Ideaya Biosciences, Inc. · NASDAQ:IDYA
Ideaya Biosciences — Investor Presentation (August 2019)
26 slides from Ideaya Biosciences's investor presentation, Aug 12, 2019
Slide 1: IDEAYA Biosciences Corporate Presentation August 2019
IDEAYA Biosciences Corporate Presentation August 2019 Exhibit 99.2
Slide 2: Safe Harbor Statement
Safe Harbor Statement CONFIDENTIAL 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
Slide 3: IDEAYA Highlights
IDEAYA HIGHLIGHTS Synthetic Lethality (SL) Direct Targeting of Oncogenic Pathways PRECISION MEDICINE TARGET CLASSES IDEAYA Biosciences Oncology Focused Precision Medicine Company Werner Syndrome Helicase is Required for the Survival of Cancer Cells with Microsatellite Instability Mutations in GNA11
Slide 4: IDEAYA Organization: Proven Leadership Team From Top Oncology Companies
IDEAYA Organization Proven Leadership Team From Top Oncology Companies Michael Dillon, Ph.D. SVP, Chief Scientific Officer, Head of Research Julie Hambleton, M.D. SVP, Chief Medical Officer, Head of Development Jeff Hager, Ph.D. SVP, Chief Technology Officer, Head of Target Discovery and External In
Slide 5: IDEAYA's Precision Medicine Oncology Pipeline
IDEAYA’s Precision Medicine Oncology Pipeline Indication Biomarker Preclinical IND Phase 1 Phase 2 Phase 3 Status IDE196 PKC inhibitor MUM Mono GNAQ/11 Ph1 Data at AACR April 2019 Solid Tumors GNAQ/11 Ph1/2 Basket Trial FPI Q2’19 MUM Combos GNAQ/11 Preclinical Validation NSCLC + EGFRi PKC-delta Prec
Slide 6: IDE196 Compound Profile
IDE196 Compound Profile IDE196 is a potent and selective Protein Kinase C (PKC) Inhibitor IDE196 IC50 (nM) PKC Activity Classical Novel Atyp. alpha beta 1 beta 2 gamma delta epsilon eta theta zeta 25 66 58 11 4 3 1 3 >2000 Single Agent IDE196 Induces Tumor Regression 92.1 mutant GNAQ xenograft Poten
Slide 7: GNAQ or GNA11 Mutations Can Lead to Activation of PKC Signaling
Mutations in small GTPases, GNAQ or GNA11, can lead to activation of PKC signaling, a genetic driver of cancer Van Raamsdonk, CD, et. al, Nature 2009; Van Raamsdonk CD, et. al, NEJM 2010; Piperno-Neumann S, et. al, J Clin Oncol 2014; Oncotarget, May 2016, Carita et al Activating GNAQ or GNA11 mutati
Slide 8: GNAQ/GNA11 Mutations Basket
GNAQ/GNA11 Mutations Basket GNAQ/GNA11 Mutations Found in Multiple Cancers Phase 1/2 Tissue Type Agnostic Basket Trial FPI Q2 2019 Foundation Medicine Patient Database GNAQ/GNA11 mutations found in 1.4% of tumors, of which ~25% are likely pathogenic (“hotspot”) Functional validation ongoing for acti
Slide 9: Metastatic Uveal Melanoma (MUM)
Metastatic Uveal Melanoma (MUM) Removal of the eye (”enucleation”) Surgery to save eye Radiation treatment Iodine-125 plaque Proton beam Other treatments Laser, tumor resection Treatment Options for Primary Disease ~ 90% of uveal melanoma patients harbor activating GNAQ or GNA11 mutation ~ 50% of uv
Slide 10: IDE196 Phase 1 Dose Escalation Monotherapy Results in MUM
IDE196 Phase 1 Dose Escalation monotherapy results in Metastatic Uveal Melanoma AACR 2019, Novartis Data; Data cut-off: Sep 30 2018; Response data by investigator assessment Treatment LXS196 200 mg BID LXS196 300 mg BID LXS196 400 mg BID -30 22/30 (73%) Disease Control Rate (SD+PR+CR) 8/30 (27%) Tum
Slide 11: Prior Clinical Trials in MUM Show Unmet Medical Need
Prior clinical trials in MUM show unmet medical need IDE196 Phase 1 monotherapy data provides potential to be backbone of care in Metastatic Uveal Melanoma Agent Trial Disease Control Rate % (SD+PR+CR) >30% Tumor Regression ORR % (CR+PR) Duration of CR/PR Responses (days) Median PFS (months) IDE196
Slide 12: GNAQ & GNA11 Mutations Found in ctDNA of Uveal Melanoma Patients
GNAQ & GNA11 Mutations Found in ctDNA of Uveal Melanoma Patients Circulating Tumor DNA (ctDNA) of GNAQ/GNA11 Mutations Targeting to identify patients earlier in disease to enhance response Circulating GNAQ/GNA11 mutations may be an early indicator of disease progression Plan to use ctDNA diagnostics
Slide 13: Existing Diagnostics Provide Path to Execute Basket Trial
Existing Diagnostics Provide Path to Execute GNAQ/GNA11 & PKC Fusions Basket Trial GNAQ/GNA11 mutations listed on Foundation NGS panel GNAQ/GNA11 mutations listed on ctDNA liquid biopsy panel PKC fusions listed on Illumina fusion panel GNAQ/GNA11 mutations listed on ctDNA liquid biopsy panel Point M
Slide 14: GNAQ/GNA11 Mutations and TMB in Skin Melanoma
