IDEAYA Biosciences Interim IDE397 Phase 1 Clinical Data and Q1 2022 Corporate Update

Made public by

Ideaya Biosciences

sourced by PitchSend

1 of 18

Creator

ideaya-biosciences

Category

Healthcare

Published

2022

Slides

Transcriptions

#1March 15, 2022 NASDAQ: IDYA IDEAYA Biosciences Interim IDE397 Phase 1 Clinical Data and Q1 2022 Corporate Update IDEAVA 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 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. 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 10Q for the quarter ended September 30, 2021, 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 IDEAVA#33 Agenda IDE397 Interim Phase 1 Clinical Data Update GSK Option Data Package and Collaboration Economics. Phase 1/2 Clinical Development Plan Clinical Pharmacokinetic Data ■ Clinical Adverse Events IDE397 Pharmacodynamic Data Preclinical Tumor Pharmacodynamic Data . . Clinical Plasma and Tumor Pharmacodynamic Data ● PK/PD Analysis and Projected Clinical Efficacy Next Steps Corporate Update Other Pipeline Programs, 2022 Target Milestones, 2021 Financials gsk IDEA A IDEAVA BIOSCIENCES#4GSK Option Data Package Timing and Scope of Data Supporting GSK Opt-In Decision 1 Observation of MTD - or - Determination of Expansion Dose Monotherapy Dose Escalation MTAP Deletion in Solid Tumors Monotherapy Expansion Cohorts Targeting Expansion Cohorts Mid-Year 2022 MAT2A Option Data Package 2 Targeting Option Data Package Delivery Mid-Year 2022 Preclinical Data Non-Clinical Safety GSK Collaboration Economics for MAT2A Option Exercise Fee: $50M, subject to Opt-In and HSR clearance If GSK elects to Opt-In: 80%/20% GSK/IDEAYA Development Cost Share $ 465M Development / Regulatory Milestones $ 475 M Sales Milestones 50%/50% U.S. Net Profits Share Ex-US royalties of tiered high single-digit to sub-teen double digit % Pharmacokinetic Data and Pharmacodynamic Data In Vivo Efficacy (e.g., 40+ PDX Models) Clinical Data • . Safety and Tolerability Data Pharmacokinetic Data Pharmacodynamic Data (SAM, SDMA) (1) Pursuant to GSK Collaboration, Option and License Agreement 4 (2) MAT2A Program Diligence Data (Preclinical, Clinical, CMC, Toxicology and Regulatory Data) to be delivered to GSK within 30 days of Option Data Package gsk IDEAYA BIOSCIENCES#55 IDE397 Phase 1/2 Clinical Development Plan Comprehensive Approach for Concurrent Evaluation of Monotherapy and Combinations Phase 1 Dose Escalation and Expansion Strategy 1 IND Cleared Monotherapy Dose Escalation MTAP Deletion in Solid Tumors (e.g., NSCLC, pancreatic, thymic) FPI April 2021 Q3 2021 PK/PD Expansion Cohorts 2 IDE397 RDE Mono Expansion in NSCLC (n= 20+) IDE397 RDE Mono Expansion in EsophagoGastric (n=20+) IDE397 RDE Mono Expansion in Basket 1 (n= 20+) IDE397 RDE Mono Expansion in Basket 2 (n= 20+) Targeting Expansion Cohorts mid-2022 Combo Escalation (1) Potential Clinical Development Plan for IDE397 subject to ongoing Phase 1 monotherapy dose escalation data, preclinical evaluation, and GSK Opt-In (2) Tumor Biopsy Cohorts: PK-Pharmacokinetic, PD-Pharmacodynamic IDE397 + Docetaxel NSCLC (n= 16+) IDE397 + Paclitaxel EsophagoGastric (n= 16+) IDE397 + SOC Agent Expansion IDE397 + NCP SOC NCP Standard of Care Novel Combination Partner Preclinical and Early Clinical Data support Clinical Development Focus on NSCLC, Esophagogastric and Other Solid Tumors such as Head and Neck, Bladder and Pancreatic (e.g., in Potential Basket Cohorts) gsk IDEAVA BIOSCIENCES#6IDE397 Clinical Pharmacokinetic Data Exposures are Dose Proportional and Achieved Active Exposure Targets # IDE397 Pharmacokinetic (PK) Data IDE397 PK Parameters at Steady State Plasma IDE397 Conc. 1 100x 10x 1x 0 8 16 24 Hours post-dose 1 Y-axis concentration scale discloses relative values as indicated Cycle 1 Day 15 Cohort 5 Cycle 1 Day 15 Cohort Cohort Cohort Cohort Cohort 1 2 3 4 5 Стах 1 1.0 x 3.6 x 4.3 x 12.0 x 17.5 x max Cohort 4 AUC 24h¹ 1.0 x 4.0 x 4.9 x 13.6 x 19.8 x -Cohort 3 max 1 C. and AUC 24h values normalized to Cohort 1 -Cohort 2 -Cohort 1 Target efficacious exposure range based on in vivo preclinical models - - IDE397 PK Profile Flat temporal PK profiles, with low Cmax/Cmin ratio Dose-proportional increase in exposures (AUC and Cmax) Cohort 1 to 5 Achieved target efficacious exposure range of in vivo preclinical models PK properties support acceptable dosing regimen Cohort 5 cleared without observing MTD 6 IDEAYA Data #Based on preclinical PK/PD analysis Currently enrolling Cohort 6; first patient cleared without DLT gsk IDEA A BIOSCIENCES#7IDE397 Adverse Events Summary No Drug-Related Serious Adverse Events (SAEs) & MTD Not Yet Observed No Dose Limiting Toxicities Observed Drug-Related Adverse Events Number of Patients with Drug-Related AE's by Grade (n=14 total) Safety Summary n=14 (%) All Cause Adverse Events (AEs) 10 AEs 14 (100%) Grade 3/4 AES SAES 7 (50%) / 1 (7%) 8 5 (43%) AEs leading to interruption Drug-Related AEs 5 (36%) AEs 10 (71%) 2 Grade 3/4 AEs SAES 1 (7%)* / 0 (0%) AEs leading to interruption 0 (0%) 1 (7%)* * Grade 3 weakness/asthenia 6 4 III. 0 Any Grade Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Drug-related AEs occurring in >10% of patients include low grade nausea, decreased appetite, diarrhea, dehydration and thrombocytopenia No drug related Grade 4 or 5 AE's; Cohort 5 cleared without observing MTD Currently enrolling Cohort 6; first patient cleared DLT window 7 IDEAYA Data as of March 4, 2022 (based on preliminary analysis of unlocked database from Cohorts 1 though 5) gsk IDEAA IDEAYA BIOSCIENCES#88 IDEAYA Data IDE397 Pharmacodynamic Biomarker Data Mechanism of Action and Key Pharmacodynamic Markers MAT2A Inhibition is Synthetic Lethal with MTAP Loss IDE397 Selectively Inhibits SDMA and pre-mRNA Splicing Tumor-specific MTAP deletion IDE397 MAT2A Hit 2 (15% of cancer) 220 120 100 80 60 50 MTA Hit 1 SAM 40 30 Partial antagonist PRMT5 Required Cofactor 20 Methylation of splicing factors (SDMA) Pre-mRNA Splicing (Essential) DMSO IDE397 (μM) IDE397 (μM) 0.24 0.74 2.2 6.7 DMSO 0.24 0.74 HCT116 HCT116 2.2 MTAP-deleted Multivariate