Oric Pharmaceuticals, Inc. · NASDAQ:ORIC
Oric Pharmaceuticals — Investor Presentation (January 2024)
43 slides from Oric Pharmaceuticals's investor presentation, Jan 9, 2024
Slide 1: Company Overview January 2024
Exhibit 99.1 Company Overview January 2024
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding ORIC Pharmaceuticals, Inc.’s (“ORIC”, “we”, “us”
Slide 3: ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer
ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer • Two potential best-in-class programs advancing towards pivotal studies Broad Pipeline of Potential First-in-Class and Best-in-Class Programs • Additional preclinical programs targeting novel and validated targets Precision Oncology
Slide 4: Executive Team with Expertise in Building Leading Oncology Companies
Executive Team with Expertise in Building Leading Oncology Companies • Previously CFO of Ignyta (acquired by Roche), raised over $500mm in capital Jacob Chacko, MD Chief Executive Officer • TPG Capital (completed $10bn of aggregate acquisitions) and McKinsey • Board member of 4D Molecular Therapeuti
Slide 5: Clinical Pipeline Focused on Advancement of ORIC-114 and ORIC-944
Clinical Pipeline Focused on Advancement of ORIC-114 and ORIC-944 Lead Lead Program Indication Identification Optimization IND Enabling Phase 1 Phase 2 Phase 3 Key Differentiation PRODUCT CANDIDATES NSCLC, Breast & ✓ CNS active ORIC-114 Phase 1b: ORIC-114 single agent Tumor agnostic ✓ Well tolerated
Slide 6: Substantial Progress in 2023: Well Positioned to Build Value in 2024 and Beyond
Substantial Progress in 2023: Well Positioned to Build Value in 2024 and Beyond 2023 Accomplishments and Next Steps ✓ Phase 1b dose escalation data presented at ESMO 2023 demonstrated potential best-in-class profile, ORIC-114 with favorable safety and both systemic and CNS activity in heavily pre-tr
Slide 7: ORIC-114 Brain Penetrant EGFR/HER2 Exon Inhibitor
ORIC-114 Brain Penetrant EGFR/HER2 Exon 20 Inhibitor
Slide 8: ORIC-114 Is a Promising Candidate for Patients with EGFR and HER2 Exon 20 Mutations
ORIC-114 Is a Promising Candidate for Patients with Tumors Harboring EGFR and HER2 Exon 20 Insertion Mutations, Including Those with Brain Metastases ORIC-114 Target Product Profile • Selectively targets EGFR and HER2 with high potency against exon 20 insertion mutations • Exquisite kinome selectivi
Slide 9: ORIC-114 Designed to Selectively Target EGFR and HER2 Exon 20
ORIC-114 Was Designed to Selectively Target EGFR and HER2 with High Potency Against Exon 20 Insertion Mutations Kinome Selectivity Comparison CLN-081 Furmonertinib BLU-451* Mobocertinib ORIC-114 Off-target Wildtype (WT) Kinases Inhibited 80-100% at 1mM ORIC-114 CLN-081 Furmonertinib BLU-451 Mobocert
Slide 10: ORIC-114 Demonstrates Potent In Vivo Activity in EGFR Exon 20 Models
ORIC-114 Demonstrates Potent In Vivo Activity in EGFR Exon 20 Insertion Models In Vivo Efficacy – NSCLC EGFR Exon 20 Insertion Models EGFR Exon 20 insNPH EGFR Exon 20 insASV EGFR Exon 20 insG 3000 800 800 Vehicle Vehicle Vehicle ORIC-114 (4 mg/kg QD) ORIC-114 (4 mg/kg QD) ORIC-114 (4 mg/kg QD) 600 6
Slide 11: Drugs Lacking CNS Activity Often Have Worse Clinical Outcomes in NSCLC
Drugs Lacking CNS Activity Often Have Worse Clinical Outcomes in NSCLC Case Study on NSCLC Targeted Therapy without CNS Activity: Mobocertinib • In mobocertinib’s phase 1/2 trial, ~35% of patients had CNS metastases at baseline Patients WITHOUT 8.1 CNS Metastases at Baseline • Patients with CNS meta
Slide 12: Superior Brain Penetration of ORIC-114 Differentiates from Comparators
