10-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)

For the fiscal year ended December 31, 2022

For the transition period from to

Commission File Number 001-38915

IDEAYA Biosciences, Inc.

(Exact name of Registrant as specified in its Charter)

7000 Shoreline Court, Suite 350South San Francisco, California 94080

(Address of principal executive offices) (Zip Code)

Registrant’s telephone number, including area code: (650) 443-6209

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

Title of each class TradingSymbol(s) Name of each exchange on which registered

Common Stock, $0.0001 par value per share IDYA Nasdaq Global Select Market

Securities registered pursuant to Section 12(g) of the Act: None

Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes☐No☒

Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes☐No☒

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.

Large accelerated filer ☐ Accelerated filer ☐

Non-accelerated filer ☒ Smaller reporting company ☒

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐

Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes☐No☒

The aggregate market value of the voting and non-voting common equity held by non-affiliates of the Registrant, based on the closing price of the shares of common stock on The NASDAQ Stock Market on June 30, 2022, was $493.3 million. Shares of common stock held by each executive officer and director and by each other person who may be deemed to be an affiliate of the registrant, have been excluded from this computation. The determination of affiliate status for this purpose is not necessarily a conclusive determination for other purposes.

As of March 3, 2023, the registrant had 48,387,222 shares of common stock, $0.0001 par value per share, outstanding.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the registrant’s definitive Proxy Statement relating to the 2022 Annual Meeting of Stockholders are incorporated herein by reference in Part III of this Annual Report on Form 10-K to the extent stated herein. The proxy statement will be filed with the Securities and Exchange Commission within 120 days of the registrant’s fiscal year ended December 31, 2022.

TABLE OF CONTENTS

Page

PART I

Item 1. Business 1

Item 1A. Risk Factors 39

Item 1B. Unresolved Staff Comments 94

Item 2. Properties 94

Item 3. Legal Proceedings 94

Item 4. Mine Safety Disclosures 94

PART II

Item 6. Selected Financial Data 95

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 110

Item 8. Financial Statements and Supplementary Data 110

Item 9A. Controls and Procedures 111

Item 9B. Other Information 111

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 111

PART III

Item 10. Directors, Executive Officers and Corporate Governance 112

Item 11. Executive Compensation 112

Item 14. Principal Accounting Fees and Services 112

PART IV

Item 15. Exhibits, Financial Statement Schedules 113

NOTE REGARDINGFORWARD-LOOKING STATEMENTS

This Annual Report on Form 10-K 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 and Section 21E of the Securities Exchange Act of 1934. All statements other than statements of historical facts contained in this Form 10-K, 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 Annual Report on Form 10-K 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 Annual Report on Form 10-K and are subject to a number of risks, uncertainties and assumptions described under the sections in this Annual Report on Form 10-K entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in this Annual Report on Form 10-K. These forward-looking statements are subject to numerous risks, including, without limitation, the following:

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the scope, progress, results and costs of developing our product candidates or any other future product candidates, and conducting preclinical studies and clinical trials, including our IDE397 Phase 1 and IDE196 Phase 1/2 clinical trials;

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our clinical and regulatory development plans;

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the scope, progress, results and costs related to the research and development of our precision medicine target and biomarker discovery platform, including costs related to the development of our proprietary libraries and database of tumor genetic information and specific cancer-target dependency networks;

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our expectations about the impact of the COVID-19 pandemic on our business, and operations, including clinical trials, manufacturing suppliers and collaborators, and on our results of operations and financial condition;

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the availability of companion diagnostics for biomarkers associated with our product candidates and any future product candidates, or the cost of coordinating and/or collaborating with certain diagnostic companies for the manufacture and supply of companion diagnostics;

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the timing of and costs involved in obtaining and maintaining regulatory approval (or certification in certain foreign jurisdictions) for any of current or future product candidates and companion diagnostics, and any related restrictions, limitations, and/or warnings in the label of an approved product candidate;

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our expectations regarding the potential market size and size of the potential patient populations for IDE397, IDE196, our other product candidates and any future product candidates, if approved for commercial use;

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the timing and amount of any option exercised, milestone, royalty or other payments we may or may not receive pursuant to any current or future collaboration or license agreement, including under the Collaboration, Option and License Agreement with GSK;

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our ability to maintain existing, and establish new, strategic collaborations, licensing or other arrangements and the financial terms of any such agreements, including our Collaboration, Option and License Agreement with GSK, our Clinical Trial Collaboration and Supply Agreements with Pfizer Inc., our License Agreement with Novartis and our Option and License Agreement with Cancer Research United Kingdom, or CRUK, and University of Manchester;

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the timing of commencement of future nonclinical studies and clinical trials and research and development programs;

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our ability to acquire, discover, develop and advance product candidates into, and successfully complete, clinical trials;

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our intentions and our ability to establish collaborations and/or partnerships;

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the timing or likelihood of regulatory filings and approvals for our product candidates;

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our commercialization, marketing and manufacturing capabilities and expectations;

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our intentions with respect to the commercialization of our product candidates;

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the pricing and reimbursement of our product candidates, if approved;

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the implementation of our business model and strategic plans for our business, product candidates and technology platforms, including additional indications for which we may pursue;

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the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates, including the projected terms of patent protection;

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our potential involvement in lawsuits in connection with enforcing our intellectual property rights;

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our potential involvement in third party interference, opposition, derivation or similar proceedings with respect to our patent rights and other challenges to our patent rights and patent infringement claims;

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estimates of our expenses, future revenue, capital requirements, our needs for additional financing and our ability to obtain additional capital;

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our future financial performance; and

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developments and projections relating to our competitors and our industry, including competing therapies and procedures.

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.

Summary of Principal Risks Associated with Our Business

Our business is subject to numerous risks and uncertainties, including those described in Part I, Item 1A, “Risk Factors” in this Annual Report on Form 10-K. You should carefully consider these risks and uncertainties when investing in our securities. The principal risks and uncertainties affecting our business include the following:

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We are an early-stage biopharmaceutical company with a limited operating history and no products approved for commercial sale. We have incurred significant losses since our inception, and we anticipate that we will continue to incur significant losses for the foreseeable future, which, together with our limited operating history, makes it difficult to assess our future viability;

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We are very early in our development efforts. Our business is dependent on the successful development of our product candidates, future product candidates, and companion diagnostics for biomarkers associated with our product candidates and future product candidates;

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In connection with the Collaboration, Option and License Agreement with GSK, if GSK terminates any development program under its collaborations with us, whether as a result of our inability to meet milestones or otherwise, any potential revenue from those collaborations will be significantly reduced or eliminated, and our results of operations and financial condition will be materially and adversely affected;

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As an organization, we have never completed a clinical trial, and may be unable to do so for any of our product candidates;

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The successful development of targeted therapeutics, including therapeutics involving direct targeting of an oncogenic pathway and synthetic lethality therapeutics, including our portfolio of synthetic lethality small molecule inhibitors, as well as any related diagnostics, is highly uncertain;

iii

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Preclinical and clinical drug development is a lengthy and expensive process with an uncertain outcome. We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of any product candidates, which could result in increased costs to us, delay or limit our ability to generate revenue and adversely affect our business, financial condition, results of operations and prospects. Furthermore, results of earlier studies and trials may not be predictive of future trial results;

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We may find it difficult to enroll patients in our clinical trials given the limited number of patients who have the diseases for which our product candidates are being developed. If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected;

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If we are unable to successfully develop molecular diagnostics for biomarkers that enable patient selection and/or that demonstrate drug-target interaction, or experience significant delays in doing so, we may not realize the full commercial potential of our product candidates;

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We rely on third parties for the manufacture of our product candidates for preclinical and clinical development and expect to continue to do so for the foreseeable future. This reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or products or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts;

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We face significant competition in an environment of rapid technological and scientific change, and our failure to effectively compete may prevent us from achieving significant market penetration. Most of our competitors have significantly greater resources than we do and we may not be able to successfully compete;

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If we fail to attract and retain senior management and key scientific personnel, our business may be materially and adversely affected;

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The COVID-19 pandemic, or any other pandemic, epidemic or outbreak of an infectious disease may materially and adversely affect our business and operations, including the pace of enrollment in and conduct of current or future clinical trials;

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Our success depends on our ability to obtain and maintain protection for our intellectual property and our proprietary technologies, to successfully enforce our intellectual property rights and to avoid infringing the rights of others; and

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Our stock price has been and may continue to be volatile and you may not be able to resell shares of our common stock at or above the price you paid.

PART I

Item 1. Business.

Company Overview

We are a synthetic lethality-focused 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 most likely to benefit. We are applying these capabilities to develop a robust pipeline in precision medicine oncology, with a research and development focus in synthetic lethality—which represents an emerging class of precision medicine targets.

We believe synthetic lethality, as an emerging class of precision medicine, represents one of the most exciting, potentially impactful new areas of development in oncology, and we are investing a significant portion of our resources to become a leader in this emerging field. We are establishing a broad pipeline of clinical and preclinical programs directed to synthetic lethality targets. We are also investing in and enhancing our capabilities for identification and validation of new synthetic lethality targets. For targets of interest, we plan to discover therapeutic drugs and identify relevant biomarkers for patient selection.

Our clinical pipeline continues to mature – with three clinical-stage product candidates being evaluated in four active clinical trials. Our most advanced clinical program is evaluating darovasertib, or IDE196, a small molecule protein kinase C, or PKC, inhibitor, in combination with crizotinib, an investigational cMET inhibitor, in a Phase 2 clinical trial in patients having metastatic uveal melanoma, or MUM, and separately as a single-agent in a Phase 2 clinical trial as neoadjuvant and adjuvant therapy in patients having primary uveal melanoma, or UM. IDE397, our small molecule methionine adenosyltransferase 2a, or MAT2A, inhibitor, is being evaluated in Phase 2 clinical trial in monotherapy expansion and in selected combinations in Phase 1 dose escalation in patients having tumors with methylthioadenosine phosphorylase, or MTAP, gene deletion. IDE161, our small molecule poly (ADP-ribose) glycohydrolase, or PARG, inhibitor, is being evaluated in a Phase 1/2 clinical trial in patients having tumors with homologous recombination deficiency, or HRD.

Darovasertib is a clinical-stage PKC inhibitor that we are evaluating as a synthetic lethal combination therapy in patients having genetically-defined cancers having GNAQ or GNA11 gene mutations. Darovasertib, which we in-licensed from Novartis, is being clinically evaluated in a Phase 2 clinical trial designated as IDE196-001 in combination with Pfizer's investigational cMET inhibitor, crizotinib, in MUM, pursuant to our Clinical Trial Collaboration and Supply Agreement, or Pfizer Agreement, with Pfizer. Subject to U.S. Food and Drug Administration, or FDA, guidance, we plan to evaluate darovasertib and crizotinib as a combination therapy in MUM in a Phase 2/3 potentially registration-enabling clinical trial pursuant to a second Clinical Trial Collaboration and Supply Agreement, or the Second Pfizer Agreement.

We are also evaluating darovasertib as a single agent in a separate Phase 2 clinical trial as neoadjuvant and adjuvant therapy in primary UM. This clinical trial, designated as IDE196-009, includes a first cohort of UM patients with large tumors who would, without neoadjuvant treatment, otherwise undergo enucleation as a primary interventional treatment, and a second cohort of UM patients with small or medium tumors who would otherwise undergo radiation therapy, such as plaque brachytherapy. Each of these neoadjuvant cohorts will be treated with darovasertib prior to a primary interventional treatment until maximum benefit or six months, at which time they will undergo a primary interventional treatment, and will subsequently be treated with darovasertib for up to an additional six months as follow-up adjuvant therapy.

We own or control all commercial rights in our darovasertib program, including in MUM and UM.

IDE397 is a MAT2A inhibitor for patients with solid tumors having MTAP deletions – a patient population estimated to represent approximately 15% of solid tumors. We are enrolling patients into a Phase 1/2 clinical trial designated as IDE397-001 to evaluate IDE397 as monotherapy in patients having certain tumors with MTAP gene deletion with an initial primary focus on non-small cell lung cancer, or NSCLC, esophagogastric cancer, and bladder cancer. We have initiated combination dose escalation cohorts for combinations of IDE397 with chemotherapy agents, including pemetrexed and taxanes.

We are also planning to evaluate IDE397 in combination with AMG 193, the Amgen investigational methylthioadenosine-, or MTA-cooperative protein arginine methyltransferase 5, or PRMT5, inhibitor, in patients having tumors with MTAP deletion, in an Amgen-sponsored clinical trial pursuant to a Clinical Trial Collaboration and Supply Agreement, or Amgen CTCSA, with Amgen Inc., or Amgen. We are prioritizing the IDE397 / AMG 193 clinical combination and, at this time are discontinuing enrollment into the IDE397-001 clinical trial cohorts evaluating chemotherapy combinations. We own or control all commercial rights in our MAT2A program. This approach is based on favorable preclinical combination efficacy

and tolerability data observed with the IDE397 / AMG 193 combination, and on the proposed target enrollment and budget for the planned global clinical trial pursuant to the Amgen CTCSA.

