UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-Q

(Mark One)

For the quarterly period ended March 31, 2025

OR

For the transition period from to

Commission File Number: 001-38915

IDEAYA Biosciences, Inc.

(Exact name of registrant as specified in its charter)

(650) 443-6209

(telephone number, including area code)

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

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, 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.

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 ☒

As of May 2, 2025, the registrant had 87,581,963 shares of common stock, $0.0001 par value per share, outstanding.

NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Quarterly Report on Form 10-Q contains forward-looking statements. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements other than statements of historical facts contained in this Form 10-Q, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research and development costs, timing and likelihood of success, plans and objectives of management for future operations and future results of anticipated products, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements.

In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this Quarterly Report on Form 10-Q are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this Quarterly Report on Form 10-Q and are subject to a number of risks, uncertainties and assumptions described under the sections in this Quarterly Report on Form 10-Q entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in this Quarterly Report on Form 10-Q. These forward-looking statements are subject to numerous risks, including, without limitation, the following:

Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties.

Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not occur or be achieved, and actual results could differ materially from those projected in the forward-looking statements. We qualify all of our forward-looking statements by these cautionary statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

IDEAYA Biosciences, Inc.

Form 10-Q for Quarterly Period Ended March 31, 2025

Table of Contents

IDEAYA Biosciences, Inc.

(in thousands, except share and per share amounts)

(Unaudited)

The accompanying notes are an integral part of these condensed financial statements.

IDEAYA Biosciences, Inc.

(in thousands, except share and per share amounts)

(Unaudited)

The accompanying notes are an integral part of these condensed financial statements.

IDEAYA Biosciences, Inc.

(in thousands, except share amounts)

(Unaudited)

The accompanying notes are an integral part of these condensed financial statements.

IDEAYA Biosciences, Inc.

(in thousands)

(Unaudited)

The accompanying notes are an integral part of these condensed financial statements.

IDEAYA Biosciences, Inc.

Notes to Condensed Financial Statements (Unaudited)

The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q. Some of the information contained in this discussion and analysis or set forth elsewhere in this Quarterly Report on Form 10-Q, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this Quarterly Report on Form 10-Q, our actual results could differ materially from the results described, in or implied, by these forward-looking statements. Please also see the section of this Quarterly Report on Form 10-Q titled “Note Regarding Forward-Looking Statements.”

Overview

We are a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. Our approach integrates small molecule drug discovery with extensive capabilities in identifying and validating translational biomarkers to develop targeted therapies for select patient populations that are most likely to benefit from these targeted therapies. Our small molecule drug discovery expertise includes discovery and development of small molecule therapeutics. We are applying these capabilities and approach to develop a robust pipeline in precision medicine oncology.

Our clinical pipeline includes six potential first-in-class clinical-stage product candidates – darovasertib (PKC), IDE397 (MAT2A), IDE849 (DLL3), IDE275 / GSK959 (Werner Helicase), IDE161 (PARG), and IDE705 / GSK101 (Pol Theta Helicase). We own or control all commercial rights of three of these product candidates: darovasertib, IDE397, and IDE161, and own or control all commercial rights outside of greater China for IDE849. We are also advancing several development candidates, including IDE892, a potential best-in-class MTA-cooperative PRMT5 inhibitor for which we are targeting an investigational new drug, or IND, filing in mid-year 2025; IDE034, a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload bispecific antibody drug conjugate, or BsADC, program for which we are targeting an IND filing in the second half of 2025; and IDE574, a potential first-in-class KAT6/7 dual inhibitor program for which we are targeting an IND filing in the second half of 2025. We also have multiple earlier-stage preclinical programs. We have established selective, value-accretive collaborations with leading pharmaceutical companies to support our clinical development activities.

Darovasertib – PKC Inhibitor Clinical Candidate in Uveal Melanoma (UM)

Darovasertib (IDE196) is our most advanced clinical-stage product candidate, which we in-licensed from Novartis. Darovasertib is a potent, selective small molecule inhibitor of protein kinase C, or PKC, which we are developing for genetically defined cancers having GNAQ or GNA11 gene mutations. PKC is a protein kinase that functions downstream of the GTPases GNAQ and GNA11.

We have enrolled over 300 patients as of May 5, 2025, and have opened multiple clinical sites, including international sites, in our potential registration-enabling Phase 2/3 clinical trial, designated as IDE196-002. The purpose of the clinical trial is to evaluate darovasertib in combination with crizotinib, Pfizer’s investigational cMET inhibitor, in patients having metastatic uveal melanoma, or MUM, with human leukocyte antigen-, or HLA-A*02:01 negative, or HLA-A2(-), serotype, as part of a second Clinical Trial Collaboration and Supply Agreement, or the Second Pfizer Agreement, with Pfizer.

In December 2024, we announced the recommendation of a move-forward dose and the completion of the Part 2a dose optimization for the potential registration-enabling Phase 2/3 trial evaluating the combination of darovasertib and crizotinib in the first-line, or 1L, setting in patients with HLA-A2(-) MUM. We are continuing enrollment in Part 2b with the selected optimal dose.

We are targeting a median progression free survival, or PFS, readout for the Phase 2/3 registration-enabling trial of the darovasertib and crizotinib combination in 1L HLA-A2(-) MUM by year-end 2025.

We are enrolling additional HLA-A*02:01 positive, or HLA-A2(+), patients as an independent clinical strategy to address HLA-A2(+) MUM patients, in our ongoing Phase 2 clinical trial, designated as IDE196-001.

We are targeting a median overall survival, or OS, readout from our Phase 2 clinical trial, designated as IDE196-001, in over 40 1L MUM patients at a medical conference in the second half of 2025. The readout will include both 1L HLA-A2(-) and HLA-A2(+) MUM patients.

We are also supporting evaluation of darovasertib as single-agent neoadjuvant and adjuvant therapy in primary uveal melanoma, or UM, in an ongoing investigator-sponsored clinical trial, or IST, captioned as “Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma,” or NADOM, led by St. Vincent’s Hospital in Sydney with the participation of Alfred Health and the Royal Victorian Eye and Ear Hospital in Melbourne.

We enrolled 95 patients as of December 31, 2024 in our Phase 2 clinical trial, designated as IDE196-009, evaluating darovasertib as single-agent neoadjuvant and adjuvant therapy in patients having primary uveal melanoma, or UM, with ongoing enrollment and multiple clinical sites open. We are targeting two clinical data updates from this Phase 2 clinical trial to be presented at medical conferences in mid-2025 and the second half of 2025. The mid-2025 update will be focused on vision data and the plaque brachytherapy patients, and the update in the second half of 2025 is expected to include over 90 UM patients from both the enucleation and plaque brachytherapy eligible cohorts.

In September 2024, we announced interim clinical data from the ongoing Phase 2 Company-sponsored trial and provided a regulatory update on a potential Phase 3 registration-enabling clinical trial in neoadjuvant UM patients based on a Type C meeting held with the U.S. Food and Drug Administration, or FDA. In April 2025, we provided a further regulatory update on the potential Phase 3 registrational trial design for darovasertib in neoadjuvant UM patients based on a Type D meeting held with the FDA. Based on the Type D meeting, we currently project approximately 520 patients will be randomized 2:1 to receive darovasertib or control in two cohorts. The two cohorts include enucleation-eligible UM patients (n=120) and plaque brachytherapy, or PB,-eligible UM patients (n=400). Primary endpoints, which are supportive of full approval based on the FDA Type D Meeting, include eye preservation rate for enucleation patients and proportion of patients with best corrected visual acuity 15-letter loss from time of randomization and time of completion of PB for the PB cohort, with event-free survival (EFS) as a required secondary endpoint for both cohorts. Commencement of the Phase 3 registration-enabling trial for darovasertib in neoadjuvant UM is targeted for the first half of 2025.

In June 2024, we announced interim clinical data from the ongoing investigator-sponsored Phase 2 trial of darovasertib as neoadjuvant/adjuvant treatment in UM, which was included in an oral presentation at the American Society of Clinical Oncology, or ASCO, 2024 Annual Meeting, and preliminary clinical data from our Phase 2 trial of darovasertib for neoadjuvant UM.

