IDEAYA Biosciences, Inc. (IDYA)

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations.

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, development and commercialization of transformative therapies for cancer. Our approach integrates expertise in small-molecule drug discovery, structural biology and bioinformatics with robust internal capabilities in identifying and validating translational biomarkers to develop tailored, potentially first-in-class targeted therapies aligned to the genetic drivers of disease. We have built a deep pipeline of product candidates focused on synthetic lethality and antibody-drug conjugates (ADCs), for molecularly defined solid tumor indications. Our clinical development strategy is to evaluate our product candidates in rational combinations, where appropriate, and earlier in the course of disease in the adjuvant and neoadjuvant setting, which we believe has the potential to maximize their impact. Our mission is to bring forth the next wave of precision oncology therapies that are more selective, more effective, and deeply personalized with the goal of altering the course of disease and improving clinical outcomes for patients with cancer.

Our current clinical pipeline of potential first-in-class product candidates spans four focus areas, as described below.

Darovasertib for Uveal Melanoma

Darovasertib is an oral, potent and selective small molecule inhibitor of protein kinase C and our most advanced clinical program. We are developing darovasertib for uveal melanoma (UM), a rare, aggressive form of ocular cancer, in both the metastatic and pre-metastatic settings of UM, as described below.

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Metastatic UM (mUM). We are evaluating darovasertib in combination with crizotinib, Pfizer’s oral c-MET inhibitor, in a potentially registration-enabling, Phase 2/3 trial (OptimUM-02) for human leukocyte antigen-A*02:01 negative (HLA*A2(-)), patients with first line mUM. In April 2026, we reported positive topline data from the OptimUM-02, which met its primary endpoint demonstrating as statistically significant improvement in median progression free survival as assessed by blinded independent central review. We presented complete data from the primary analysis of the OptimUM-02 trial in a late-breaking oral presentation at the 2026 American Society of Clinical Oncology meeting in Chicago, Illinois.

We plan to complete a new drug application (NDA) submission in the second half of 2026 to support a potential U.S. approval. Pursuant to Food and Drug Administration's (FDA) authorization, we have begun pre-submitting components of the NDA under the Oncology Center of Excellence Real-Time Oncology Review program (RTOR), which allows an applicant to pre-submit components of its NDA for review before the complete filing is submitted to provide a more efficient review process and ensure safe and effective treatments are available to patients as early as possible.

We are also evaluating the combination of darovasertib and crizotinib in HLA*A2:01 positive (HLA*A2(+)), mUM patients in our ongoing, single-arm Phase 2 OptimUM-01 trial. We plan to present updated clinical data from this trial at the 2026 European Society for Medical Oncology (ESMO) Congress being held in October in Madrid, Spain. These data will be included as part of our NDA submission to the FDA to support regulatory discussions that have the potential to expand the labeled indication of darovasertib. We also plan to publish data from OptimUM-01 for potential inclusion in clinical practice guidelines to support potential use of the combination in certain HLA*A2(+) mUM patients. Inclusion in the clinical practice guidelines, if achieved, is intended to provide healthcare professionals with an evidence-based rationale to consider use of darovasertib in appropriate patients, and may support payer coverage for such patients.

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Neoadjuvant UM. We are evaluating single-agent darovasertib in the neoadjuvant setting of primary UM, where the goal of treatment is to prevent enucleation (surgical eye removal), preserve vision prior to and post-plaque brachytherapy and potentially delay or prevent progression to metastatic disease. We plan to present updated clinical data at ESMO from the ongoing Phase 2 OptimUM-09 trial of neoadjuvant darovasertib. Based on ongoing patient recruitment considerations for the global Phase 3 OptimUM-10 trial we are assessing optimal capital allocation across our portfolio, including accelerating investment into other high-value programs. As part of this assessment, we are evaluating whether published data from the OptimUM-09 trial could provide a pathway for inclusion in clinical practice guidelines, supporting the use and payer coverage of darovasertib in the neoadjuvant setting of primary uveal melanoma. If successful, this approach has the potential to accelerate patient access while reducing the investment required to support clinical utility in this setting.

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Adjuvant UM. In collaboration with our partner, Servier, we have initiated a global Phase 3 registrational trial (OptimUM-11) of darovasertib and crizotinib in the adjuvant setting of primary UM. The trial is expected to enroll approximately 450 primary UM patients with increased risk of metastasis, irrespective of HLA status, randomized 1:1 to 12 months treatment with the combination or observation. The primary endpoint of the trial is relapse-free survival.