Superior Brain Penetration of ORIC-114 Differentiates from Comparator Exon 20 Targeted Agents ORIC-114 Properties Allowed ORIC-114 Exhibits High Ratio of Free (Unbound) Optimization of Brain Exposure Brain/Plasma Exposure in Mice • Minimal pump engagement 10 ─ Key pumps that limit brain penetration,
Slide 13: First-In-Human Phase 1b Study of ORIC-114
First-In-Human Phase 1b Study of ORIC-114 Phase 1b, Multicenter, Open-Label Study Dose Expansion (Part II) Accelerated Approval Dose Escalation (Part I) All Patients +/- CNS mets Cohorts (Ph 2) EGFR ex20 NSCLC +/- CNS Key Eligibility naïve to EGFR ex20 therapy • Advanced solid tumors RP2D 1 ─ EGFR e
Slide 14: ORIC-114 Patient Disposition and Baseline Characteristics
ORIC-114 Phase 1 Patient Disposition and Baseline Characteristics Patient Disposition and Baseline Characteristics EGFR Ex20 HER2 Ex20 HER2+ Total (n=21) (n=24) (n=5) (N=50) 63 (31,80) 63 (25,86) 66 (48,68) 63 (25,86) Age, years, median(range) • 50 patients were treated with 10 (48) 11 (46) 3 (60) 2
Slide 15: ORIC-114 Has Been Generally Well Tolerated
ORIC-114 Has Been Generally Well Tolerated Despite More Heavily-Pretreated Patients and Less Stringent Enrollment Criteria for Prior Therapy and CNS Disease Treatment Related Adverse Events Occurring in ≥10% of Patients <45 mg TDD 45 – 60 mg TDD ≥75 mg TDD Total (n=18) (n=23) (n=9) (N=50) • Well tol
Slide 16: EGFR Exon 20: Tumor Regression Observed Across All Active Doses
EGFR Exon 20: Tumor Regression Observed Across All Active ORIC-114 Doses Preliminary Activity (NSCLC patients with EGFR exon 20 and treated at ≥45 mg TDD) 60 40 20 0 -20 uPR Total Daily Dose -40 PR PR 90 mg -60 75 mg 60 mg -80 45 mg -100 CR Prior EGFR + + - - + + + + + + - + - + + exon 20 therapy CN
Slide 17: Confirmed Complete Intracranial and Systemic Response in EGFR Exon 20 Patient
Confirmed Complete Intracranial and Systemic Response in Patient with EGFR Exon 20 Mutated NSCLC and Active CNS Metastases Progressed on Prior EGFR Exon 20 Targeted Therapy • Patient: 55F with EGFR exon 20 mutated NSCLC • Prior therapy: Pemetrexed/cisplatin and amivantamab • Metastases at baseline
Slide 18: ORIC-114 Only EGFR Exon Inhibitor with Systemic and CNS Complete Response
ORIC-114 Is the Only EGFR Exon 20 Inhibitor to Demonstrate a Systemic Complete Response and CNS Complete Response, Despite More Challenging Patients Comparison of Selected Eligibility Criteria, Baseline Characteristics, and Clinical Activity • EGFR exon 20 inhibitor clinical Amivantamab CLN-081 Sunv
Slide 19: HER2 Exon 20: Tumor Regression Observed Across All Active Doses
HER2 Exon 20: Tumor Regression Observed Across All Active ORIC-114 Doses Preliminary Activity (NSCLC patients with HER2 exon 20 and treated at ≥45 mg TDD) 60 40 20 0 -20 uPR uPR Total Daily Dose -40 PR 90 mg -60 PR 75 mg 60 mg -80 45 mg -100 PR Prior HER2 - + - - - - + - - - - + - therapy CNS Metast
Slide 20: ORIC-114 Activity Against Atypical EGFR Mutations
In Addition to EGFR Exon 20, ORIC-114 Also Demonstrates Excellent Preclinical Activity Against Atypical Mutations in EGFR, Revealing an Additional Opportunity ORIC-114 In Vitro and In Vivo Activity in Atypical EGFR Mutations ORIC-114 Demonstrates Superior In Vitro Potency ORIC-114 Induces Complete T
Slide 21: ORIC-114 Planned Next Steps and Potential Registrational Paths
ORIC-114 Planned Next Steps and Potential Registrational Path(s) 2024 2025 - 2026 2027 ❑ EGFR exon 20 inhibitor-naïve Phase 1b Dose ❑ EGFR atypical mutations Expansion ❑ HER2 exon 20 EGFR exon 20, naïve to prior exon 20 EGFR exon 20, post-amivantamab Multiple Potential Potential Phase 2 NDA Filings