IDE161 is a clinical-stage, potent and selective small molecule inhibitor of PARG for patients having tumors with defined biomarkers based on genetic mutations and/or molecular signatures, with an initial focus on patients with HRD. PARG represents a novel and differentiated target in the same clinically validated pathway as poly (ADP-ribose) polymerase, or PARP. We are evaluating IDE161 in a Phase 1/2 clinical trial designated as IDE161-001 to determine the safety, tolerability, pharmacokinetic, or PK, and pharmacodynamic, or PD, properties and preliminary efficacy of IDE161 as monotherapy in patients having tumors with HRD, such as BRCA1/2-mutant breast and ovarian cancer patients. A clinical focus will include an expansion cohort of breast cancer patients having tumors with HRD which are estrogen receptor positive, or ER+, and human epidermal growth factor receptor 2 negative, or Her2-. We will also evaluate an expansion cohort of ovarian cancer patients with HRD, and a basket expansion cohort of patients having other solid tumors with HRD. We own or control all commercial rights in our PARG program.

In addition, we also have several preclinical research programs advancing toward the clinic. We have preclinical programs for a small molecule inhibitor targeting DNA Polymerase Theta, or Pol Theta or POLQ, in collaboration with GlaxoSmithKline, or GSK, for solid tumors with HRD including BRCA mutations. We also have a preclinical program for a small molecule inhibitor targeting Werner Helicase, or WRN, in collaboration with GSK, in tumors with high microsatellite instability, or MSI high. Additionally, we have multiple wholly-owned early preclinical research programs directed toward next-generation synthetic lethality targets, in each case for patients with solid tumors characterized by a proprietary biomarker or a gene signature.

We have assembled a team of cancer biologists, drug discovery chemists, translational biologists and drug development professionals with broad experience at leading oncology organizations. Our team is led by our Chief Executive Officer, Yujiro S Hata. We are also guided by a renowned scientific advisory board made up of key scientific and clinical thought leaders.

Strategy

Our objective is to develop and commercialize innovative precision medicine drugs that indirectly or directly target the genetic drivers of cancer in order to provide therapies for defined patient populations. The principal components of our strategy are to:

Continue to efficiently develop our clinical-stage product candidates, darovasertib, an orally available small molecule inhibitor of PKC, IDE397, an orally available small molecule inhibitor of MAT2A, and IDE161, an orally available small molecule inhibitor of PARG. We are currently conducting a Phase 2 trial evaluating darovasertib as a combination therapy with crizotinib in patients with MUM, a population in which greater than 90% of patients have tumors harboring GNAQ or GNA11 mutations. We are also conducting a company-sponsored Phase 2 clinical trial and, separately, supporting an investigator-sponsored clinical trial, or IST, in each case to evaluate darovasertib in neoadjuvant and adjuvant primary UM. We are currently evaluating IDE397 in a Phase 2 monotherapy dose expansion cohort in patients with tumors having MTAP-deletion. We have received FDA authorization of our Investigational New Drug Application, or IND, and are preparing to initiate dosing of a first patient in a Phase 1/2 clinical study to evaluate IDE161 in solid tumors, including tumors having HRD.

Advance our preclinical pipeline of small molecule product candidates in synthetic lethality into clinical development. Our synthetic lethality pipeline includes multiple preclinical research programs, including our Pol Theta Helicase and Werner Helicase programs. We are, in collaboration with GSK, planning to submit an IND to the U.S. FDA to support a GSK-sponsored Phase 1/2 first-in-human clinical evaluation of our Pol Theta Helicase inhibitor development candidate, or DC, in combination with niraparib for patients having tumors with HRD. We are also planning, in collaboration with GSK, identification of a Werner Helicase development candidate. We are also continuing to invest in our earlier, broader portfolio of synthetic lethality programs, including certain identified next-generation synthetic lethality programs.

Broaden our pipeline of targeted therapies and apply our core capabilities to establish a leading franchise in the field of synthetic lethality. We are continuing our target identification and validation activities for advancing new synthetic lethality targets and associated biomarkers, with active programs for several next-generation synthetic lethality targets. We continue to invest in core functional capabilities, including in drug discovery, bioinformatics and translational biology.

Collaborate with leaders in the field of diagnostics to enable the identification of defined patient populations for our product candidates. Our precision medicine approach leverages the availability or development of companion diagnostics to identify patients for which our product candidates will be most effective.

Collaborate under our existing strategic partnerships and identify additional strategic collaborations to accelerate development timelines and maximize the commercial potential of our targeted product candidates. We have entered into the Pfizer Agreements for evaluation of the darovasertib in combination with crizotinib in MUM. We entered into the Amgen CTCSA to clinically evaluate IDE397 in combination with AMG 193, the Amgen investigational MTA-cooperative PRMT5 inhibitor, in patients having MTAP-deletion solid tumors. We have entered into a strategic partnership and collaboration with GSK for our synthetic lethality programs targeting Pol Theta and Werner Helicase pursuant to the Collaboration, Option and License Agreement with GSK, or GSK Collaboration Agreement. We will selectively evaluate strategic collaborations for our targeted product candidates with biopharmaceutical partners whose research, development, commercial, marketing, and geographic capabilities complement our own.

Pipeline – Overview and Program Goals

We are applying our capabilities and approach to develop a portfolio of targeted therapeutics for defined patient populations, with a focus in synthetic lethality.

(1)Pursuant to Pfizer Agreements

(2)Pursuant to Amgen CTCSA

(3)Pursuant to Cancer Research UK/Manchester Agreement

(4)Pursuant to GSK Collaboration, Option and License Agreement

Our precision medicine pipeline currently includes three clinical-stage assets, darovasertib, IDE397 and IDE161. Darovasertib is a PKC inhibitor being evaluated in combination with crizotinib, an investigational cMET inhibitor, in a Phase 2 clinical trial in MUM. Darovasertib is being separately evaluated as a single-agent neoadjuvant and adjuvant therapy in a Phase 2 clinical trial in primary UM. IDE397 is a MAT2A inhibitor being evaluated in a monotherapy Phase 2 dose expansion cohort in patients with solid tumors having MTAP deletion. IDE161 is a PARG inhibitor being evaluated in a Phase 1/2 clinical trial in patients having solid tumors, including tumors having HRD. We wholly own or control all commercial rights in and to each of these three clinical programs, including darovasertib, IDE397 and IDE161.

Our pipeline also includes preclinical research programs directed to synthetic lethality targets Pol Theta, Werner Helicase, and other next-generation synthetic lethality targets, the profiles of which are summarized below.

All data and the status of each program are as of March 1, 2023, unless otherwise noted.

Darovasertib (GNAQ or GNA11 Mutations)

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We are evaluating darovasertib, a clinical stage PKC inhibitor, in our ongoing late Phase 2 clinical trial designated as IDE196-001 as a combination therapy with Pfizer’s investigational cMET inhibitor, crizotinib, in patients with MUM, a population in which greater than 90% of patients have tumors harboring GNAQ or GNA11 mutations.

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Subject to FDA feedback following our scheduled meeting in the first quarter of 2023, we plan to initiate a potentially registration-enabling Phase 2/3 clinical trial to evaluate darovasertib and crizotinib as a combination therapy in MUM pursuant to the Second Pfizer Agreement.

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We are planning to present a summary of the potentially registration-enabling Phase 2/3 clinical trial design reflecting FDA guidance, if any, following our scheduled meeting with the FDA.

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We are increasing enrollment to include additional first-line, or 1L, patients in the ongoing Phase 2 clinical trial evaluating darovasertib in combination with crizotinib in MUM.

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We are planning to present a clinical data update, including clinical efficacy (e.g., overall response rate, or ORR, median progression free survival, or PFS) in approximately 20 1L patients, from this ongoing Phase 2 clinical trial in mid-year, or the second or third quarter of, 2023. The timing of such clinical data update may be influenced by data maturity, including for example, appropriate interim assessments of median duration of response, or DOR, median PFS, and/or median overall survival, or OS.

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We are also evaluating darovasertib as a single agent in a company-sponsored Phase 2 clinical trial designated as IDE196-009 as neoadjuvant and adjuvant therapy in primary UM. We are separately supporting evaluation of darovasertib as (neo)adjuvant therapy in primary UM in an ongoing IST captioned as “Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma” (NADOM) led by St. Vincent’s Hospital in Sydney with participation of Alfred Health and the Royal Victorian Eye and Ear Hospital in Melbourne.

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We are planning to present additional interim clinical data in 2023 from the IST evaluating darovasertib as neoadjuvant therapy in UM as further preliminary clinical proof-of-concept in neoadjuvant UM.

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

IDE397 (MTAP Gene Deletion)

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We are developing our synthetic lethality product candidate, IDE397, a clinical stage MAT2A inhibitor, for patients having solid tumors with MTAP deletions, which represents approximately 15% of all solid tumors.

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We have initiated a Phase 1/2 clinical trial designated as IDE397-001 to evaluate IDE397 in monotherapy and combination cohorts in patients with solid tumors having MTAP deletion.

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We are currently enrolling into a Phase 2 monotherapy expansion cohort in selected indications, including squamous cell NSCLC, esophagogastric cancer, and bladder cancer. We are also continuing to enroll patients, in parallel, into the monotherapy Phase 1 dose escalation portion of the clinical trial with a goal to determine the dose limiting toxicity, or DLT. We have initiated combination dose escalation cohorts for combinations of IDE397 with chemotherapy agents, including pemetrexed and taxanes.

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We are collaborating with Amgen pursuant to the Amgen CTCSA to initiate an Amgen-sponsored Phase 1/2 clinical trial to evaluate IDE397 in combination with AMG 193, the Amgen investigational MTA-cooperative protein arginine methyltransferase 5, or PRMT5, inhibitor, in patients having tumors with MTAP deletion.

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We are prioritizing the AMG 193 clinical combination, and at this time are discontinuing enrollment into the IDE397-001 clinical trial cohorts evaluating IDE397 and chemotherapy combinations. This approach is based on favorable preclinical combination efficacy and tolerability data observed with the IDE397 / AMG 193 combination, and on the proposed target enrollment and budget for the planned global clinical trial pursuant to the Amgen CTCSA.

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We observed preliminary clinical PD response in early cohorts of the dose-escalation portion of the IDE397 monotherapy Phase 1 clinical trial including peripheral S-adenosyl methionine, or SAM, and tumor symmetric dimethyl arginine, or SDMA. We also observed dose-dependent circulating tumor DNA, or ctDNA, molecular response from the dose escalation cohorts. These data collectively demonstrate robust target engagement and a dose- and/or exposure-dependent tumor pharmacodynamic response.

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

PARG Program (HRD, including BRCA)

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An IND for clinical evaluation of IDE161 in solid tumors was authorized by the FDA in the fourth quarter of 2022 following completion of its safety review.

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We are initiating a Phase 1/2 clinical trial designated as IDE161-001 to evaluate IDE161, a PARG inhibitor, for the treatment of patients having solid tumors with HRD, such as BRCA1/2-mutant breast and ovarian cancer patients. We are preparing to initiate dosing of a first patient in the Phase 1 dose escalation portion of this clinical trial in the first quarter of 2023, with a planned initial starting dose of IDE161 in the dose escalation that is estimated to be approximately one-half of the projected human efficacious dose, based on preclinical studies.

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The Phase 1/2 clinical trial will evaluate IDE161 as monotherapy with a focus on an expansion cohort of breast cancer patientshaving tumors with HRD which are ER+ and Her2-. This patient population of ER+ / Her2- breast cancer with HRD represents approximately 10% to 14% of breast cancer. The Phase 1/2 clinical trial will also include an expansion cohort of ovarian cancer patients having tumors with HRD, and a basket expansion cohort of other solid tumors with HRD.

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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 Cancer Research UK and University of Manchester.

Pol Theta Program (HRD, including BRCA Mutation)

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We are pursuing our preclinical synthetic lethality Pol Theta program, in collaboration with GSK, for solid tumors with HRD, including BRCA mutations.

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In collaboration with GSK, we initiated IND-enabling studies for our Pol Theta Helicase small molecule inhibitor development candidate in the first half of 2022 and are targeting submission of an IND to the U.S. FDA in the second quarter of 2023 to support a GSK-sponsored clinical trial for evaluation of the Pol Theta Helicase development candidate in first-in-human studies.

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We have the potential to receive up to $20 million in aggregate milestone payments from GSK for certain milestones, which may occur as we, in collaboration with GSK, advance a Pol Theta Helicase inhibitor from preclinical development into early Phase 1 clinical trials.

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In August 2022, we achieved the first preclinical development milestone in connection with IND-enabling studies to support evaluation of Pol Theta Helicase inhibitor DC, triggering a $3.0 million milestone payment, and have the potential to receive up to an additional $7.0 million for advancing this development candidate through IND effectiveness trials.

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Following selection of the Pol Theta Helicase inhibitor development candidate, GSK is leading further research and development for the Pol Theta program pursuant to the GSK Collaboration Agreement.

WRN Program (MSI-High)

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We are progressing our synthetic lethality Werner Helicase program, in collaboration with GSK, for patients with MSI-high tumors.

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We observed Werner Helicase inhibitor in vivo efficacy in a cell derived xenograft, or CDX, model with approximately 100% tumor growth inhibition.

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We are, in collaboration with GSK, targeting nomination of a Werner Helicase inhibitor development candidate in 2023.

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We have the potential to receive up to $20 million in aggregate milestone payments from GSK for certain milestones, which may occur as we, in collaboration with GSK, advance a Werner Helicase inhibitor from preclinical development into early Phase 1 clinical trials, including up to $3 million in connection with IND-enabling studies and up to an additional $7 million for advancing a DC through IND effectiveness trials.