ASCO Clinical Data from Investigator-Sponsored Phase 2 Trial

In our ongoing investigator-sponsored Phase 2 trial of darovasertib as neoadjuvant/adjuvant treatment in UM, 15 patients planned for enucleation with localized UM were treated twice daily with a 300 mg dose of darovasertib in the Phase 2 investigator-sponsored clinical trial as of May 14, 2024. An initial safety cohort of three patients was treated for one month, and the remaining 12 patients were treated in an expansion cohort for up to six months with darovasertib as neoadjuvant treatment prior to their primary intervention (enucleation, plaque brachytherapy or external beam radiotherapy, or EBRT) across three Australian centers. As of May 14, 2024, 13 patients had completed neoadjuvant darovasertib treatment, 11 patients received adjuvant darovasertib treatment after primary treatment of UM, with five patients completing the planned six months of therapy. As of May 14, 2024, 75% (nine out of 12 enucleation patients) had confirmed preservation of the eye, by conversion from planned enucleation to plaque brachytherapy or EBRT, and approximately 67% (eight out of 12 enucleation patients) observed greater than 30% tumor shrinkage (maximum tumor volume change) after six months. Median tumor shrinkage (maximum tumor volume change) in the 12 enucleation patients was approximately 47% after six months. The darovasertib monotherapy neoadjuvant treatment had a manageable adverse event, or AE, profile with no drug-related serious adverse events, or SAEs, observed in the investigator-sponsored Phase 2 trial. Drug-related AEs in the trial were predominantly Grade 1 or Grade 2, and 20% of patients reported at least one drug-related Grade 3 AE.

Company-Sponsored Phase 2 Trial

In September 2024, we provided a clinical data update in which we observed encouraging clinical activity in our Phase 2 Company-sponsored trial. Collectively with the IST trial, the clinical efficacy data from the Phase 2 Company-sponsored trial substantiate clinical proof of concept for the use of darovasertib in the neoadjuvant uveal melanoma setting. The Phase 2 Company-sponsored trial used a data cutoff date of August 15, 2024, with an enrollment cutoff date of May 13, 2024.

We evaluated 31 enucleation and 18 plaque brachytherapy UM patients who were treated with darovasertib neoadjuvant therapy in the Phase 2 Company-sponsored and IST trials. We observed approximately 59%, or 29 of the 49 total evaluable patients, with greater than or equal to 20% ocular tumor shrinkage by product of diameters and approximately 49%, or 24 of the 49 total evaluable patients, with greater than or equal to 30% ocular tumor shrinkage by product of diameters. We also observed an approximately 61% eye preservation rate in enucleation patients. We found evidence predicting visual preservation by reducing the amount of radiation associated with plaque brachytherapy. We observed a manageable AE profile from the Phase 2 Company-sponsored trial. In 38 patients, 11% of patients experienced a Grade 3 or higher AE and 5% of patients experienced a serious AE rate. We also observed a discontinuation rate of 3%. The most common AEs observed included diarrhea, nausea, vomiting and fatigue.

We are pursuing a clinical strategy for darovasertib to broadly address UM, alternatively referred to as ocular melanoma, in both primary and metastatic settings. Greater than 90% of UM patients have tumors harboring GNAQ or GNA11 mutations. There are no FDA-approved systemic therapies for primary UM as either neoadjuvant or adjuvant therapies. There are likewise no FDA-approved therapies for patients having MUM with HLA-A*02:01 negative, or HLA-A2(-), serotype. These primary UM patients and HLA-A2(-) MUM patients collectively represent approximately 85% of all ocular melanoma patients. We have a separate, independent clinical strategy to address HLA-A*02:01 positive, or HLA-A2(+), MUM patients.

The potentially addressable patient population for MUM is estimated to include an annual incidence of approximately 4,500 patients across the United States and Europe. (Neo)Adjuvant UM represents a significant expansion opportunity for darovasertib – with a potential annual incidence of approximately 12,000 patients aggregate in North America, Europe and Australia.

We own or control all commercial rights in our darovasertib program in UM, including in MUM and in primary UM, subject to certain economic obligations pursuant to our exclusive, worldwide license to darovasertib with Novartis.

Darovasertib – Potential Registration-Enabling Clinical Trial in First-Line HLA-A2(-) MUM

The protocol of the Phase 2/3 clinical trial design incorporates guidance and feedback following our Type C meeting with the FDA in March 2023. This protocol includes an integrated Phase 2/3 open-label study-in-study design in first-line MUM patients with an HLA-A2(-) serotype. The clinical trial design employs a Phase 2 portion with median progression free survival, or PFS, as a primary endpoint for potential accelerated approval. Patients enrolled in Phase 2 will continue on treatment within the same study and will be considered, together with additional enrolled patients, to evaluate OS as the primary endpoint of the Phase 3 confirmatory portion of the clinical trial to support a potential full approval.

In the Phase 2 portion of the clinical trial, approximately 260 patients will be randomized on a 2:1 basis for treatment with the darovasertib and crizotinib combination in the treatment arm or investigators choice in the control arm, selected from (a) a combination of ipilimumab (ipi) and nivolumab (nivo), (b) PD1-targeted monotherapy or (c) dacarbazine. The treatment arm of the Phase 2 portion of the clinical trial includes a nested study to confirm the move forward combination dose for the integrated Phase 2/3 clinical trial – including cohorts at the Phase 2 expansion doses of (i) darovasertib 300 mg BID + crizotinib 200 mg BID and (ii) darovasertib 200 mg BID + crizotinib 200 mg BID. Under the nested study design, patients enrolled in the cohort at the move forward dose will be included within the Phase 2/3 registrational clinical trial. The Phase 2 portion of the clinical trial contemplates an efficacy and safety data set of approximately 200 patients randomized 2:1 with the treatment arm at the move forward dose to support a potential accelerated approval based on median PFS by blinded independent central review, or BICR, as a primary endpoint. Accelerated approval is intended to allow for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a demonstration of effectiveness on a surrogate endpoint.

Patients enrolled in Phase 2 at the selected dose would continue on treatment and be included in the Phase 3 study analysis, supplemented by enrollment of approximately 120 additional patients into the Phase 3 portion of the clinical trial, with 2:1 randomization on the same basis as the Phase 2 portion. Efficacy data from the Phase 3 could support potential full approval using median OS as a primary endpoint.

In December 2024, we announced the recommendation of a move-forward dose and the completion of the Part 2a dose optimization for the potential registration-enabling Phase 2/3 trial evaluating the combination of darovasertib and crizotinib in the 1L setting in patients with HLA-A2(-) MUM. We are continuing enrollment in Part 2b with the selected optimal dose.

In May 2023, we expanded our relationship with Pfizer to support the Phase 2/3 registrational trial to evaluate darovasertib and crizotinib as a combination therapy in MUM by entering into Amendment No. 1 to the Second Pfizer Agreement. Under Amendment No. 1 to the Second Pfizer Agreement, Pfizer will provide us with a first defined quantity of crizotinib at no cost, as well as an additional second defined quantity of crizotinib at a lump-sum cost.

In December 2024, we entered into Amendment No. 5 to the Pfizer Agreement for the supply of crizotinib in the Phase 1/2 clinical trial for Pfizer to provide us a defined quantity of crizotinib at defined costs.

Prevalence of HLA-A2*02:01 Negative Serotype in MUM

Data from darovasertib clinical trials in MUM demonstrate that approximately 70% of MUM patients with known HLA-A*02:01, or HLA-A2 status were HLA-A2(-). As reported at ESMO 2023, the HLA-A2 status was known in subsets of patients enrolled in clinical trials evaluating darovasertib. Prevalence of HLA-A2(+) and HLA-A2(-) in MUM patients was determined from a first data set of n=149 MUM patients treated with darovasertib as monotherapy or in a combination arm of a clinical trial, and separately in a second data set of n=118 MUM patients treated with the darovasertib and crizotinib combination. These data include 102 of 149 (68%) of patients in the all-treatment subset and 81 of 118 (69%) patients in the darovasertib and crizotinib combination treatment subset.

