Tumor Cancer cell DKK1 Sirexatamab (DKN-01) treatment neutralizes DKK1 and stimulates an immune mediated anti-tumor response. sirexatamab (DKN-01) Activates NK cells, reprograms macrophagesinto the tumor-attacking M1 subtype and promotes T cell infiltration. Reduces MDSCs and tumor suppressive M2 macrophages in the TME. Reduces angiogenesis and inhibits pro-oncogenic PI3K/AKT signaling.

SIREXATAMAB (DKN-01) Colorectal cancer development

Colorectal cancer background • Includes right colon (cecum, ascending and transverse colon) and left colon (descending colon, sigmoid, and rectum) • When symptoms appear, such as rectal bleeding, anemia, or abdominal pain, most patients already have advanced stage disease where cancers are aggressive and incurable • Third most frequent cancer globally and the second leading cause of cancer-related death • Globally, over 2,000,000 new cases and 1,000,000 deaths per year • In the US, estimated 155,000 cases and more than 50,000 deaths per year 10 Source: WHO, American Cancer Society

Bevacizumab benchmark studies demonstrate need for new options for today’s heterogeneous second-line patient population ML18147 409 5.4% E3200 286 22.7% SLAVE 228 25.7% Bevacizumab + Chemo Bevacizumab + Chemo Bevacizumab + Chemo* *SLAVE included N=198 left sided CRC patients. This subgroup has an ORR of 22.7% Bevacizumab-experienced Bevacizumab-naïve EGFR-experienced Treatment Study ORR Population PFS OS 11.2 5.7 7.3 7.1 12.9 16.2 Significant unmet needs in 2L patients 11

DeFianCe study design 12 Randomized phase 2 study of FOLFIRI/FOLFOX and bevacizumab +/- sirexatamab (DKN-01) as second-line treatment of advanced colorectal cancer Primary: PFS (Investigator assessed) Secondary: • ORR • OS Sirexatamab (DKN-01) + SOC chemotherapy (FOLFIRI or mFOLFOX6) + bevacizumab SOC chemotherapy (FOLFIRI or mFOLFOX6) + bevacizumab N=94 N=94 Key eligibility criteria: • One prior 5-FU based therapy for advanced colorectal adenocarcinoma • RECIST v1.1 measurable disease • MSS and absence of BRAFV600 mutation N=188* 1:1 Safety run in IA safety review Sirexatamab (DKN-01) + SOC + bevacizumab N=33 OBJECTIVES *Right-sided mCRC capped at 45 Key Exploratory Populations: – DKK1 biomarker high – VEGF-naive Data update as of March 12, 2025, representing nearly 6 months from last patient enrolled

DKK1 BIOMARKER POPULATION

32% higher response rate (48% vs 16%) with sirexatamab by Investigator Assessment DKK1-high subgroup – upper quartile 14 Response Sirexatamab Experimental N=25 Control N=19 n (%) n (%) CR 0 (0) 0 (0) PR 12 (48) 3 (16) ORR 95% CI 48% (27.8, 68.7) 16% (3.4, 39.6) p value p=0.0067 SD 11 (44) 12 (63) DCR 92% 79% PD 2 (8) 3 (16) No assessment 0 (0) 1 (5) On Study 10 1

32% higher response rate (48% vs 16%) with sirexatamab by Investigator Assessment DKK1-high subgroup – upper quartile 15 Response Sirexatamab Experimental N=25 Control N=19 n (%) n (%) CR 0 (0) 0 (0) PR 12 (48) 3 (16) ORR 95% CI 48% (27.8, 68.7) 16% (3.4, 39.6) p value p=0.0067 SD 11 (44) 12 (63) DCR 92% 79% PD 2 (8) 3 (16) No assessment 0 (0) 1 (5) On Study 10 1

35% higher response rate (40% vs 5%) with sirexatamab by BICR DKK1-high subgroup – upper quartile 16 Response Sirexatamab Experimental N=25 Control N=19 n (%) n (%) CR 1 (4) 0 (0) PR 9 (36) 1 (5) ORR 95% CI 40% (21.1, 61.3) 5% (0.1, 26.0) p value p<0.001 SD 11 (44) 10 (53) Non-CR / Non-PD 1 (4) 1 (5) DCR 88% 63% PD 2 (8) 4 (21) NE/NA 1 (4) 3 (16) On Study 10 1

3.5 month longer Progression-free Survival with sirexatamab DKK1-high subgroup – upper quartile 17 • Statistically significant improvement in PFS • Median: 9.36 vs. 5.88 m • HR 0.46 • p = 0.0248 • 10 Experimental Arm patients remain on study drug vs. 1 Control Arm

Sirexatamab significantly improved Overall Survival DKK1-high subgroup – upper quartile 18 • Statistically significant improvement in OS • 8 deaths Control Arm vs. 1 death Experimental Arm • Median: Not Yet Reached vs. 9.49 m • HR 0.09 • p = 0.0018