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We plan to continue further research and development of our Werner Helicase program in collaboration with GSK pursuant to the GSK Collaboration Agreement.

Other Synthetic Lethality Pipeline Programs (Defined Biomarkers)

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We have initiated early preclinical research programs targeting multiple synthetic lethality targets, or SLTs, which we believe are next-generation SLTs, for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures.

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We own or control all commercial rights in our next-generation SLT programs.

Synthetic Lethality Target and Biomarker Discovery Platform

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We have established a comprehensive platform to computationally and empirically identify synthetic lethality target and biomarker pairs in defined patient populations.

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We own or control all commercial rights in programs directed to targets identified in on our synthetic lethality and biomarker discovery platform.

Therapies Based on Precision Medicine / Synthetic Lethality

Precision Medicine / Synthetic Lethality Pipeline Overview

We are actively pursuing the discovery and development of small molecule inhibitors of selected targets based on synthetic lethality and synthetic lethality combinations. Our pipeline in precision medicine / synthetic lethality comprises clinical stage product candidates, including darovasertib, IDE397, and IDE161, and multiple preclinical programs targeting Pol Theta, Werner Helicase and next-generation synthetic lethality targets. Our synthetic lethality pipeline is complemented by a robust target and biomarker discovery platform. For each synthetic lethality target, we are simultaneously pursuing identification and validation of both therapeutic and tumor-associated biomarker(s) for patient selection.

In addition to these programs, we are actively identifying and validating novel synthetic lethality targets through our internal research as well as through collaborations with academic and clinical institutions, including the University of California, San Diego, the Broad Institute of MIT and Harvard, or Broad Institute, and Cancer Research UK.

Scientific Rationale – Synthetic Lethality

Synthetic lethality is emerging as an important therapeutic paradigm in the treatment of cancer. It was first defined by Calvin Bridges in 1922 based on the observation that certain combinations of gene mutations resulted in lethality despite the fact the single mutations in either gene were viable.

Cancer cells often contain genetic changes that lead to alterations in pathways such as DNA repair and metabolism. These changes endow the cancer cells with certain properties such as the ability to replicate by bypassing normal control mechanisms. However, removing these important regulators of cell function may also make these cancer cells more dependent on backup pathways that can then be targeted to achieve a therapeutic effect. We are using small molecule inhibitors against targets in DNA damage repair, or DDR, pathways or in tumor metabolism pathways, that have potentially less effects on the viability of normal cells, but are designed to result in lethality in cancer cells having specific underlying genetic alterations. Cancer targets based on synthetic lethality are ideal for precision medicine approaches because each product candidate inherently has a tumor-associated genetic biomarker to facilitate patient selection.

Darovasertib – PKC Inhibitor for Ocular Melanoma Patients having Tumors with GNAQ or GNA11 Mutations

Darovasertib (IDE196) is our most advanced clinical-stage product candidate. Darovasertib is a potent, selective small molecule inhibitor of 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 are pursuing a clinical strategy for darovasertib to broadly address ocular melanoma, alternatively referred to as uveal melanoma – a patient population with a significant unmet medical need. There are no FDA approved systemic therapies for primary uveal melanoma as either neoadjuvant or adjuvant therapies. There are likewise no FDA approved therapies for patients having metastatic uveal melanoma, with HLA-A*02:01 negative, or HLA-A(-), serotype. These primary UM patients and HLA-A(-) MUM patients collectively represent approximately 85% of all ocular melanoma patients.

We are clinically evaluating darovasertib in an ongoing Phase 1/2 clinical trial, designated as IDE196-001, in solid tumors harboring GNAQ or GNA11 hotspot mutations. Our current focus for this clinical trial is to evaluate darovasertib in combination with crizotinib in patients having MUM. We have previously also evaluated darovasertib in combination with

binimetinb, Pfizer’s MEK inhibitor, and as monotherapy in a basket cohort of other solid tumor indications such as skin melanoma, or cutaneous melanoma.

We have initiated and preparing to enroll primary UM patients to clinically evaluate darovasertib as monotherapy in a company-sponsored Phase 2 clinical trial, designated as IDE196-009 as a potential neo-adjuvant and/or adjuvant therapy in primary, non-metastatic UM, and separately, are supporting enrollment of primary UM patients in an IST in coordination with St. Vincent’s Hospital Sydney, captioned as the “Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma” (NADOM) study.

Darovasertib – Scientific Rationale and Opportunity

PKC belongs to a family of closely related protein kinases that are involved in various aspects of signal transduction, such as transmitting extracellular growth factor or cytokine signals to other protein kinases involved in cellular proliferation or transcription regulation. PKC is important for signal transduction and survival of cells with constitutively active mutations in GNAQ or GNA11. Inactivation of PKC by specific inhibitors or reduction in protein expression using RNA all highlight the essential role of PKC in cells with GNAQ or GNA11 mutations.

Activating mutations in GNAQ or GNA11 are found in approximately 90% of uveal melanoma patients, and considered with mutations in adjacent proteins which activate the PKC pathway, in approximately 95% of uveal melanoma patients. These mutations result in a dependency on PKC activity which we believe may sensitize these tumors to the effects of darovasertib.

Uveal melanoma is a cancer of the eye and the most common primary intraocular malignancy in adults. Treatment of the primary lesion depends on several factors, including tumor size and location within the eye. Patients with larger-sized primary UM tumors, which represent approximately 20% of UM patients, are typically treated by enucleation, or surgical removal of the affected eye. Patients with smaller- or medium-sized primary UM tumors, which collectively represent approximately 80% of UM patients, are typically treated with radiation therapy, such as plaque brachytherapy or laser therapy. Patients who receive radiation therapy typically experience vision impairment or vision loss consequential to the primary interventional therapy. Although primary treatments are generally effective in preventing local recurrence in over 80% of cases, the consequences of these treatments - loss of the eye and/or loss of vision – are clinically undesirable for individual patients. There are no FDA approved systemic therapies for primary uveal melanoma as either neoadjuvant or adjuvant therapies.

Approximately 50% of uveal melanoma patients undergoing primary interventional treatments eventually develop metastatic disease, most commonly presenting in the liver.

Patients with metastatic uveal melanoma have a very poor prognosis, and there are currently no FDA approved therapies for patients having metastatic uveal melanoma with HLA-A(-) haplotype. Metastases are most frequently localized to the liver where curative surgical approaches are rare, and chemotherapy or immunotherapy has limited efficacy. Without treatment, median overall survival of patients with metastatic uveal melanoma is approximately two to eight months. Historical response rates for uveal melanoma generally range from 0% to 10% across treatment types. A meta-analysis of 29 Phase 2 clinical trials of various therapies in metastatic uveal melanoma from 1988 to 2015 demonstrated no improvement in clinical response, with a medium progression free survival of 3.29 months, median overall survival of 10.2 months, and a 1-year overall survival rate of only 43%. The poor prognosis associated with metastatic disease and the lack of effective therapies highlight the need for novel therapeutic approaches that specifically target metastatic uveal melanoma.

We have estimated the addressable population in major market countries, consisting of the US, the twenty-eight countries in Europe, or EU28, and Japan, for patients having solid tumors with GNAQ or GNA11 mutations to include an annual incidence of about 8,700 in primary uveal melanoma and of about 4,500 in metastatic uveal melanoma. Thus, the total addressable population for UM and MUM in such major market countries is estimated to be about 13,200 patients.

Darovasertib / Crizotinib Synthetic Lethality Combination Therapy – Metastatic Uveal Melanoma (MUM)

Our clinical trial strategy in MUM is to pursue darovasertib as a combination therapy with crizotinib pursuant to the Second Pfizer Agreement. We initiated a Phase 2 expansion cohort in June 2021 to evaluate the darovasertib / crizotinib combination therapy in MUM. As of August 31, 2022, we have enrolled a total of 67 MUM patients at the combination expansion doses of 300mg twice-a-day darovasertib and 200mg twice-a-day crizotinib, inclusive of 21 first-line MUM patients.

We are continuing patient enrollment into the Phase 2 clinical trial to evaluate the darovasertib / crizotinib combination in MUM. In particular, we are prioritizing and increasing enrollment of first-line MUM patients into this ongoing Phase 2 clinical trial based on observed preliminary clinical efficacy, including confirmed partial responses.

In September 2022, we reported interim clinical data from the Phase 2 expansion cohort evaluating darovasertib and crizotinib synthetic lethal combination in MUM, based on a data and analyses cutoff of June 26, 2022. The interim Phase 2 clinical data update is based on an initial 37 patients enrolled in the darovasertib and crizotinib combination study at the

combination expansion doses as of the data analysis cutoff date of June 26, 2022. Out of the 37 patients enrolled, there were 35 patients evaluable for efficacy and 2 non-evaluable patients. The 2 non-evaluable patients were both pretreated and withdrew from the trial prior to the first tumor scan. Neither of the two non-evaluable patients progressed due to disease: 1 patient withdrew consent and 1 patient discontinued early due to fatigue. The reported data are preliminary and based on an unlocked database as of the data analyses cutoff date of June 26, 2022, except one confirmatory scan after the data cutoff date or as otherwise noted.

We observed encouraging clinical activity in Phase 2 clinical trial evaluating darovasertib and crizotinib synthetic lethal combination in MUM patients in the expansion dose cohort. These investigator-reviewed data by RECIST 1.1 which we reported in September 2022: (i) 89% of patients show tumor shrinkage in Any-Line MUM: 31 of 35 evaluable patients showed tumor shrinkage as determined by target lesion size reduction; (ii) 83% disease control rate, or DCR, in Any-Line MUM: 29 of 35 evaluable patients showed stable disease or better as determined by target lesion size reduction; (iii) 50% ORR, in First-Line MUM: 4 of 8 evaluable patients had a confirmed partial response, or PR; (iv) 31% ORR in Any-Line MUM: 11 of 35 evaluable patients had a confirmed PR; (v) 43% of patients with greater 30% Tumor Reduction in Any-Line MUM: 15 of 35 evaluable patients observed PR with greater 30% tumor reduction, including 11 confirmed and 4 unconfirmed PR; (vi) Median Study Follow-Up of 6.5 months for First-Line MUM patients and 7.8 months for Any-Line MUM patients; (vii) Median Duration of Response, or DOR, in evaluable First-Line MUM patients has not yet been reached and 4 of 4 patients with confirmed PR’s in First-Line MUM remain in response; median DOR in evaluable Any-Line MUM patients has not yet been reached and 7 of 11 patients with confirmed PR’s in Any-Line MUM remain in response; and (viii) PFS in First-Line MUM patients has not yet been reached and is greater than 5 months in evaluable First-Line MUM patients; median PFS for evaluable Any-Line MUM patients is approximately 5 months.

We believe that these data provide clinical proof-of-concept for the efficacy of the darovasertib and crizotinib synthetic lethal combination treatment and support further clinical evaluation.

The darovasertib and crizotinib combination therapy has indicated a manageable adverse event profile in MUM patients (n=37) at the combination expansion doses, with a low rate of drug-related serious adverse events (SAEs). Patients reported predominantly Grade 1 or 2 drug-related adverse events; all patients experienced at least one drug-related adverse event, of which 76% were reported as Grade 1 or 2 and 24% were reported as Grade 3. As of the data analysis cutoff date of June 26, 2022, we observed no Grade 4 or Grade 5 drug-related adverse events. One patient discontinued treatment permanently due to a drug-related adverse event (fatigue).

We observed one Grade 5 SAE of a patient enrolled after the data cutoff date of June 26, 2022, which we believe was not likely related to study therapies and most likely due to disease progression. This patient had rapid disease progression and massive disease burden at the time of initial treatment. The treating investigator assessed the death (unknown cause) as most likely related to disease progression, and possibly related to the study therapies. Principal investigators on the study reviewed the event and concluded that the death was most likely due to disease progression. Based on the rapid clinical progression over a period of approximately five weeks – from pre-screening scan (approximately 40% tumor involvement) to baseline scan (over 80% tumor involvement), and worsening clinical symptoms such as ascites through the event, we concluded that the death was not likely related to study therapies and most likely due to disease progression. We submitted an initial report of the patient data and conclusions to the FDA on August 3, 2022, along with supplemental material, and the FDA acknowledged receipt. No follow-up questions have been received from the FDA and the trial remains ongoing.

These data are also consistent with the company’s clinical translational research which showed Phase 1 clinical partial responses to darovasertib monotherapy associated with low cMET activity, as measured by gene signature score or cMET expression. We identified cMET as a potential biomarker and a cMET inhibitor as potential combination agent though our translational research studies, or darovasertib cMET Translational Studies. In these studies, we observed preclinical synergy between darovasertib and crizotinib in relevant cellular models under conditions simulating a tumor microenvironment in the liver, the site of approximately 90% of uveal melanoma metastases. Additionally, we conducted a retrospective analysis of human clinical samples from the Novartis IDE196 Phase 1 clinical trial, which also independently supported cMET expression / activation as potential biomarker / combination agent. We presented data summarizing the results of certain darovasertib cMET translational studies at AACR in April 2021.

Based on preliminary analyses of darovasertib clinical data from the monotherapy and combination arms of our clinical trial, and based on the darovasertib mechanism of action, we anticipate darovasertib clinical activity independent of Human Leukocyte Antigen, or HLA, status in GNAQ/11-mutation cancers.