Darovasertib – Strategy for HLA-A*02:01 Positive MUM

Based on clinical data from the Phase 2 clinical trial evaluating darovasertib and crizotinib in MUM as reported at ESMO 2023, and based on the darovasertib mechanism of action, we anticipate darovasertib will have clinical activity independent of HLA-A2 status in GNAQ/11-mutation cancers.

We are enrolling additional HLA-A2(+) MUM patients as an independent clinical strategy to address HLA-A2(+) MUM patients, in our ongoing Phase 2 clinical trial, designated as IDE196-001. This strategy demonstrates our commitment to fully address the high unmet medical need in MUM. Such clinical trial data from darovasertib and crizotinib combination treatment in HLA-A2(+) MUM could support publication and potential inclusion in NCCN Clinical Practice Guidelines in Oncology.

Darovasertib – Orphan Drug Designation in UM, Fast Track Designation in MUM and Breakthrough Therapy Designation in Neoadjuvant UM

In April 2022, the FDA designated darovasertib as an Orphan Drug in UM, including primary and metastatic disease. Under an Orphan Drug designation, darovasertib may be entitled to certain tax credits for qualifying clinical trial expenses, exemption from certain user fees and, subject to FDA approval of a New Drug Application, or NDA, for darovasertib in UM, eligibility for seven years of statutory marketing exclusivity during which the FDA is prohibited from approving a subsequent same drug for the same rare disease or condition except in limited circumstances, such as a subsequent drug that demonstrates clinical superiority. As an FDA-designated Orphan Drug, darovasertib may also be excluded from certain mandatory price negotiation provisions of the 2022 Inflation Reduction Act, if approved for a single indication only.

In November 2022, the FDA granted Fast Track designation to our development program investigating darovasertib in combination with crizotinib in adult patients being treated for MUM. The Fast Track designation makes our darovasertib and crizotinib development program eligible for various expedited regulatory review processes, including generally more frequent FDA interactions, such as meetings and written communications, potential eligibility for rolling review of a future NDA and potential accelerated approval and priority review of an NDA.

In March 2025, the FDA granted Breakthrough Therapy Designation, or BTD, for darovasertib for the neoadjuvant treatment of adult patients with primary UM for whom enucleation has been recommended. Under the license agreement with Novartis, we paid Novartis a $1.0 million milestone payment in April 2025. BTD is designed to expedite the development and regulatory review of promising therapies for serious or life-threatening conditions where preliminary clinical evidence suggests substantial improvement over existing treatments. The designation facilitates more intensive FDA guidance, cross-disciplinary collaboration, and eligibility for rolling submission and priority review.

Darovasertib – Phase 2 Trials in Neoadjuvant and Adjuvant Therapy in UM

We are clinically evaluating the potential for darovasertib as neoadjuvant or adjuvant therapy, or both, also referred to as (neo)adjuvant therapy, in primary, non-metastatic UM patients. We previously reported preliminary clinical data in the neoadjuvant setting showing evidence of anti-tumor activity that we believe supports further clinical evaluation of darovasertib to determine its potential as a neoadjuvant therapy to either save the eye by avoiding enucleation, or to reduce the tumor thickness in the eye, enabling treatment with less radiation to preserve vision, and as an adjuvant therapy, to potentially extend relapse free survival.

We enrolled 95 patients as of December 31, 2024 in our Phase 2 clinical trial, designated as IDE196-009, evaluating darovasertib as single-agent neoadjuvant and adjuvant therapy in patients having primary UM with ongoing enrollment and multiple clinical sites open. The purpose of the clinical trial is to evaluate single-agent darovasertib as neoadjuvant treatment of primary UM prior to primary interventional treatment of enucleation or radiation therapy and also as adjuvant therapy following the primary treatment. An amendment to the study protocol was submitted to the FDA in July 2024 to enable dosing of darovasertib therapy up to 12 months.

We are additionally supporting evaluation of darovasertib as (neo)adjuvant therapy in primary UM in the ongoing NADOM IST. Pursuant to an as-amended protocol for the NADOM study, UM patients who would otherwise undergo enucleation are instead treated with single agent darovasertib as neoadjuvant treatment for up to six months or maximum benefit. This reflects an increase in potential treatment duration versus the initial approach of one month neoadjuvant therapy, following which these patients will undergo a primary interventional treatment. Patients will subsequently be treated with darovasertib for up to six months as follow-up adjuvant therapy after the primary interventional treatment.

Darovasertib – Potential Registration-Enabling Clinical Trial in Neoadjuvant UM

A Type C meeting was held with the FDA in September 2024 and a Type D meeting was subsequently held in April 2025 for the clinical trial design of a potential Phase 3 registration-enabling clinical trial in neoadjuvant UM patients. For the potential Phase 3 clinical trial, we currently project approximately 520 patients will be randomized 2:1 for treatment with darovasertib in the treatment arm or the control arm. Based on the currently targeted clinical trial design, there will be two cohorts enrolled, including enucleation eligible UM patients and plaque brachytherapy eligible UM patients. For the enucleation cohort, the randomization will be with or without darovasertib as neoadjuvant therapy. For the plaque brachytherapy cohort, the randomization will be darovasertib followed by plaque brachytherapy versus plaque brachytherapy alone.

Based on guidance and information provided in the FDA Type D meeting, we expect that eye preservation rate (exceed lower bound of 10% eye preservation rate with a 95% confidence interval) will be the primary endpoint for enucleation UM patients. Proportion of patients with best corrected visual acuity 15-letter loss from time of randomization and time of completion of PB will be the primary endpoint for plaque brachytherapy UM patients. Vision detriment will be measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) of >15-letters lost. No detriment to Event-Free-Survival, or EFS, in the treatment arms will be a required secondary endpoint. No detriment is defined as overlapping confidence intervals.

Additional secondary endpoints include overall response rate (>20% ocular tumor shrinkage by product of diameters), proportion of patients with clinically significant macular edema, proportion of subjects with 20/200 vision loss or worse (legal blindness), and proportion of subjects with reduction of radiation dose of >20% delivered to key eye structures.

The registrational study will enroll UM patients with a high risk for metastatic disease. Patients with moderate to high risk for vision loss will also be enrolled in the plaque brachytherapy eligible UM cohort. Based on the FDA meeting, there is a potential for consideration of a broad indication label in neoadjuvant UM for subjects with low, intermediate and high risk for metastatic disease. We anticipate approximately 18 months of data maturity from the last patient enrolled to an initial readout for no detriment to EFS in the treatment arms. 300mg BID darovasertib will be the move-forward dose for the registrational trial. Commencement of the Phase 3 registration-enabling trial for darovasertib in neoadjuvant UM is targeted for the first half of 2025.

IDE397 – MAT2A Inhibitor in Tumors with MTAP Deletion

IDE397 is a clinical-stage, potent, selective small molecule inhibitor of methionine adenosyltransferase 2a, or MAT2A, which we are developing for patients having solid tumors with MTAP deletion. The prevalence of methylthioadenosine phosphorylase, or MTAP, gene deletion is estimated to be approximately 15% of human solid tumors. MTAP deletion in patient tumors is identified by commercial or institutional next generation sequencing, or NGS, panels or by MTAP immunohistochemistry, or IHC, assay with confirmation by NGS.

MTAP-null cells lack the ability to metabolize 5-methylthioadenosine, or MTA, which is an essential step in a biochemical pathway involved in salvaging the metabolite S-adenosyl methionine, or SAM. Increased levels of MTA partially inhibit the methyltransferase PRMT5 for which SAM is the methyl-donor substrate for methylation of various proteins. This partial inhibition of PRMT5 by increased levels of MTA renders MTAP-null cells more dependent on the activity of MAT2A, an enzyme that is responsible for the synthesis of SAM. Because of this enhanced dependence, loss of MTAP results in synthetic lethality when MAT2A is pharmacologically inhibited.