Slide 22: ORIC-114 Significant Commercial Opportunity Across Multiple Patient Populations
ORIC-114 Is Pursuing a Significant Commercial Opportunity Across Multiple Patient Populations that Do Not Have CNS Active Agents Approved or in Late-Stage Development Estimated US Prevalence of Exon 20 Insertions (% of NSCLC) 10 14.0% .0% ORIC-114 Target Population: 12.5% 6.5% of NSCLC 18 2..0 0% %
Slide 23: ORIC-944 Allosteric PRC2 Inhibitor
ORIC-944 Allosteric PRC2 Inhibitor
Slide 24: ORIC-944 Is a Promising Next-Generation PRC2 Inhibitor for Prostate Cancer
ORIC-944 Is a Promising Next-Generation PRC2 Inhibitor Focused on Patients with Prostate Cancer ORIC-944 Target Product Profile • Allosteric inhibitor of PRC2 by selectively targeting EED • Picomolar biochemical potency Selective and Potent Promising Phase 1b • Significant single agent activity demo
Slide 25: PRC2 Plays Pivotal Role in Transcriptional Regulation and Cancer
PRC2 Plays Pivotal Role in Transcriptional Regulation and Cancer PRC2 Function PRC2 Background PRC2 • Two druggable subunits: – EED: responsible for histone binding; target of ORIC-944 EZH2 – EZH2: responsible for histone methylation; target of first- EED generation inhibitors • Dysregulation of PRC
Slide 26: ORIC-944 Targets the EED Subunit of PRC2
ORIC-944 Targets the EED Subunit of PRC2 and Has Demonstrated Superior Single Agent In Vivo Efficacy and Favorable Drug Properties EED Inhibition May Improve Upon EZH2 Inhibitors ORIC-944 Induces Complete Regression in DLBCL Model 1250 • ORIC-944 allosterically inhibits PRC2 by targeting EED • Allos
Slide 27: ORIC-944 Strong Single-Agent Activity in Prostate Cancer Models
ORIC-944 Demonstrated Strong Single-Agent Activity in Prostate Cancer Models In Vivo Efficacy – Prostate Cancer Models Androgen-Insensitive Prostate Cancer Enzalutamide-Resistant AR-v7+ Prostate Cancer 2000 1000 Vehicle 1500 750 Vehicle Enzalutamide 1000 500 Enzalutamide **** **** ORIC-944 500 250 O
Slide 28: PRC2 Epigenetic Dysregulation in Prostate Cancers Treated with AR Inhibitors
PRC2 Epigenetic Dysregulation Plays a Key Mechanistic Role During the Progressive Reprogramming of Prostate Cancers Treated with AR Inhibitors AR Independent Prostate Cancer AR Dependent Prostate Cancer • Prostate cancer cells evade therapies by cellular reprogramming to an AR independent state • PR
Slide 29: ORIC-944 Synergizes with AR Inhibitors in Preclinical Models
ORIC-944 Synergizes with AR Inhibitors in Preclinical Prostate Cancer Models Combination Potential of PRC2 and AR Inhibition Preclinical Synergy Assessment Synergy Score Results 10 and above = Synergy ORIC-944 PF-1497 Synergistic • Synergy observed with ORIC-944 combination with + enzalutamide + enz
Slide 30: Pfizer Data Validates Synergy of PRC2 and AR Inhibitors
Pfizer Phase 1 Data Clinically Validates Synergy of PRC2 Inhibitor and AR Inhibitor in Prostate Cancer Updated PF-06821497 Phase 1 Data in Prostate Cancer (1Q23 Pfizer Earnings Call) Early rPFS data are encouraging and notably longer than historical controls In the control arm of the CARD study, rPF
Slide 31: First-In-Human Phase 1b Study of ORIC-944
First-In-Human Phase 1b Study of ORIC-944 in Metastatic Prostate Cancer Phase 1b, Multicenter, Open-Label Study Dose Escalation Dose Escalation Objectives ❑ Strong drug properties Key Eligibility ❑ Long half-life • Metastatic prostate ORIC-944 cancer ❑ Dose proportional exposures • Single agent • Pr
Slide 32: ORIC-944 Potential Best-in-Class Pharmacokinetic Profile