Pursuant to our license agreement with Novartis, except for Novartis’ ongoing Phase 1 clinical trial, we control all future clinical development, and all commercial rights to darovasertib, and may rely on and incorporate data previously submitted to the FDA by Novartis into our own regulatory submissions.

Darovasertib – Orphan Drug Designation and Fast Track Designation

In April 2022, the FDA designated darovasertib as an Orphan Drug in UM, including MUM, under 21 C.F.R Part 316. Under an Orphan Drug designation, we 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, seven years of statutory marketing exclusivity.

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

Darovasertib – Potentially Registration-Enabling Clinical Trial in MUM

Subject to FDA feedback and following our scheduled meeting in the first quarter of 2023, we plan to initiate a potentially registration-enabling Phase 2/3 clinical trial to evaluate darovasertib and crizotinib as a combination therapy in MUM pursuant to the Second Pfizer Agreement.

We have proposed to the FDA a potential registrational clinical trial based on a randomized integrated Phase 2/3 clinical trial. In the proposed protocol for an integrated Phase 2/3 clinical trial, first-line MUM patients with an HLA-A*02:01 negative serotype would be randomized on a 2:1 basis for treatment with the darovasertib / crizotinib combination in the treatment arm or investigator’s choice in the control arm. An interim Phase 2 data review could occur to evaluate ORR and PFS, in support of potential accelerated approval. Patients enrolled in Phase 2 would continue on treatment within the same study, together with additional enrolled patients, to evaluate PFS and OS in support of a Phase 3 confirmational data set. We plan to discuss several topics with the FDA in a meeting prior to initiation of the potential registrational clinical trial, including dose optimization and contribution of components. We anticipate conducting a two-cohort dose-optimization lead-in study, in recognition of the FDA’s Project Optimus, to confirm the proposed combination dose for the integrated Phase 2/3 clinical trial. Patients included in the lead-in study cohort at the dose selected for the integrated Phase 2/3 clinical trial will also be included as patients in the integrated Phase 2/3 clinical trial.

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. Following any accelerated approval, we would need to continue the Phase 3 portion as a post-approval confirmatory trial to verify the predicted clinical benefit for ongoing approval.

We are planning to separately address MUM patients with an HLA-A*02:01 positive serotype. In one example, a separate randomized clinical trial could include a darovasertib / crizotinib combination treatment arm and an investigators choice control arm. Data from this clinical study could support publication and potential inclusion in NCCN Clinical Practice Guidelines in Oncology.

Darovasertib - Neoadjuvant and Adjuvant Therapy – Uveal Melanoma (UM)

We are clinically evaluating the potential for darovasertib as neoadjuvant and/or adjuvant therapy, also referred to as (neo)adjuvant therapy, in primary, non-metastatic UM patients. The preliminary clinical data in the neoadjuvant setting shows evidence of anti-tumor activity and we believe supports further clinical evaluation of darovasertib to determine its potential 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.

In January 2023, we initiated a company-sponsored Phase 2 clinical trial designated as IDE196-009 to evaluate darovasertib as neoadjuvant treatment of uveal melanoma prior to primary interventional treatment of enucleation or radiation therapy, and also as adjuvant therapy following the primary treatment.

The clinical protocol includes neoadjuvant treatment with darovasertib to maximum benefit up to 6 months, primary treatment, then up to 6 months of follow-up adjuvant therapy.

In the neoadjuvant setting, one cohort of UM patients with large tumors will be treated with darovasertib until maximum benefit or six months, at which time they will undergo a primary interventional treatment. The neoadjuvant endpoint for this large-sized tumor cohort is eye preservation – for example, a patient who would otherwise have undergone enucleation is instead eligible for radiation treatment. Another neoadjuvant cohort of UM patients with small or medium tumors will be treated with darovasertib until maximum benefit or six months, at which time they will undergo radiation therapy. Neoadjuvant endpoints for this small- or medium-sized tumor cohort include (i) reducing the radiation dose that the patient received, relative to the radiation dose they would have otherwise received without the neoadjuvant treatment, and (ii) functional vison preservation.

In the adjuvant setting, each of the two neoadjuvant cohorts will be treated with darovasterib for up to six months as follow-up adjuvant therapy after the primary interventional treatment. The adjuvant endpoints for this portion of the clinical trial include relapse free survival and useful vision.

We are additionally supporting evaluation of darovasertib as (neo)adjuvant therapy in primary UM in an ongoing IST captioned as “Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma” (NADOM) led by St. Vincent’s Hospital in Sydney with participation of Alfred Health and the Royal Victorian Eye and Ear Hospital in Melbourne.

In September 2022 and in December 2022, we reported observed clinical activity supporting potential darovasertib use in the (neo)adjuvant uveal melanoma setting, including responses of patients with UM orbital tumors. These clinical data collectively showed reductions in tumor size, based on ultrasound, PET or MRI, and clinical benefit in 5 of 5 patients with an ocular tumor. These data include 3 UM patients from the IST as measured by ultrasound, and 2 MUM patients with ocular lesions from IDEAYA’s ongoing IDE196-001 clinical trial, with 1 MUM patient evaluated by PET scan, and 1 MUM patient evaluated by MRI. In particular, the observations reported in September included: (i) a darovasertib monotherapy patient with metastatic disease and an intact primary lesion in the eye had a reduction of approximately 74% in the eye lesion as measured by PET Standard Uptake Value at an initial scan after approximately 2 weeks on therapy, with observed improvement in visual symptoms in the affected eye; this patient remained on therapy for approximately 7 months; (ii) a darovasertib and crizotinib combination patient with metastatic disease and an intact primary lesion in the eye observed tumor shrinkage of approximately 67% by RECIST 1.1 as a contribution to an overall confirmed PR, with improvement in visual symptoms in the affected eye; this patient is continuing on therapy as of approximately 5 months; and (iii) a second darovasertib and crizotinib combination MUM patient with an intact primary lesion observed a reduction of the ocular lesion based on preliminary scan after the data cut-off date. The observations reported in December further included: (iv) a darovasertib monotherapy neoadjuvant UM patient with a primary ocular lesion enrolled in the NADOM IST observed a reduction of approximately 20% by RECIST 1.1 at the first scan after 27 days on therapy, with an observed decrease in ocular vasculature; and (v) a second darovasertib monotherapy neoadjuvant UM patient with a primary ocular lesion enrolled in the NADOM IST observed a reduction in the ocular lesion based on preliminary scan after the data cut-off date; these two patients were enrolled in the NADOM IST and were continuing on therapy as of approximately 1 month of treatment, pursuant to the IST protocol at that time.

We believe that these clinical observations provide a basis for further clinical investigation to evaluate whether darovasertib can improve current primary treatment paradigms, which typically include radiotherapies and/or enucleation of the eye as primary interventional treatments. Our regulatory strategy includes evaluation of potential clinical endpoints such as vision and organ preservation which would be temporally proximal to the primary interventional treatments, potentially enabling a discussion with regulatory authorities on an accelerated approval pathways.

Darovasertib – Other Potential Indications

We are currently prioritizing (neo)adjuvant primary UM as an expansion opportunity for darovasterib. We have, however, also considered and/or preclinically evaluated several other potential expansion opportunities in oncology for darovasertib, including (i) darovasertib in combination with crizotinib in cMET-driven solid tumors such as HCC or NSCLC, and (ii) darovasertib in combination with a KRAS inhibitor in KRAS-driven solid tumors.

In March 2022, we entered into a third Clinical Trial Collaboration and Supply Agreement, or the Third Pfizer Agreement, pursuant to which we may, subject to preclinical evaluation and portfolio priorities, evaluate darovasertib and crizotinib as a combination therapy in cMET-driven tumors such as HCC or NSCLC in a Phase 1 clinical trial. If we initiate a Phase 1/2 clinical trial to evaluate this combination, we would sponsor the clinical trial, provide darovasertib and pay for the costs of this combination study. Pfizer would provide crizotinib for this combination study at no cost to us.

IDE397 – MAT2A Inhibitor in Tumors with MTAP Deletion

IDE397 is a clinical-stage, potent, selective small molecule inhibitor of MAT2A, which we are developing for patients having solid tumors with MTAP deletions. The prevalence of MTAP deletions is estimated to be approximately 15% of all human 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 metabolite 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 are enrolling patients into a Phase 2 clinical trial designated as IDE397-001 to evaluate IDE397 as monotherapy and in combination therapies for patients having certain tumors with MTAP gene deletion.

For monotherapy, we are enrolling into Phase 2 expansion cohorts with an initial focus on non-small cell lung cancer, or NSCLC, esophagogastric cancer, and bladder cancer. In parallel, we are continuing to enroll additional patients into the dose escalation portion of the Phase 1 clinical trial. We have initiated dose escalation studies of IDE397 in combination with chemotherapy agents, including pemetrexed and taxanes.

In collaboration with Amgen, we are planning to 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 the Amgen CTCSA. The combination of IDE397 with AMG 193 is a novel and potential first-in-class synthetic lethality combination which targets two distinct and mechanistically complementary nodes of the MTAP methylation pathway – MAT2A and PRMT5, providing a complementary approach for targeting MTAP-null tumors.

We entered into the Amgen CTCSA in July 2022 to clinically evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with the Amgen investigational small molecule MTA-cooperative inhibitor of PRMT5, AMG 193, in patients having MTAP-deletion solid tumors, in a Phase 1/2 clinical trial, or the IDE397/AMG 193 Combination Study. Pursuant to the mutually non-exclusive Amgen CTCSA, Amgen is the sponsor of the IDE397/AMG 193 Combination Study and will provide AMG 193, we will provide IDE397 and each party will pay for fifty percent (50%) of the external third-party costs of the IDE397/AMG 193 Combination Study. Each party will be responsible for its own internal costs and expenses in support of the IDE397/AMG 193 Combination Study. We and Amgen will jointly own clinical data and all intellectual property, if any, relating to the combined use of IDE397 and AMG 193 from the IDE397/AMG 193 Combination Study. Each party retains commercial rights to its respective compounds, including with respect to use as a monotherapy or combination agent. We have formed a joint oversight committee responsible for coordinating all regulatory and other activities under the Amgen CTCSA.

We are obtaining patient biopsies for translational research from dose escalation cohorts in the IDE397 Phase 1 clinical trial and we also plan to obtain patient biopsies from expansion and combination cohorts in the clinical trial. We are obtaining solid tumor biopsies from a more limited number of consenting patients, as well as liquid biopsies from blood samples from a greater number of consenting patients. We are evaluating pharmacodynamic, or PD, biomarkers, such as peripheral or plasma SAM and tumor SDMA, as well as circulating tumor DNA molecular response from patient liquid biopsy blood samples.

Early clinical PK and PD data demonstrate robust target engagement and a dose- and/or exposure-dependent tumor pharmacodynamic response. We reported preliminary clinical PK, PD, and tolerability data in January 2022 and in March 2022. This clinical data included observed dose-proportional pharmacokinetic exposures across dose ranges of Cohort 1 through Cohort 5 of the Phase 1 dose escalation. The observed exposures across dose ranges of Cohort 4 and Cohort 5 were approximately in range of active exposure targets established from preclinical models. Data from dose escalation cohorts through Cohort 5 showed preliminary clinical activity with monotherapy, including pharmacodynamic response in plasma SAM, dose- and/or exposure-dependent pharmacodynamic modulation, and tumor reductions or stasis in multiple patients with MTAP deleted advanced or metastatic solid tumors. The reported data demonstrated a dose- and/or exposure-dependent pharmacodynamic modulation, reflected as a reduction in plasma SAM, a proximal pharmacodynamic marker, in evaluable plasma samples across dose ranges of Cohort 1 through Cohort 5. These data also reflected a dose- and/or exposure-dependent pharmacodynamic modulation of SDMA in evaluable tumor biopsies from Cohort 4 through Cohort 5. We observed tumor shrinkage in multiple patients in early dose escalation Cohorts 2 and 3 (n=3, n=2, respectively), including in a Cohort 2 NSCLC patient (approximately 15% reduction in target lesions) and in a Cohort 3 adenoid cystic carcinoma patient with a lung metastasis (approximately 11% reduction in target lesions), pursuant to RECIST v1.1 criteria.

We reported additional clinical PD data in July 2022 from our translational analysis of patient liquid biopsy samples based on ctDNA molecular responses. These data were obtained using the GuardantOMNITM platform for genomic analysis of ctDNA. Molecular responses were evaluated based on changes in mean variant allele frequency, or VAF, on-treatment after one treatment cycle as compared to pre-treatment baseline. Patients whose ctDNA showed a reduction of greater than 50% mean VAF following treatment with IDE397 were characterized as having a molecular response, or ctDNA MR, as reported in Zhang et al (Cancer Discovery, August 2020).

IDE397 ctDNA molecular response data from the dose escalation cohorts demonstrates robust target engagement and a dose- and/or exposure-dependent tumor pharmacodynamic response. Molecular responses were evaluable for thirteen patients with liquid biopsy samples available at pretreatment and after the first treatment cycle. Across dose escalation Cohort 1 through Cohort 6, a ctDNA molecular response was observed in 4 of 13 evaluable patients, reflecting a 31% ctDNA MR. Notably, ctDNA molecular responses were observed in 3 of 4 evaluable patients treated with IDE397 at higher doses in Cohort 5 or Cohort 6, reflecting a 75% ctDNA MR. Consistent with preclinical observations and preliminary signals of clinical activity, ctDNA molecular responses were also observed in 2 of 2 evaluable NSCLC patients, reflecting a 100% ctDNA MR.