We have enrolled patients into a Phase 1/2 clinical trial, designated as IDE397-001, to evaluate IDE397 for patients having certain tumors with MTAP gene deletion, with an initial focus in MTAP-deletion urothelial cancer, or UC, and non-small cell lung cancer, or NSCLC. We are proceeding with enrollment of MTAP-deletion patients into a monotherapy Phase 1/2 expansion cohort with an initial focus on high priority solid tumor types, including UC and NSCLC. We have selected a move-forward Phase 2 expansion dose for IDE397 monotherapy, based on AE profile and preliminary clinical efficacy observed, including multiple partial responses by RECIST 1.1.

We own all right, title and interest in and to IDE397 and the MAT2A program, including all worldwide commercial rights thereto.

Company-Sponsored Phase 1/2 Monotherapy Expansion in MTAP-Deletion Urothelial and Lung Cancer

In July 2024, we announced clinical data for the IDE397 Phase 1/2 monotherapy expansion dose demonstrating preliminary clinical efficacy in heavily pre-treated MTAP-deletion UC and NSCLC patients. The patients evaluated had a median of two prior lines of therapy, ranging from one to seven prior lines of treatment. The reported Phase 1/2 clinical data were based on 18 evaluable MTAP-deletion patients, including seven UC patients, four adenocarcinoma squamous NSCLC patients, and seven squamous NSCLC patients at the expansion dose of 30 mg once-a-day, or QD, of IDE397. In the interim update for 18 evaluable patients, with a data analysis cutoff date of June 21, 2024, we reported an overall response rate of approximately 39% (one complete response and six partial responses by RECIST 1.1 evaluation), which included two unconfirmed partial responses (one UC patient that had a 100% tumor reduction in the target lesion at the last CT-scan assessment and one adenocarcinoma squamous NSCLC patient which were both confirmed in our October 2024 update). We also observed a disease control rate of 94%, including one complete response, six partial responses and 10 stable disease by RECIST 1.1 evaluation. In addition, we observed tumor shrinkage in 14 of the 18 evaluable patients. 11 of the evaluable patients are still on treatment and five of the seven responses by RECIST 1.1 evaluation remain in response. We also reported a ctDNA molecular response, or MR, rate of 81%, representing 13 of 16 reportable patients with 50% or greater ctDNA reduction (several quality control failures of patient samples precluded the other patients from MR analysis).

Regarding safety data, we also reported a favorable AE profile at the 30 mg QD expansion dose. Approximately 5.6% of patients experienced a Grade 3 or higher drug-related AE at the 30 mg QD dose, represented by one instance of Grade 3 asthenia, and no drug-related SAEs were observed. We observed no drug-related AEs leading to discontinuations, and one non-evaluable patient discontinued due to rapid clinical progression of cancer fatigue and drug-unrelated AEs in the first cycle of treatment. We anticipate that the favorable AE profile and dosing convenience of a 30 mg QD tablet has the potential to enable long-term dosing and combination development.

In October 2024, we announced Phase 1 expansion data for IDE397 in MTAP-deletion UC and NSCLC patients in a late breaker abstract oral presentation at the 36th edition of the EORTC-NCI-AACR Symposium, or ENA 2024, in Barcelona, Spain. The patients evaluated had a median of two to three prior lines of therapy, ranging from one to seven prior lines of treatment. The reported clinical data were based on 27 evaluable MTAP-deletion patients, including 10 UC patients, nine adenocarcinoma NSCLC patients, and eight squamous NSCLC patients at the expansion dose of 30 mg QD of IDE397. In the update of 27 evaluable patients, with a data analysis cutoff date of August 22, 2024, we reported an overall response rate of approximately 33% (one complete response and eight partial responses by RECIST 1.1 evaluation). Nine of nine responses were confirmed by RECIST 1.1, including four UC patients, of which one was a complete response, three squamous NSCLC patients, and two adenocarcinoma NSCLC patients. Two patients were confirmed after the data cutoff date. We also observed an overall response rate by RECIST 1.1 evaluation by solid tumor type. For MTAP-deletion UC patients, the confirmed overall response rate was 40%, or 4 out of 10 patients, for MTAP-deletion squamous NSCLC patients, the confirmed overall response rate was approximately 38%, or 3 out of 8 patients, and for MTAP-deletion adenocarcinoma NSCLC patients, the confirmed overall response rate was approximately 22%, or 2 out of 9 patients. In addition, we observed a disease control rate of 93%, including one complete response, eight partial responses and 16 stable disease by RECIST 1.1 evaluation, reflecting 25 of 27 evaluable patients with stable disease or better. Of the 27 evaluable patients, 15 are still on treatment. The median duration of treatment has not been reached and is greater than 6.2 months. The median time to response is approximately 2.7 months. The median duration of response and median progression free survival data is still immature. Three UC patients were on treatment greater than 250 days, four squamous NSCLC patients were on treatment greater than 200 days, and three adenocarcinoma NSCLC patients were on treatment greater than 200 days. We also reported a ctDNA MR rate of 81%, representing 17 of 21 reportable patients with 50% or greater ctDNA reduction and approximately 33%, representing 7 of 21 reportable patients, with a deep 90% or greater ctDNA reduction (several quality control failures of patient samples precluded the other patients from MR analysis). All 17 MRs were rapid occurring at the first ctDNA sample analysis.

We continued to report favorable AE profile at the 30 mg QD expansion dose. Approximately 18% of patients experienced a Grade 3 or higher drug-related AE at the 30 mg QD dose, and no drug-related SAEs were observed. No drug-related AEs leading to discontinuations were observed. We anticipate that the favorable AE profile and dosing convenience of a 30 mg QD tablet has the potential to enable long-term dosing and combination development, including with MTA-cooperative PRMT5 inhibitors and topoisomerase payload ADCs.

We are collaborating with Gilead Sciences, Inc., or Gilead, to clinically evaluate IDE397 in combination with Trodelvy (sacituzumab govitecan-hziy), Gilead’s Trop-2 directed antibody drug conjugate, or ADC, in patients having MTAP-deletion UC, in our Phase 1 clinical trial pursuant to a Clinical Study Collaboration and Supply Agreement, or CSCSA, with Gilead.

The first patient was dosed on the Phase 1 trial in June 2024. The Phase 1 clinical trial is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with Trodelvy in MTAP-deletion UC patients (NCT04794699). Pursuant to the Gilead CSCSA, we and Gilead retain the commercial rights to our respective compounds, including with respect to use as a monotherapy or combination agent. We are the study sponsor and Gilead will provide the supply of Trodelvy. IDE397 monotherapy or in combination with Trodelvy has not been approved by any regulatory agency, and the efficacy and safety of this combination has not been established.

In October 2024, we reported the first preliminary clinical case study of the IDE397 and Trodelvy combination in MTAP-deletion UC at ENA 2024, including a partial response by RECIST 1.1 in a patient case report with a genetic co-alteration of MTAP-deletion and a FGFR3-TACC3 fusion, and rapid and deep first-evaluation MRs with ctDNA reduction of greater than 95% observed. The partial response reported at ENA 2024 has confirmed by RECIST 1.1.

In February 2025, we expanded our clinical study collaboration with Gilead and entered into an additional CSCSA, or the Second Gilead CSCSA, to evaluate the IDE397 and Trodelvy combination in MTAP-deletion NSCLC.

In April 2025, we initiated Phase 1/2 expansion for IDE397 in combination with Trodelvy in MTAP-deletion UC based on preliminary safety and clinical efficacy data.

We were collaborating with Amgen to clinically evaluate IDE397 in combination with AMG 193, the Amgen investigational MTA-cooperative PRMT5 inhibitor, in patients having tumors with MTAP-deletion, in an Amgen-sponsored clinical trial pursuant to our Clinical Trial Collaboration and Supply Agreement with Amgen, or the Amgen CTCSA. In February 2025, we and Amgen mutually agreed to wind down the IDE397 and AMG 193 clinical combination study and will not pursue dose expansion.

