Oric Pharmaceuticals, Inc. · NASDAQ:ORIC
Oric Pharmaceuticals — Investor Presentation (January 2025)
43 slides from Oric Pharmaceuticals's investor presentation, Jan 13, 2025
Slide 1: Company Overview January 2025
Exhibit 99.1 Company Overview January 2025
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 • Potential best-in-class TKI targeting NSCLC with EGFR exon 20, HER2 exon 20, and EGFR atypical mutations Lead Programs Advancing toward Pivotal Studies • Potential best-in-class PRC2 inhibitor targeting mCRPC • Pipeline built from
Slide 4: Executive Team with Expertise in Building Leading Oncology Companies
Executive Team with Expertise in Building Leading Oncology Companies Jacob Chacko, MD • Previously CFO at Ignyta (acquired by Roche), raised >$500m in capital Chief Executive Officer • TPG Capital (completed $10bn of aggregate acquisitions) and McKinsey & Company • Board member of 4D Molecular and B
Slide 5: Clinical Pipeline Focused on Advancement of ORIC-114 and ORIC-944
Clinical Pipeline Focused on Advancement of ORIC-114 and ORIC-944 Discovery / Clinical Anticipated Program Indication IND Enabling Phase 1/2 Pivotal / Phase 3 Collaboration Data Milestones PRODUCT CANDIDATES Mid-2026 • 1L combination with SC amivantamab EGFR exon 20 • 1L monotherapy 1H26 (1) NSCLC •
Slide 6: Substantial Progress in 2024: Well Positioned to Build Value in 2025 and Beyond
Substantial Progress in 2024: Well Positioned to Build Value in 2025 and Beyond 2024 Accomplishments and Next Steps ü Completed dose escalation, selected provisional RP2Ds, and initiated multiple dose expansion cohorts ü Executed clinical supply agreement with JNJ to evaluate ORIC-114 in combination
Slide 7: ORIC-114 Brain Penetrant EGFR/HER2 Inhibitor
ORIC-114 Brain Penetrant EGFR/HER2 Inhibitor
Slide 8: ORIC-114: Potential Best-in-Class TKI for EGFR and HER2 Mutated NSCLC
ORIC-114: Potential Best-in-Class TKI to Overcome Limitations of Approved and Investigational Agents for EGFR and HER2 Mutated NSCLC KEY LIMITATIONS of approved and investigational agents • Lack of CNS activity in populations with high rate of CNS metastases leads to suboptimal clinical outcomes • T
Slide 9: ORIC-114 Selectively Targets EGFR and HER2 with High Potency
ORIC-114 Selectively Targets EGFR and HER2 with High Potency Against EGFR Exon 20 Insertion, HER2 Exon 20 Insertion and EGFR Atypical Mutations Kinome Selectivity Comparison ORIC-114 Firmonertinib Zipalertinib Lazertinib BDTX-1535 Off-target Kinases Inhibited ≥80% at 1mM ORIC-114 Firmonertinib Zipal
Slide 10: ORIC-114 Demonstrates Potent In Vivo Activity in EGFR Exon 20 Insertion 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 Vehicle Vehicle Vehicle ORIC-114 (4 mg/kg QD) ORIC-114 (4 mg/kg QD) ORIC-114 (4 mg/kg QD) 112% TGI 127% TGI
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 ─ Key pumps that limit brain penetration, PG
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) Key Eligibility EGFR ex20 NSCLC +/- CNS • Advanced solid tumors naïve to EGFR ex20 therapy RP2D 1 ─ EGFR e
Slide 14: ORIC-114 Phase 1b 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 Regressions Across Multiple Active ORIC-114 Doses
EGFR Exon 20: Tumor Regressions Across Multiple Active ORIC-114 Doses Preliminary Activity (NSCLC patients with EGFR exon 20 and treated at ≥45 mg TDD) uPR Total Daily Dose PR PR 90 mg 75 mg 60 mg 45 mg CR Prior EGFR + + - - + + + + + + - + - + + exon 20 therapy CNS Metastases + + + + + + - + - + +
Slide 17: Confirmed Complete Intracranial and Systemic Response in EGFR Exon 20 NSCLC 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 20 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 Regressions Across Multiple Active ORIC-114 Doses