ORIC-944 Has Demonstrated a Potential Best-in-Class Pharmacokinetic Profile Preliminary Phase 1b Pharmacokinetic Data Clinical Half-Life Comparison Key Takeaways 15 • Excellent pharmacokinetic profile observed to date ─ Increased exposure with dose level >10 hours ─ Low inter-patient variability 10
Slide 33: ORIC-944 Robust and Consistent Target Engagement
ORIC-944 Has Demonstrated Robust and Consistent Target Engagement Preliminary Phase 1b Pharmacodynamic Data Inhibition of PRC2 Activity Key Takeaways (% H3K27me3 Reduction in Monocytes) Once Daily Dosing (QD) 200 mg 400 mg 600 mg 900 mg • Robust target engagement demonstrated with once- 0 daily mono
Slide 34: ORIC-944 Advancing into Combination Development
ORIC-944 Is Advancing into Combination Development Based on Phase 1 Results Phase 1b, Multicenter, Open-Label Study Initial Phase 1b Results Phase 1b Dose Expansion • Potential best-in-class drug properties with half-life Key Eligibility >10 hours supporting once-daily dosing • Metastatic prostate O
Slide 35: ORIC-533 Orally Bioavailable Small Molecule Inhibitor of CD73
ORIC-533 Orally Bioavailable Small Molecule Inhibitor of CD73
Slide 36: ORIC-533 Potential Best-in-Class CD73 Inhibitor for Multiple Myeloma
ORIC-533 Is a Potential Best-in-Class Inhibitor of CD73 and First-in-Class for the Treatment of Multiple Myeloma ORIC-533 Target Product Profile • Adenosine is immunosuppressive and impairs antitumor immunity • CD73 reverses immunosuppression in preclinical studies CD73 Has Significant • CD73 inhibi
Slide 37: Initial Phase 1b Results of ORIC-533 in Multiple Myeloma
Initial First-In-Human Phase 1b Results of ORIC-533 in r/r Multiple Myeloma Were Presented at ASH 2023 Phase 1b, Multicenter, Open-Label Study Phase 1b Dose Escalation Initial Phase 1b Results ✓ Clinical half-life of ~24 hours supports QD dosing Key Eligibility ✓ Well tolerated safety profile with n
Slide 38: ORIC-613 Highly Selective PLK4 Inhibitor
ORIC-613 Highly Selective PLK4 Inhibitor
Slide 39: ORIC Developing Small Molecule PLK4 Inhibitors Targeting TRIM37-Amplified Cancer
ORIC Is Developing Small Molecule Inhibitors of PLK4 Targeting TRIM37-Amplified Breast Cancer Via Synthetic Lethality PLK4 Inhibition Is Synthetically Lethal to ORIC Small Molecule Inhibitor of PLK4 Tumor Cells with TRIM37 Amplifications Discovery and Development Rationale Normal Cell • Polo-like ki
Slide 40: ORIC PLK4 Inhibitors Potent, Selective, with Single Agent Activity
ORIC Small Molecule Inhibitors of PLK4 Are Highly Potent and Selective, and Demonstrate Single Agent Activity In Vivo ORIC PLK4 Inhibitors Are Potent and Selective ORIC PLK4 Inhibitors Demonstrate Single Agent with Targeted Activity in TRIM37 Amplified Cell Lines Activity in TRIM37 Amplified Xenogra
Slide 41: Key Takeaways
CGrIC Key Takeaways
Slide 42: Clinical Pipeline Focused on Advancement of ORIC-114 and ORIC-944
Clinical Pipeline Focused on Advancement of ORIC-114 and ORIC-944 Lead Lead Program Indication Identification Optimization IND Enabling Phase 1 Phase 2 Phase 3 Key Differentiation PRODUCT CANDIDATES NSCLC, Breast & ✓ CNS active ORIC-114 Phase 1b: ORIC-114 single agent Tumor agnostic ✓ Well tolerated
Slide 43: ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer
ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer • Two potential best-in-class programs advancing towards pivotal studies Broad Pipeline of Potential First-in-Class and Best-in-Class Programs • Additional preclinical programs targeting novel and validated targets Precision Oncology
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