Analysis of Transcript Splicing HCT116 5Day-MAT2Ai- MTAP-/- 5Day-PRMT5i- SDMA HCT116 5Day-MAT2Ai- 5Day-PRMT5i- Vinculin 0 Drug-induced splicing changes 1000 2000 3000 Skipped Exon (SE) Retained Intron (RI) MXE-Event A5SS A3SS gsk IDEAVA BIOSCIENCES#9IDE397 Preclinical Pharmacodynamic Data Complete Suppression (95-100%) of Tumor SDMA in Multiple MTAP-Deleted PDX Models Tumor SDMA and Tumor Growth Inhibition in NSCLC CDX Model Deep SDMA Inhibition Observed Across Many PDX Models SDMA modulation corresponds to TGI NCI-H838 MTAP-/- CDX Model Tumor SDMA (% of Vehicle) 100- 9 IDEAYA Data 75- 50- 25- 0 Tumor SDMA (IHC) TGI 101 T 3 30 IDE397 Dose (mg/kg) Tumor Growth Inhibition (TGI, %) 15 100 11 -75 -50 -25 Vehicle 30 mg/kg % Reduction of Tumor SDMA (by IHC-Score) 100- 80- 60- 40- 20- TGI (%)- 116 92 79 119 93 68 67 65 47 NSCLC GASTRIC and ESOPHAGEAL BLADDER 9 of 12 MTAP-/- models evaluated have 80-100% reduction of tumor SDMA as compared to time-matched vehicle control group (PDX in vivo models dosed at 30 mg/kg) gsk IDEAVA BIOSCIENCES#10IDE397 Preclinical Efficacy and Pharmacodynamic Data Observed 100% Tumor SDMA Reduction at 30 mg/kg QD Dose in NSCLC MTAP PDX Model NSCLC SCC PDX Model (LXFE 2276) Vehicle, SDMA IHC 20x 92% TGI H-score 85 1000- 800- Vehicle IDE397 30mg/kg QD Mean Tumor Volume (mm³) ± S.E.M. 600- 400- 200- 0 10 10 IDEAYA Data 7 14 Study Day 21 LXFE 2276 T 28 - 29 IDE397 30 mg/kg QD, SDMA IHC 20x H-score 0 gsk IDEAVA BIOSCIENCES#11Mean Tumor Volume (mm³) ± S.E.M. 11 IDEAYA Data IDE397 Preclinical Efficacy and Pharmacodynamic Data Observed 95% Tumor SDMA Reduction at 30 mg/kg QD Dose in NSCLC MTAP PDX Model NSCLC SCC PDX Model (LXFE 2234) Vehicle, SDMA IHC 20x 116% TGI H-score 250 800- Vehicle 600- 400- 200 HIGH HH IDE397 30mg/kg QD 7 14 21 28 Study Day LXFE 2234 IDE397 30 mg/kg QD, SDMA IHC 20x H-score 16 gsk IDEAVA BIOSCIENCES#12IDE397 Clinical Phase 1 Interim Plasma Pharmacodynamic Data Robust Plasma SAM Reduction (Targeting >60%) Observed Across All Cohorts Cohort 5 Plasma SAM Reduction Over Cycle 1 Increase in Plasma SAM Inhibition at Higher Exposures 12 IDEAYA Data Plasma SAM (ng/ml) 60 p = 0.049 77% Reduction 0 Pre-tx Post-tx (C2D1) % Plasma SAM inhibition 80 60. 50 40 20 0 0.01x 0.1x 1x 10x 100x IDE397 Plasma Conc 1 1 x-axis concentration scale discloses relative values as indicated C1D1 Pre C1D1 6H C1D15 6H C1D1 Pre: cycle 1 day 1 pre-dose C1D1 6H: cycle 1 day 16hr post dose C1D15 6H: cycle 1 day 15 6hr post dose gsk IDEAVA BIOSCIENCES#1313 On Treatment Predose IDE397 Clinical Phase 1 Interim Tumor Pharmacodynamic Data Exposure-Dependent Tumor SDMA Reduction Observed in Target Tumor Types Cohort 3: Pancreatic Cancer <5% Reduction of Tumor SDMA Tumor SDMA IHC, 20X Cohort 4: Pancreatic Cancer 100% Reduction of Cytoplasmic Tumor SDMA 12% Reduction of Nuclear Tumor SDMA Tumor SDMA IHC, 20X Cohort 5: NSCLC 95% Reduction of Tumor SDMA Tumor SDMA IHC, 20X AUC = 1.0 x 'SS IDEAYA Data: % Reduction of Tumor SDMA measured by IHC H-Score 1 AUC ss values normalized to Cohort 3 value On