HER2 Exon 20: Tumor Regressions Across Multiple Active ORIC-114 Doses Preliminary Activity (NSCLC patients with HER2 exon 20 and treated at ≥45 mg TDD) uPR uPR Total Daily Dose PR 90 mg PR 75 mg 60 mg 45 mg PR Prior HER2 - + - - - - + - - - - + - therapy CNS Metastases + - - + - - - - - + + - - at B
Slide 20: ORIC-114 Preclinical 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: Clinical Collaboration with Johnson & Johnson to Evaluate ORIC-114 Plus Amivantamab
ORIC Entered into a Clinical Collaboration with Johnson & Johnson to Evaluate ORIC-114 Plus Amivantamab in 1L NSCLC Patients with EGFR Exon 20 • ORIC-114 plus SC amivantamab to be evaluated in 1L NSCLC with EGFR exon 20 insertions ─ Phase 1b combination study initiation expected in 1Q25 Collaboratio
Slide 22: ORIC-114 Planned Next Steps and Potential Registrational Paths
ORIC-114 Planned Next Steps and Potential Registrational Path(s) 2025 2026 2027+ • EGFR exon 20 inhibitor-naïve Phase 1b • EGFR atypical mutations Cohorts • HER2 exon 20 EGFR exon 20, naïve to prior exon 20 Multiple Potential Potential Phase 2 NDA Filings in 2027 EGFR atypical mutations Registration
Slide 23: ORIC-114 Is Pursuing a Significant Commercial Opportunity
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) 12.0% 14.0% ORIC-114 12.5% Target Population: 7%+ of NSCLC 10.0% 12.0% 8.0
Slide 24: ORIC-944 Allosteric PRC2 Inhibitor
ORIC-944 Allosteric PRC2 Inhibitor
Slide 25: ORIC-944: Potential Best-In-Class PRC2 Inhibitor for Prostate Cancer
ORIC-944: Potential Best-In-Class PRC2 Inhibitor to Overcome Limitations of Early Generation PRC2 Inhibitors for Prostate Cancer KEY LIMITATIONS of approved and investigational agents • Poor in vitro and in vivo potency across preclinical prostate cancer models for early generation PRC2 inhibitors •
Slide 26: 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: EZH2 – EED: responsible for histone binding; target of ORIC-944 – EZH2: responsible for histone methylation; target of first- EED generation inhibitors • Dysregulation of PRC
Slide 27: EED and EZH2 Inhibition Provides Equivalent Activity in Prostate Cancer Models
EED and EZH2 Inhibition Provides Equivalent Activity in Prostate Cancer Models Over the Long-term, EED Inhibition May Improve Upon EZH2 Equivalent Transcriptional Changes Observed Upon Initial Inhibition by EED and EZH2 with Respect to Resistance • ORIC-944 allosterically inhibits PRC2 by targeting
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 Dependent Prostate Cancer AR Independent Prostate Cancer • Prostate cancer cells evade therapies by cellular reprogramming to an AR independent state • PR
Slide 29: ORIC-944: A Rationally Designed Next-Generation PRC2 Inhibitor
ORIC-944: A Rationally Designed Next-Generation PRC2 Inhibitor Potential Best-in-Class PRC2 Inhibitor Landscape in Prostate Cancer CPI-1205 Tazemetostat Mevrometostat ORIC-944 st st nd rd Key Features (1 gen) (1 gen) (2 gen) (3 gen) Superior potency vs. st 1 gen programs across Cellular Potency Cell
Slide 30: ORIC-944 Demonstrates Superior In Vitro Potency vs. First-Gen PRC2 Inhibitors
ORIC-944 Demonstrates Superior In Vitro Potency vs. First-Gen PRC2 Inhibitors In Vitro Potency in Prostate Cancer Cells LNCaP CWR22PC (AR-Positive Cells) (AR-Positive Cells) ORIC-944 demonstrates potency in AR+ prostate cancer cell lines comparable to mevrometostat and superior to tazemetostat and C
Slide 31: ORIC-944 Single-Agent Activity in Preclinical Prostate Cancer Model
ORIC-944 Single-Agent Activity in Preclinical Prostate Cancer Model Compares Favorably to Previously Reported Data from Epizyme with Tazemetostat Review of Published Preclinical Data: Prostate Cancer In Vivo Efficacy ORIC-944 In Vivo Efficacy by ORIC Tazemetostat In Vivo Efficacy by Epizyme 1000 750
