#1September 2023 NASDAQ: IDYA IDEAYA Biosciences Improving Lives Through Transformative Precision Medicines IDEAYA BIOSCIENCES#22 Safe Harbor Statement Certain statements in this presentation and the accompanying oral commentary are forward-looking statements. These statements relate to future events or the future financial performance of IDEAYA Biosciences, Inc. (the "Company") and involve known and unknown risks, uncertainties and other factors that may cause the actual results, levels of activity, performance or achievements of the Company or its industry to be materially different from those expressed or implied by any forward-looking statements. In some cases, forward-looking statements can be identified by terminology such as “may,” “will,” “could,” “would,” “should,” “expect,” "plan," "anticipate," "intend," "believe," "estimate,” “predict,” “potential" or other comparable terminology. All statements other than statements of historical fact could be deemed forward-looking, including the potentially addressable patient population for the Company's programs, any expectations regarding the Company's target discovery platform or new target validation efforts as creating opportunities for research and development initiatives; any projections of financial information, market opportunities, cash runway or profitability; any statements about historical results that may suggest trends for the Company's business; any statements of the plans, strategies, and objectives of management for development programs or future operations; any statements about the timing of preclinical research, clinical development, regulatory filings, manufacturing or release of data; any statements of expectation or belief regarding future events, potential markets or market size, technology developments, or receipt of cash milestones, option exercise fees or royalties; and any statements of assumptions underlying any of the items mentioned. The Company has based these forward-looking statements on its current expectations, assumptions, estimates and projections. While the Company believes these expectations, assumptions, estimates and projections are reasonable, such forward-looking statements are only predictions and involve known and unknown risks and uncertainties, many of which are beyond the Company's control. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property, and other matters that could affect the sufficiency of existing cash to fund operations. These and other important factors may cause actual results, performance or achievements to differ materially from those expressed or implied by these forward-looking statements. The forward-looking statements in this presentation are made only as of the date hereof. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see the Company's periodic filings with the Securities and Exchange Commission (the "SEC"), including its Annual Report on Form 10-K for the year ended December 31, 2022, and any current and periodic reports filed thereafter. Except as required by law, the Company assumes no obligation and does not intend to update these forward-looking statements or to conform these statements to actual results or to changes in the Company's expectations. This presentation concerns anticipated products that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA). It is currently limited by Federal law to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated. BIOSCIENCES IDEAYA#33 IDEAYA Biosciences Highlights Leading Precision Medicine Oncology focused biotechnology company advancing transformative First-in-Class targeted and Synthetic Lethality (SL) therapies for cancer patients Broad Pipeline of Key Emerging Targets - Ph 2/3 Registrational: Darovasertib (PKC) MUM ■ - Ph 2: Darovasertib (Neo)Adjuvant Primary UM 2023 Target Milestones Darovasertib (PKC) / Crizotinib – Registrational in MUM - Phase 2/3 Registrational Trial - Phase 2 Program Update including ctDNA Data (ESMO Q4 '23) - - Ph 2: IDE397 (MAT2A) Ph 1: IDE397 + AMG 193 (PRMT5MTA) Ph 1: IDE161 (PARG) Ph 1: GSK101 (IDE705) (Pol Theta Helicase) Preclinical Lead Optimization: Werner Helicase Pharma Collaborations with Pfizer (CTCSA), Amgen (CTCSA), GSK (with ~$2B in potential milestones) Balance Sheet of ~$510M to fund ops into 20271,2 NASDAQ: IDYA (1) Includes aggregate of $510.1 M cash, cash equivalents and marketable securities as of June 30, 2023 (2) IDEAYA Form 10-Q dated August 10, 2023 as filed with the U.S. Securities and Exchange Commission IND=Investigational New Drug - Darovasertib (PKC) - Phase 2 in Primary UM Phase 2 in Neoadjuvant / Adjuvant UM (IST Update Q4 '23) IDE397 (MAT2A) - Phase 1/2 Phase 2 Monotherapy Expansion in High-Priority Tumors Phase 1 Amgen-Sponsored IDE397 + AMG 193 ■ IDE161 (PARG) - Phase 1/2 - Phase 1 Expansion in HRD Tumors (Program Updates H2'23) ■ GSK101 (IDE705) (Pol Theta Helicase) - Phase 1/2 Phase 1 GSK-Sponsored GSK101 + Niraparib (FPI Q4'23) Werner Helicase - Development Candidate (Nomination H2 '23) IDEA A BIOSCIENCES#44 Leading Functional Genomics and Synthetic Lethality Platform The Next Frontier in Precision Medicine Oncology Functional Genomics and SL provides a powerful approach to discover novel precision medicine therapies with patient biomarkers, including MTAP-deletion (~15% of solid tumors), BRCA/HRD (Breast, Prostate, Ovarian, Others), and high-MSI (15% GI Cancers) nature REVIEWS GENETICS • Functional genomics combines human genetics with advances in Al and machine learning to develop effective precision medicines Synthetic lethality occurs when the simultaneous perturbation of two genes results in cell death • Large-scale screening for novel synthetic lethal targets has progressed through advances in molecular biology (e.g., RNA interference, CRISPR-Cas9 editing) and bioinformatics RNA processing Chromatin & transcription Ribosome & translation Mitochondria Peroxisome Nature Reviews Genetics, Vol. 18, 2017, Hieter, et al., as edited by IDEAYA Metabolism & amino acid biosynthesis Secretion & vesicle transport Protein folding & glycosylation Cell wall biosynthesis Nuclear- cytoplasmic transport Nuclear migration & protein degradation Reference: Charles Boone Mitosis & chr. segregation DNA replication & repair Cell polarity & morphogenesis - IDEAVA BIOSCIENCES#55 IDEAYA Leadership Team and Scientific Advisory Board Experienced Team & Scientific Thought Leaders in Precision Medicine Oncology IDEAYA Executives & R&D Leadership Yujiro Hata, M.B.A. Chief Executive Officer, Director FLEXUS ONYX ENANTA AMGEN BIOSCIENCES Bristol-Myers Squibb Pharmaceuticals Matthew Maurer, M.D. Head of Clinical Oncology & Medical Affairs Bristol-Myers Squibb COLUMBIA Darrin Beaupre, M.D., Ph.D. Chief Medical Officer Pfizer pharmacyclics AMGEN Mick O'Quigley, M.B.A. Head of Development Operations Genentech AMGEN Michael White, Ph.D. Chief Scientific Officer Pfizer UT Southwestern Medical Center. Paul Barsanti, Ph.D. Chief Technology Officer AM VENTURES 5 nurix NOVARTIS CHIRON Paul Stone, J.D. Chief Financial Officer 5AM VENTURES ILYPSA AMGEN Jason Throne, J.D. Chief Legal Officer 0 neotract THORATEC CORPORATION IDEAYA Scientific Advisory Board Frank McCormick, Ph.D. SAB Chair UCSF, Professor and former Director, Helen Diller Cancer Center Former President AACR; Founder and CSO, Onyx Karlene Cimprich, Ph.D. Professor, Chemical and Systems Biology and (by courtesy) Biochemistry, Member, Stanford Cancer Institute, Stanford University Trey Ideker, Ph.D. UCSD, Professor, Co-Director Cancer Genomes & Networks Program, Research