Our evaluation of IDE397 as a clinical candidate is supported by preclinical data. We have evaluated the efficacy of IDE397 as monotherapy in over forty solid tumor patient derived xenograft, or PDX, models with homozygous MTAP deletions. Results of this IDE397 MTAP-deletion PDX panel study were reported at AACR 2021 and showed in vivo efficacy in multiple MTAP-null xenograft models demonstrating tumor growth inhibition, or TGI, when MAT2A was pharmacologically inhibited with IDE397 as monotherapy. In this study, we observed greater than 60% TGI in approximately 75% of the models and greater than 75% TGI in approximately 50% of models, in each case across major solid tumor types. We also observed tumor regressions, with greater than 100% TGI, in multiple PDX models and across multiple solid tumor types, including in NSCLC as well as in bladder and gastric cancer PDX models.

In NSCLC, data from the preclinical PDX panel study has shown greater than 60% TGI in 12 independent NSCLC PDX models out of 14 models evaluated, including in seven NSCLC adenocarcinoma PDX models out of nine evaluated and in five NSCLC squamous carcinoma PDX models out of five evaluated. Tumor regressions were observed in three of six NSCLC squamous PDX models, including a complete response in one model.

In preclinical efficacy studies with IDE397 and potential combination agents, we observed in vivo efficacy with enhanced TGI and/or tumor regressions for IDE397 in combination with taxanes such as paclitaxel and docetaxel, with pemetrexed, and with a small molecule MTA-cooperative inhibitor targeting PRMT5, in relevant MTAP-null xenograft models.

We own all right, title and interest in and to IDE397 and the MAT2A program, including all worldwide commercial rights thereto. We had previously granted an option to GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.4), Limited, an affiliate of GSK plc, in connection with the GSK Collaboration Agreement, to obtain an exclusive license to further develop and commercialize IDE397, as well as other IDEAYA compounds, if any, directly targeting MAT2A. In August 2022, we received notice from GSK waiving its rights to exercise its option to obtain such an exclusive license. This decision from GSK was based on an IDE397 option data package which we had delivered to GSK. The option data package was comprised of preclinical data and clinical data from the IDE397 monotherapy dose escalation study of the Phase 1 clinical trial, including safety and tolerability data, pharmacokinetic data and pharmacodynamic data. As a consequence of GSK’s waiver of its option rights, we retain and fully own all right, title and interest in and to IDE397 and the MAT2A program.

IDE161 - PARG Inhibitor in Tumors with Homologous Recombination Deficiency

IDE161 is a clinical-stage small molecule inhibitor of PARG being evaluated in a Phase 1/2 clinical trial desigated as IDE161-001 for patients having tumors with 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 PARP. PARG hydrolyzes poly (ADP-ribose), or 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. An IND application for clinical evaluation of IDE161 in solid tumors was submitted to and has been cleared by the FDA in the fourth quarter of 2022 following completion of its safety review.

We are initiating a Phase 1/2 clinical trial to evaluate IDE161 for the treatment of patients having solid tumors with HRD, such as BRCA1/2-mutant breast and ovarian cancer patients. For the Phase 1 dose escalation portion of this clinical trial, the protocol includes an initial starting dose of IDE161 of approximately one-half of the projected human efficacious dose, based on preclinical studies.

The Phase 1/2 clinical trial will evaluate IDE161 as monotherapy with a clinical focus in an expansion cohort of breast cancer patients having tumors with HRD which are ER+ and Her2-. This patient population of ER+ / Her2- breast cancer with HRD represents approximately 10% to 14% of breast cancer. The Phase 1/2 clinical trial will also include an expansion cohort of ovarian cancer patients having tumors with HRD, and a basket expansion cohort of other solid tumors with HRD.

Our evaluation of IDE161 as a clinical candidate is supported by preclinical data. We have evaluated the efficacy of IDE161 and other PARG inhibitors as monotherapy across a number of solid tumor CDX and PDX models with specific genetic alterations. IDE161 has demonstrated dose-dependent in vivo efficacy as monotherapy with tumor regression or stasis in multiple CDX models and PDX models, including in breast cancer and ovarian cancer. We have observed a differentiated

response of IDE161 relative to PARP inhibitors in multiple in vivo breast cancer HRD models which are ER+ and Her2-. In vivo studies in CDX and PDX models have also shown evidence of differentiation from a PARP inhibitor, niraparib, including enhanced TGI relative to such PARP inhibitor and, in certain models, tumor regressions in models which are refractory to such PARP inhibitor.

We have also shown in vitro that multiple endogenous HRD cell lines are selectively sensitive to IDE161 relative to a PARP inhibitor in biochemical assays. Additionally, cellular response profiles across a panel of 269 cell lines which include 31 lineages inform a mechanistic basis for PARG inhibitor sensitivity for patients having tumors with HRD as well as tumors characterized by other potential predictive biomarkers, such as replication stress, nucleotide excision repair and/or parylation cycle. We have also observed dose-dependent modulation of a PD biomarker, PAR polymer chains, across multiple in vivo CDX models, including in ovarian cancer, gastric cancer and breast cancer models.

In January 2022, we exercised our option under the Evaluation, Option and License Agreement, or CRUK/Manchester Agreement, between IDEAYA and Cancer Research Technologies, also known as Cancer Research United Kingdom, or Cancer Research UK, and the University of Manchester, pursuant to which we hold exclusive worldwide license rights covering a broad class of PARG inhibitors.

We have an ongoing strategic collaboration with the Broad Institute focused on synthetic lethality target and biomarker discovery. Through this collaboration with the Broad Institute, we are evaluating paralog CRISPR knockdown in selected cell lines in conjunction with pharmacological inhibition of PARG to inform patient selection and combination strategies in ovarian and breast cancer.

Pol Theta Helicase DC – Pol Theta Helicase Inhibitor in Tumors with Homologous Recombination Deficiency

We are advancing our preclinical Pol Theta Helicase DC for planned clinical evaluation, in collaboration with GSK. Our Pol Theta Helicase DC is targeting Pol Theta 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 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, show higher Pol Theta expression and synthetic lethality when Pol Theta is knocked down with siRNA. 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 binding domain.

In collaboration with GSK, we have selected a development candidate small molecule inhibitor of Pol Theta Helicase, or ATPase, domain. We are, in collaboration with GSK, planning for first-in-human clinical evaluation of our Pol Theta Helicase inhibitor DC in combination with niraparib for patients having tumors with HRD.

We have shown combination efficacy of our Pol Theta Helicase inhibitors with multiple PARP inhibitors, including niraparib in various in vivo models. Tumor regressions were observed in combination studies, including a durable response, for example out to 80 days, in multiple in vivo xenograft models.

Following selection of the Pol Theta Helicase inhibitor development candidate, GSK is leading further development for the POLQ program pursuant to the GSK Collaboration Agreement. We have the potential to receive an aggregate of up to $20 million in milestone payments from GSK for certain milestones, which may occur as we, in collaboration with GSK, advance our Pol Theta Helicase DC from preclinical development into early Phase 1 clinical trials, including up to $10 million aggregate for advancing this DC through IND effectiveness. In August 2022, we achieved the first preclinical development milestone in connection with ongoing IND-enabling studies to support evaluation of Pol Theta Helicase inhibitor DC, triggering a $3.0 million milestone payment receivable, and have the potential to receive up to an additional $7.0 million for advancing the Pol Theta Helicase inhibitor DC through IND effectiveness trials.

WRN Inhibitors in Tumors with High Microsatellite Instability

We are also continuing to advance our preclinical research in collaboration with GSK for an inhibitor targeting Werner Helicase protein for patients having tumors with high MSI.

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. MSI 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. High MSI is present in about 15% of gastrointestinal tumor cancers, including in approximately 22% of stomach adenocarcinoma and 16% of colorectal cancer. Tumors with high MSI 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 have demonstrated in vivo efficacy with tumor regression and PD response in a relevant MSI high model. We have observed selectivity of our WRN inhibitor and validation of the synthetic lethal relationship to tumors with high MSI over tumors with microsatellite stable, or MSS, based on a lack of in vivo pharmacological response in relevant MSS xenograft models.

We are, in collaboration with GSK, planning for nomination of a Werner Helicase inhibitor development candidate.

We plan to continue further preclinical development in collaboration with GSK pursuant to the GSK Collaboration Agreement. We have the potential to receive up to $20 million in aggregate milestone payments from GSK for certain milestones which may occur as we, in collaboration with GSK, advance a Werner Helicase inhibitor from preclinical into early Phase 1 clinical trials. These milestones include up to $10 million aggregate for a development candidate through IND effectiveness - $3 million in connection with IND-enabling studies and $7 million upon IND effectiveness trials.

Next-Generation Synthetic Lethality Pipeline Programs

We have initiated early preclinical research programs targeting multiple SLTs, which we believe are next-generation SLTs, for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures.

We own or control all commercial rights in our next-generation SLT programs.

Synthetic Lethality Target and Biomarker Discovery Platform

Synthetic lethality has been since inception of our company, and continues to be, our core research focus. We have invested significantly and continue to invest in capabilities for identification and validation of new synthetic lethality targets and biomarkers for patient selection. For targets of interest, we advance our research to discover therapeutic drugs and to further qualify relevant biomarkers.

Our synthetic lethality research platform integrates a broad set of computational and functional capabilities. These capabilities collectively reflect the convergence of advancements in biology, molecular biology, chemistry and information technologies. For example, molecular biology approaches such as gene knockdown using siRNA, gene editing using CRISPR, quantitative DNA/RNA analysis, protein expression profiling and genomic sequencing can be applied across broad cell lines to create substantial data sets. Data analytics and computational approaches are used to mine such data sets to identify novel targets and biomarker hypotheses. These hypotheses are experimentally validated by developing and applying relevant biological assays.

We have established a comprehensive platform to computationally and empirically identify high value synthetic lethal pairs in defined patient populations. This platform integrates synthetic lethality relationship data across parallel data sets, each including orthogonal content based on particular screening efforts. These screens include evaluation of curated, genetically defined and preselected model cell sets indicative of targeted patient populations. Our platform includes a proprietary library and data set resulting from our DECIPHERTM Dual CRISPR Synthetic Lethality library constructed in collaboration with University of California, San Diego. The platform will also include data from our proprietary PAGEOTM, or Paralogous Gene Evaluation in Ovarian cancer, library being developed in collaboration with the Broad Institute utilizing the Sellers laboratory CRISPR paralog screening platform to evaluate functionally redundant paralogous genes across ovarian cancer subtypes. Additionally, we are members of the DepMap (Cancer Dependency Map) consortium led by the Broad Institute, through which we have access to a comprehensive data set of genome-wide cell-based screens, including isogenic screens, conducted by the Broad Institute and other contributing institutes, including pre-publication access to new data releases. As a further component of our synthetic lethality platform, we are conducting computational data mining and analysis of relevant public databases, such as The Cancer Genome Atlas, or TCGA, cBioPortal, and Cancer Cell Line Encyclopedia, or CCLE, among others. Such computational approaches include our proprietary algorithms which enable us to determine synthetic lethality targets and biomarkers enabling patient stratification.

We have established internal bioinformatics capabilities, which are supplemented by external resources. We are applying these capabilities and resources to integrate using proprietary algorithms and unsupervised machine learning across each of

the orthogonal data sets in our platform. These integrated, comprehensive analysis efforts allow us to determine synthetic lethality target / biomarker pairs with the strongest signals across the data sets. Potential therapeutic targets are ranked based on several factors, including the strength of the synthetic lethal interaction, potential drugability, potential clinical development path, and potential market opportunity. The most promising therapeutic targets are validated empirically.

DECIPHERTM 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.

PAGEOTM 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.

Drug Discovery and Program Biomarker Discovery Platform

We are also continuing to invest in our capabilities to advance our research on newly identified synthetic lethality targets of interest, including to enable discovery of therapeutic drugs and program relevant biomarkers. 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.

As examples of aspects of our drug discovery platform, we use our INQUIRETM Chemical Library to enhance our synthetic lethality drug discovery platform. INQUIRE is a proprietary, expert-curated small-molecule library of over 200,000 chemical compounds, which we believe will enhance our hit discovery capabilities across a broad range of novel synthetic lethality targets and historically difficult-to-drug target classes, such as helicases and endonucleases.

We use our HARMONY TM machine-learning engine to empower evaluation and decisions related to structure-activity-relationships analyses, empowering our drug-discovery platform.

Impact of COVID-19 Pandemic on Clinical Trials – Darovasertib, IDE397 and IDE161

We continue to monitor the COVID-19 pandemic and its potential impact on the ongoing darovasertib, IDE397 and IDE161 clinical programs and timing of clinical data results. Generally, initiation of clinical trial sites, patient enrollment and ongoing monitoring of enrolled patients, including obtaining patient computed tomography, or CT, scans, may be impacted for our clinical trials.

For our clinical programs, patients enrolled in the ongoing clinical trials and sites affected by COVID-19 restrictions are adapting to logistical constraints on activities, such as travel and site visits. For example, patients are continuing on therapy, which are oral drugs and are being shipped to and self-administered by patients at home. Patients are being monitored through a combination of telemedicine visits and local visits. COVID‐19 infection rates have fluctuated over the course of the pandemic in the countries and states in which our clinical trial sites are located.

