Ideaya Biosciences, Inc. · NASDAQ:IDYA
Ideaya Biosciences — Investor Presentation (September 2023)
41 slides from Ideaya Biosciences's investor presentation, Sep 11, 2023
Slide 1: IDEAYA Biosciences
September 2023 NASDAQ: IDYA IDEAYA Biosciences Improving Lives Through Transformative Precision Medicines
Slide 2: Safe Harbor Statement
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, uncertainti
Slide 3: IDEAYA Biosciences Highlights
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 • 2023 Target Milestones - Ph 2/3 Registrational: Darov
Slide 4: Leading Functional Genomics and Synthetic Lethality Platform
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 (Brea
Slide 5: IDEAYA Leadership Team and Scientific Advisory Board
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. Darrin Beaupre, M.D., Ph.D. Michael White, Ph.D. Paul Stone, J.D. Chief Executive Officer, Director Chief Medical O
Slide 6: IDEAYA Precision Medicine Oncology Platform
IDEAYA Precision Medicine Oncology Platform Fully-Integrated Target, Biomarker, Drug Discovery and Translational Capabilities Translational Research and Opportunity Expansion Drug Discovery and Genomics – DNA and RNA Analysis Pharmacological Validation Proteomics – Protein Expression Profiling Targe
Slide 7: IDEAYA Functional Genomics and Synthetic Lethality Platform
IDEAYA Functional Genomics and Synthetic Lethality Platform 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
Slide 8: IDEAYA Precision Medicine Oncology Drug Discovery Platform
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 INQUIRE™ Proprietary Chemical Library Full suite of capabilities in structural biology, Expert-curated
Slide 9: IDEAYA's Potential First-in-Class Precision Medicine Oncology Pipeline
IDEAYA’s Potential First-in-Class Precision Medicine Oncology Pipeline Building an Industry Leading and Fully-Integrated Biotechnology Company Precision Medicine Pipeline Pre- IND Potential Modality/Indication Biomarker clinical Enabling Phase 1 Phase 2 Registrational Program Goals / Achievements Co
Slide 10: Darovasertib – Potential to Broadly Impact Uveal Melanoma
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 Darovasertib is an oral, potent and selective PKC inhibitor G
Slide 11: Phase 2 Clinical Trial - Comparatively High-Risk, Poor Prognosis Population
Phase 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* Tebentasfusp First-Line Phase 3# Darovasertib + Crizotinib Baseline Characteristics Tebe Arm Control Arm^ Any-Line n=63
Slide 12: First-Line MUM Clinical Efficacy
First-Line MUM Clinical Efficacy Observed Compelling Confirmed Overall Response Rate and Disease Control Rate Darovasertib + Crizotinib Phase 2 Confirmed 45% ORR and 90% DCR First-Line MUM (n= 20) Response by RECIST 1.1 Evaluable First-Line MUM (N=20) Confirmed ORR (9/20) 45% Best Tumor Response (%)
Slide 13: Any-Line MUM and Hepatic-Only MUM Clinical Efficacy
Any-Line MUM and Hepatic-Only MUM Clinical Efficacy Clinical Efficacy irrespective of HLA-A2 Status and in Hepatic & Extra-Hepatic Metastases Darovasertib + Crizotinib Phase 2 Confirmed 30% ORR and 87% DCR Any-Line MUM (n=63) Response by RECIST 1.1 Evaluable Best Tumor Response (%) Any-Line MUM (N=6
Slide 14: Median PFS in First-Line, Any-Line and Hepatic-Only MUM
Median PFS in First-Line, Any-Line and Hepatic-Only MUM Observed Compelling Median Progression Free Survival with Encouraging Trend Any-Line MUM Swimlane Plot Darovasertib + Crizotinib Phase 2 Median Progression Free Survival • First-Line (n=20): ~7 months • Any-Line (n=63): ~7 months Median PFS h
Slide 15: Darovasertib + Crizotinib First-Line MUM Combo Efficacy