in Dual-CRISPR and SL interaction maps Kornelia Polyak, M.D., Ph.D. Professor of Medicine at Dana-Farber Cancer Institute, Harvard Medical School, and a co-leader of the Dana-Farber Harvard Cancer Center Cancer Cell Biology Program William Sellers, M.D. Broad Institute, Dana Farber, and Harvard, Professor Novartis, Former Head Oncology Research, SL Project Drive initiative Elizabeth Swisher, M.D. University of Washington, Professor; Co-Leader, Breast and Ovarian Cancer Research Program, Seattle Cancer Care Alliance Principal Investigator on multiple PARP inhibitor trials IDEAVA BIOSCIENCES#66 IDEAYA Precision Medicine Oncology Platform Fully-Integrated Target, Biomarker, Drug Discovery and Translational Capabilities Target & Biomarker Discovery and Validation . • . Bioinformatics, including Al Algorithms Dual CRISPR, CRISPR, Chemogenomics Genetically Engineered Models Drug Discovery and Pharmacological Validation Key emerging novel targets identified, such as Werner Helicase, Pol Theta Helicase and PARG DECIPHER™ - Dual CRISPR SL Library in DDR Cell Lines in collaboration with UCSD PAGEOTM - Paralogous Gene Evaluation in Ovarian in collaboration with Broad Institute Machine Learning and Multi-Omics platform Structure Based Drug Design Small Molecule Chemistry Protein Degrader Capabilities Translational Research and Opportunity Expansion Genomics - DNA and RNA Analysis Proteomics - Protein Expression Profiling Tissue (IHC, IF) and Liquid Biopsies Analysis Crystal structures for SL discovery programs obtained to enable structure-based design INQUIRE™ Chemical Library - proprietary, expert-curated small-molecule library • HARMONY™ Machine-Learning engine empowers drug discovery platform Differentiated clinical / candidate compounds discovered, including IDE397, IDE161 and GSK101/IDE705 (Pol Theta Helicase) • . . Translational research to define clinical biomarkers Opportunity expansion through broad cell panel screening Pharmacodynamic biomarker analysis to confirm target modulation and correlation with clinical activity IDEAVA BIOSCIENCES#7IDEAYA Functional Genomics and Synthetic Lethality Platform S Novel Target and Biomarker Discovery and Validation Target and Biomarker Discovery & Validation Platform IDEAYA Functional Genomics Platform integrates proprietary and public data sets with orthogonal and complementary content Bioinformatic analysis enables identification and validation of synthetic lethal target / biomarker interactions across vast datasets Robust SL interactions validated genetically (Dual CRISPR, paralogues, isogenic pairs, CRISPR/siRNA), pharmacologically and in vivo Data-to-Knowledge Enterprise fueled by multi-omic patient and molecular data across public, partnership and proprietary data sets via IDEAYA Bioinformatics Platform Public Data Partnership Data Proprietary Data DECIPHER™ Dual CRISPR SL Library in DNA Damage Repair (2) PAGEO™M Paralogous Gene Evaluation in Ovarian Cancer (1) Я я 1 Paralog A Paralog B +/- Inhibitor Machine Learning and Multi-Omics Integration Dimensionality Reduction Clustering Methods -4 -10 1 Feature Selection Enrichment Analyses Predictive Modeling Evaluation of DNA Damage Targets synthetic lethal with tumor suppressor or oncogenes Evaluation of SL targets in context of functionally redundant paralogous genes in ovarian cancer Д Partnership Datasets Public Databases TCGA BioPortal CCLE Targets, Biomarkers and MOA Target Evaluation and Prioritization depmap portal FOUNDATIONINSIGHTS TM PROJECTGENIE Genomics Evidence Neoplasia Information Exchange Project Achilles MSK-IMPACT™ Kettering Memorial Ste 7 (1, 2) IDEAYA Proprietary Libraries and Datasets - Strategic Collaborations with Broad Institute (1) and UC San Diego(2) IDEAVA BIOSCIENCES#88 + IDEAYA Precision Medicine Oncology Drug Discovery Platform Structure-Based Drug Design & Proprietary Chemical Library Enable "Hard to Drug" Targets Structural Biology & Structure Based Drug Design Full suite of capabilities in structural biology, biophysics, & computational chemistry Ligand bound co-crystal structures resolved to enable Structure Based Drug Design for each of the Synthetic Lethality drug-discovery programs Multiple potential "first-in-world" co-crystal structures resolved, including for PARG, Pol Theta Helicase and Werner Helicase INQUIRE™ Proprietary Chemical Library Expert-curated HTS library to enhance hit discovery capabilities against novel SL targets classes, such as helicases and endonucleases Enhances IDEAYA's SL Drug Discovery Platform and competitive differentiation HARMONY™ Proprietary Machine-Learning Internal Machine-Learning engine empowers discovery platform through effective prioritization leading to efficient SAR cycles IDEAVA BIOSCIENCES#9IDEAYA's Potential First-in-Class Precision Medicine Oncology Pipeline Building an Industry Leading and Fully-Integrated Biotechnology Company Precision Medicine Pipeline Modality/Indication Collaborations Commercial (IDEAYA) Biomarker Pre- clinical IND Enabling Phase 1 Phase 2 Potential Registrational Program Goals / Achievements +CMET¹ Combination 1L HLA-A2(-) MUM GNAQ/11 Phase 2 (AA) / Phase 3 Registrational Trial * Initiated Darovasertib +CMET¹ Combination GNAQ/11 PKC HLA-A2(+) MUM ^ Pfizer (1) HLA-A2(+) Clinical Trial ^ WW Commercial Rights (Neo) Adjuvant UM GNAQ/11 Monotherapy Solid Tumors MTAP IDE397 MAT2A Combinations MTAP Solid Tumors IDE161 PARG Breast, Ovarian HRD Cancers GSK101 +Niraparib Combo4 Pol Theta Helicase Solid Tumors HR Mutations Phase 2 Clinical Trial Initiated IST Update Q4 2023 Phase 2 Monotherapy Expansion in NSCLC, Bladder, Esophageal and Gastric Cancers Phase 1 IDE397 + AMG 193 (PRMT5¡MTA) Amgen-Sponsored Combination Study Initiated Phase 1 Monotherapy Expansion in HRD Tumors Program Updates H2 2023 Phase 1 GSK101 (IDE705) + Niraparib Earned $7M Milestone IND Clearance WW Commercial Rights AMGEN (2) CANCER RESEARCH (3) WW Commercial Rights UK WRN Werner Helicase Gl Cancers High-MSI Development Candidate H2 2023 Potential $3M Milestone IND-Enabling Studies GSK (4) GSK (4) Global Royalties US 50/50 Profit Share Ex-US Royalties Platform Solid Tumors Defined Biomarkers New Target / Biomarker Discovery & Validation Drug Discovery / Translational Biology WW Commercial Rights 9 +Integrated Phase 2/3 enables potential Accelerated Approval (AA, Phase 2) and potential Full Approval (Phase 3) based on FDA Type C Meeting Q1 2023 ^ Targeting enrollment of additional HLA-A2(+) patients in a separate clinical trial (e.g., ongoing IDE196-001 Phase 2 clinical trial) (1) Pursuant to Pfizer Clinical Trial Collaboration and Supply Agreements for Darovasertib/Crizotinib Combination in MUM; IDEAYA retains all Darovasertib Commercial Rights (2) Pursuant to Amgen Clinical Trial Collaboration and Supply Agreement for IDE397 + AMG 193, an investigational MTA-cooperative PRMT5 inhibitor; Amgen will sponsor the study and the parties will jointly share external costs of the study (3) Pursuant to CRUK Evaluation, Option and License Agreement; IDEAYA controls all PARG Commercial Rights (4) Pursuant to GSK Collaboration, Option and License Agreement: Pole: Global Royalties; WRN: 50/50 US Profits + ex-US Royalties MAT2A-methionine adenosyltransferase 2a, MTAP-methylthioadenosine phosphorylase, MTA-methylthioadenosine, PRMT5-protein arginine methyltransferase 5 (PRMT5), PARG= poly (ADP-ribose) glycohydrolase, DDT = DNA Damage Target, WRN = Werner Helicase, Pole = DNA Polymerase Theta, HRD = homologous recombination deficiency, MSI = microsatellite instability, PKC = protein kinase C, MUM = metastatic uveal melanoma, UM = uveal melanoma, Crizo = crizotinib, NSCLC = non-small cell lung cancer, WW = worldwide, HLA-A2(-) = HLA-A2*02:01 Negative; HLA-A2(+) = HLA-A2*02:01 Positive = Target Program Milestones IDEA A BIOSCIENCES#1010 Darovasertib - Darovasertib – Potential to Broadly Impact Uveal Melanoma Potential First-in-Class and Best-in-Class in (Neo)adjuvant UM and Metastatic UM Mutations in GNAQ / GNA11 activate PKC Signaling, a genetic driver of Uveal Melanoma anna GNAQ or GNA11 11. PIP DAG PKC RASGRP3 RAS BY GDP GTP q/11 q/11 Q209L IP MARCKS Daro Ca2 Ca2+ Daro Mono Rationale in Primary UM Single Agent Daro Induces Tumor Regression Uveal Melanoma Xenograft (92.1 mutant GNAQ) 1200 Vehicle Daro 150 mg/kg BID RAF MEK P ERK Darovasertib is an oral, potent and selective PKC inhibitor GNAQ or GNA11 (~95%) and other upstream mutations activate PKC signaling in UM and MUM patients UM is typically treated with radiation and/or enucleation, with no approved systemic therapies for Neoadjuvant UM MUM occurs in approximately 50% of UM patients and predominantly as liver metastasis in ~90% of MUM patients, with no approved therapies for HLA-A*02:01 negative MUM Daro + Crizo Combo Rationale for Use in Metastatic Uveal Melanoma (MUM) Daro Phase 1 Monotherapy Efficacy Association with CMET Expression 6 5 радра88 + 2Pfizer Activation of PKC and CMET Pathways with Observed CMET Overexpression in MUM Liver Metastases PKC Signaling HGF/MET Signaling CMET CMETI wwwwwwww Tumor volume (mm3) mean ± SEM 1000- 800- 600 400 stop dosing 200 re-dose 150mpk bid MET Signature Score 800 0 20 30 40 50 60 70 80 50 100 110 Days post tumor implantation Van Raamsdonk, CD, et. al, Nature 2009; Van Raamsdonk CD, et. al, NEJM 2010; Piperno-Neumann S, et. al, J Clin Oncol 2014 -1 PD SD<6mos SD>=6mos PR Ph 1 Clinical Outcomes PD=Progressive Disease, SD=Stable Disease, PR=Partial Response IDEAYA Data, AACR 2021 + Pfizer Clinical Trial Collaboration and Supply Agreements for Darovasertib + Crizotinib Combination in MUM IDEAYA owns or controls all commercial rights in darovasertib, including in Primary UM and MUM GDP GNAQ or GNA11 Q209L Daro wwwwww PKCб/E Cancer Cell Survival and Proliferation GA IDEA A BIOSCIENCES#11Phase 2 Clinical Trial - Comparatively High-Risk, Poor Prognosis Population Disease Burden Significantly Higher in Both Any-Line and First-Line MUM Population+ * IDE196-001 Phase 2* Darovasertib + Crizotinib Tebentasfusp First-Line Phase 3# Baseline Characteristics Any-Line n=63 (%) First-Line n=20 (%) < 65 35 (56) 10 (50) Tebe Arm n=252 (%) 64 Median Control Arm^ n=126 66 Median Age ≥65 28 (44) 10 (50) F 32 (51) 9 (45) 124 (49) 64 (51) Sex M 31 (49) 11 (55) 128 (51) 62 (49) 0 43 (68) 14 (70) 192 (76) 85 (67) ECOG PS 1 20 (32) 6 (30) 49 (19) 31 (25) Normal 25 (40) 10 (50) Baseline LDH >ULN 38 (60) 10 (50) 90 (36) 46 (37) ≤3.0 cm 22 (35) 8 (40) 139 (55) 70 (56) Largest metastatic lesion 3.1 to 8.0 cm 35 (56) 9 (45) 92 (37) 46 (37) ≥ 8.1 cm 6 (10) 3 (15) 21 (8) Location of metastases Hepatic Only Extrahepatic Only 20 (32) 10 (50) 131 (52) 3 (5) 0 9 (4) Hepatic and Extrahepatic 40 (64) 10 (50) 11 + Cross-trial comparisons are not based on head-to-head studies and are presented for informational purposes; no direct comparisons are being made *IDEAYA Data as of March 08, 2023 (based on preliminary analysis of unlocked database by investigator review) # N Engl J Med 2021; 385:1196-1206; ECOG data missing in Tebentafusp and Control arm of 4% and 7% respectively ^Investigator Choice distribution in the control group: 103 (82%) received pembrolizumab, 16 (13%) received ipilimumab, and 7 (6%) received dacarbazine. 111 (44) 10 (8) 59 (47) 10 (8) 55 (44) IDEA A BIOSCIENCES#1212 First-Line MUM Clinical Efficacy Observed Compelling Confirmed Overall Response Rate and Disease Control Rate Darovasertib + Crizotinib Phase 2 First-Line MUM (n= 20) Confirmed 45% ORR and 90% DCR Best Tumor Response (%) 60% 50% 40% 30% 20% 10% 0% -10% -20% -30% ess -40% -50% -60% -70% -80% + Confirmed Partial Response + + Response by RECIST 1.1 Evaluable First-Line MUM (N=20) Confirmed ORR (9/20) 45% PD Tumor Shrinkage (19/20) 95% >30% Tumor Shrinkage (11/20) 55% SD Best Overall Response CPR (9/20) 45% PR uPR (1/20) 5% SD (8/20) 40% DCR (18/20) 90% Clinical Efficacy supports Registrational Strategy in First-Line MUM to Enhance Patient Benefit IDEAYA Data: preliminary analysis of unlocked database as of 03/08/2023 by investigator review; data cutoff based on treatment Day 1 of Cycle 1 (C1D1) as of 9/22/2022, based on 20 evaluable First-Line MUM patients ORR = Overall Response Rate; DCR = Disease Control Rate; CPR = Confirmed Partial Response; uPR = Unconfirmed Partial Response; SD = Stable Disease IDEAVA BIOSCIENCES#1313 Any-Line MUM and Hepatic-Only MUM Clinical Efficacy Clinical Efficacy irrespective of HLA-A2 Status and in Hepatic & Extra-Hepatic Metastases 60% 50% 40% 30% Darovasertib + Crizotinib Phase 2 Any-Line MUM (n=63) Confirmed 30% ORR and 87% DCR Response by RECIST 1.1 Any-Line MUM Best Tumor Response (%) Best Tumor Response (%) 20% 10% 0% -10% -20% -30% -40% -50% First Line Patients Pretreated Patients -60% -70% Heavily pretreated with 68% having >1 prior line and 43% with >2 prior lines of therapy in metastatic setting -80% 40% 30% 20% 10% 0% -10% -20% -30% -40% -50% -60% -70% -80% Evaluable (N=63) 30% PD Confirmed ORR (19/63) 92% Tumor Shrinkage (58/63) SD 41% >30% Tumor Shrinkage (26/63) Best Overall Response PR CPR (19/63) + + +++++ ++ uPR (4/63) + + + SD (32/63) + Confirmed Partial Response +++ 30% 6% 51% 87% DCR (55/63) Darovasertib + Crizotinib Phase 2 Hepatic-Only MUM (n= 20) + + + + + + Confirmed Partial Response + Confirmed 35% ORR and 100% DCR Response by RECIST 1.1 Evaluable PD in Hepatic-Only MUM (N=20) Confirmed ORR (7/20) 35% SD Tumor Shrinkage (20/20) 100% >30% Tumor Shrinkage (9/20) 45% PR Best Overall Response CPR (7/20) UPR (1/20) SD (12/20) DCR (20/20) 35% 5% 60% 100% IDEAYA Data: preliminary analysis of unlocked database as of 03/08/2023 by investigator review, C1D1 cutoff as of 9/22/2022, based on 63 evaluable Any-Line and 20 evaluable Hepatic-Only (includes 1L and 2L+/pre-treated) MUM patients ORR = Overall Response Rate; DCR = Disease Control Rate; CPR = Confirmed Partial Response; uPR = Unconfirmed Partial Response; SD = Stable Disease IDEA A BIOSCIENCES#14Median PFS in First-Line, Any-Line and Hepatic-Only MUM Observed Compelling Median Progression Free Survival with Encouraging Trend Any-Line MUM Swimlane Plot 00 First Response Progressive Disease Stable Disease End of Treatment Ongoing Treatment 10 12 14 16 18 20 22 24 Darovasertib + Crizotinib Phase 2 • Median Progression Free Survival First-Line (n=20): ~7 months Any-Line (n=63): ~7 months Median PFS has increased versus previously reported mPFS of ~5 months (n=35, September 2022*) Hepatic-Only (n=20): ~11 months 14 IDEAYA Data: preliminary analysis of unlocked database as of 03/08/2023 by investigator review, C1D1 cutoff as of 9/22/2022, based on 63 evaluable Any-Line MUM patients IDEAYA Press Release September 11, 2022 IDEAVA BIOSCIENCES 0 2 4 6 Months Since C1D1#15Darovasertib + Crizotinib First-Line MUM Combo Efficacy Examples of cPRS with Significant Tumor Shrinkage in First-Line MUM Patients First-Line MUM Patient 40+ year old HLA-A2 positive patient with Class 1A diagnosis metastasized after ~6 years Diffuse disease in liver and pelvis with elevated LDH of 800 normalized within one month of treatment Large tumors (SLD = 210 mm) reduced by 49% On treatment for over 15 months Baseline 12 months