Additionally, enrollment into our clinical trials may be delayed by circumstances resulting from the COVID-19 pandemic, including for example, as a result of increases in COVID-19 infection rates in the states in which our clinical trial sites are located, and by clinical site-specific policies and practices related to COVID-19. The specific impact on enrollment into these clinical trials is currently uncertain.

We plan to continue to use third-party service providers, including clinical research organizations, or CROs, and clinical manufacturing organizations, or CMOs, to carry out our preclinical and clinical development and manufacture and supply of

our preclinical and clinical materials to be used during the development of our product candidates. To date, the COVID-19 pandemic has not materially affected our supply chain or development schedule, but further escalation of the health crisis has the potential to cause delays in our supply chain and manufacturing operations, which could materially adversely impact our business.

Competition

Our industry is very competitive and subject to change based on ongoing advances in technology. Although we believe that our approach, strategy, scientific capabilities, knowledge and experience provide us with competitive advantages, we expect to have substantial competition from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide. Many of our competitors have significantly greater financial, technical and human resources. Smaller and early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

As a result, our competitors may discover, develop, license or commercialize products before or more successfully than we do. We face competition with respect to product candidates in our pipeline, and will face competition with respect to future product candidates, from segments of the pharmaceutical, biotechnology and other related markets that pursue targeted approaches to addressing activating genetic and other molecular alterations in cancer.

For darovasertib, we are not aware of other companies actively developing clinical-stage therapeutics directed to PKC as a target for solid tumors. MingSight is developing a PKC beta inhibitor in chronic lymphocytic leukemia and diabetic macular edema, both in Phase 1 studies. Varian Biopharmaceuticals is advancing a preclinical-stage atypical PCK iota inhibitor, including as a dermatologic gel formulation for potential topical treatment of Basal Cell Carcinoma, or BCC. Exscientia is developing a PKC theta inhibitor in inflammatory diseases in Phase 1 studies. HotSpot Therapeutics is advancing a program targeting PKC-theta. We are aware of other companies that are conducting research and development of potential therapies for primary UM or for MUM based on other targets and approaches. For example, Aura Biosciences is developing AU-011 a virus-like drug conjugate (VDC) as local treatment for early-stage choroidal melanoma. Immunocore is developing and commercializing Tebentafusp, also known under its branded name as Kimmtrakfor the treatment of adult patients with HLA-A*02:01-positive unresectable or metastatic uveal melanoma. Novartis is developing DYP688, an antibody-drug-conjugate, or ADC, with a GNAQ-11 inhibitor payload in a Phase 1/2 clinical trial in MUM.

For IDE397, Servier Pharmaceuticals, LLC, or Servier, is preclinically evaluating a small molecule MAT2A inhibitor designated as S95035. Servier is also clinically evaluating a small molecule MAT2A inhibitor designated as S95033, and formerly designated as AG270, in patients having tumors with MTAP deletion, following its acquisition of the Agios Pharmaceuticals’, or Agios’, commercial, clinical and research-stage oncology portfolio, including AG270.

For IDE161, we are not aware of any other clinical-stage therapies targeting PARG. Several companies are conducting preclinical research to develop PARG inhibitors, including Sumitomo, Nodus Oncology and Satya Pharma Innovations, and based on information and belief, potentially NeoMed Institute and 858 Therapeutics.

For our preclinical pipeline of synthetic lethality therapeutics, potential competition includes established companies as well as earlier-stage emerging biotechnology companies. Multiple established companies have been involved with research and development in synthetic lethality, such as AstraZeneca (Lynparza), Merck, Novartis, Pfizer (Talzenna), GSK (Zejula), Servier, Sumitomo and Roche. Additionally, several other early-stage companies or institutes are active in respect of synthetic lethality research or development, including 858 Therapeutics, Anticancer Bioscience, Artios, Breakpoint Therapeutics, Calico, Cyteir, Eikon, Foghorn Therapeutics, FoRx Therapeutics, KSQ, MetaboMed, MOMA Therapeutics, NeoMed, Nimbus, Nodus Oncology, Repare, Ribon, Ryvu Therapeutics, Satya Pharma Innovations, Silicon Therapeutics (acquired by Roivant Sciences), Tango, Vividion, Xpose and Zai Labs.

Intellectual Property

Intellectual property, including patents, trade secrets, trademarks and copyrights, is important to our business. We endeavor to establish, maintain and enforce intellectual property rights that protect our business interests.

Our patent portfolio, including patents owned by or exclusively licensed to us, is built on a program-by-program basis with a goal of establishing broad protection that generally includes, for each product candidate compound and for selected alternative back-up compounds, claims directed to composition of matter, pharmaceutical compositions, and methods of treatment using such pharmaceutical compositions. For some programs, our portfolio may also include claims directed to

methods of treatment involving biomarker-enabled patient identification or selection, methods of treatment involving particular dosing approaches, polymorphs, formulations and/or methods of synthesis. We are seeking and maintaining patent protection in the United States and key foreign jurisdictions.

As of February 3, 2023, we own or exclusively in-license patents and patent applications, comprising approximately 51 distinct patent families, protecting our technology across our pipeline. Excluding applications that we are not currently prosecuting, our portfolio consists of 15 issued U.S. patents, approximately 35 pending U.S. applications, 16 pending applications under the Patent Cooperation Treaty, or PCT, 37 issued foreign patents and approximately 101 pending foreign applications in approximately 44 foreign jurisdictions, including without limitation countries included in major markets in North America, Europe, and Asia, each having expiration dates ranging from 2035 to 2043. The nominal expiration of our patents and patent applications does not account for any applicable patent term adjustments or extensions.

As of February 3, 2023, as relating to our PKC program, including darovasertib, we own or have exclusively in-licensed from Novartis patents and patent applications comprising approximately six issued U.S. patents, approximately 26 issued foreign patents, approximately six pending U.S. applications, one pending PCT application, and approximately 27 pending applications in approximately 18 foreign jurisdictions which we are currently prosecuting, including without limitation countries included in major markets in North America, Europe, and Asia. These in-licensed patents and applications are directed to composition of matter, pharmaceutical compositions and methods of treatment, including treatment of uveal melanoma. These solely owned or in-licensed patent applications, if granted, would expire between 2035 and 2043, without taking into account any applicable patent term adjustments or extensions. In addition, the PKC program portfolio includes one U.S. patent application and two PCT applications which are jointly owned with Pfizer directed to methods of treatment for certain combination treatments.

As of February 3, 2023, as relating to our MAT2A program, including IDE397, we own patents and patent applications comprising approximately three issued U.S. patents, approximately one issued foreign patent, 12 pending U.S. applications, approximately four pending PCT applications and approximately 30 pending foreign applications in approximately 26 foreign jurisdictions which we are currently prosecuting, including without limitation countries included in major markets in North America, Europe, and Asia. These solely owned or in-licensed patent applications, if granted, would expire between 2039 and 2043, without taking into account any applicable patent term adjustments or extensions. In addition, the MAT2A program portfolio also includes one pending U.S. application directed to methods of treatment of cancer which is jointly owned with Amgen pursuant to the Amgen CTCSA.

As of February 3, 2023, as relating to our PARG program, including IDE161, we own or have exclusively in-licensed from Cancer Research UK and University of Manchester, patents and patent applications comprising approximately two issued U.S. patents, 10 issued foreign patents, four pending U.S. application, and approximately 23 pending foreign applications in approximately 16 foreign jurisdictions which we are currently prosecuting, including without limitation countries included in major markets in North America, Europe, and Asia. . These solely owned or in-licensed patent applications, if granted, would expire between 2035 and 2043, without taking into account any applicable patent term adjustments or extensions.

Our patent portfolio also supports programs in our synthetic lethality preclinical pipeline, including U.S. patent applications directed to composition of matter, pharmaceutical compositions and/or methods of treatment of cancer for each of our POLQ (HR), WRN (high MSI), and certain next-generation SLT programs.

Strategic Relationships

We own or control all commercial rights in our three most advanced programs, each of which are clinical-stage programs – darovasertib, IDE397 and IDE161. We have entered into strategic relationships for these programs – for example, to in-license certain intellectual property rights or to enable evaluation of combination therapies, such as through combination drug supply or clinical trial collaborations to evaluate combinations. For darovasertib, we have an exclusive license agreement with Novartis and separately, we have established clinical trial collaboration and supply agreements with Pfizer in support of our clinical evaluation of darovasertib in combination with crizotinib in MUM. For IDE397, we entered into the Amgen CTCSA to clinically evaluate IDE397 in combination with AMG 193, the Amgen investigational MTA-cooperative PRMT5 inhibitor, in patients having MTAP-deletion solid tumors. For PARG, we have an exclusive license agreement with Cancer Research UK and University of Manchester.

We have entered into a strategic partnership and collaboration with GSK for our preclinical synthetic lethality programs targeting Pol Theta and Werner Helicase, pursuant to the GSK Collaboration Agreement. We own all commercial rights in our earlier next-generation synthetic lethality programs, for which our small molecule compounds are being discovered and/or developed internally with our own resources, as supplemented by certain service providers such as CROs.

We have established collaborative relationships with other companies for access to their proprietary database of patient samples, and/or for their genetic screening services on their proprietary platform. We have also established a collaborative relationship with Ventana (Roche Diagnostics) for development of molecular diagnostics for various research programs.

We have established certain development manufacturing and service relationships with CMOs for darovasertib, IDE397 and IDE161. We have an agreement with STA Pharmaceutical Hong Kong Limited, or STA Pharmaceutical, for the synthesis of the API and formulation for darovasertib, and for the manufacturing of IDE196 drug product. We have an agreement with STA Pharmaceutical for the synthesis of the API and formulation for IDE397, and with Bioduro for the manufacturing of IDE397 drug product. We have an agreement with Pharmaron for the synthesis of the API and formulation for IDE161, and with STA Pharmaceutical for the manufacturing of IDE161 drug product. We have established arrangements with CMOs as well for packaging, labeling and distribution of darovasertib, IDE397 and IDE161. We also have established clinical services relationship with CROs to support our conduct of clinical trials for our darovasertib, IDE397 and IDE161 programs.

In addition to these existing strategic license relationships, existing and planned development manufacturing and service arrangements, and existing and planned clinical services arrangements, we have various existing agreements and relationships with service providers, such as CROs, which are enabling execution of various research and development activities for each of our pipeline programs. In particular, such agreements are directed to chemistry and compound synthesis, compound analysis and characterization, structural biology, computational biology, biological assay and model development, in vitro screening, in vivo screening, translational biomarker diagnostic development, bioinformatics, toxicology and formulation, among other activities.

We may also evaluate future strategic opportunities to accelerate development timelines and maximize the commercial potential of our product candidates. We plan to selectively evaluate strategic collaborations with biopharmaceutical partners whose research, development, commercial, marketing, and geographic capabilities complement our own.

Agreements

Clinical Trial Collaboration and Supply Agreements with Pfizerfor Darovasertib

In March 2020, we entered into the Pfizer Agreement, pursuant to which the parties will work on combination studies, as portions of the Company’s Phase 1/2 clinical trial in MUM and other solid tumors harboring activating GNAQ or GNA11 mutations. As amended in September 2020, April 2021 and September 2021, Pfizer supplies us with their MEK inhibitor, binimetinib, and with an investigational cMET inhibitor, crizotinib, for clinical evaluation of combinations of darovasertib independently with each of the Pfizer compounds, in patients with tumors harboring activating GNAQ or GNA11 mutations. Under the Pfizer Agreement, we are sponsor of the combination studies, and will provide darovasertib and pay for the costs of the combination studies. Pfizer will provide binimetinib and crizotinib for the respective combination studies at no cost to us. We and Pfizer will jointly own clinical data from the combination studies and will also jointly own inventions, if any, relating to the combined use of darovasertib and binimetinib, or independently, to the combined use of darovasertib and crizotinib. We and Pfizer have formed a joint development committee responsible for coordinating all regulatory and other activities under the agreement.

Pfizer may terminate the agreement if Pfizer believes binimetinib or crizotinib is being used in an unsafe manner. Either party may terminate the agreement for patient safety reasons, if any regulatory action prevents the supply of its drug or if a party ceases development of its drug. Either party may terminate the agreement for the other party’s material breach that remains uncured for thirty days. If the agreement is terminated, we must return any unused binimetinib or unused crizotinib, as applicable, to Pfizer. If Pfizer terminates the agreement because of our material breach, we will be required to reimburse Pfizer certain manufacturing costs for the binimetinib or crizotinib supplied under the agreement.

We have further expanded the scope of our relationship with Pfizer, entering into additional agreements to facilitate evaluation of darovasertib in combination with crizotinib in a potential registrational clinical trial in MUM and separately, in combination with crizotinib in other cMET-driven tumor indications.

In March 2022, we and Pfizer entered into the Second Pfizer Agreement pursuant to which we may, subject to FDA feedback and guidance, evaluate darovasertib and crizotinib as a combination therapy in MUM in a planned Phase 2/3 potential registration-enabling clinical trial. Pursuant to the Second Pfizer Agreement, we are the sponsor of the planned combination trial and we will provide darovasertib and pay for the costs of the combination trial; Pfizer will provide crizotinib for the planned combination trial at no cost to us for up to an agreed-upon number of MUM patients. We and Pfizer will jointly own clinical data from the planned combination trial and all inventions relating to the combined use of darovasertib and crizotinib. We and Pfizer will form a joint development committee responsible for coordinating all regulatory and other activities under the Second Pfizer Agreement.