Treatment Predose AUC SS = 2.4 x On Treatment Predose AUC S₁ = 5.9 x SS gsk IDEA A BIOSCIENCES#1414 IDE397 Clinical Phase 1 Interim Tumor Pharmacodynamic Data 95% Reduction in Tumor SDMA Tumor SDMA in Cohort 5 NSCLC Patient Predose 95% Reduction of Tumor SDMA Tumor SDMA IHC, 20X H-score: 280 % of total number of cells scored 100 80 60 40 20 8620 0 Cohort 5 NSCLC Patient IHC Scores Observed AUC ss value in Cohort 5 NSCLC patient within predicted target efficacious exposure range# Plasma SAM Reduction of 79% Tumor SDMA Reduction of 95% #Based on preclinical PK/PD analysis On Treatment H-score: 13 IDEAYA Data: % Reduction of Tumor SDMA measured by IHC H-Score Pre-Dose Post-Dose 3+ 2+ 1+ 0 Staining Intensity - High (+3) to Low (0) gsk IDEAA IDEAYA BIOSCIENCES#15IDE397 Preclinical and Clinical Pharmacodynamic Data Summary Robust Plasma SAM and Exposure-Dependent Tumor SDMA Biomarkers Preclinical & Interim Phase 1 Clinical Data Preclinical IDE397 at 30mg/kg demonstrates regressions with observed ~80-100% tumor SDMA reduction in multiple MTAP-deleted in vivo PDX models Interim Phase 1 Clinical Data IDE397 achieves targeted plasma SAM reduction of >60% across all Phase 1 doses of Cohort 1 through Cohort 5 IDE397 demonstrates exposure-dependent tumor pharmacodynamic data in target tumor types, including ~95% reduction of tumor SDMA in Cohort 5 15 IDEAYA Data PK/PD AUC Comparing Preclinical to Clinical Experience AUC SS 1 7.8 x Mouse 30 mg/kg H838 TGI 101% SDMA reduction 99% Human (NSCLC) Cohort 5 C1D15 5.2 x Mouse 10 mg/kg H838 TGI 94% 2.6 x Human (pancreatic) Cohort 4 C1D15 Mouse 3 mg/kg H838 TGI 80% SDMA reduction 70% Human (pancreatic) 1.0 x Cohort 3 C1D15 Mouse 1 mg/kg H838 TGI 60% 1 AUCss values normalized to Cohort 3 value gsk IDEAVA BIOSCIENCES#16IDE397 Next Steps and Phase 1 Program Summary Key Upcoming Milestones • Targeting to deliver GSK Option Data Package Mid-Year 2022 - Potential $50 million Option Exercise Fee • Targeting to initiate IDE397 Monotherapy Expansion and Combination Escalation Cohorts Mid-Year 2022 - Mono Expansion Cohorts to include NSCLC and Combinations with Taxanes and other Standard of Care Combination Agents IDE397 Phase 1 Interim Clinical Data Summary • Favorable PK profile supports acceptable dosing regimen • • • • No drug-related SAEs observed through Cohort 5 and MTD not yet observed Robust plasma SAM and exposure dependent tumor pharmacodynamics observed in target tumor types Cohort 6 enrollment ongoing; first patient cleared without DLT Favorable Preliminary Risk / Benefit Profile vs. Historical - IDE397: Observed preliminary signals of clinical activity, including robust pharmacodynamic modulation and tumor shrinkage Dose-proportional exposure across all Cohorts 1 through 5 with favorable drug exposure relative to AE profile MTD not yet observed with no drug-related SAEs through Cohort 5 GSK PRMT5: 26% SAES (53% Grade 3/4) at 400mg QD Expansion Dose (n=19)* AG-270: 18% Grade 3 or higher AE at 200mg QD Expansion Dose (n=11), and 67% Grader 3 or higher AE at 200mg BID (n=6)** 16 * ESMO 2019; ** AACR-NCI-EROTC Triple Meeting, 2019, DCR = Disease Control Rate gsk BIOSCIENCES IDEAVA#1717 Corporate Update Darovasertib Phase 2 Clinical and Preclinical PARG, Pol Theta and WRN Programs Maturing • Darovasertib (PKC) GNAQ/11, CMET Tumors Daro + Crizotinib (cMETI) - Ph2 in MUM Metastatic Uveal Melanoma GNAQ/11 Skin Melanoma Daro Monotherapy - Ph 1 (IST) Primary Adjuvant UM Expansion Opportunities - Preclinical Daro + KRASi in KRAS Tumors Daro + Crizo in cMET Tumors Key Updates Daro + Crizo clinical data presented December 2021 showed robust clinical activity with manageable side effect profile in MUM, including 100% DCR (n=16) Expanded relationship with Pfizer under clinical collaboration and supply agreements in support of potential registrational trial in MUM, subject to FDA feedback, and of evaluation in cMET driven tumors Targeting FDA guidance and clinical data update in MUM mid-2022, including tolerability, clinical efficacy (1) IDEAYA Earnings Release issued March 15, 2022 (2) Includes cash, cash equivalents and marketable securities as of December 31, 2022 IDE161 (PARG) HRD / BRCA IDE161 Development Candidate Key Updates Observed in vivo efficacy with enhanced TGI or tumor regressions in niraparib-resistant models Exercised option for an exclusive worldwide license from CRUK and University of Manchester Targeting IND submission Q4 2022 Werner Helicase MSI-High WRN Helicase Inhibitor - Lead Series Key Updates Targeting Development Candidate 2023 Potential for up to $20 million in aggregate milestone payments from GSK for preclinical to early Phase 1 Pol Theta HRD / BRCA Pol Theta Inhibitor - Candidate Selection Key Updates Demonstrated in vivo efficacy in BRCA2 xenograft model in combination with niraparib, a PARPI IND enabling studies H1 2022 Potential for up to $20 million aggregate milestone payments from GSK for preclinical to early Phase 1 Financial Results Fourth Quarter and Full Year 2021 Key Updates Strong Balance Sheet with ~$368 M in Cash 1,2 Anticipated to fund planned operations into 2025 Operating Expenses ~$21 M Q4 and ~$78 M Full Year IDEAVA BIOSCIENCES

Download to PowerPoint

Download presentation as an editable powerpoint.

Related

Fiscal 3Q Investor Presentation image

Fiscal 3Q Investor Presentation

Healthcare

FY23 Full-Year Results Presentation image

FY23 Full-Year Results Presentation

Healthcare

Healthcare Network P&L Statement and Expansion Projects image

Healthcare Network P&L Statement and Expansion Projects

Healthcare

Accreditation and Quality Assurance Overview image

Accreditation and Quality Assurance Overview

Healthcare

Investment Highlights image

Investment Highlights

Healthcare

Investor Presentation image

Investor Presentation

Healthcare

IDEAYA Biosciences Interim IDE397 Phase 1 Clinical Data and Q1 2022 Corporate Update image

IDEAYA Biosciences Interim IDE397 Phase 1 Clinical Data and Q1 2022 Corporate Update

Healthcare

BioAtla Investor Presentation Deck image

BioAtla Investor Presentation Deck

Healthcare