In October 2024, we presented a preclinical poster presentation on the antitumor activity by combinatorial inhibition of MAT2A and PRMT5 in MTAP-deleted tumors at ENA 2024. We are targeting to enable our wholly-owned clinical combination of IDE397 and IDE892, our potential best-in-class MTA-cooperative PRMT5 inhibitor development candidate, in the second half of 2025 in MTAP-deletion NSCLC.

There are currently no FDA-approved therapies for patients with MTAP-deletion solid tumors, highlighting the unmet medical need. The priority MTAP-deletion solid tumor types for the IDE397 Phase 1/2 monotherapy program are UC and NSCLC. MTAP-deletion prevalence has been reported at over 15% in NSCLC and over 25% in UC, based on The Cancer Genome Atlas, or TCGA, database. We estimate that the MTAP-deletion annual incidence in the United States in NSCLC and UC is approximately 48,000 patients, based on the 2024 Surveillance, Epidemiology, and End Results database. In addition, there are several potential expansion MTAP-deletion solid tumor types that are also being considered for monotherapy and combination development, including pancreatic, head and neck, gastric, and squamous esophageal cancer, among others. Based on the TCGA database, MTAP-deletion prevalence in pancreatic, head and neck, gastric and squamous esophageal cancer represents an aggregate U.S. annual incidence of approximately 27,000 patients.

We own all rights, title, and interest in and to IDE397 and IDE892, including all worldwide commercial rights thereto.

IDE849 (DLL3) Program with Hengrui Pharma

In December 2024, we entered into an exclusive License Agreement, or the Hengrui Pharma License Agreement, with Jiangsu Hengrui Pharmaceuticals Co., Ltd., or Hengrui Pharma, pursuant to which Hengrui Pharma granted us an exclusive worldwide license outside of Greater China for IDE849 (SHR-4849), a potential first-in-class Phase 1 DLL3 TOP1i ADC. DLL3 has been reported to be expressed in multiple solid tumor types, including in small cell lung cancer, or SCLC, and Neuroendocrine Tumors, or NETs, at approximately 85% and 20-40%, respectively. DLL3 has limited extracellular expression in normal tissues, making it a promising therapeutic target in these tumor types, for which there remains significant unmet medical need.

IDE849 has shown promising antitumor activity in preclinical studies, including tumor regression as a monotherapy in multiple models. IDE849 is currently being evaluated by Hengrui Pharma in an ongoing Phase 1 trial in China in SCLC patients. In the ongoing Phase 1 dose escalation, IDE849 has reached therapeutic dose levels where multiple partial responses have been observed as of the data cutoff date of December 10, 2024. Among 11 evaluable SCLC subjects treated at therapeutic dose levels, 8 partial responses by RECIST 1.1 were observed, resulting in an overall response rate of ~73% (including both confirmed and unconfirmed responses, with all unconfirmed responses pending further evaluation). As of the data cutoff date, treatment related adverse events, or TRAEs were predominantly Grade 1 or 2. The Phase 1 dose escalation is ongoing with no reported drug-related discontinuations, and the maximum tolerated dose has not yet been reached. The most common TRAEs observed were white blood cell count decreased, anemia, neutrophil count decreased, nausea and platelet count decreased. In January 2025, Hengrui Pharma selected expansion doses for their Phase 1 trial. Clinical efficacy and safety data from over 40 SCLC patients in the multi-site open label Phase 1 trial, including the dose escalation and multiple expansion doses, is targeted to be presented at a medical conference in the third quarter of 2025.

In May 2025, we received U.S. IND clearance for the initiation of a Phase 1 clinical trial to evaluate IDE849 in solid tumors. We are targeting to evaluate IDE849 clinically in a multi-site global clinical trial as a monotherapy agent in SCLC and NETs and multiple DLL3 upregulated solid tumor types, and to evaluate IDE849 in a clinical combination with our potential first-in-class PARG inhibitor, IDE161, in the second half of 2025. Based on the FDA guidance, we will begin the Phase 1 study in the United States at a IDE849 starting dose that is equivalent to one of the expansion doses being evaluated in the ongoing Phase 1 study (NCT06443489) by partner Hengrui Pharma, where multiple confirmed partial responses have been observed by RECIST 1.1. We have also published preclinical data demonstrating IDE161 has combination synergy in-vitro and enhances the durability of TOP1-payload ADCs in preclinical in vivo models.

Under the terms of the Hengrui Pharma License Agreement, Hengrui Pharma is eligible to receive upfront and milestone payments totaling $1.045 billion, including a $75.0 million upfront fee, up to $200.0 million in development and regulatory milestone payments, plus commercial success-based milestones. Hengrui Pharma is also eligible to receive mid-single to low-double digit royalties on net sales outside of Greater China.

We own or control all commercial rights outside of greater China for IDE849.

IDE275 (GSK959) - WRN Inhibitor in Tumors with High Microsatellite Instability

We discovered IDE275 (GSK959), our Werner, or WRN, Helicase inhibitor clinical development candidate and evaluated IDE275 (GSK959) in preclinical studies in collaboration with GSK. IDE275 (GSK959) targets WRN for patients having tumors with MSI-High.

WRN protein is a RecQ enzyme involved in the maintenance of genome integrity. Germline loss of function mutations in WRN lead to premature aging and pre-disposition to cancer. Microsatellite instability is a change in the DNA content of a tumor cell in which the number of repeats of microsatellites, short repeated sequences of DNA, differ as cells divide. MSI-High is present in about 15% of gastrointestinal tumor cancers, including in approximately 22% of stomach adenocarcinoma and 16% of colorectal cancer. Tumors with MSI-High are routinely assessed in multiple diagnostic profiling tests.

WRN is a protein having several functional domains, and we have shown that the helicase functional domain of WRN is responsible for this synthetic lethal interaction, as reflected in our publication in Cell Press – iScience, Werner Syndrome Helicase is Required for the Survival of Cancer Cells with Microsatellite Instability (March 2019).

We, in collaboration with GSK, have demonstrated preclinical in vivo efficacy with tumor regression and PD response in a relevant MSI-High model. We have observed selectivity of our Werner Helicase inhibitor and validation of the synthetic lethal relationship to tumors with MSI-High over tumors with MSS based on a lack of in vivo pharmacological response in relevant MSS xenograft models.

We, in collaboration with GSK, received IND clearance for IDE275 (GSK959), a potential first-in-class WRN inhibitor, in October 2024 to enable first-in-human clinical evaluation of IDE275 (GSK959) for patients having tumors with MSI-High. GSK initiated a Phase 1/2 clinical trial for IDE275 (GSK959), following FDA allowance to proceed with the clinical trial. GSK will lead clinical development for the Werner Helicase program. GSK is responsible for 80% of global research and development costs, and we are responsible for 20% of such costs. GSK holds a global, exclusive license to develop and commercialize the Werner Helicase Inhibitor DC.

In April 2025, we, in collaboration with GSK, presented an oral presentation in the New Drugs on the Horizon series and three poster presentations at the American Association for Cancer Research, or AACR, 2025 Annual Meeting, on the potential best-in-class preclinical profile in the MSI-H setting for IDE275 (GSK959), with a unique binding mode from previously reported WRN inhibitors. A Trial in Progress poster for the ongoing SYLVER Phase 1/2 study (NCT06710847) was also presented at AACR 2025.

In October 2023, we achieved and earned a $3.0 million milestone in connection with IND-enabling studies. In October 2024, we earned a $7.0 million milestone payment for the IND clearance of IDE275 (GSK 959). We have the potential to earn up to an additional $10.0 million milestone payment upon initiation of Phase 1 clinical dose expansion.

We are also eligible to receive further aggregate late-stage development and regulatory milestones of up to $465.0 million. Upon commercialization, we will be eligible to receive commercial milestones of up to $475.0 million, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the Werner Helicase Inhibitor DC – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

IDE161 – PARG Inhibitor in Tumors with Homologous Recombination Deficiency

We are evaluating IDE161, a potential first-in-class small molecule poly (ADP-ribose) glycohydrolase, or PARG, inhibitor, in a Phase 1/2 clinical trial, designated as IDE161-001 for patients having tumors with homologous recombination deficiency, or HRD, and potentially other genetic and/or molecular signatures. PARG is a novel target in a clinically validated biological pathway. PARG functions as a regulator of DNA repair in the same biochemical pathway as poly-(ADP-ribose) polymerase, or PARP. PARG hydrolyzes PAR chains that are polymerized by PARP enzymes, completing the PAR cycle. Small molecule inhibitors of PARG result in a dose dependent increase in cellular PAR after DNA damage. PARG is a mechanistically distinct target relative to PARP.