Separately, in March 2022, we and Pfizer also entered into the Third Pfizer Agreement pursuant to which we may, subject to preclinical validation and FDA feedback and guidance, evaluate darovasertib and crizotinib as a combination therapy in

cMET-driven tumors such as NSCLC and/or HCC in a Phase 1 clinical trial. Pursuant to the Third Pfizer Agreement, we are the sponsor of the planned combination trial and we will provide darovasertib and pay for the costs of the combination trial; Pfizer will provide crizotinib for the planned combination trial at no cost to us. We and Pfizer will jointly own clinical data from the planned combination trial and all inventions relating to the combined use of darovasertib and crizotnib. We and Pfizer will form a joint development committee responsible for coordinating all regulatory and other activities under the Third Pfizer Agreement.

Exclusive License Agreement with Novartis for Darovasertib

In September 2018, we entered into a license agreement with Novartis to develop products based on Novartis’ small molecule PKC inhibitors, including Novartis’ LXS196 oncology product candidate, which we have renamed as IDE196, and which has a non-proprietary name of darovasertib.

Under the license agreement, Novartis granted to us a worldwide, exclusive, sublicensable license to research, develop, manufacture, and commercialize certain defined compounds and products, including IDE196 and certain other PKC inhibitors as well as companion diagnostic products, collectively referred to as the licensed products, for any purpose. The license grant is subject to Novartis’ retained rights to complete its ongoing Phase 1 clinical trial of darovasertib, designated in their clinical trial as LXS196. Novartis also agreed to transfer to us certain materials and know-how relating to the licensed products or arising from the ongoing Phase 1 clinical trial of darovasertib.

We are solely responsible for the manufacturing and commercialization of the licensed products, subject to Novartis’ rights under the ongoing clinical trial of darovasertib. We have certain obligations to supply darovasertib and licensed products for compassionate use, named patient and similar programs in connection with the ongoing clinical trial. We are obligated to use commercially reasonable efforts to develop one licensed product and to commercialize and obtain regulatory approval for at least one licensed product in the United States and in specified European countries.

All inventions, know-how, data and results resulting from our activities under the license agreement, including activities relating to our own clinical trials, will be exclusively owned by us. All inventions, know-how, data and results resulting from Novartis’ activities connected with Novartis’ ongoing Phase 1 clinical trial for IDE196 will be exclusively owned by Novartis, and subject to the license to us. Ownership of all other inventions and know-how will be determined according to U.S. patent law, with Novartis’ interest subject to the license to us.

We control the prosecution and maintenance of the patents exclusively licensed to us, with Novartis retaining step-in rights if we do not continue such prosecution and maintenance. If we fail to maintain or prosecute any exclusively licensed patent and Novartis exercises this step-in right, our license to the relevant patents will terminate in the relevant country. We have the first right to enforce any exclusively licensed patents, while Novartis retains the right to representation. If we do not bring an action to enforce any exclusively licensed patent, Novartis has the right to bring such action, and we will have the right to representation.

We paid Novartis an upfront payment of $2.5 million and issued 263,615 shares of our Series B redeemable convertible preferred stock concurrently with the execution of the license agreement. Subject to completion of certain clinical and regulatory development milestones, we agreed to make milestone payments in the aggregate of up to $9.0 million, and subject to achievement of certain commercial sales milestones, we agreed to make milestone payments in the aggregate of up to $20.0 million. We also agreed to pay mid to high single-digit tiered royalty payments based on annual worldwide net sales of licensed products, payable on a licensed product-by-licensed product and country by country basis until the latest of the expiration of the last to expire exclusively licensed patent, the expiration of regulatory exclusivity, and the ten year anniversary of the first commercial sale of such product in such country. The royalty payments are subject to reductions for lack of patent coverage, loss of market exclusivity, and payment obligations for third-party licenses.

The license agreement continues in force on a licensed product-by-licensed product and country by country basis until the latest of the expiration of the last to expire exclusively licensed patent, the expiration of regulatory exclusivity, and the ten year anniversary of the first commercial sale of such product in such country.

We may terminate the license agreement in its entirety or on a licensed product-by-licensed product basis without cause on 60 days’ prior written notice. Either party may terminate the license agreement for the other party’s material breach that remains uncured for 90 days. In addition, Novartis has the right to terminate the license agreement immediately upon our insolvency.

Upon termination by Novartis for material breach or for our insolvency, or upon termination by us without cause, at Novartis’ written request and in return for consideration that will be negotiated at such time, we will grant to Novartis a perpetual, irrevocable, worldwide, sublicensable, nonexclusive or exclusive license, under all patent rights and know-how controlled by us that are related to and actually used as of the date of termination in the development, manufacture, and commercialization of licensed products, for Novartis to develop, manufacture, and commercialize the licensed products.

Clinical Trial Collaboration and Supply Agreement with Amgen for IDE397

In July 2022, the Company entered into the Amgen CTCSA with Amgen to clinically evaluate IDE397 in combination with AMG 193, the Amgen investigational small molecule MTA-cooperative inhibitor of PRMT5, in patients having MTAP-null solid tumors, in a Phase 1/2 clinical trial. Under the mutually non-exclusive Amgen CTCSA, the Company will provide IDE397 drug supply to Amgen, who will be the sponsor of the Phase 1 clinical combination trial evaluating IDE397 and AMG 193. The Company and Amgen will jointly share external costs of the study and will jointly oversee clinical development of the combination therapy through a Joint Oversight Committee responsible for coordinating all regulatory and other activities under the Amgen CTCSA. The parties will jointly own collaboration data and combination-related intellectual property, if any, arising from the combination clinical trial. The Company and Amgen each retain commercial rights to their respective compounds, including with respect to use as a monotherapy agent or combination agent.

Exclusive Option and License Agreement with Cancer Research UK for IDE161

In April 2017, we entered into the CRUK/Manchester Agreement with Cancer Research UK and University of Manchester, which was amended on April 24, 2019 and on March 3, 2020, for the development and commercialization of licensed products comprising pharmaceutical preparations of PARG inhibitors for all therapeutic uses.

Under this agreement, Cancer Research UK and University of Manchester have granted to us, and we have in turn granted to Cancer Research UK and University of Manchester, non-exclusive, sublicensable, royalty-free licenses to carry out non-clinical research during the research term, which ended with our exercise of our option described below. The non-clinical research was governed by a joint research committee comprised of representatives from each party. During the research term, no party was to undertake a drug discovery program in PARG inhibitors other than under this agreement.

Cancer Research UK also granted us the exclusive option to obtain an exclusive, sublicensable, worldwide, royalty-bearing license, under certain Cancer Research UK background intellectual property and Cancer Research UK’s interest in any intellectual property jointly developed under the agreement, to research, develop, manufacture, and commercialize licensed products, as well as a non-exclusive, sublicensable, royalty-free, freedom-to-operate license under related intellectual property. Cancer Research UK and University of Manchester retain certain rights under the licensed intellectual property for academic, non-commercial research and teaching.

In the March 2020 second amendment to the CRUK/Manchester Agreement, the parties reduced the license fee due at exercise of our option, extended the research period to March 2021, and also extended the option period, during which we have rights to exercise an option to certain license rights. The expanded collaborative research included evaluation of an IDEAYA proprietary small molecule PARG inhibitor in multiple in vitro and in vivo ovarian cancer xenograft models. This research was also evaluating replication stress signature as a potential patient selection biomarker. The extended option period was for up to four additional years from March 2020, including an initial one year period to March 2021 and an additional eighteen month extension to September 2022, which has now been elected pursuant to our certification of ongoing program research activities.

In January 2022, we exercised our option under the CRUK/Manchester Agreement, pursuant to which we hold exclusive worldwide license rights covering a broad class of PARG inhibitors.

Following our option exercise, we gained sole control and responsibility for the research, development, manufacture, and commercialization of the licensed PARG inhibitors. Cancer Research UK has also agreed to transfer its know how relating to the research, development or manufacturing of the licensed PARG inhibitors to us.

We were obligated to use reasonable efforts to research a PARG inhibitor during the research term, and we are obligated to develop a PARG inhibitor for the treatment of a cancer indication now that we exercised the option.

Each party is the sole owner of any intellectual property it develops solely under the agreement, and the parties will be joint owners of any jointly developed intellectual property. Each party grants the other a non-exclusive, fully-paid, royalty free, irrevocable, sublicensable, perpetual license to its rights in such jointly created intellectual property to make, use and sell inventions claimed in the joint patents, except for those joint patents exclusively licensed to us under the agreement following our exercise of the option.

Before our exercise of the option, Cancer Research UK was responsible for the prosecution and maintenance of Cancer Research UK background patents specifically relating to PARG, while we were responsible for the prosecution and maintenance of patents covering inventions developed under the agreement as project intellectual property. Cancer Research

UK and University of Manchester had the first right to enforce the patents covering inventions developed under the agreement as project intellectual property and we had the right to participate in such actions.

Following our exercise of the option, we have assumed Cancer Research UK’s prosecution and maintenance responsibilities for the Cancer Research UK background patents specifically relating to PARG and we obtained the first right to enforce such patents as well as the patents covering inventions developed under the agreement as project intellectual property, and Cancer Research UK will have the right to participate.

We pay all expenses associated with prosecution and maintenance and each party bears its own costs for enforcement. If we abandon the patents covering inventions developed under the agreement as project intellectual property, Cancer Research UK will thereafter be responsible for prosecuting and maintaining such patents. If we abandon such patents, Cancer Research UK and University of Manchester will be responsible for paying the expenses associated with the prosecution and maintenance of such patents.

In addition to an upfront fee of £100,000 and a one-time option exercise fee of £250,000, each of which have been paid, we have certain potential milestone-dependent financial obligations, including: (a) subject to completion of certain clinical and regulatory milestones, payments of up to £19.5 million per broad disease classification block – for example, in oncologic diseases, up to £13.0 million aggregate for a first achievement of such clinical and regulatory milestones and up to £6.5 million aggregate for a second achievement of such clinical and regulatory milestones; (b) subject to certain sales milestones, payments of up to £9 million per broad disease classification block – for example, in oncologic diseases, up to £6.0 million aggregate for a first achievement of such sales milestones and up to £3.0 million aggregate for a second achievement of such sales milestones; and (c) low single-digit tiered royalty payments based on aggregate worldwide net sales of all products, payable on a product-by-product and country-by-country basis until the later of the last-to-expire patent covering such product in such country and the ten year anniversary of the first commercial sale of such licensed product in such country.

Certain of the clinical and regulatory milestones are related to and may be due and payable by us if certain milestones are achieved in connection with the IDE161-001 Phase 1/2 clinical trial. We may be obligated to make aggregate payments of up to £2,250,000, subject to achievement of certain milestones through the Phase 1 and Phase 2 portions of the clinical trial in oncologic diseases - including aggregate payments of up to £1,500,000 for milestones relating to a first tumor histology (e.g., a breast cancer) and aggregate payments of up to £750,000 for milestones relating to in a different second tumor histology (e.g., ovarian cancer).

The royalty payments are subject to reductions for payment obligations in the event third-party licenses are required to develop or commercialize the product or if the product is not covered by certain patents.

Following our exercise of the option, if we sublicense certain intellectual property developed under the agreement or Cancer Research UK background patents specifically relating to PARG, we will also have an obligation to pay to Cancer Research UK low double digit percentage of sublicense revenue we receive, if any. If the agreement is terminated due to our material breach, then we are eligible to receive a percentage of sublicensing revenue that Cancer Research UK receives for licensing intellectual property.

If the agreement is terminated by Cancer Research UK and University of Manchester pursuant to any of their termination rights, then Cancer Research UK and University of Manchester will have exclusive, worldwide rights to project intellectual property. If we terminate the agreement for material breach, then the licenses we receive upon exercise of the option survive, and our payment obligations will be reduced. Following our exercise of the option, the licenses we receive upon exercise of the option survive expiration of the agreement.

Collaboration, Option and License Agreement with GSK for Pol Theta and Werner Helicase

In June 2020, we entered into the GSK Collaboration Agreement with GSK, pursuant to which we and GSK have entered into a strategic partnership and collaboration for our synthetic lethality programs targeting MAT2A, Pol Theta and Werner Helicase. On July 27, 2020, or the Effective Date, the GSK Collaboration Agreement became effective upon the parties’ receipt of Hart-Scott-Rodino Antitrust Improvements Act clearance, or HSR Clearance. We received from GSK an up-front payment of $100.0 million in cash following the Effective Date.

GSK Collaboration – MAT2A Program

Under the MAT2A program, the Company led research and development efforts through the early clinical development stage, and granted GSK an option to obtain an exclusive license to further the development and commercialization of MAT2A products arising out of the MAT2A program, or the Option.

The Company delivered an Option data package to GSK pursuant to the GSK Collaboration Agreement comprising preclinical and clinical data resulting from the Company's conduct of a dose-escalation portion of the MAT2A Phase 1 monotherapy clinical trial, following which, the Option was exercisable by GSK within a specified period of time.