Antibody-Drug Conjugates / DNA Damage Response Combinations

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IDE849 is a potential first-in-class, DLL3 TOP1 ADC being evaluated by our partner, Hengrui Pharma, in a multi-site, open label Phase 1 clinical trial in China in patients with small-cell lung cancer (SCLC) and neuroendocrine carcinomas (NEC). Hengrui plans to provide a clinical data update from this trial at ESMO, and is targeting to initiate a Phase 3 registrational trial in China in refractory SCLC by the end of 2026. We are also conducting a global Phase 1/2 trial of IDE849 in SCLC and NEC and plan to provide our first clinical data from this trial in the second half of the year. We are also having discussions with the FDA to align on the design of a Phase 3 registrational trial of IDE849 in refractory SCLC and/or NEC, and plan to provide more detail on the proposed trial design with our data update in the second half of the year, with the goal of initiating the registrational trial by the end of 2026.

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IDE034 is a potential first-in-class, B7H3/PTK7 bispecific TOP1 ADC. We are currently conducting a Phase 1 dose escalation trial and are targeting to provide a clinical data update by the end of 2026 or early 2027. Dosing of the first patient with IDE034 in the first quarter of 2026 triggered a $5.0 million milestone payment to Biocytogen, pursuant to our Option and License Agreement.

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IDE161 is a potential first-in-class, oral small molecule poly (ADP-ribose) glycohydrolase (PARG) inhibitor in a Phase 1 dose optimization trial to inform combination studies with IDE849 and other TOP1-based ADCs where PARG inhibition may synergize with the payload to deepen responses. We are conducting a Phase 1 clinical combination trial of IDE161 with IDE849 in SCLC, NEC, and potentially other DLL3-overexpressing solid tumors. We may also evaluate clinical combinations of IDE161 with IDE034 (B7H3/PTK7) and potentially other TOP1 ADCs in collaboration with third parties.

Methylthioadenosine phosphorylase (MTAP) Deficiency

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IDE892 is a potential first-in-class, oral small molecule MTA-cooperative inhibitor of protein arginine methyltransferase 5 (PRMT5) being developed for patients with MTAP-deleted solid tumors. We are currently evaluating IDE892 both as a monotherapy and in combination with IDE397, our proprietary inhibitor of MAT2A, in Phase 1/2 dose escalation trials in MTAP-deleted cancers, with a focus on pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). In May 2026, we entered into a Clinical Supply Collaboration Agreement with Roche to evaluate IDE892 in combination with RG6505, Roche's Phase 1 pan-RAS inhibitor, in MTAP-deleted, RAS-mutant PDAC. We are targeting to begin a Phase 1 combination trial in the second half of 2026.

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IDE397 is a potential first-in-class, oral small molecule inhibitor of methionine adenosyltransferase 2a (MAT2A), which we are developing for patients with MTAP-deleted solid tumors. IDE397 is currently being evaluated in a Phase 1/2 combination cohort with IDE892 in MTAP-deleted cancers. Expansion is planned by the end of 2026 or early 2027, with an initial clinical focus on MTAP-deleted NSCLC. Dual inhibition of MAT2A and PRMT5 has demonstrated durable and well-tolerated tumor regressions in preclinical MTAP-deleted tumor models, including in NSCLC.

KAT6/7

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IDE574 is a potential first-in-class, oral small molecule equipotent dual inhibitor of the lysine acetyltransferase (KAT) 6 and 7, both of which have been shown to support cancer cell survival. We are currently conducting a Phase 1 dose escalation trial in patients with breast, lung, prostate and colorectal cancers.

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 under our former collaboration agreement with GSK and the upfront payment received from Servier under the Servier License Agreement. As of June 30, 2026, we had cash, cash equivalents and marketable securities of approximately $1.24 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. For information about our specific program costs and expenses, see Note 10. Significant Agreements and Note 13. Segment Information.

Our net losses were $211.0 million and $149.7 million for the six months ended June 30, 2026 and June 30, 2025, respectively. As of June 30, 2026, we had an accumulated deficit of $947.5 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, by 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 financi

[Excerpt truncated for page length; source filing is linked above.]