Many lesions distorting and replacing the liver Marked improvement across all lesions 15 IDEAYA Data as of 03/08/2023 (based on preliminary analysis of unlocked database); tumor lesion reductions by investigator review First-Line MUM Patient • • 40+ year old HLA-A2 negative patient with Class 1A diagnosis metastasized in ~1 year Many liver lesions with maximal target lesion reduction of 65% Ongoing response Remains on treatment at 10 months Baseline 8 months Many liver lesions & target lesion Marked improvement across all lesions IDEAVA BIOSCIENCES#16Darovasertib + Crizotinib Combination Clinical Summary in MUM Highly Differentiated Clinical Efficacy & AE Profile Observed*** Darovasertib + Crizotinib Cabozantinib Mono / Crizotinib Mono Selumetinib + DTIC Target/Mechanism PKC + CMET CMET MEK + Chemotherapy Study Name(s) NCT03947385 A091201^/NCT05063058^^^^ NCT01974752^^^ NCT02626962## Population 1L/2L/3L+ MUM (n=63) 1L+ MUM (n=31) / 1L (n=6) 2L (n=1) MUM 1L+ MUM (n=97) 1L MUM (n=52) Patient Selection NA NA/MET Overexpression NA Ipi + Nivo CTLA4 + PD1 ΝΑ Tebentafusp HLA-A2-0201 Bi-Specific IMCgp100-102# 2L+ MUM (n=127) HLA-A2-positive Oral Tablets Oral Capsules 33% 51.6% / NA 23% ^^/NA Drug Form Tolerability (Grade ≥3 Drug-Related AE) % of Patients with Tumor Shrinkage Confirmed ORR% (by RECIST 1.1) Median PFS First-Line = 95% / Any-Line = 92% / Hepatic Only 100%* = First-Line = 45% / Any-Line = 30% / Hepatic Only = 35%* First-Line: ~7 months / Any-Line: ~7 months / Hepatic-Only: 11 months* 0% / 0% 2 months/ NA + Cross-trial comparisons are not based on head-to-head studies and are presented for informational purposes; no direct comparisons are being made ++ ESMO 2022: F. Dimitriou, et.al: IPI + Nivo Combo in HLA-A2-0201 MUM reports ~6% ORR (2 PRS out of 33 patients) * IDEAYA Data: preliminary analysis of unlocked database as of 03/08/2023 by investigator review, and C1D1 cutoff as of 9/22/2022 11.5% 3% (not confirmed ORR) 2.8 months 3 months 4.7% 2.8 months # Based on Immunocore reported 2L+ study data (to reflect comparative patient population) and by independent review and ORR% was with confirmed PRs; ## ASCO 2021, J. Piulats, et. Al, Ipi = ipilimumab, nivo = nivolumab, ORR% did not require PR/CR confirmation ^ Randomized Phase II Trial and Tumor Mutational Spectrum Analysis from Cabozantinib versus Chemotherapy in Metastatic Uveal Melanoma (Alliance A091201); Clin Cancer Res 2020;26:804-11 Oral Capsules + chemo IV infusion IV Infusion (Weekly) 63% (All Cause) 58% 46.5% 35% ^^ 27%^ 44% ^^ 16 ^^ Estimated from Waterfall plot ^^^ Journal of Clinical Oncology, Carjaval, et. al, 2018; 1232-1239;1 European Journal of Cancer, Leyraz, et. al, 2022; 146-155 ΑΛΛΑ IDEA A BIOSCIENCES#1717 Accelerated Approval Trial Design in First-Line HLA-A2 Negative MUM FDA Guided Design: Open Label Ph2/3 Evaluation of Daro + Crizo vs. Investigator's Choice FDA Project Front Runner: Target First-Line approval strategy to enhance patient benefit in MUM FDA Accelerated Approval: Address unmet need in MUM, which has limited effective treatment options Integrated Phase 2/3 Study within Study Enables Potential Accelerated Approval & Full Approval Targeting FPI Q3 2023 Median PFS Median OS Phase 2 A Daro + Crizo Investigator's Choice Phase 3 2:1 Randomization ~230 Ph 2/3 Patients + 2:1 Randomization +~120 Ph 3 Patients Accelerated Approval Full Approval FDA Fast Track Designation for Daro + Crizo in MUM A Nested study to confirm move forward dose: (i) Daro 300 mg BID + Crizo 200 mg BID or (ii) Daro 200 mg BID + Crizo 200 mg BID Phase 2 study contemplates data set of n=200 patients randomized 2:1 with treatment arm at move forward dose in support of potential accelerated approval based on mPFS Daro Darovasertib, Crizo = Crizotinib, MUM-Metastatic Uveal Melanoma, HLA-A2 = HLA-A2*02:01 Serotype, IC = Investigator's Choice, Ipi = ipilimumab, nivo = nivolumab; DTIC = dacarbazine 2:1 Randomization Daro + Crizo vs Investigator's Choice (IC = Ipi + Nivo, PD1, or DTIC) Primary Endpoints (BICR) Accelerated Approval: mPFS Full Approval: mOS IDEAVA BIOSCIENCES#1818 Darovasertib Monotherapy in (Neo)adjuvant Primary Uveal Melanoma Clinical Experience: Observed 100% of Patients (9 of 9) with Ocular Tumor Reduction^ IDEAYA Phase 2 and IST ongoing to evaluate Darovasertib Current Treatment Approach following diagnosis of UM depends on tumor size and location: Enucleation in Large Tumors (~ 20%) Radiation in Small/Medium Tumors (~80%) Plaque Brachytherapy Clinical Experience in UM and MUM Patients Neoadjuvant UM Enucleation Cohort ** (n=6) Treatment Duration (mo) MUM Intact Primary Ocular Tumors* (n=3) Plaque Placement lodine-125 Plaque Surgery, UCLA Poor Vision (≤20/200) occurs in about 70%-80% of patients with UM (including enucleation) Neoadjuvant / Adjuvant Systemic Therapy goals: Avoid Nucleation → Save the Eye Reduce Tumors and Radiation Dose → Protect Vision Reduce Occurrence of Metastasis → Save Lives Paradigm Shifting Opportunity to Broadly Impact UM, with annual incidence of ~8,000 - 10,000 patients in US, EU + Neoadjuvant UM or MUM patients treated with Darovaserib + Crizotinib Best Ocular Tumor Response (%) 1 1 0% -10% -20% -30% -40% Treatment Duration (mo) Γ I 2 4 1 4 7 0.5 11 I 0% -10% -20% + -30% I -60% Eye Saved -40% -50% -60% I -70% I + -80% | Eye -90% Saved -100% -50% -70% -80% -90% I CASE STUDIES + Darovasertib + Crizotinib + Each Reported Case has shown a Reduction in Size of Ocular Eye Lesion ** Data by investigator assessment as of April 15, 2023, from (i) NADOM IST courtesy of Professor Anthony Joshua, MBBS, PhD, FRACP, St. Vincent's Hospital, with update as of June 22, 2023 for monotherapy NADOM IST patient who was spared enucleation (ii) Compassionate Use Case; for NADOM IST, by initial protocol the first 3 neoadjuvant UM patients were required to stop treatment at ~1 month; IST protocol was subsequently amended to treat up to 6 months ^ Best Ocular Tumor Response based on maximal % reduction in measured Apical Height or Longest Basal Diameter (LBD) * Ocular tumor shrinkage measured by investigator assessment by either MRI, ultrasound, CT-scan, or PET scan (0.5 month scan for MUM patient, SUV Max% tumor response) IDEA A BIOSCIENCES#19Case Studies of Saved Eyes: Neoadjuvant Treatment of UM Patients Initial Cases of Systemic Neoadjuvant Therapy resulting in Prevention of Enucleation Case 1: Eye Saved by Neoadjuvant Treatment +^ UM patient was blind in one eye, developed a large ocular tumor in other eye causing vision loss, and diagnosed with UM Large Ocular Lesion – 16.5 mm Apical Height x 18 mm LBD Tumor Shrinkage observed at each month of treatment with Darovasertib + Crizotinib (~30% at 1 mo and ~80% at 4 mo) Avoided Enucleation and prevented complete blindness Restored > Normal Vision with neoadjuvant treatment and intraocular lens replacement for treatment of cataracts Residual Tumor treated with Plaque Brachytherapy Patient remains on Daro + Crizo Combination Therapy Baseline Scan: 16.5mm Apical Height 4 Month Scan: 3.5 mm Apical Height Regressed Tumor Not Impeding Optic Disc & Macula Large Tumor Impeding Optic Disc & Macula Macula + * Baseline Scan Case 2: Eye Saved by Neoadjuvant Treatment UM patient with large tumor enrolled in NADOM IST study Reduction in Tumor Size of ~24% observed following 4 mo neoadjuvant treatment with darovasertib Tumor Proximity to Optic Disc and Macula - observed increased separation from tumor following treatment for 3 mo Avoided Enucleation and Preserved Vision Residual Tumor treated with Plaque Brachytherapy Tumor