In January 2022, GSK waived its rights under the GSK Collaboration Agreement to initiate, or request that the Company initiate, prior to GSK’s exercise of the Option, a Phase 1 combination clinical trial for a MAT2A product and GSK’s Type I PRMT inhibitor (GSK3368715) product, or the MAT2A Combination Trial. Accordingly, the Company has no further obligation under the GSK Collaboration Agreement to supply MAT2A product for the MAT2A Combination Trial at its own cost. IDEAYA’s obligation to supply the MAT2A compound under MAT2A Combination Study was deemed a material right under the GSK Collaboration Agreement. See Note 11, Revenue Recognition, for more information.

In August 2022, the Company received notice from GSK waiving its rights to exercise its Option, or the GSK MAT2A Option Waiver, pursuant to the GSK Collaboration Agreement. As such, the Company retains and fully owns all right, title and interest in and to IDE397 and the MAT2A program, including all worldwide commercial rights thereto. The Company will be responsible for the costs of further research and clinical development activities that the Company conducts for the MAT2A program following the GSK MAT2A Option Waiver. The Option was deemed a material right under the GSK Collaboration Agreement. See Note 11, Revenue Recognition, for more information.

GSK Collaboration - Pol Theta Program

Pursuant to the GSK Collaboration Agreement, GSK holds a global, exclusive license to develop and commercialize POLQ products arising out of the POLQ program. Following selection of the Pol Theta Helicase inhibitor development candidate, GSK will lead clinical development for the POLQ program. GSK will be responsible for all research and development costs for the POLQ program, including those costs, if any, incurred by us.

We will be eligible to receive future development and regulatory milestones of up to $485.0 million, with respect to each POLQ product, including as applicable, for multiple POLQ products that target certain alternative protein domains or are based on alternative modalities. Included within such development and regulatory milestones, we have the potential to receive up to $20 million in aggregate milestone payments from GSK for certain milestones, which may occur as we, in collaboration with GSK, advance a Pol Theta helicase inhibitor from preclinical development into early Phase 1 clinical trials, including up to $10 million aggregate for advancing this DC through IND effectiveness.

In June 2022, the Company announced the nomination of a Pol Theta Helicase inhibitor DC and in August 2022, announced the achievement of an initial preclinical development milestone in connection with ongoing IND-enabling studies to support evaluation of Pol Theta Helicase inhibitor DC, triggering a $3.0 million milestone payment, with the potential to receive up to an additional $7.0 million for advancing the Pol Theta Helicase inhibitor DC through IND effectiveness.

The Company is also entitled to receive tiered royalties on global net sales of POLQ products by GSK, its affiliates and their sublicensees ranging from high single digit to sub-teen double digit percentages, subject to certain customary reductions

Additionally, we are eligible to receive up to $475.0 million of commercial milestones with respect to each POLQ product. We believe there are potential synergies to evaluate a combination between our Pol Theta program and GSK’s approved PARP inhibitor, ZejulaTM, targeting the BRCA mutant and HRD patient population.

GSK Collaboration - Werner Helicase Program

Pursuant to the GSK Collaboration Agreement, GSK holds a global, exclusive license to develop and commercialize WRN products arising out of the WRN program. We and GSK will collaborate on ongoing preclinical research for the WRN program, and GSK will lead clinical development for the WRN program, with IDEAYA responsible for 20% and GSK responsible for 80% of such global research and development costs. The cost-sharing percentages will be adjusted based on the actual ratio of U.S. to global profits for WRN products, as measured three and six years after global commercial launch thereof.

We will be eligible to receive future development milestones of up to $485.0 million, with respect to each WRN product, including as applicable, for multiple WRN products that are based on alternative modalities. Included within such development and regulatory milestones, we have the potential to receive up to $20 million in aggregate milestone payments from GSK for certain milestones, which may occur as we, in collaboration with GSK, advance a WRN product from

preclinical development into early Phase 1 clinical trials, including up to $10 million aggregate for advancing this DC through IND effectiveness.

Additionally, we will be eligible to receive up to $475.0 million of commercial milestones with respect to each WRN product. We will be entitled to receive 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of WRN products by GSK, its affiliates and their sublicensees ranging from high single digit to sub-teen double digit percentages, subject to certain customary reductions. We will have a right to opt-out of the 50% U.S. net profit share and corresponding research and development cost share for the WRN program, and would be eligible to receive tiered royalties on U.S. net sales of WRN products by GSK, its affiliates and their sublicensees at the same royalty rates as for global non-U.S. net sales thereafter, with economic adjustments based on the stage of the WRN program at the time of opt-out.

GSK Collaboration - General

Under the terms of the GSK Collaboration Agreement, subject to certain exceptions, we and GSK will not, directly or through third parties, develop or commercialize other products whose primary and intended mechanism of action is the modulation of WRN or POLQ or MAT2A prior to the GSK MAT2A Option Waiver for an agreed upon period of time. We and GSK will form a joint steering committee, joint development committees, and joint commercialization committees responsible for coordinating all activities under the GSK Collaboration Agreement.

GSK’s 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.

Each party has the right to sublicense its rights under the GSK Collaboration Agreement subject to certain conditions.

The GSK Collaboration Agreement will continue in effect on a product-by-product and country-by-country basis until the expiration of the obligation to make payments under the GSK Collaboration Agreement with respect to such product in each country, unless earlier terminated by either party pursuant to its terms. Either we or GSK may terminate the GSK Collaboration Agreement for the other party’s insolvency or certain uncured breaches. We may terminate the GSK Collaboration Agreement if GSK or any of its sublicensees or affiliates challenge certain patents of the Company. GSK may terminate the GSK Collaboration Agreement in its entirety or on a target-by-target basis upon 90-day notice to us.

The GSK Collaboration Agreement contains various representations, warranties, covenants, dispute resolution mechanisms, indemnities and other provisions generally customary for transactions of this nature.

Sales and Marketing

We intend to become a fully-integrated biopharmaceutical company. This will enable us to realize our goal of delivering transformative drugs to patients. We currently hold worldwide commercialization rights to each of our product candidates, and intend to retain significant rights in key markets. In light of our stage of development, we have not yet established sales and marketing capabilities. We are planning for potential commercial operations, including for sales and marketing capabilities, subject to initiation of the potentially registrational Phase 2/3 clinical trial for darovasertib.

We plan to build our own sales force to commercialize approved products, if any, in the United States and potentially in Europe and other selected foreign countries, and we expect to initiate commercial readiness activities in anticipation of receiving marketing approvals. We believe a moderately sized specialty sales force would enable us to reach oncologists who specialize in treating the patient populations for our product candidates. We may enter into distribution and other marketing arrangements with third parties for any of our product candidates that obtain marketing approval.

We also plan to build a marketing and sales management organization to create and implement marketing strategies for any products that we market through our own sales organization and to oversee and support our sales force.

Manufacturing

We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates and our biomarker diagnostics for preclinical and clinical testing, as well as for future commercial manufacture of any drugs and diagnostics that we may commercialize. We do not own or operate, and currently have no plans to establish, any manufacturing facilities.

In general, we plan to establish agreements with contract manufacturing organizations, or CMOs, for synthesis of the active pharmaceutical ingredient, or API, manufacturing of drug product comprising such API, as well as packaging, labeling and distribution.

We have also established supply arrangements with one or more CMOs for IDE397 in support of our current clinical development needs.

We have also established our own supply arrangements with one or more CMOs for IDE196 in support of our current clinical development needs.

We have also established our own supply arrangements with one or more CMOs for IDE161 in support of our current clinical development needs.

Our lead product candidates darovasertib, IDE397 and IDE161 are each small molecules that can be manufactured in reliable and reproducible synthetic processes from readily available starting materials. We believe the synthetic chemistry is amenable to scale-up using standard manufacturing equipment and processes. We expect that the compounds being discovered and developed for our other pipeline programs, including Pol Theta, and WRN, and other future programs, will also be small molecule product candidates that can be produced at contract manufacturing facilities.

In many cases, we anticipate that the biomarker diagnostic may be commercially available on an existing third-party diagnostic panel or assay. In cases where such biomarker diagnostic is not already commercially available, we generally expect to establish agreements with strategic partners for clinical supply of companion diagnostics for biomarkers associated with the targeted therapeutics we are developing.

Government Regulation

Government authorities in the United States, at the federal, state and local level, and in other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing and export and import of products such as those we are developing. A new drug must be approved by the FDA through the new drug application, or NDA, process before it may be legally marketed in the United States.

U.S. Drug Development Process

In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or the FDCA, and its implementing regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval may subject an applicant to administrative or judicial sanctions. These sanctions could include the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us.

The process required by the FDA before a drug may be marketed in the United States generally involves the following:

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completion of preclinical laboratory tests, animal studies and formulation studies in accordance with good laboratory practice, or GLP, regulations and other applicable regulations;

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submission to the FDA of an IND, which must become effective before clinical trials in humans may begin;

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approval by an independent institutional review board, or IRB, at each clinical site before each clinical trial may be initiated;

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performance of adequate and well-controlled human clinical trials in accordance with good clinical practice, or GCP, regulations to establish the safety and efficacy of the proposed drug for its intended use;

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submission to the FDA of an NDA;

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satisfactory completion of an FDA advisory committee review, if applicable;

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satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with current good manufacturing practice, or cGMP, regulations to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; and

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FDA review and approval of the NDA.

Once a pharmaceutical product candidate is identified for development, it enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information and analytical data, to the FDA as part of the IND. The sponsor will also include a protocol detailing, among other things, the objectives of the first phase clinical trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated, if the first phase lends itself to an efficacy evaluation. Some preclinical testing may continue even after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. A clinical hold also may be imposed by the FDA at any time during a clinical trial due to safety concerns or non-compliance with specific FDA requirements, and the clinical trial may not continue until the FDA notifies the sponsor that the hold has been lifted.

All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCP regulations, which include the requirement that all research subjects provide their informed consent in writing for their participation in any clinical trial. They must be conducted under protocols detailing the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the safety and effectiveness criteria to be evaluated. Each protocol must be submitted to the FDA as part of the IND. An IRB at each institution participating in the clinical trial must review and approve each protocol before a clinical trial commences at that institution and must also approve the information regarding the clinical trial and the consent form that must be provided to each clinical trial subject or his or her legal representative, monitor the clinical trial until completed and otherwise comply with IRB regulations.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

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Phase 1: The product candidate is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion and, if possible, to gain an early indication of its effectiveness. In the case of some products for severe or life-threatening diseases, such as cancer, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing is often conducted in patients. Sponsors sometimes designate their Phase 1 clinical trials as Phase 1a or Phase 1b. Phase 1b clinical trials are typically aimed at confirming dosing, pharmacokinetics and safety in a larger number of patients. Some Phase 1b studies evaluate biomarkers or surrogate markers that may be associated with efficacy in patients with specific types of diseases.

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Phase 2: This phase involves clinical trials in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and appropriate dosage.

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Phase 3: Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population, generally at geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk-benefit ratio of the product candidate and provide, if appropriate, an adequate basis for product labeling.

Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA.

The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients. In addition, some clinical trials are overseen by an independent group of qualified experts organized by the sponsor, known as a data safety monitoring board or committee. Depending on its charter, this group may determine whether a clinical trial may move forward at designated check points based on access to certain data from the clinical trial.

During the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points. These points may be prior to submission of an IND, at the end of Phase 2, and before an NDA is submitted. Meetings at other times may be requested. These meetings can provide an opportunity for the sponsor to share information about the data gathered to date, for the FDA to provide advice, and for the sponsor and the FDA to reach agreement on the next phase of development. Sponsors typically use the meetings at the end of the Phase 2 clinical trial to discuss Phase 2 clinical results and present plans for the pivotal Phase 3 clinical trials that they believe will support approval of the new drug.

Concurrent with clinical trials, companies may conduct additional animal studies and also develop additional information about the chemistry and physical characteristics of the drug and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently

producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug. In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

While the IND is active and before approval, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or laboratory testing suggesting a significant risk to humans, and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.

There are also requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries. Sponsors of certain clinical trials of FDA-regulated products are required to register and disclose specified clinical trial information, which is publicly available at www.clinicaltrials.gov. Information related to the product, patient population, phase of investigation, clinical trial sites and investigators and other aspects of the clinical trial is then made public as part of the registration. Sponsors are also obligated to discuss the results of their clinical trials after completion. Disclosure of the results of these clinical trials can be delayed until the new product or new indication being studied has been approved.

U.S. Review and Approval Process

The results of product development, preclinical and other non-clinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the drug, proposed labeling and other relevant information are submitted to the FDA as part of an NDA requesting approval to market the product. The submission of an NDA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances. The FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity. The FDA conducts a preliminary review of all NDAs within the first 60 days after submission, before accepting them for filing, to determine whether they are sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In this event, the NDA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it for filing. Under the Prescription Drug User Fee Act, or PDUFA, the FDA has agreed to certain performance goals in the review of NDAs through a two-tiered classification system, standard review and priority review. According to the current PDUFA performance goals for new molecular entity NDAs, the FDA endeavors to review and act on applications within ten months of the 60-day filing date under standard review, and within six months of the 60-day filing date under priority review.

IDYA US Equity

IDYA · 10-K · period ended 2022-12-31

Item 1. Business.

IDYA US Equity☆

IDYA · 10-K · period ended 2022-12-31

Item 1. Business.

IDYA US Equity