Darovasertib + Crizotinib First-Line MUM Combo Efficacy Examples of cPRs with Significant Tumor Shrinkage in First-Line MUM Patients First-Line MUM Patient First-Line MUM Patient • 40+ year old HLA-A2 positive patient with Class 1A diagnosis • 40+ year old HLA-A2 negative patient with Class 1A diagn
Slide 16: Darovasertib + Crizotinib Combination Clinical Summary in MUM
Darovasertib + Crizotinib Combination Clinical Summary in MUM Highly Differentiated Clinical Efficacy & AE Profile Observed+, ++ Cabozantinib Mono / Darovasertib + Crizotinib Selumetinib + DTIC Ipi + Nivo Tebentafusp Crizotinib Mono Target / Mechanism PKC + cMET cMET MEK + Chemotherapy CTLA4 + PD1 H
Slide 17: Accelerated Approval Trial Design in First-Line HLA-A2 Negative MUM
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 FrontRunner: Target First-Line approval strategy to enhance patient benefit in MUM FDA Accelerated Approval: Address unmet need in
Slide 18: Darovasertib Monotherapy in (Neo)adjuvant Primary Uveal Melanoma
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 Clinical Experience in UM and MUM Patients Current Treatment Approach following diagnosis of U
Slide 19: Case Studies of Saved Eyes: Neoadjuvant Treatment of UM Patients
Case Studies of Saved Eyes: Neoadjuvant Treatment of UM Patients Initial Cases of Systemic Neoadjuvant Therapy resulting in Prevention of Enucleation Baseline Scan: 16.5mm Apical Height 4 Month Scan: 3.5 mm Apical Height Case 1: Eye Saved by Neoadjuvant Treatment + ^ Regressed Tumor UM patient was b
Slide 20: (Neo)Adjuvant Darovasertib in Primary Uveal Melanoma (UM)
(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 Primary Targeting FPI Local Q3 2023 Therapy Primary Endpoints Neoadjuva
Slide 21: Darovasertib Clinical & Commercial Strategy in Uveal Melanoma Indication
Darovasertib 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
Slide 22: MAT2A Inhibition is Synthetic Lethal with MTAP Deletion
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 Endogenous Suppression in MTAP-/- PDX Models Methionine Methylation Pathway Suppression in MTAP(-/-) Squamous Lung (LUSC) MTAP SDM
Slide 23: IDE397 Demonstrates Broad Efficacy across MTAP-deficient PDX Models
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 IDE397 In Vivo Efficacy in LUSC PDX Models TGI with IDE397 (30mpk) in MTAP-/- PDX Panel Blank blank Observed T
Slide 24: IDE397 Clinical Data Summary – Monotherapy Dose Escalation Cohorts
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 80 76 = Cohort 5 and 6 Dose ctDNA Molecular Response: 70 = Cohort 1 to 4 Dose IDE397 Dose-Depend
Slide 25: MAT2Ai Combination Strategy
MAT2Ai Combination Strategy Clinical Combination focus on IDE397 + PRMT5MTA based on Compelling Preclinical Efficacy IDE397 + MTA-Cooperative PRMT5 Inhibitor Deep and Durable Anti-Tumor and PD Response with Combination+ enables Maximal Pathway Suppression* * PRMT5MTA-1 PRMT5MTA-1 NSCLC MTAP (-/-) CD
Slide 26: Combination Effect of MAT2A Inhibitor and PRMT5MTA Inhibitor
Combination Effect of MAT2A Inhibitor and PRMT5MTA Inhibitor Combined Inhibition Deepens Biological Response through Maximal Pathway Suppression Gene Expression Analysis Alternative Splicing Analysis Retained Intron Analysis BlankCombination Deepens Observed Combination Increases Alternative Splicin
Slide 27: MAT2Ai Combination Strategy
MAT2Ai Combination Strategy IDE397 (MAT2A) + AMG 193 (PRMT5MTA) Preclinical Efficacy IDE397 (MAT2Ai) + AMG 193 (PRMT5MTAi) * Observed Durable Complete Responses Observed Complete Responses (CR) @ Study Day ~40+ durable through Study Day ~100 NSCLC MTAP-/- CDX Model Doses were below maximally efficac
Slide 28: IDE397 Phase 1/2 Clinical Development Plan
IDE397 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 • Monotherapy Expansion showing Clinical Efficacy - with Respo
Slide 29: IDEAYA's Potential First-in-Class Synthetic Lethality DDR Pipeline