Overview

We are a precision medicine oncology company committed to the discovery, development and commercialization of transformative therapies for cancer. Our approach integrates expertise in small-molecule drug discovery, structural biology and bioinformatics with robust internal capabilities in identifying and validating translational biomarkers to develop tailored, potentially first-in-class targeted therapies aligned to the genetic drivers of disease. We have built a deep pipeline of product candidates focused on synthetic lethality and antibody-drug conjugates (ADCs), for molecularly defined solid tumor indications. Our clinical development strategy is to evaluate our product candidates in rational combinations, where appropriate, and earlier in the course of disease in the adjuvant and neoadjuvant settings, which we believe has the potential to maximize their impact. Our mission is to bring forth the next wave of precision oncology therapies that are more selective, more effective, and deeply personalized with the goal of altering the course of disease and improving clinical outcomes for patients with cancer.

Our current clinical pipeline consists of nine potential first-in-class product candidates across four clinical focus areas, as described below.

Darovasertib for Uveal Melanoma

Darovasertib is an oral, potent and selective small molecule inhibitor of protein kinase C (PKC) and our most advanced clinical program. We are developing darovasertib for uveal melanoma (UM), a rare, aggressive form of ocular cancer in both the metastatic and pre-metastatic settings of UM, as described below.

•
Metastatic UM (mUM). We are evaluating darovasertib in combination with crizotinib, Pfizer’s oral c-MET inhibitor, in a potentially registration-enabling, Phase 2/3 trial (OptimUM-02) for human leukocyte antigen-A*02:01 negative (HLA*A2(-)), patients with first line (1L) mUM. We expect to report topline data, including progression free survival (PFS) data, from this trial in the first quarter of 2026. The data from OptimUM-02 may enable an accelerated approval filing in the United States. In December 2025, we completed full enrollment of 437 patients in OptimUM-02, and plan to submit overall survival (OS) data from these patients, when available, to support a full approval filing in this indication.

We are also evaluating the combination of darovasertib and crizotinib in HLA*A2:01 positive (HLA*A2(+)), mUM patients in our ongoing, single-arm Phase 2 OptimUM-01 trial. We expect to complete enrollment of approximately 100 patients in this trial by the second quarter of 2026 with data used to support a potential future submission to the FDA to expand the labeled use for darovasertib and/or a national comprehensive cancer network (NCCN) compendia listing to enable use of the combination in these patients.

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Neoadjuvant UM. We are also evaluating darovasertib as a monotherapy in the neoadjuvant setting of primary UM, where the goal of treatment is to prevent enucleation (surgical eye removal), preserve vision prior to and post-plaque brachytherapy and potentially delay or prevent progression to metastatic disease. In 2025, we initiated a randomized Phase 3 trial of darovasertib in the neoadjuvant setting (OptimUM-10), which will enroll approximately 450 patients across two cohorts of plaque brachytherapy-eligible (PB) and enucleation-eligible (EN) patients. We plan to complete enrollment in this trial by the first half of 2027.

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Adjuvant UM. We plan to initiate a global Phase 3 combination trial (OptimUM-11) of darovasertib and crizotinib in the adjuvant setting of primary UM in the first half of 2026. The trial is expected to enroll approximately 450 patients with high to medium-high risk of metastasis, randomized 1:1 to the combination of darovasertib and crizotinib or placebo. The primary endpoint of this trial is relapse-free survival (RFS).

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In August 2025, we entered into an exclusive license agreement with Les Laboratoires Servier (Servier), for the development and commercialization of darovasertib outside of the United States. We received an upfront payment of $210.0 million and are eligible to receive up to $320.0 million in milestone payments, clinical trial cost sharing and clinical trial cost reimbursement, as well as double-digit royalties on net sales in all territories outside of the United States.

Antibody-Drug Conjugates (ADC) / DNA Damage Response (DDR) Combinations

•
IDE849 is a potential first-in-class, DLL3 TOP1 ADC being evaluated by our partner, Hengrui Pharma, in a multi-site, open label Phase 1 clinical trial in China in patients with small-cell lung cancer (SCLC) and neuroendocrine carcinomas (NEC). We are currently conducting a global Phase 1 trial of IDE849 in SCLC, with the goal of initiating a monotherapy registrational trial in the second line/refractory setting (2L+) of SCLC and/or NEC by the end of 2026.