We are progressing with enrollment of patients having tumors with HRD into the Phase 1 expansion portion of the Phase 1/2 clinical trial. We selected an initial Phase 1/2 monotherapy expansion dose for IDE161 in endometrial cancer, based on AE profile and preliminary efficacy observed. In parallel, we are also continuing with Phase 1 monotherapy dose optimization. Our clinical strategy focus for the IDE161 program is on enrollment for the combination with IDE849.

In September 2023, we received Fast Track Designation from the FDA for IDE161 for the treatment of adult patients having advanced or metastatic ovarian cancer with germline or somatic BRCA 1/2 mutations who are platinum resistant and have received prior antiangiogenic and PARP inhibitor therapies and for the treatment of adult patients having advanced or metastatic hormone receptor positive, or HR+, Her2- breast cancer with germline or somatic BRCA 1/2 mutations who have progressed following treatment with at least one line of a hormonal therapy, a CDK4/6 inhibitor therapy and a PARP inhibitor therapy.

Under each Fast Track designation, the IDE161 development program in BRCA1/2 mutant (m) breast and ovarian cancers is eligible for various expedited regulatory review processes, including generally more frequent FDA interactions (e.g., meetings, written communications), potential eligibility for rolling review, accelerated approval, and priority review of a future NDA.

In March 2024, we entered into a Clinical Trial Collaboration and Supply Agreement, or the Merck CTCSA, with Merck (known as MSD outside of the United States and Canada). We are evaluating IDE161 in combination with Merck's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with MSI-High, and microsatellite stable, or MSS, endometrial cancer. Under the Merck CTCSA, Merck will provide KEYTRUDA® to us, and we will sponsor the Phase 1 clinical combination trial.

In October 2024, we presented preclinical results on the IDE161 and ADC combination rationale as a poster at ENA 2024.

In December 2024, the first patient was dosed with IDE161 in combination with KEYTRUDA in the Company-sponsored Phase 1 clinical trial. The safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE161 in combination with KEYTRUDA is being evaluated as an arm in IDE161-001 (NCT05787587), a Company-sponsored Phase 1 trial of IDE161 in solid tumors.

In April 2025, we presented preclinical data on immune checkpoint inhibitor (ICI)-driven anti-tumor immunity at AACR 2025.

We are targeting to present preclinical combination mechanism and synergy efficacy data of IDE161 with TOP1-payload based ADCs at a medical conference in the third quarter of 2025.

We entered into an exclusive license under the Evaluation, Option and License Agreement with Cancer Research Technologies Ltd., also known as Cancer Research United Kingdom, or CRT, and the University of Manchester, pursuant to which we hold exclusive worldwide license rights covering a broad class of PARG inhibitors.

In April 2023, we incurred an obligation to pay milestone payments in an aggregate amount of £750,000 to CRT based upon the achievement of certain milestones relating to first and second tumor histologies in connection with the Phase 1 portion of the IDE161-001 Phase 1/2 clinical trial in oncologic diseases. We will be obligated to make additional payments to CRT aggregating up to £18.75 million upon the achievement of specific development and regulatory approval events for development of a PARG inhibitor in oncologic diseases, including an aggregate of up to £1.5 million and up to £2.25 million for the achievement of certain Phase 2 and Phase 3 development milestones, respectively, in each case as relating to first and second tumor histologies.

We own or control all commercial rights in our PARG program, subject to certain economic obligations pursuant to our exclusive, worldwide license to certain PARG inhibitors, including IDE161, with CRT and University of Manchester.

IDE705 (GSK101) – Pol Theta Helicase Inhibitor in tumors with Homologous Recombination Deficiency

We discovered IDE705 (GSK101), our DNA Polymerase Theta, or Pol Theta, Helicase inhibitor clinical development candidate, and evaluated IDE705(GSK101) in preclinical studies in collaboration with GSK. IDE705 (GSK101) targets the helicase domain of the Pol Theta protein for patients having solid tumors with BRCA or other mutations associated with HRD.

Pol Theta is involved in a DNA repair process called microhomology mediated end joining, or MMEJ, that is utilized when homologous recombination mediated repair is compromised, as happens in the case of certain BRCA1 or BRCA2 mutations. The expression of Pol Theta is largely absent in normal cells, but tumor cells harboring double strand break repair defects, such as BRCA1 or BRCA2 mutations, show higher Pol Theta expression and synthetic lethality when Pol Theta is inhibited. Pol Theta is a large protein with two functional domains: a DNA polymerase domain and an ATP-dependent DNA helicase domain, sometimes referred to as an ATPase domain, linked by a RAD51 central region.

GSK is evaluating IDE705 (GSK101) in combination with niraparib, the GSK small molecule inhibitor of PARP for the treatment of patients having tumors with BRCA or other HRD, in a GSK-sponsored Phase 1 clinical trial. GSK has dosed the first patient, and enrollment is ongoing in the dose escalation portion of this study.

GSK is leading clinical development of IDE705 (GSK101) pursuant to the Collaboration, Option and License Agreement with GSK, or GSK Collaboration Agreement. GSK is responsible for all research and development costs for the Pol Theta program.

In August 2023, we earned a $7.0 million payment for a milestone based on acceptance of the IND by the FDA. An earlier preclinical development $3.0 million milestone payment from GSK was achieved in August 2022 in connection with ongoing IND-enabling studies to support the evaluation of IDE705 (GSK101). We have the potential to receive an additional $10.0 million milestone payment upon initiation of Phase 1 clinical dose expansion.

We have the potential to earn further aggregate late-stage development and regulatory milestones of up to $465.0 million. Upon commercialization, we will be eligible to receive commercial milestones of up to $475.0 million, and tiered royalties on global net sales of GSK101 – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

IDE892 – MTA-cooperative PMRT5 inhibitor

In December 2024, we selected IDE892, a potential best-in-class MTA-cooperative PRMT5 inhibitor, as a development candidate. IDE892 was discovered through our iterative physics-based ligand design and optimization platform, and is a highly potent and selective MTA-cooperative PRMT5 inhibitor with best-in-class potential and favorable drug-like properties. IDE892 has demonstrated exceptionally selective antiproliferative activity in MTAP-deleted tumor cell models and durable complete responses in combination with MAT2A inhibitor IDE397 in challenging MTAP-deletion preclinical models.

IDE892 enables a wholly-owned clinical combination between the PRMT5 and MAT2A mechanisms and delivers potentially greater efficacy in MTAP-deletion solids tumors through this rational combination approach, including favorable potency, selectivity, and synergistic combination potential with MAT2A inhibitor IDE397.

Development of IDE892 is ongoing to support an IND filing to the FDA in mid-year 2025, subject to satisfactory completion of ongoing preclinical and IND-enabling studies.

In April 2025, we presented preclinical data providing insights into metabolite kinetics and PRMT5 dysregulation in MTAP-deficient cancers at AACR 2025.

We are also targeting to enable our wholly-owned clinical combination of IDE397 and IDE892 in the second half of 2025 in MTAP-deletion NSCLC.

IDE034 (B7H3/PTK7) program with Biocytogen

In July 2024, we entered into an Option and License Agreement, or the Biocytogen Option and License Agreement, with Biocytogen Pharmaceuticals (Beijing) Co., Ltd., (Biocytogen, HKEX: 02315), or Biocytogen, pursuant to which Biocytogen granted us an option for an exclusive worldwide license for a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program, or the Option. B7H3/PTK7 has been found to be co-expressed in multiple solid tumor types, including double-digit percent prevalence in lung, colorectal, and head and neck cancers, among others. Based on preclinical data, the potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program has the potential to be developed as a monotherapy agent and used in combination with multiple programs in our pipeline targeting DDR-based therapies, including our PARG inhibitor IDE161.