Distance of tumor tip to optic disk at baseline 3 Month Scan Tumor Patient remains on Darovasertib as Adjuvant Therapy + Ocular tumor shrinkage based on % reduction in tumor apical height; LBD = Largest Basal Diameter 19 ^ Data and images courtesy of Dr Rod O'Day, LLB (Hons), BSc, MBBS (Hons), FRANZCO, Ocular Oncology Unit Royal Victoria Eye and Ear Hospital, Melbourne Australia. Additional patient care provided by Dr Daniel McKay, MBBS(Hons) FRANZCO FRCPA and Dr John McKenzie, MBBS, FRACS, FRCOphth, FRANZCO * Data and images courtesy of Professor Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent's Hospital in Sydney, a principal investigator in the NADOM IST Optic Disc Increased separation of tumor after 3 mo treatment BIOSCIENCES IDEAVA#20(Neo)Adjuvant Darovasertib in Primary Uveal Melanoma (UM) Paradigm Shifting Opportunity to Save the Eye, Protect Vision and Save Lives Phase 2 Study of Darovasertib Monotherapy as Neoadjuvant Therapy followed by Adjuvant Therapy Targeting FPI Q3 2023 Primary Local Therapy Adjuvant 20 20 Neoadjuvant Enucleation Cohort (n~40) Brachytherapy Cohort (n~40) Treatment to Maximum Benefit up to 6 Months Primary Endpoints • Safety • Cohort 1: Eye Preservation Adjuvant Therapy + Follow-Up • Cohort 2: Decrease in Radiation Dose Secondary Endpoints Adjuvant Therapy + Follow-Up • Useful Vision (1 yr) • Relapse Free Survival (RFS) Treatment up to 6 Months • Local (1 yr) . Distal (3 yr) Neoadjuvant Proof of Concept Adjuvant Proof of Concept Three Independent Approaches for demonstrating Clinical Benefit and defining potential Approval Pathways Enucleation Cohort Save the Eye Brachytherapy Cohort Protect Vision Adjuvant Therapy Save Lives BIOSCIENCES IDEAVA#21Darovasertib Clinical & Commercial Strategy in Uveal Melanoma Indication High Unmet Need and Multiple First-Line Opportunities across the Patient Journey Indication is the Diagnostic: +95% of UM patients harbor GNAQ/GNA11 or upstream activating mutation of PKC-signaling, enabling Broad Applicability of Darovasertib in this Indication HLA-A2-Negative (~60-65% of UM / MUM)** No FDA Approved Therapies* Neoadjuvant UM Daro Phase 2 Enucleation Define Accelerated Approval Daro Phase 2 Radiation Define Accelerated Approval Path Path No FDA Approved Therapies* Uveal Melanoma Patient Journey Adjuvant UM First-Line MUM Pretreated MUM Daro Phase 2 Define Accelerated Approval Path Therapies* No FDA Approved Daro + Crizo Registrational Trial Accelerated Approval Daro + Crizo Target NCCN / Compendia Listing HLA-A2-Positive (~35-40% of UM / MUM)** Target Treatment Duration Target Clinical Endpoints Annual Incidence US/EU** Total Prevalence US/EU** >6 months Eye & Vision Preservation >6 months Relapse Free Survival mPFS + ~3 months ORR, mPFS, MOS mPFS + ~3 months ORR, MPFS, MOS ~8-10k ~100k ~8-10k ~100k ~4-5k ~14k FDA Orphan Drug Designation in Uveal Melanoma+ 21 *No FDA approved systemic therapies in multiple UM and MUM indications across the patient journey **IDEAYA data: HLA-A2-positive and HLA-A2-negative prevalence in MUM based on IDEAYA clinical trial data; US/EU MUM annual incidence and total prevalence based on market research analysis Orphan Drugs benefit from certain tax credits and may be excluded from certain mandatory price negotiation provisions of the 2022 Inflation Reduction Act IDEAVA BIOSCIENCES#2222 MAT2A MAT2A Inhibition is Synthetic Lethal with MTAP Deletion Strategies to address MTAP-/- Prevalence in ~15% of all Solid Tumors MTAP-MAT2A Synthetic Lethality Biology MTAP Methionine MAT2A is key enzyme that produces SAM in cells MTAP deletion leads to MTA accumulation MAT2A MAT2A inhibitor MTA accumulation partially inhibits PRMT5 MTA MTA PRMT5 Inhibition of MAT2A results in reduction of SAM, starving PRMT5 of its substrate MTA Endogenous Suppression in MTAP-/- PDX Models AMGEN® Methylation Pathway Suppression in MTAP(-/-) Squamous Lung (LUSC) SDMA Effect Size (PDX Tissue Microarray) Full Cohort MTAP(-/-) Fraction -log10(pval) 6- 4- 2- LUSC LUSC 300- Nuclear SDMA H-score 200₁- 100)- p-value <0.0001 0. MTAP wt n=44 MTAP (-/-) n=12 Histology 2 no sig. diff. ° Protein Methylation SAM Loss of methylation function of PRMT5 results in defects in RNA splicing, gene expression and genome integrity 0- Histology 2 -0.25 0.00 0.25 Effect Size 0.50 0.75 1.00 IDEAYA Data: AACR 2023 (M. Fischer et al.) - Volcano plot comparing nuclear SDMA H- Score by IHC in MTAP(-/-) relative to MTAP wt across tissue microarray (TMA) of treatment-naïve PDX models; LUSC shows most significance effect across tumor histologies Nuclear SDMA H-score 300 200- 100 - 0 - MTAP wt n=13 MTAP (-/-) n=6 IDEAVA BIOSCIENCES#2323 Tumor Growth Inhibition (%) 100- 50- IDE397 Demonstrates Broad Efficacy across MTAP-deficient PDX Models Deep Regressions observed in NSCLC-squamous (LUSC), Esophageal and Bladder Cancers IDE397 Efficacy: 47 MTAP-/- PDX Models TGI with IDE397 (30mpk) in MTAP-/- PDX Panel 150- IDE397 In Vivo Efficacy in LUSC PDX Models Observed Tumor Regressions in 50% of LUSC PDX Models Vehicle IDE397 30mg/kg QD PDX1 750- PDX2 750- Pancreatic Head & Neck Gastric Bladder NSCLC-AC Esophageal NSCLC squamous SDMA Suppression in Residual Tumors* at End of Study 100- SDMA, Inhibition (%) Histology 1 Histology 2 Histology 3 Bladder NSCLC-AC IDEAYA Data; *2 of 8 LUSC unevaluable due to insufficient residual tumor burden Esophageal NSCLC squamous Mean Tumor Volume mm³ 500- Mean Tumor Volume mm³ 1200- 1000- 800- 600- 400- 200- 250- 0 7 PDX3 0 7 14 IDEAYA Data 14 Study Day 21 28 Study Day Mean Tumor Volume mm³ 21 28 0 Mean Tumor Volume mm³ 1500- 1000- 500- 500- 250- PDX4 0 T 0 14 21 7 14 21 28 Study Day 28 35 42 49 56 Study Day IDEAVA BIOSCIENCES#2424 IDE397 Clinical Data Summary - Monotherapy Dose Escalation Cohorts ctDNA Molecular Response demonstrates Tumor Pharmacodynamic Modulation Molecular Response Waterfall (Baseline to C2D1) 586 135 97 100 90 76 = Cohort 5 and 6 Dose 80 70 = Cohort 1 to 4 Dose 60 50 40 30 20 11 8 10 1 0 -10 -20 -13 -14 -30 -40 -50 -60 -70 -51 -58 -67 -80 -90 -100 -100 Dose Cohort 3 Tumor Type Parotid Cohort 3 Pancreatic Cohort 5 Cohort 1 Sarcoma Pancreatic Cohort 4 Pancreatic Cohort 2 Thymic Cohort 4 Cohort 4 Cohort 1 Pancreatic Melanoma Pancreatic Cohort 5 NSCLC Cohort 2 Cohort 6 Cohort 5 NSCLC Bladder Pancreatic IDEAYA Data: Guardant OMNITM ctDNA Molecular Response (n=13 evaluable IDE397 Phase 1 dose escalation samples) Molecular Response ctDNA Molecular Response: IDE397 Dose-Dependent Tumor Pharmacodynamic Modulation 100% (2 of 2) Molecular Responders in NSCLC 75% (3 of 4) Molecular Responders in Cohort 5 and Cohort 6 Patients 31% (4 of 13) Molecular Responders across all dose- escalation Cohorts 1 to 6 IDEAVA BIOSCIENCES#25MAT2Ai Combination Strategy AMGEN® Clinical Combination focus on IDE397 + PRMT5MTA based on Compelling Preclinical Efficacy IDE397 + MTA-Cooperative PRMT5 Inhibitor enables Maximal Pathway Suppression* Maximal Pathway Suppression Methionine Hit 2 MAT2A IDE397 Deep and Durable Anti-Tumor and PD Response with Combination* PRMT5MTA-1 NSCLC MTAP (-/-) CDX -O- Vehicle IDE397 3 mg/kg IDE397 30 mg/kg 2000- PRMT5MTA-125 mg/kg PRMT5MTA-1 100 mg/kg IDE397 3 mg/kg + PRMT5MTA-1 25 mg/kg PRMT5MTA-1 Pancreatic MTAP (-/-) CDX PRMT5MTA-1 25 mg/kg -- Vehicle ▲ IDE397 3 mg/kg IDE397 3 mg/kg + PRMT5MTA-1 25 mg/kg 1500- MTA Hit 1 MTA PRMT5 MTAP MTA Hit 3 PRMT5MTA MTA SAM Methylation of Splicing Factors (SDMA) In Vivo Efficacy Confirmed in Multiple Models Pre-mRNA Splicing (Essential) Enhanced Combination Efficacy Observed in multiple Tumor Indications and Across Representative