GNAQ/GNA11 Mutations and TMB in Skin Melanoma BRAF/NRAS & GNAQ/GNA11 Profile GNAQ/GNA11 mutations in Skin Melanoma are associated with low Tumor Mutation Burden & mutually exclusive with BRAF/NRAS Skin Melanoma BRAF – non-V600E BRAF – V600E* NRAS- MT* GNAQ/GNA11- Q209 GNAQ/GNA11-R183 = exclusivity =
Slide 15: PKC-delta Implicated in EGFRi Resistance
PKC-delta implicated in EGFRi Resistance IDE196 Potential Indication Expansion EGFRi-resistant NSCLC Targeting PKC-delta as a Therapeutic Strategy against Heterogeneous Mechanisms of EGFR Inhibitor Resistance in EGFR-Mutant Lung Cancer Inhibition of PKC-delta sensitizes TKI-resistant EGFR-mutant NSC
Slide 16: IDE196 Phase 1/2 Basket Trial Design
IDE196 Phase 1/2 Basket Trial Design Expanding the Value of IDE196 to Other Solid Tumors IDE196 PKC inhibitor Phase 1 MUM (Ongoing) Phase 1/2 GNAQ/GNA11 Basket Trial GNAQ/GNA11 Hotspot Metastatic Uveal Melanoma Cutaneous Melanoma (CM), Colorectal, Other Solid Tumors MUM: IDE196 combos NSCLC: IDE196
Slide 17: IDEAYA Synthetic Lethality Approach
IDEAYA Synthetic Lethality Approach Synthetic Lethality Background Synthetic Lethality (SL) Platform & Capabilities Emerging Class of Precision Medicine Targets TSG = tumor suppressor gene Generating, validating and integrating vast synthetic lethality data sets: Discovery of novel precision medicin
Slide 18: IDEAYA Synthetic Lethality Pipeline
Today IDEAYA Synthetic Lethality Pipeline IDEAYA is advancing the next generation of biomarker-enabled Synthetic Lethality programs HRD = Homologous Recombination Deficiency, MSI = Microsatellite Instability MAT2A MTAP Deletion PARG BER, BRCA Pol-Theta HRD/BRCA Dual CRISPR SL Targets PARP HRD/BRCA L
Slide 19: MAT2A Inhibition is Synthetic Lethal with MTAP Deletion
MAT2A Inhibition is Synthetic Lethal with MTAP Deletion MTAP Deletion Prevalence ~15% of all Solid Tumors MTAP Deletion Prevalence MTAP-MAT2A SL Biology Data from The Cancer Genome Atlas data in cBioPortal Cancer Type N MTAP Deletions (%) Glioblastoma 592 41 Mesothelioma 87 32 Esophageal 95 28 Bladd
Slide 20: MAT2A Inhibitors Demonstrate Synthetic Lethality in MTAP-Null Cell Lines
IDEAYA MAT2A Inhibitors Demonstrate Synthetic Lethality in Multiple MTAP-Null Cell Lines & PD Modulation of SAM Levels PD Modulation: SAM Levels in HCT116 Cell Line Synthetic Lethality in HCT116 Cell Line IDB361 IDEAYA data Structurally Enabled Lead Optimization IDB proprietary MAT2Ai co-crystal str
Slide 21: MAT2A Inhibitors Demonstrate In Vivo Efficacy and PD Modulation
IDEAYA MAT2A inhibitors demonstrate potent in vivo efficacy and PD modulation in HCT116 MTAP-/- xenograft model Lead series of IDEAYA MAT2A inhibitors Demonstrate ~60-100% tumor growth inhibition (TGI) at efficacious dose ranges of 3 to 30 mg/kg QD Comparable to higher TGI than Agios AGI-25696 at ≥1
Slide 22: IDB361 Favorable In Vivo Efficacy Relative to AGI-25696
IDB361 demonstrates favorable in vivo efficacy relative to AGI-25696 in HCT116 MTAP-null model In vivo efficacy in HCT116 MTAP-null model IDEAYA data IDB361 Start of dosing 3 mg/kg QD 79% TGI 30 mg/kg QD 101% TGI 30 mg/kg QD 0% TGI 300 mg/kg QD 70% TGI Start of dosing AGI-25696
Slide 23: IDEAYA MAT2A Inhibitor Program Target Product Profile
IDEAYA MAT2A Inhibitor Program Target Product Profile Attributes Agios MAT2A Published Compounds / Data IDEAYA Program Goals MAT2A Cell Potency 970 nM (AGI-24512) (1,3) More Potent In Vitro Compound MTAP-null vs MTAP-wt Cell Potency 8.5x (AGI-24512) (1,3) Broader Therapeutic Window In vivo efficacy
Slide 24: Pol theta Drug Discovery
Pol theta Drug Discovery Pol theta Synthetic Lethality Program Candidate Biomarkers: BRCA/HRD Pol theta Biomarker IDEAYA Pol theta inhibitor cell potency in DLD1 BRCA2 line In vivo evaluation of lead series ongoing Pol theta synthetic lethality with BRCA1/2 in HCCT116 cells Synthetic Lethal Screen w
Slide 25: Werner Drug Discovery
Discovery: completed multiple hit discovery campaigns using a range of screening formats and compound libraries Screening: robust suite of biochemical and biophysical assays to identify WRN inhibitors and differentiate false positives Lead Series: identified a lead series with <100 nanomolar IC50 po
Slide 26: IDEAYA's Precision Medicine Oncology Pipeline: Target Milestones through 2020
IDEAYA’s Precision Medicine Oncology Pipeline Target Milestones through 2020 Indication Biomarker Preclinical IND Phase 1 Phase 2 Phase 3 Target Milestone through 2020 IDE196 PKC inhibitor MUM Mono GNAQ/11 Regulatory Path Solid Tumors GNAQ/11 Ph1/2 Interim Data MUM Combos GNAQ/11 Ph1/2 Clinical Comb
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