IDEAYA’s Potential First-in-Class Synthetic Lethality DDR Pipeline Synthetic Lethality with Tumor-Promoting defects in DNA Repair Mechanisms IDE161 GSK101 φ Werner φ PARG Inhibitor Pol Theta Helicase Inhibitor Helicase Inhibitor Clinical Candidate Development Candidate Preclinical Lead-Optimization
Slide 30: PARG Inhibition is Synthetic Lethal with HRD
PARG 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 Mechanisms of Tolerance PARGi PARPi ↓ ↓ Fork Reve
Slide 31: IDE161: Potential First-in-Class Phase 1 PARG Inhibitor
IDE161: Potential First-in-Class Phase 1 PARG Inhibitor IDE161 Profile: Potent, Selective with Favorable Properties IDE161 induces Selective DDR Synthetic Lethal in HRD Blank IDE161-induced DNA Damage Response • IDE161 is a potent, selective small molecule PARGi for tumors with HRD MSD Assay ECL c
Slide 32: IDE161 shows Selective Sensitivity in HRD and Differentiation from PARPi
IDE161 shows Selective Sensitivity in HRD and Differentiation from PARPi IDE161 Sensitivity Profile in Cell Panel IDE161 Selective Sensitivity vs PARPi IDE161 Sensitivity in HRD Breast Cancer *Cellular response profiles reveal mechanistic * HRD cell lines are selectively sensitive * Response to IDE1
Slide 33: IDE161 is Active and Well-Tolerated in HRD ER+ Her2- Breast Cancer Models
IDE161 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 Regression in BRCA-altered Breast Cancer PDX Models • * Durable regressions (vs ER+ / Her2- Breast Can
Slide 34: IDE161 Demonstrates Favorable Safety Profile in Preclinical Studies
IDE161 Demonstrates Favorable Safety Profile in Preclinical Studies Non-Clinical Pharmacology and Toxicology Studies Support Clinical Evaluation IDE161 Differentiates versus PARPi in Nonclinical Safety Studies • IDE161 well tolerated PARP inhibition causes myelosuppression in rat and dog at clinical
Slide 35: IDE161 Clinical Development Strategy
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 ER+, Her2- Breast Cancer Patients with HRD Tumors ~10% to ~14% of Breast Cancer * IDE161 Monothe
Slide 36: Polymerase Theta (Pol Theta) Synthetic Lethality Program
Pol Theta Polymerase Theta (Pol Theta) Synthetic Lethality Program Potential First-in-Class Helicase Inhibitor is Synthetic Lethal to HR and NHEJ Perturbation Role of Pol Theta in Tumor Biology Pol Theta Inhibitor Drug Discovery Pol Theta Inhibitor Synergy in HRD Pol Theta is an error-prone multi-do
Slide 37: GSK101 (IDE705): Potential First-in-Class Pol Theta Helicase Inhibitor
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 BRCA 1/2 Clinical Reversions Clinical Development Strategy GSK101 + PARPi BRCA Reversions Mediated by MMEJ Pol
Slide 38: Werner Helicase is Synthetic Lethal with Microsatellite Instability
Werner Werner Helicase is Synthetic Lethal with Microsatellite Instability Targeting Development Candidate in H2 2023 Werner Helicase Inhibitors Phenocopy Genetic SL in MSI-High Cancers Werner Helicase Synthetic Lethal with High-MSI Nanomolar Potency, Biochemical and Cellular Activity, and Selectivi
Slide 39: Werner Helicase is Synthetic Lethal with Microsatellite Instability
Werner Helicase is Synthetic Lethal with Microsatellite Instability Targeting Development Candidate in H2 2023 In Vivo Efficacy and Selectivity* 1500 MSI-H 1500 Discovery of Potent and Selective WRN Inhibitors Mean tumor volume (mm3) Werner Helicase Inhibitor Drug Discovery 1000 Solved >85 X-ray Co-
Slide 40: Werner Inhibitor In-Vivo Efficacy in MSI-High Models
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 Immuno-Refractory (Genetic Sensitivity) (Pharmacological Sensitivity) Strategic Co
Slide 41: Building a Fully-Integrated Biotech in Precision Medicine Oncology
Building 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 prov
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