Sirexatamab statistically significant benefit across endpoints DKK1-high subgroup – upper quartile 19 Sirexatamab Experimental Arm (n=25) Control Arm (n=19) ORR by IA 48.0% 15.8% p = 0.0067 ORR by BICR 40.0% 5.3% p < 0.001 Median PFS 9.36 months 5.88 months HR 0.46 95% CI: 0.21, 1.02 p = 0.0248 Event-Free PFS 6 months: 9 months: 12 months: 68.9% 55.7% 33.4% 48.0% 24.7% 16.5% Median OS Not Yet Reached 9.49 months HR 0.09 95% CI: 0.01, 0.69 p = 0.0018 Patients on study drug 10 1

Sirexatamab statistically significant benefit across endpoints DKK1-high subgroup – upper median 20 Sirexatamab Experimental Arm (n=50) Control Arm (n=38) ORR by IA 40.0% 23.7% p = 0.0467 ORR by BICR 40.0% 10.5% p < 0.001 Median PFS 7.66 months 7.23 months HR 0.57 95% CI: 0.33, 0.99 p = 0.0218 Event-Free PFS 6 months: 9 months: 12 months: 71.7% 47.8% 33.5% 54.0% 28.5% 9.5% Median OS Not Yet Reached Not Yet Reached HR 0.32 95% CI: 0.1, 1.08 p = 0.0269 Patients on study drug 18 6

NO PRIOR ANTI-VEGF POPULATION

Sirexatamab improved ORR by 22% (55% vs. 33%) by Investigator Assessment No prior anti-VEGF subgroup 22 Sirexatamab Experimental N=49 Control N=46 Response n (%) n (%) CR 0 (0) 2 (4) PR 27 (55) 13 (28) ORR 95% CI 55% (40.2, 69.3) 33% (19.5, 48.0) p value p=0.0116 SD 19 (39) 24 (52) DCR 94% 85% PD 0 (0) 4 (9) No assessment 3 (6) 3 (7) On Study 23 8

Sirexatamab improved ORR by 22% (55% vs. 33%) by Investigator Assessment No prior anti-VEGF subgroup 23 Sirexatamab Experimental N=49 Control N=46 Response n (%) n (%) CR 0 (0) 2 (4) PR 27 (55) 13 (28) ORR 95% CI 55% (40.2, 69.3) 33% (19.5, 48.0) p value p=0.0116 SD 19 (39) 24 (52) DCR 94% 85% PD 0 (0) 4 (9) No assessment 3 (6) 3 (7) On Study 23 8

Sirexatamab doubled ORR 45% vs. 22% as assessed by BICR No prior anti-VEGF subgroup 24 Response Sirexatamab Experimental N=49 Control N=46 n (%) n (%) CR 0 (0) 2 (4) PR 22 (45) 8 (17) ORR 95% CI 45% (30.7, 59.8) 22% (11.0, 36.4) p value p=0.0066 SD 20 (41) 24 (52) Non-CR / Non-PD 2 (4) 1 (2) DCR 90% 76% PD 0 (0) 4 (9) NE/NA 5 (10) 7 (15) On Study 23 8

2.6 month longer Progression-free Survival with sirexatamab No prior anti-VEGF subgroup 25 • Statistically significant improvement in PFS • Median: 10.94 vs. 8.34 m • HR 0.59 • p = 0.0386 • 23 Experimental Arm patients remain on study drug vs. 8 Control Arm

Overall Survival No prior anti-VEGF subgroup 26 • Early advantage in OS with limited number of events • 4 deaths Control Arm vs. 1 death Experimental Arm • Median: Not Yet Reached vs. Not Yet Reached • HR 0.22 • p = 0.0719

Sirexatamab statistically significant benefit across endpoints No prior anti-VEGF subgroup 27 Sirexatamab Experimental Arm (n=49) Control Arm (n=46) ORR by IA 55.1% 32.6% p = 0.0116 ORR by BICR 44.9% 21.7% p = 0.0066 Median PFS 10.94 months 8.34 months HR 0.59 95% CI: 0.32, 1.07 p = 0.0386 Event-Free PFS 6 months: 9 months: 12 months: 79.7% 57.8% 40.9% 66.5% 46.2% 20.4% Median OS Not Yet Reached Not Yet Reached HR 0.22 95% CI: 0.03, 2.01 p = 0.0719 Patients on study drug 23 8

INTENT-TO-TREAT POPULATION

Sirexatamab improved ORR by 10% (36% vs. 26%) by Investigator Assessment Intent-to-Treat (ITT) population 29 Sirexatamab Experimental N=94 Control N=94 Response n (%) n (%) CR 0 (0) 2 (2) PR 34 (36) 22 (23) ORR 95% CI 36% (26.5, 46.7) 26% (17.0, 35.6) p value p=0.0536 SD 47 (50) 55 (59) DCR 86% 84% PD 6 (6) 7 (7) No assessment 7 (7) 8 (9) On Study 34 24