•
IDE034 is a potential first-in-class, B7H3/PTK7 bispecific TOP1 ADC. We received investigational new drug (IND) clearance from the FDA in the fourth quarter of 2025 and expect to achieve first-patient-in (FPI) in our Phase 1 dose escalation trial in the first quarter of 2026. Dosing of the first patient with IDE034 will trigger a $5.0 million milestone payment to Biocytogen, pursuant to our Option and License Agreement.

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IDE161 is a potential first-in-class, oral small molecule poly (ADP-ribose) glycohydrolase (PARG) inhibitor in a Phase 1 dose optimization trial to inform future combination studies with IDE849 and other TOP1-based ADCs where PARG inhibition may synergize with the payload to deepen responses. We plan to initiate a Phase 1 clinical combination trial of IDE161 with IDE849 in SCLC, NEC, and potentially other DLL3-overexpressing solid tumors in the second quarter of 2026. We may also evaluate clinical combinations of IDE161 with IDE034 (B7H3/PTK7) and potentially other TOP1 ADCs in collaboration with third parties.

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IDE705 is a potential first-in-class, oral small molecule inhibitor of the helicase domain of Pol Theta that had been in a Phase 1 combination trial with niraparib, GSK’s small molecule inhibitor of PARP, in patients with BRCA+ or other HRD-positive tumors. In December 2025, GSK notified us of its intention to terminate the Agreement, which will be effective March 9, 2026. We plan to begin preclinical studies evaluating the potential of IDE705 to enhance the efficacy of TOP1 ADCs in solid tumors, as we are doing with IDE161, within our focus area of ADC/DDR combinations.

MTAP Pathway

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IDE397 is a potential first-in-class, oral small molecule inhibitor of methionine adenosyltransferase 2a (MAT2A), which we are developing for patients with solid tumors with methylthioadenosine phosphorylase (MTAP) gene deletion. We are conducting a Phase 1/2 clinical trial pursuant to a Clinical Study Collaboration and Supply Agreement (CSCSA) with Gilead to evaluate IDE397 in combination with Trodelvy (sacituzumab govitecan-hziy), Gilead’s Trop-2 directed TOP1 ADC, in patients with MTAP-deletion urothelial cancer (UC), and non-small cell lung cancer (NSCLC). We are targeting to provide the next clinical data update from the combination trial in UC at a medical conference in 2026.

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IDE892 is a potential first-in-class, oral small molecule MTA-cooperative inhibitor of PRMT5 being developed for patients with MTAP-deleted lung cancer and other high priority MTAP-deleted solid tumor indications. We expect to begin conducting a Phase 1 dose escalation trial with IDE892 monotherapy in the first quarter of 2026 with the goal of advancing into combination trials with IDE397 in MTAP-deleted NSCLC in the second quarter of 2026.

Next Generation Therapies

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IDE574 is a potential first-in-class, oral small molecule equipotent dual inhibitor of the lysine acetyltransferase (KAT) 6 and 7, both of which have been shown to support cancer cell survival. In January 2026, we received IND clearance from the FDA and are targeting to begin a Phase 1 dose escalation trial in patients with breast, lung, prostate and colorectal cancers in the first quarter of 2026.

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IDE275 is a potential first-in-class, oral small molecule inhibitor of the helicase domain of the Werner protein (WRN), a RecQ enzyme involved in the maintenance of genome integrity. In December 2025, GSK notified us of its intention to terminate the Agreement, which will be effective March 9, 2026. Once complete, we intend to continue the dose expansion phase of the Phase 1 trial to inform the next phase of clinical development.

Corporate Update

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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 and Servier. As of December 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. For information about our specific program costs and expenses, see Note 10. Significant Agreements.

Our net losses were $113.7 million and $274.5 million for the years ended December 31, 2025 and 2024, respectively. As of December 31, 2025, we had an accumulated deficit of $736.5 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 December 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 Annual Report on Form 10-K filed on February 17, 2026.

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 obtain regulatory approval and commercialize one of our product candidates in the future. Our revenue consists exclusively of collaboration revenue under the Servier License Agreement for the year ended December 31, 2025 and the GSK Collaboration Agreement for the year ended December 31, 2024, including amounts that are recognized related to previously received upfront payments, development and regulato

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