In November 2024, we announced the selection of IDE034, a potential first-in-class B7H3/PTK7 topo-I-payload BsADC, as a development candidate and the exercise of the Option. Under the terms of the Biocytogen Option and License Agreement, we paid Biocytogen an upfront fee and an exercise fee for the Option totaling $6.5 million.

We are targeting an IND submission to the FDA in the second half of 2025 for IDE034, subject to satisfactory completion of ongoing preclinical and IND-enabling studies.

Biocytogen is eligible to receive total potential upfront, option exercise and milestone payments equal an aggregate of $406.5 million, including development and regulatory milestone payments of up to $100.0 million. Our royalty obligations continue with respect to each country and each product until the later of (i) the date on which such product is no longer covered by certain intellectual property rights in such country and (ii) the 10th anniversary of the first commercial sale of such product in such country.

IDE574 - KAT6/7 inhibitor

Our development candidate IDE574, is a potential first-in-class KAT6/7 inhibitor which is an equipotent, highly selective, small molecule dual inhibitor of the lysine acetyltransferase (KAT) 6 and 7, both of which have been shown to support cancer cell survival. IND-enabling studies to support the potential clinical evaluation of IDE574 monotherapy in patients with breast and lung cancers with 8p11 amplification are ongoing, as well as additional opportunities in the setting of lineage addiction. Based on our biomarker evaluation, 8p11 amplification prevalence is projected to be approximately 15% in breast cancer and 17.5% in squamous NSCLC.

IDE574 selectively inhibits both KAT6 and KAT7 while sparing other structurally similar KAT molecules. KAT6 and KAT7 are mechanistically intertwined epigenetic modulators of cell identity and lineage commitment programs corrupted by oncogenic transformation. Dual KAT6/7 inhibition with IDE574 delivers robust and durable anti-tumor activity, superior to KAT6 inhibition alone, in preclinical tumor models with 8p11 amplifications, as well as in biomarker selected indications dependent upon lineage-specific transcription factor activity.

In April 2025, we presented preclinical data on dual inhibition’s impact on epigenetics and adaptive drug resistance at AACR 2025.

We are targeting an IND submission to the FDA in the second half of 2025 for IDE574, subject to satisfactory completion of ongoing preclinical and IND-enabling studies.

Next-Generation Precision Medicine Pipeline Programs

We have initiated early preclinical research programs focused on pharmacological inhibition of several new targets, or NTs, for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures. We believe these research programs have the potential for discovery and development of first-in-class or unique-in-class or best-in-class therapeutics. Collectively, we believe these efforts will further advance our multi-pronged clinical and business strategy. We own or control all commercial rights in our next-generation NT programs.

New Target and Biomarker Discovery Platform

Since the inception of the company, our core research has and continues to be focused on precision medicine oncology, with synthetic lethality as a central tenet. We have invested significantly and continue to invest in capabilities for identification and validation of new precision medicine targets and biomarkers for patient selection. These investments include both additional research personnel and capital investments, which will enhance our capabilities broadly, including in target validation, biological assay development, protein synthesis, structural biology, computational chemistry, and analytical chemistry, among other core functional areas. For targets of interest, we advance our research to discover therapeutic drugs and to further qualify relevant biomarkers.

Collaboration with ATTMOS

We are collaborating with ATTMOS to build a physics-based computational small molecule discovery platform that rapidly unlocks what are currently perceived as undruggable oncology targets. The focus of the partnership is to engineer and optimize a workflow solution for high-throughput absolute binding free energy perturbation predictions (ABFEP) of first-in-class drug candidate molecules. This approach enables application of gold-standard physics-based statistical mechanics calculations of protein-ligand affinities at the scale required for virtual screens and represents what could become the industry's go-to standard for high-speed and high probability-of-success drug hit-finding against structurally-enabled novel biological targets.

The collaboration leverages the Amber molecular dynamics suite as the GPU-accelerated back-end free energy simulation engine. We train and evaluate ABFEP-based active learning cycles based on extensive ground-truth data sets derived from its successful wet-lab drug discovery campaigns against novel targets. These models will be used to screen enormous libraries of synthetically tractable chemical space for accurate and efficient de novo discovery of small molecule ligands for new targets.

Precision Medicine Research Platform

We have established a robust precision medicine research platform with capabilities for identification and validation of new targets and biomarkers, drug discovery and translational biology. Our approach integrates small molecule drug discovery with extensive capabilities in identifying and validating translational biomarkers to develop targeted therapies for select patient populations that are most likely to benefit from these targeted therapies. Our small molecule drug discovery expertise includes discovery and development of small molecule therapeutics.

The drug discovery platform includes our proprietary chemical library, INQUIRE™, structure-based drug design enabled by extensive structural biology and crystallography capabilities with over 200,000 chemical compounds, and our proprietary content-based machine-learning engine, HARMONY™, providing effective and efficient molecular design and structure-activity-relationship, or SAR, cycles. We have deep research and development expertise in synthetic lethality – which represents an emerging class of precision medicine targets. We are applying these capabilities to develop a robust pipeline in precision medicine oncology.

DECIPHER™ Dual CRISPER Synthetic Lethality Library – UCSD

We have constructed our DECIPHER Dual CRISPR library for synthetic lethality target and biomarker discovery in collaboration with the University of California, San Diego, and bioinformatics analysis and validation are ongoing. The DECIPHER 1.0 library is focused on DNA Damage Repair targets across various tumor suppressor genes and oncogenes of interest that were selected based on their known prevalence and role in solid tumors, enabling evaluation of approximately 50,000 independent gene knockout combinations of DDR pathway related drug targets across known tumor suppressor genes.

PAGEO™ Paralogous Gene Evaluation in Ovarian Cancer and Dep Map Consortium – Broad Institute

We have an ongoing strategic collaboration with the Broad Institute focused on synthetic lethality target and biomarker discovery. This collaboration will use the large-scale CRISPR paralog screening platform developed at the laboratory of William R. Sellers, M.D., Core Institute Member, Broad Institute, to evaluate functionally redundant paralogous genes across ovarian cancer subtypes and to generate novel target and biomarker hypotheses. Dr. Sellers, who also serves on our Scientific Advisory Board, is the principal investigator for the strategic collaboration. We have also become a member of the Broad DepMap (Cancer Dependency Map) consortium led by the Broad Institute to further enhance our efforts in bioinformatics and cell-based screening for synthetic lethality target and biomarker discovery and validation.

Small and Medium Enterprise Status from the European Medicines Agency

In June 2024, we were granted Small and Medium Enterprise, or SME, status by the European Medicines Agency, or EMA. This enables us to have access to administrative, regulatory and financial support, including fee reductions for scientific advice and regulatory procedures across all our programs.

Prospectus Supplement - At-the-Market Facility

On January 19, 2024, we entered into a new Open Market Sales Agreement, or the January 2024 Sales Agreement, with Jefferies LLC, or Jefferies, relating to an at-the-market offering program under which we may offer and sell, from time to time at our sole discretion, shares of common stock, par value $0.0001 per share, or common stock, having aggregate gross proceeds of up to $350.0 million through Jefferies as sales agent.

During the three months ended March 31, 2025, we sold an aggregate 984,000 shares of our common stock for aggregate net proceeds of $25.0 million at a weighted average sales price of approximately $26.00 per share under the at-the-market offering pursuant to the January 2024 Sales Agreement with Jefferies as sales agent. As of March 31, 2025, approximately $156.6 million of common stock remained available to be sold pursuant to the January 2024 Sales Agreement.

We may cancel our at-the-market program at any time upon written notice, pursuant to its terms.