Sirexatamab improved ORR by 10% (36% vs. 26%) by Investigator Assessment Intent-to-Treat (ITT) population 30 Sirexatamab Experimental N= 94 Control N= 94 Response n (%) n (%) CR 0 (0) 2 (2) PR 34 (36) 22 (23) ORR 95% CI 36% (26.5, 46.7) 26% (17.0, 35.6) p value p=0.0536 SD 47 (50) 55 (58) DCR 86% 84% PD 6 (6) 7 (7) No assessment 7 (7) 8 (9) On Study 34 24

Sirexatamab improved ORR by 17% (33% vs. 16%) assessed by BICR Intent-to-Treat (ITT) population 31 Response Sirexatamab Experimental N=94 Control N=94 n (%) n (%) CR 1 (1) 2 (2) PR 30 (32) 13 (14) ORR 95% CI 33% (23.6, 43.4) 16% (9.2, 25.0) p value p=0.0023 SD 46 (49) 51 (54) Non-CR / Non-PD 2 (2) 4 (4) DCR 84% 74% PD 6 (6) 8 (9) NE/NA 9 (10) 16 (17) On Study 34 24

Tail population advantage in Progression-free Survival Intent-to-Treat (ITT) population 32 • Separation after the median indicates tail population showing advantage in PFS • Median: 7.82 vs. 8.31 m • HR 0.83 • p = 0.1809 • With 10 additional Experimental Arm patients on study drug compared to Control Arm (34 vs. 24), potential for PFS to improve with additional follow-up

Overall Survival Intent-to-Treat (ITT) population 33 • OS not mature due to limited number of events • 13 deaths Control Arm vs. 10 deaths Experimental Arm

Sirexatamab benefit across ORR endpoints, survival data still to mature Intent-to-Treat (ITT) population 34 Sirexatamab Experimental Arm (n=94) Control Arm (n=94) ORR by IA 36.2% 25.5% p = 0.0536 ORR by BICR 33.0% 16.0% p = 0.0023 Median PFS 7.82 months 8.31 months HR 0.83 95% CI: 0.56, 1.24 p = 0.1809 Event-Free PFS 6 months: 9 months: 12 months: 68.1% 49.3% 33.1% 68.2% 45.0% 21.1% Median OS Not Yet Reached Not Yet Reached Patients on study drug 34 24

MARKET OPPORTUNITY

Large potential colorectal cancer market opportunity Global Incidence and Deaths US: 155,000 patients and 53,000 deaths ROW: 1,900,000 patients and 910,000 deaths Second-Line Treated Patients US: 30,000 patients Largest 7 non-US markets: 160,000 patients First-Line Treated Patients for Advanced Disease US: 45,000 patients Largest 7 non-US markets: 265,000 patients ~5% ~10% ~25% ~50% EGFR inhibitor + Chemo RAS/BRAF wt Left Sided encorafenib + EGFR inhibitor + Chemo BRAF V600E HER2 agent combination HER2- amplified + RAS/BRAF wt Bevacizumab + Chemo Other ~10% MSI-H Checkpoint Inhibitor • DKK1 biomarker high = ~25% - ~50% • VEGF-naïve = ~50% Sources: American Cancer Society, World Health Organization, Company estimates 36

Potential Phase 3 Trial: 2nd Line Metastatic CRC 37 Primary Endpoint • BICR assessed Objective Response Rate (Accelerated Approval) • Overall Survival (Confirmatory Endpoint) Potential patient populations • DKK1-high • Anti-VEGF naïve Chemo + bev + placebo Patient Enrollment Chemo + bev + sirexatamab (DKN-01) Randomized 1:1 Trial Design: Global, randomized, 2-arm, placebo-controlled Phase 3 Patient Population: 2 nd Line metastatic CRC progressed on front-line therapy

Summary of preliminary results 38 • Statistically significant improvement in ORR, PFS, and OS in DKK1-high (upper quartile) patients and the DKK1-high (upper median) patients • Represent 25%-50% of the global 2L CRC market • Statistically significant improvement in ORR and PFS in VEGF-naïve patients, which is expected to represent ~50% of the global 2L market and suggests a future opportunity in 1L patients • ITT population trending positive on ORR with a tail population advantage after the median PFS that has the potential to improve with additional follow-up • Higher number of sirexatamab patients currently remaining on study drug, overall and in these important subgroups, provide potential for the data to continue to strengthen as follow-up continues • Sirexatamab has a large market opportunity in CRC patients with high medical need

FL-501 Anti-GDF-15 monoclonal antibody

GDF-15 Blood stream Stressed сells Cancer cachexia GDF-15 expression leads to an immuno-suppressive TME Heart failure Decline in renal function Hyperemesis gravidarum GFRAL GDF-15 Other GDF-15 related diseases Circulating GDF-15 triggers its effects by binding to its receptor (GFRAL) in the hindbrain Immuno-suppression in cancers GDF-15 expression leads to an immuno-suppressive TME Respiratory diseases The role of GDF-15 in cachexia and cancer 40

GDF-15 Blood stream Stressed сells Weight gain, normal appetite, improved muscle mass Cardioprotective effects Renoprotective effects Improved maternal health GFRAL Immuno stimulation in tumor microenvironment Pulmonary improvement FL-501 FL-501 mechanism of action 41

company presentation LEAP THERAPEUTICS March 26, 2025