PRMT5MTA Inhibitors + Mean Tumor Volume (mm³) ± S.E.M. 1500- 1000- 500- 0+ ō 0 10 20 30 40 50 60 Study Day Mean Tumor Volume (mm³) ± S.E.M. 1000- 500- 0- 10 20 30 40 50 60 Study Day MTAP-deleted Tumor SDMA IHC Scores PRMT5MTA-2 NSCLC MTAP (-/-) CDX -- Vehicle 100% PRMT5MTA-2 30 mg/kg IDE397 3 mg/kg + 75%- ✰IDE397 3 mg/kg PRMT5MTA-2 30 mg/kg 2000- 50%- 1500- 25%- Mean Tumor Volume (mm³) ± S.E.M. 1000- 500- IDE397 Vehicle 3 mg/kg ☐ ☐ ☐ ☐ 3+ 2+ 1+ 0 25 * Clinical evaluation pursuant to Amgen Clinical Trial Collaboration and Supply Agreement for clinical evaluation of IDE397 and AMG 193, an Amgen investigational MTA-cooperative PRMT5 inhibitor; Amgen will sponsor the study; IDEAYA and Amgen will jointly share external costs of the study T 0 10 20 30 40 50 60 Study Day SDMA IHC nuclear staining intensity distribution, pathologist scored, as percent of total tumor cells evaluated per sample; tumor samples from HCT116 MTAP (-/-) CDX models collected 2 hrs post-dose on Treatment Day 2 + IDEAYA Data: AACR 2023, M. Fischer et al. based on evaluation of multiple representative MTA-cooperative PRMT5 inhibitors, designated as PRMT5MTA-1, PRMT5MTA-2 IDEA A BIOSCIENCES PRMT5¡MTA IDE397 + PRMT5iMTA#26Combination Effect of MAT2A Inhibitor and PRMT5MTA Inhibitor Combined Inhibition Deepens Biological Response through Maximal Pathway Suppression Gene Expression Analysis Combination Deepens Observed Monotherapy Activity HCT 116 MTAP (-/-) ° ° ° ° . ° ° Alternative Splicing Analysis Combination Increases Alternative Splicing Events HCT 116 MTAP (-/-) IDE397 PRMT5MTA-2 IDE397 + PRMT5MTA-2 Retained Intron Analysis Combination shows Selective Response by Retained Introns Analysis^ HCT 116 MTAP (-/-) n=87 n=413 HALLMARK PATHWAYS IDE397 ° ° ° ° ° ° num DE in Leading Edge ° ° ° • 25 ° ° о о 75 ° ° NES ° 2 ° ° ° ° ° ° ° O o O o ° . ° ° ° ° ° о ° OOOOOOOO • • OO●●● ° PRMT5MTA Combo -1 0.5 0 Quantitative Assessment of IDE397 / PMRT5i Effect on pre-mRNA Splicing >2800 significant Splicing Events only in the Combination Treatment Arm+ MTAP (-/-) -Log10(Padj) MTAP wt -Log10(Padj) 25 25 15 75 25 0 75 75 n-1 Significance in treatment in treatment ⚫ not significant Analysis by RNAseq; Color = Normalized Enrichment Score (NES); Shape = Number of Differentially Expressed (DE) Genes in Leading Edge; Black Circular Border = Statistically Signifcant (P.adj <0.05) + Identified as novel splice junctions or as not meeting significance criteria in monotherapy arms Color = heatmap of Z-scored TMM-normalized counts per million 26 IDEAYA Data: AACR 2023 M. Fischer et. al.; PRMT5MTA = representative MTA-cooperative PRMT5 inhibitor, including designated as PRMT5MTA-2 0 -30 -20 -10 0 10 20 30 ^ Retained Introns by DEXseq for Combination Treatment Arm IDEAVA BIOSCIENCES#27MAT2Ai Combination Strategy IDE397 (MAT2A) + AMG 193 (PRMT5MTA) Preclinical Efficacy IDE397 (MAT2Ai) + AMG 193 (PRMT5MTA¡) Tumor Volume (mm³) Observed Durable Complete Responses NSCLC MTAP-/- CDX Model On Treatment 2000 1500- 1000- 500 Dosing (PO) Vehicle AMG 193 10 mg/kg AMG 193 30 mg/kg IDE397 3 mg/kg AMG 193 10 mg/kg + IDE397 3 mg/kg AMG 193 30 mg/kg + IDE397 3 mg/kg Off Treatment T TT T TT 10 20 30 40 50 60 70 80 90 Complete Response Complete Response 100 110 Days (post cell implantation) AMGEN® Observed Complete Responses (CR) @ Study Day ~40+ durable through Study Day ~100 Doses were below maximally efficacious preclinical dose for each of IDE397 and AMG 193, with IDE397 dosed at 3 mg/kg QD (1/10th of typical preclinical dose) → Therapeutic Window Well tolerated in vivo with No Observed Body Weight Loss Observed selective sensitivity in MTAP-null tumors (no observed TGI in MTAP-wt tumors) % Initial Body Weight 120- 100- 80- 80 60- 40- 20 No Body Weight Loss 0 0 5 10 15 20 25 30 35 Dosing (PO) דן 40 27 IDEAYA / Amgen Data: AACR 2023, M. Fischer et al. Days (post cell implantation) * Pursuant to Amgen Clinical Trial Collaboration and Supply Agreement for clinical evaluation of IDE397 and AMG 193, an Amgen investigational MTA-cooperative PRMT5 inhibitor; Amgen will sponsor the study; IDEAYA and Amgen will jointly share external costs of the study IDEAVA BIOSCIENCES#28IDE397 Phase 1/2 Clinical Development Plan Clinical Strategy Focus on Select Monotherapy and High Conviction Combination IDE397 Development Candidate - Clinical Profile • Exposure-Dependent Pharmacokinetic (PK) Profile with low Cmax:Cmin • Robust, Exposure-Dependent Pharmacodynamic (PD) Response Monotherapy Expansion showing Clinical Efficacy - with Responses in Multiple High-Priority Tumor Types early in Dose Expansion, including a confirmed PR IDE397 is uniquely positioned to evaluate efficacy in MTAP pathway, with a favorable PK/PD profile and observed therapeutic window Mono Expansion in Select MTAP-null Tumor Histologies IDE397 RDE Mono Expansion Basket: NSCLC, Esophageal, Gastric, Bladder Focus or Additional Indication Expansion Combination Cohorts - Clinical Proof of Concept in MTAP-null Tumors AMGEN IDE397 + AMG 193 MTA-Cooperative PRMT5i#^: Solid Tumors Other Potential Indications or Combinations Addressable Patient Population of ~50,000 estimated in US, EU5 and JP across priority tumors - NSCLC, bladder, gastric, and esophageal cancers # AMG193 = Amgen's investigational MTA-cooperative PRMT5 inhibitor 28 ^ Amgen reported that initial data for AMG 193 monotherapy expansion demonstrated responses in multiple tumor types (See Amgen earnings release and corporate presentation dated August 3, 2023) IDEAVA BIOSCIENCES#2929 IDEAYA's Potential First-in-Class Synthetic Lethality DDR Pipeline Synthetic Lethality with Tumor-Promoting defects in DNA Repair Mechanisms IDE161 PARG Inhibitor Clinical Candidate GSK101 + Ф Pol Theta Helicase Inhibitor Development Candidate Werner Φ Helicase Inhibitor Preclinical Lead-Optimization Phase 1 First-in-Human Monotherapy in HRD Breast, Ovarian Potential to develop beyond HRD Phase 1 First-in-Human Q4 2023 Niraparib Combination in Tumors with HR Mutations and HRD Pursuant to GSK Collaboration, Option and License Agreement Targeting DC H2 2023 MSI-High Tumor Agnostic IDEAVA BIOSCIENCES#3030 PARG Inhibition is Synthetic Lethal with HRD Novel, Mechanistically-Differentiated Target in a Clinically Validated Pathway PARG Activity is required to resolve DNA Repair PARG Inhibition is Mechanistically Distinct from PARPI Replication Stress DNA Damage (SS break) PARP Binding PAR Chain Synthesis (poly-ADP ribose) Mechanisms of Tolerance Fork remodelling vs Re-priming and TLS PARP trapping PAR Chain Hydrolysis (mediated by PARG) T IDE161 (PARGI) 4 DNA Damage Repair Proteins (Recruited by PAR Chain Template) PARP and PARG inhibitors have distinct MOA and efficacy profiles PARGI ↓ Fork Reversal Fork Protection RAD51 modulators e.g. BRCA1 BRCA2 and Slowing Cell Death (Nucleolytic Degradation) PARPI ↓ Unrestrained Fork Progression Gap tolerance Run off Re-priming & DSBR TLS HR e.g. BRCA1 BRCA2 Cell Death (ssDNA gaps + DSBs) Cancer Research (Aug 2019), Cancer Research (Jul 2019), Cancer Cell (Mar 2019) Pillay et al., Progress in Biophysics and Molecular Biology 2021; McDermott et al., Cancer Cell 2019; Zeman and Cimprich, Nature Cell Biology 2014 PARG IDEAVA BIOSCIENCES#31IDE161: Potential First-in-Class Phase 1 PARG Inhibitor IDE161 Profile: Potent, Selective with Favorable Properties IDE161 is a potent, selective small molecule PARGI for tumors with HRD Demonstrated cellular activity and efficacy in biomarker defined settings Positive physical property profile Favorable preclinical tolerability IDE161 induces Selective DDR → Synthetic Lethal in HRD MSD Assay ECL counts IDE161-induced DNA Damage Response 500000 P-ATM p-KAP1 P-RPA 400000- 300000- 200000- 100000 25000 12500 6h 48h 72h % Inhibition 100 8 8 8 40- 20- 0- 80- Biochemical IC50 60- PARGI IC 50 ~0.002 UM = -8 -7 -6 -5 -4 -3 log [PARGI MM] 31 IDEAYA Data: AACR 2023 D. Munoz et al. 750000 600000 450000- 300000 150000 50000 MSD PAR Assay ECL counts 25000- IDE161-induced Cellular PAR Accumulation T T T T T T T 0.00 0.16 0.31 0.63 1.25 2.50 5.00 10.00 IDE 161 conc (uM) Normalized Z-score IDE161 low dose vs DMSO S 0 0 0.0411 0.1234 0.37 0 0.0411 0.1234 0.37 0 0.0411 0.1234 0.37 IDE161 conc (uM) IDE161 is Synthetic Lethal with BER Gene Disruption Ovarian HRD Model TYMS RFC1 PARG XRCC1 -10 EXO1 POLB LIG1 -10 -5 0 5 Normalized Z-score IDE161 high dose vs DMSO PARG poly (ADP-ribose) glycohyrdolase; PAR = poly (ADP-ribose); DDR = DNA Damage Response; HRD = Homologous Recombination Deficiency; BER = Base Excision Repair RFC1 LIG1 POLB EXO1 TYMS PARG XRCC1 Gene Network generated from whole genome CRISPR screens anchored with IDE161 using significant synthetic lethality hits across 4 models IDEA A BIOSCIENCES#32IDE161 shows Selective Sensitivity in HRD and Differentiation from PARPI 1.5 1 0.5 -0.5 0 IDE161 Sensitivity Profile in Cell Panel Cellular response profiles reveal mechanistic associations with PARGI sensitivity IDC161 Cellular IC50 (log 10 μM) IDE161 Selective Sensitivity vs PARPI HRD cell lines are selectively sensitive 5 4.5 4 to IDE161 versus PARPI PARPI Responsive Models IDE161 Sensitivity in HRD Breast Cancer Response to IDE161 is strongly associated with HRD status in Breast Cancer Cell Lines Cellular antiproliferative response to IDE161 stratified by HRR status Tumor Cell Model Breast Cervical Gastric 0.5 Ovary Pancreatic Prostate 0.0 (Breast Cancer: n=24, Wilcoxon pval=0.008) -1 -1.5 -2 -2.5 314 cell lines across 31 lineages PARGI IDE 161 IC50 (μM) 3.5 نه 5 2 1.5 IDE161 PARGI Responsive Models 1 include HRD, replication stress, nucleotide Top predictive response biomarkers* excision repair and parylation cycle * Based on univariate and multivariate pan-cancer and lineage-specific molecular feature analysis 0.5 0 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 PARPI Niraparib IC50 (μM) 32 IDEAYA Data: AACR 2023, D. Munoz et al. Log10(IC50) -0.5 -1.0- Mutation Status CHEK2 ⚫ non-HRR -1.5 ⚫ BRCA2 CHEK1, BRCA2 -2.0 • ATM BRCA1, BRCA2 BRCA1 Wild-Type Mutant* *HRR mutation status assigned according Foundation Medicine HRR gene panel: ATM, BRCA1, BRCA2, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L IDEA A BIOSCIENCES#33IDE161 is Active and Well-Tolerated in HRD ER+ Her2- Breast Cancer Models Observed PARG inhibitor Activity is Distinct from PARP Inhibition Durable Disease Control in BRCA-altered Breast Cancer CDX Durable regressions (vs stasis with niraparib) Robust dose- and time- dependent PAR accumulation Well tolerated; no body weight loss >10% Mean Tumor Volume (mm³) S.E.M. 2500- ER+ / Her2- Breast Cancer CDX Vehicle 2000- IDE161 100 mg/kg QD Niraparib 45 mg/kg QD 1500- 1000- 500- Niraparib IDE161 0+ 0 10 20 30 40 50 60 Days on Treatment Regression in BRCA-altered Breast Cancer PDX Models Mean Tumor Volume (mm³) +/- S.E.M. 1000- + Vehicle IDE161 100 mg/kg QD 800- 600- 400- 200 ER+/Her2- Breast Cancer PDX1 1000- HHHH IDE161 Mean Tumor Volume (mm³) +/- S.E.M. + Vehicle Niraparib 45 mg/kg QD 750- 500- 250- Niraparib Tumor: pg PAR/mg protein ± S.E.M. Ovarian Cancer CDX 201 600000 Vehicle 400000- 200000- IDE161 100 mg/kg QD 3 8 24 Time post Dose (h) 33 IDEAYA Data: 2023 AACR, D. Munoz et al. % Body Weight Change 10-1 - Vehicle IDE161 100 mg/kg QD Niraparib 45 mg/kg QD -20+ 0 10 20 30 IDE161 Niraparib 40 50 60 Days on Treatment Mean Tumor Volume (mm³) +/- S.E.M. 0+ T 10 20 30 40 50 0 7 14 21 28 35 Days on Treatment Days on Treatment ER+ / Her2- Breast Cancer PDX2 2000-1 1000- ■ Vehicle QD IDE161 100 mg/kg QD 1500- 1000- 500- Mean Tumor Volume (mm³) S.E.M. Vehicle Niraparib 45 mg/kg QD 750- 500- Niraparib 250- IDE161 0- 0- 0 10 20 30 40 0 7 14 21 28 35 Days on Treatment Days on Treatment IDEAVA BIOSCIENCES#34IDE161 Demonstrates Favorable Safety Profile in Preclinical Studies Non-Clinical Pharmacology and Toxicology Studies Support Clinical Evaluation IDE161 Differentiates versus PARPI in Nonclinical Safety Studies PARP inhibition causes myelosuppression in rat and dog at clinically relevant systemic exposures In contrast, IDE161 does not alter hematology parameters in rodents at relevant exposures associated with the estimated therapeutic dose % change from vehicle control IDE161 versus PARPI in Rat Studies * Niraparib Olaparib Talazoparib IDE161 • IDE161 well tolerated preclinically with tumor regressions observed at doses below mouse MTD • Human efficacious dose IDE161 Drug Product TT -20- -60- , RBC MOC NEU MBE MEU ROC NEU MOC NEU RBC Hematology Parameter * PARPI data extracted from repeat dose toxicology data presented in NDA reviews ([email protected]) and prescribing labels. Species chosen for data illustration (rat) was based on availability of data at a dose level that most closely approximated systemic exposure (AUC) associated with the clinically recommended dose. projection based on maximum efficacious dose in mouse (100 mg/kg/day) which covers cellular IC for ≥ 22 hours Data from GLP toxicology studies support a proposed safe starting dose of 0.5X the estimated therapeutic dose IDE161 API synthetic process and drug product tablet formulation developed IDEA A BIOSCIENCES 34 IDEAYA Data#3535 IDE161 Clinical Development Strategy First-in-Class Opportunity for Patients with Breast, Ovarian & Other Solid Tumors with HRD IDE161 Phase 1/2 - Mono Clinical Development Plan and Combination Options IDE161 Monotherapy Dose Escalation and Expansion in HRD Tumors Dose Escalation Expansion Cohort: ER+, Her2-, HRD Breast Cancer Expansion Cohort: HRD Ovarian Cancer Expansion Cohort: HRD Tumors (Basket) Expansion Opportunities beyond HRD Tumors IDE161 Combinations - Preclinical Safety Profile Supports Multiple Opportunities ER+, Her2- Breast Cancer Patients with HRD Tumors → ~10% to 14% of Breast Cancer Ovarian Cancer Patients with HRD Tumors → ~50% of Ovarian Cancer Facile peripheral PD Biomarker for PARGI based on measurement of PAR in blood samples (PBMC's) 100- MSD PAR Assay Human PBMC Activity in PARPİ- and Dose Escalation IDE161+ Chemotherapy Other Potential Combinations Differentiated Sensitivity Improved Safety Profile Platinum-Resistant Settings relative to PARPI's Clinical Strategic Pillars IDEAYA Data PARG poly (ADP-ribose) glycohyrdolase; PAR = poly (ADP-ribose; PBMC = peripheral blood mononuclear cells relative to PARPI's Fold Change over Baseline 10- *** 0.001 0.004 0.01 IDE161 (uM) 0.04 0.12 0.37 1.11 3.33 IDEAVA BIOSCIENCES#3636 Polymerase Theta (Pol Theta) Synthetic Lethality Program Pol Theta GSK Potential First-in-Class Helicase Inhibitor is Synthetic Lethal to HR and NHEJ Perturbation Role of Pol Theta in Tumor Biology Pol Theta is an error-prone multi-domain protein with helicase / polymerase activities ATPase domain RAD51 binding sites Polymerase domain Pol Theta DNA break end-joining is critical when canonical repair pathways fail Pol Theta Inhibitor Drug Discovery Discovered Pol Theta inhibitors with IC50 <10 nM in biochemical assays against Pole Drug-like properties of Pole inhibitors support oral dosing in humans Pol Theta Inhibitor Synergy in HRD Pol Theta inhibition is synthetic lethal with PARP inhibition in HR-deficient cancer cells Synergy mapped to D-R (HSA) Combination