2024 July Public Offering and Sale of IDEAYA Common Stock

On July 11, 2024, we completed an underwritten public follow-on offering. The offering consisted of 8,355,714 shares of common stock at an offering price to the public of $35.00 per share, including 1,127,142 shares of common stock upon the exercise in full of the overallotment option by the underwriters, as well as pre-funded warrants to purchase 285,715 shares of common stock at a public offering price of $34.9999 per underlying share, in each case before underwriting discounts and commissions. Pursuant to the offering, we received aggregate gross proceeds of approximately $302.4 million, before deducting underwriting discounts and commissions and other offering expenses, resulting in net proceeds of approximately $283.8 million, after deducting underwriting discounts and commissions and other offering expenses.

Corporate Update

We do not have any products approved for sale and have not generated any product revenue since inception. We have funded our operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK. As of March 31, 2025, we had cash, cash equivalents and marketable securities of approximately $1.05 billion, consisting primarily of money market funds, U.S. government securities, commercial paper, and corporate bonds.

Since our inception in June 2015, we have devoted substantially all of our resources to discovering and developing our product candidates. We have incurred significant operating losses to date and expect that our operating expenses will increase significantly as we advance our product candidates through preclinical and clinical development; seek regulatory approval, and prepare for, and, if approved, proceed to commercialization; acquire, discover, validate and develop additional product candidates; obtain, maintain, protect and enforce our intellectual property portfolio; and hire additional personnel. Certain program costs that contribute to our operating expenses have been and/or will be reimbursed by GSK pursuant to the GSK Collaboration Agreement, including 100% of costs we incur for research we perform in connection with the Pol Theta program and 80% of the aggregate program costs incurred by us and GSK for research each of us performs for the Werner Helicase program. We also incur costs in accordance with the Gilead CSCSA and Second CSCSA. Gilead bears internal or external costs incurred in connection with its supply of Trodelvy. We bear all internal and external costs and expenses associated with the conduct of the combination study. We also incur costs in accordance with the Merck CTCSA. Merck provides KEYTRUDA for the study at no cost to us. We bear all internal and external costs and expenses associated with the conduct of the study. We also entered into two in-licensing agreements for ADCs with topoisomerase-I-inhibitor-payloads to enable combinations with our synthetic lethality programs with Hengrui Pharma for IDE849 and Biocytogen for IDE034. See Note 10. Significant Agreements.

Our net losses were $72.2 million and $39.6 million for the three months ended March 31, 2025 and March 31, 2024, respectively. As of March 31, 2025, we had an accumulated deficit of $695.0 million.

Our ability to generate product revenue will depend on the successful development, regulatory approval and eventual commercialization of one or more of our product candidates, ourselves, or for some programs, in collaboration with our strategic partners.

Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through the sale of equity, debt financings, or other capital sources, including potential collaborations with other companies or other strategic transactions. Adequate funding may not be available to us on acceptable terms, or at all. If we fail to raise capital or enter into such agreements as and when needed, we may have to significantly delay, scale back or discontinue the development and commercialization of our product candidates.

As of March 31, 2025, we had cash, cash equivalents and short-term and long-term marketable securities of approximately $1.05 billion.

We believe that our cash, cash equivalents, and short-term and long-term marketable securities will be sufficient to fund our planned operations for at least twelve months from the date of the issuance of our Quarterly Report on Form 10-Q filed May 6, 2025.

These funds will support our efforts through potential achievement of multiple preclinical and clinical milestones across multiple programs.

Components of Operating Results

Collaboration Revenues

To date, we have not generated any revenue from product sales, and we do not expect to generate any revenue from product sales unless and until we are able to initiate a registrational clinical trial, obtain regulatory approval and commercialize one of our product candidates in the future. Our revenue consists exclusively of collaboration revenue under the GSK Collaboration Agreement, including amounts that are recognized related to previously received upfront payments and amounts due and payable to us for research and development services. The amount of revenue recognized related to the GSK Collaboration Agreement, including as related to the previously received upfront payment or to certain development milestone payments, may vary considerably by period and certain components thereof may generally decrease year-over-year as we satisfy remaining performance obligations, for example, relating to the Pol Theta and WRN R&D Services. Since December 31, 2023, we have fully recognized the contract liabilities related to the upfront payment and reimbursements for the research and development performance obligations under the GSK Collaboration Agreement. There are no remaining contract liabilities as of March 31, 2025 as we concluded all the research and development performance obligations under the GSK Collaboration Agreement.

The future revenue recognition is contingent on additional milestones earned, profit sharing and royalties on any net product sales under our collaborations. We expect that any revenue we recognize or generate under the GSK Collaboration Agreement will fluctuate from period to period due to period to period variability in milestone payments and other payments.

Operating Expenses

Research and Development Expenses

Substantially all of our research and development expenses consist of expenses incurred in connection with the discovery and development of our product candidates. These expenses include certain payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expenses for our research and product development employees, fees to third parties to conduct certain research and development activities on our behalf including fees to CMOs and CROs in support of manufacturing and clinical activity for darovasertib, IDE397, IDE849, IDE275 / GSK959, IDE161, IDE705 / GSK 101, and consulting costs, costs for laboratory supplies, costs for product licenses and allocated overhead, including rent, equipment, depreciation, information technology costs and utilities. We expense both internal and external research and development expenses as they are incurred.

We have entered into various agreements with CMOs and CROs. Our research and development accruals are estimated based on the level of services performed, progress of the studies, including the phase or completion of events, and contracted costs. The estimated costs of research and development provided, but not yet invoiced, are included in accrued liabilities on the condensed balance sheet. If the actual timing of the performance of services or the level of effort varies from the original estimates, we will adjust the accrual accordingly. Payments made to CMOs and CROs under these arrangements in advance of the performance of the related services are recorded as prepaid expenses and other current assets until the services are rendered.

Costs of certain activities, such as preclinical studies, are generally recognized based on an evaluation of the progress to completion of specific tasks. Nonrefundable payments made prior to the receipt of goods or services that will be used or rendered for future research and development activities are deferred and capitalized as prepaid expenses and other current assets on our condensed balance sheet. The capitalized amounts are recognized as expense as the goods are delivered or the related services are performed.

We do not allocate our internal costs by product candidate, including internal costs, such as payroll and other personnel expenses, laboratory supplies and allocated overhead. With respect to internal costs, several of our departments support multiple product candidate research and development programs, and therefore the costs cannot be allocated to a particular product candidate or development program. The following table summarizes our external clinical development expenses by program:

We are focusing substantially all of our resources on the development of our product candidates. We expect our research and development expenses to increase substantially during the next few years, as we seek to initiate and/or advance clinical trials for our product candidates, complete our clinical program, pursue regulatory approval of our product candidates and prepare for a possible commercial launch. Predicting the timing or the cost to complete our clinical program or validation of our commercial manufacturing and supply processes is difficult and delays may occur because of many factors, including factors outside of our control. For example, if the FDA or other regulatory authorities were to require us to conduct clinical trials beyond those that we currently anticipate, or if we experience significant delays in enrollment in any of our clinical trials, we could be required to expend significant additional financial resources and time on the completion of clinical development. Furthermore, we are unable to predict when or if our product candidates will receive regulatory approval with any certainty.

General and Administrative Expenses

General and administrative expenses consist primarily of payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expense, professional fees for legal, patent, consulting, accounting and tax services, allocated overhead, including rent, equipment, depreciation, information technology costs and utilities, and other general operating expenses not otherwise classified as research and development expenses.

We anticipate that our general and administrative expenses will increase, as a result of increased personnel costs, including salaries, benefits and stock-based compensation expense, patent costs for our product candidates, expanded infrastructure and higher consulting, legal and accounting services associated with maintaining compliance with our Nasdaq stock exchange listing and requirements of the Securities and Exchange Commission, or the SEC, investor relations costs and director and officer insurance policy premiums associated with being a public company.

Other Income

Interest Income and Other Income, Net

Interest income and other income, net consists primarily of interest income earned on our cash, cash equivalents and marketable securities.

A discussion regarding our financial condition and results of operations for the three months ended March 31, 2025 compared to the three months ended December 31, 2024 and for the three months ended March 31, 2025 compared to the three months ended March 31, 2024 is presented below.

Comparison of Three Months Ended March 31, 2025 and December 31, 2024

The following table summarizes our results of operations for the periods indicated (in thousands):