Slide 32: ORIC-944 Synergizes with AR Inhibitors in Preclinical Prostate Cancer 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 Analysis + enzalutam
Slide 33: Pfizer Phase 1 Data Clinically Validates Synergy of PRC2 and AR Inhibitors
Pfizer Phase 1 Data Clinically Validates Synergy of PRC2 Inhibitor and AR Inhibitor in Prostate Cancer Updated mevrometostat Phase 1 Data in Prostate Cancer (Pfizer Oncology Innovation Day) “Based on the strong signal, we are planning to initiate two pivotal studies in metastatic CRPC later this yea
Slide 34: ORIC-944 Increases Progression-Free Survival in Combination with AR Inhibitor
ORIC-944 Increases Progression-Free Survival in Combination with AR Inhibitor in Prostate Cancer Xenograft Tumors Progression-Free Survival in Prostate Cancer In Vivo Model 100 Vehicle Darolutamide Mevrometostat + Darolutamide ORIC-944 50 + Darolutamide 0 0 10 20 30 40 Days Post Treatment Mevrometos
Slide 35: First-In-Human Phase 1b Study of ORIC-944 in Metastatic Prostate Cancer
First-In-Human Phase 1b Study of ORIC-944 in Metastatic Prostate Cancer Phase 1b, Multicenter, Open-Label Study Single Agent Dose Escalation Single Agent Objectives q Strong drug properties Key Eligibility q Long half-life • Metastatic prostate ORIC-944 cancer q Dose proportional exposures • Single
Slide 36: ORIC-944 Has Demonstrated a 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 • Excellent pharmacokinetic profile observed to date ─ Increased exposure with dose level ─ Low inter-patient variability • No signs of CY
Slide 37: ORIC-944 Has Demonstrated 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) • Robust target engagement demonstrated with once- daily monotherapy dosing • Maximal decrease (≥75%) in H3K27me3
Slide 38: ORIC-944 Has Been Generally Well-Tolerated to Date
ORIC-944 Has Been Generally Well-Tolerated to Date Treatment-Related Adverse Events Occurring in ≥10% of Patients in Single Agent Dose Escalation Dose Level (QD) 100 mg (N=3) 200 mg (N=4) 400 mg (N=3) 600 mg (N=3) 700 mg (N=3) 800 mg (N=3) 900 mg (N=6) Total (N=25) Preferred Term, n (%) All Grade Gr
Slide 39: ORIC-944 Advanced into Combination Development with AR Inhibitors
ORIC-944 Advanced into Combination Development with AR Inhibitors Phase 1b, Multicenter, Open-Label Study (in collaboration with Johnson & Johnson and Bayer) ORIC-944 Combination Dose Escalation ORIC-944 Combination Dose Optimization ORIC-944 + apalutamide Key Eligibility ORIC-944 (QD) + Prior abira
Slide 40: ORIC-944 Plus Apalutamide Preliminary Clinical Activity in mCRPC
ORIC-944 Plus Apalutamide Has Demonstrated Preliminary Clinical Activity in Patients with mCRPC During Initial Dose Escalation Cohorts Phase 1b PSA Response Data of ORIC-944 Plus Apalutamide (in collaboration with Johnson & Johnson) 40 • Clinical activity observed in initial cohorts (n=6) ORIC-944 D
Slide 41: Key Takeaways
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 Discovery / Clinical Anticipated Program Indication IND Enabling Phase 1/2 Pivotal / Phase 3 Collaboration Data Milestones PRODUCT CANDIDATES Mid-2026 • 1L combination with SC amivantamab EGFR exon 20 • 1L monotherapy 1H26 (1) NSCLC •
Slide 43: ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer
ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer • Potential best-in-class TKI targeting NSCLC with EGFR exon 20, HER2 exon 20, and EGFR atypical mutations Lead Programs Advancing toward Pivotal Studies • Potential best-in-class PRC2 inhibitor targeting mCRPC • Pipeline built from
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