of PolQi and PARPI 100 Poor NHEJ Substrates Excessive Resection Aborted HR Theta Mediated End-Joining Pol e Microhomology Mediated End-Joining D. Wyatt et al. Mol Cell (2016) Intra- and Inter- Chromosomal Templated Insertions (MMBIR-like) % Control 50 50 IDEAYA / GSK Data Polei Niraparib Antagonism Synergy IDEAVA BIOSCIENCES#372000- 1500- -- Vehicle POLO inhibitor Niraparib POLO inhibitor + Niraparib GSK101 (IDE705): Potential First-in-Class Pol Theta Helicase Inhibitor Phase 1: Targeting First-in-Human in Q4 2023 in Combination with Niraparib (PARPi) Pol Theta Helicase In Vivo Activity GSK101 + PARPI BRCA 1/2 Clinical Reversions Clinical Development Strategy BRCA Reversions Mediated by MMEJ Pol Theta Helicase Inhibitor + PARP Inhibitor Tumor volume (mm³ ± SEM) 1000- 500- Percent reversion events 100% 75% 71% 88% 50% 25% 0% BRCA1- BRCA2- Pol Theta Helicase Inhibitors Disrupt MMEJ Alternative DNA Damage Repair: Inhibit DSB Repair by MMEJ Dysregulate Replication Fork Stabilization 37 0 10 20 30 40 50 60 Study Day 70 80 Observed Deep and Durable Responses in Multiple Xenograft Models IDEAYA / GSK Data Gene Deletion Insertion Other Substitution Wild-type Microhomology deletion Potentiate PARPI Efficacy Prevent PARPI Resistance Overcome PARPI Resistance Cancer Res. 2020, DOI: 10.1158/2159-8290 Potential Clinical Opportunities GSK Strategic Partnership: Global Royalties with GSK covering all Costs, ~$1B Milestones, incl up to $20M Preclinical / Ph1 Clinical Potential Combination with GSK's Zejula™, a PARP Inhibitor BIOSCIENCES IDEAYA#3838 Werner Helicase is Synthetic Lethal with Microsatellite Instability Targeting Development Candidate in H2 2023 Werner Helicase Inhibitors Phenocopy Genetic SL in MSI-High Cancers Nanomolar Potency, Biochemical and Cellular Activity, and Selectivity over other RecQ Helicases Werner Helicase Synthetic Lethality in MSI-High Cancer Cells TATA Normal ATAT WRN resolves TA Repeat 2° Structures to prevent Catastrophic DNA Fragmentation in MMR-deficient Cells Werner GSK Werner Helicase Synthetic Lethal with High-MSI CellPress Werner Syndrome Helicase is Required for the Survival of Cancer Cells with Microsatellite Instability IDEAYA Publication ISW MSS terminal cell count terminal cell count fold change (control) fold change (control) HCT116 LoVo 1.5- 1.0- 0.5- 0.0 0.0 cont WRN cont WRN SW620 SW948 1.5 1.0- 0.5- TATATATATATATATATATATATA MSI-H ATATATATATATATATATATATAT (TA)n repeat TATATA WAVE MMR Expanded (TA)n repeat TATATATATATATATATATAL ᎬᏆᏆᏆᏌᏆᏌᏆᏆᏌᏆᏆᎽᏆᏌ Replication slippage Cruciform formation ATR WRN proficient WRN TATATATA ATATATATA - ⚫ DS DNA breaks MUS81-EME1 WRN SLX4 TATATATATATATATATA TATATATATATATATAL Intact genome Cell Press, iScience, March 2019, Hager et al 0.0 0.0- cont WRN cont WRN Analysis of pan-cancer screen datasets reveals WRN essentiality in MSI-H cancer cell lines CCLE MSI-H CCLE MSS CCLE unannotated - ド DepMap (CRISPRko) WRNi SATATATATATATATATA TATATATATATATATATA Chromosome shattering -2.0 -1.5 -0.5 0.5 -1.0 0.0 WRN Gene Effect (Chronos) CRISPR (DepMap 22Q2 Public+Score) IDEAYA / GSK Data: AACR 2023, M. Fischer et. al. GSK Strategic Partnership: 50/50% US Profit Share and ex-US Royalties, ~$1B Milestones, incl up to $20M Preclinical / Ph1 Clinical; Cost Share 80% (GSK) / 20% (IDEAYA); Potential Combination with GSK's JemperliTM, a PD-1 IO Agent BIOSCIENCES IDEAYA#3939 Werner Helicase is Synthetic Lethal with Microsatellite Instability Targeting Development Candidate in H2 2023 Discovery of Potent and Selective WRN Inhibitors Werner Helicase Inhibitor Drug Discovery Solved >85 X-ray Co-Crystal Structures D2 τα D2 D1 Achieved >10,000,000-fold Affinity Increase Initial Hits Improved Inhibitors High Affinity Poor Druglike Properties Good Druglike Properties Low Affinity Mean tumor volume (mm³) In Vivo Efficacy and Selectivity* 1500 MSI-H 750 Vehicle WRNi % Activity wrt DMSO control D2 τα D2 D1 Biochemical activity across Target Class* 120- 100- 80- 60- Pangenomic Cellular Activity Correlation^ 10 9 8 WRN BLM ✰ RecQ1 RecQ4 RecQ5 (b)001- WRN ⚫ PRISM AUC 3 2 40- 20- 0+ 0.0001 0.001 0.01 0.1 1 10 100 1000 IDB WRNI (μM) -0.35 -0.25 -0.15 -0.05 0.05 0.15 0.25 Nanomolar potency only against WRN Pearson correlation CRISPR Knockouts Sensitivity to WRNi correlates most strongly with WRN gene dependency across the CCLE * IDEAYA / GSK Data: AACR 2023, M. Fischer et. al. ^ IDEAYA / GSK / Broad Institute Data: AACR 2023, M. Fischer et. al. Mean tumor volume (mm³) 0 2500 MSS 1250 20 Treatment day 40 Vehicle WRNi 10 Treatment day 20 IDEAYA BIOSCIENCES#4040 Werner Inhibitor In-Vivo Efficacy in MSI-High Models WRNi Shows Pharmacological Activity in Therapy-Refractory CRC MSI-High Models Werner Helicase Activity in Therapy-Refractory CRC Organoid Models Immuno-Refractory (Genetic Sensitivity) Immuno-Refractory Viability (%) sgNon (Pharmacological Sensitivity) sgWRN2 150- 125- 100- Chemo-Refractory (Genetic Sensitivity) IRCC-114-XL 125- www 100- 75- 50- 25- 0 sgNon sgPLK1 sgWRN1 sgWRN2 IDEAYA/GSK/Welcome Sanger Institute Data Viability (%) 75- 50- 25- WRNi Immuno-sensitive Immuno-refractory Strategic Collaboration with GSK US: 50%/50% Profit Share Ex-US: Royalties tiered from high single-digit to sub-teen double digit percentages Milestones: ~$1B, incl up to $20M for Preclinical through early Ph1 Clinical Cost Share: 20% IDEAYA / 80% GSK Strategic Rationale: Potential Combination with GSK's Dostarlimab, a PD-1 IO Agent → Targeting Werner Helicase Development Candidate in H2 2023 Pharmacological activity in therapy- refractory models supports clinical thesis IDEAVA BIOSCIENCES#41Building a Fully-Integrated Biotech in Precision Medicine Oncology Foundational First-in-Class Pipeline Enables a Leading Precision Medicine Oncology Franchise Darovasertib Registration-Enabling Trial with Potential Accelerated Approval in HLA-A2(-) MUM is tractable for commercial execution and provides path to potential product revenue to reinvest in broad first-in-class pipeline Emerging Pipeline of Potential First-in-Class Precision Medicine Oncology Programs with large addressable solid tumor patient populations, including Daro (Ph 2 Primary UM), IDE397 (Ph 2), IDE161 (Ph 1), GSK101 (Ph1) and Werner Helicase (Development Candidate H2 2023) Strong Balance Sheet with ~$510 M anticipated to fund operations into 2027 1,2 and opportunity for milestones Validating Pharma Partnerships and Collaborations include clinical collaborations for combination therapies with Pfizer and Amgen and strategic collaboration with GSK with ~$1 billion milestones/program CLINICAL Ph2/3 - Daro + Crizo in Metastatic UM 3 Ph2 - Darovasertib (PKC) in Primary UM Ph 2 IDE397 (MAT2A) Ph 1 - IDE397 (MAT2A) + AMG 193 (PRMT5MTA) 3 Ph 1 – IDE161 (PARG) Ph 1- GSK101 (Pol Theta Helicase) 4 2023 Foundation: 4 Clinical Programs (1) Includes aggregate of $510.1 M cash, cash equivalents and marketable securities as of June 30, 2023 IDEAYA Form 10-Q dated August 10, 2023 as filed with the U.S. Securities and Exchange Commission DEVELOPMENT CANDIDATES Werner Helicase - Dev Candidate H2 2023 4 PRECLINICAL Targeting 2 IND Filings (2025+) 5 Clinical Programs 7 Clinical Programs (2) (3) Clinical Trial Collaboration and Supply Agreements, independently with Pfizer (Darovasertib + Crizotinib) and Amgen (IDE397 + AMG193); IDEAYA retains all commercial rights (4) GSK101 Pol Theta Program Cost Share = 100% GSK with ~$1B Milestones and WW Royalties; Werner Helicase Program Cost Share = 80% GSK / 20% IDEAYA with ~$1B Milestones, 50/50 US Profit Share and Ex-US Royalties 41 IDEAVA BIOSCIENCES