Oric Pharmaceuticals, Inc. · NASDAQ:ORIC
Oric Pharmaceuticals — Investor Presentation (January 2021)
41 slides from Oric Pharmaceuticals's investor presentation, Jan 11, 2021
Slide 1: Company Overview January 2021
Company Overview January 2021 Exhibit 99.2
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 Experienced Leadership Lead Program Targeting Multiple Large Indications Broad Pipeline Strong Financial Foundation Multiple Upcoming Catalysts Heritage of discovering and developing multiple approved oncology medicines at Ignyta, Me
Slide 4: Founders and Board Members with Significant Oncology Experience
Founders and Board Members with Significant Oncology Experience Richard Scheller, PhD BOD Member, SAB Chairman of R&D BridgeBio Previously CSO Genentech and 23andMe National Academy of Sciences Board member at BridgeBio, Alector and Maze Charles Sawyers, MD Founder, SAB MSKCC and HHMI Investigator K
Slide 5: 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 TPG Capital (completed $10bn of aggregate acquisitions) and McKinsey Board member of Turning Point Therapeutics and 4D Molecular Therapeutics; previously B
Slide 6: Full Slate of Capabilities Enables Best of Breed Hybrid Approach
Full Slate of Capabilities Enables “Best of Breed” Hybrid Approach to Company Building Source Agnostic “Best Molecule Wins” Internally-Discovered Pipeline Externally-Sourced Pipeline
Slide 7: Leveraging Areas of Expertise and Proven Track Records of Success
Leveraging Areas of Expertise and Proven Track Records of Success Cancer Biomarker-driven, patient-selected trials Purpose-built targeted therapeutics Nuclear hormone receptor targets Prostate and breast cancer indications Resistance Overcoming Mechanisms responsible for treatment relapse: Innate re
Slide 8: Broad Pipeline Targeting Multiple Resistance Mechanisms
Broad Pipeline Targeting Multiple Resistance Mechanisms Program Target ID / Validation Lead Identification Lead Optimization Preclinical Phase 1 Phase 2 Phase 3 Indication Type of Resistance Prostate cancer Solid tumors Solid tumors PRODUCT CANDIDATES DISCOVERY RESEARCH PROGRAMS Multiple programs ta
Slide 9: Substantial Progress in 2020: Well Positioned to Build Value in 2021
Substantial Progress in 2020: Well Positioned to Build Value in 2021 and Beyond Corporate ORIC-101 (GR Antagonist) ORIC-533 (CD73 Inhibitor) Discovery Demonstrated potential best-in-class preclinical profile Generated compelling preclinical package with leading KOL to support single agent clinical d
Slide 10: ORIC-101 Glucocorticoid Receptor Antagonist
ORIC-101 Glucocorticoid Receptor Antagonist
Slide 11: GR Is Overexpressed in Solid Tumors and Associated with Therapy Resistance
Glucocorticoid Receptor (GR) Is Overexpressed in Solid Tumors and Associated with Therapy Resistance 3+ (High or strong) 2+ (Moderate) 1+ (Low or weak) GR Is Overexpressed in Multiple Solid Tumors (1) Elevated GR Expression Correlated with Worse Clinical Outcomes in ER-Negative Breast Cancer (2) Ele
Slide 12: GR Potentially Drives Resistance Across Large Oncology Indications
Therapeutic Area US Patient Population (1) Anti-Cancer Treatment Resistance Mechanism Potential Solution Prostate cancer ~175,000 AR modulators (e.g., Xtandi, Erleada) GR bypasses AR signaling Solid tumors ~180,000 Chemotherapy (e.g., Abraxane) GR drives tumor survival and proliferation GR Antagonis
Slide 13: Acquired Resistance to Anti-Androgen Treatment Correlated with Upregulation of GR
Acquired Resistance to Anti-Androgen Treatment Correlated with Upregulation of GR Expression Long-Term Anti-Androgen Treatment Led to Resistance In Vivo… …This Resistance Correlated to Increased GR mRNA and GR Protein Expression ** **** ** Glucocorticoid Receptor Resistance develops Source: Arora et
Slide 14: GR Expression Is Associated with Clinical Resistance to Enzalutamide
GR Expression Is Associated with Clinical Resistance to Enzalutamide in the Treatment of Prostate Cancer Initial observations from Sawyers’ lab demonstrated a correlation between increased GR expression and poor clinical response to enzalutamide, and suggest that AR inhibition may induce GR expressi
Slide 15: GR May Impede Therapeutic Response to Chemotherapy
GR May Also Impede Therapeutic Response to Chemotherapy by Enabling Pro-Survival Mechanisms Glucocorticoids ¯ Apoptosis Adhesion Inflammation EMT “Stemness” (Metabolic changes) Pro-Survival Mechanisms GR Acts as a Pro-Survival Mechanism in Tumors Counteracting GR is expected to block the transcr
Slide 16: Preliminary Proof-of-Concept with a Competitor GR Antagonist
Preliminary Proof-of-Concept Demonstrated with a Competitor GR Antagonist in Combination with Chemotherapy in Patients with Solid Tumors Relacorilant Plus Abraxane Phase 1 Data in Advanced Solid Tumors Relacorilant plus Abraxane demonstrated ORR in PDAC of 4/25 (16%) and ORR in ovarian cancer of 3/1
Slide 17: Competitor GR Antagonist Limited by Drug-Drug Interactions and Adverse Events
Competitor GR Antagonist Is Limited by Significant Drug-Drug Interactions and Serious Adverse Events When Combined with Chemotherapy In a Phase 1 clinical study, relacorilant increased the exposure of Abraxane, resulting in high rate of neutropenia (despite mandatory prophylactic G-CSF) among other
Slide 18: ORIC-101 Is a Potent and Selective GR Antagonist Designed for Oncology
ORIC-101 Is a Potent and Selective GR Antagonist Designed for Oncology ORIC-101 is a potent and selective GR antagonist with reduced potential for drug-drug interaction versus other GR antagonists (CYP2C8 plays a critical role in metabolism of taxanes and enzalutamide) Source: ORIC data. Note: In vi
Slide 19: ORIC-101 Reverses Enzalutamide Resistance in an In Vitro Prostate Cancer Model
ORIC-101 Reverses Enzalutamide Resistance in an In Vitro Prostate Cancer Model ORIC-101 Reverses GR-Driven Enzalutamide Resistance AR Inhibition Upregulates GR in Prostate Cancer Cells GR activation by glucocorticoid treatment (i.e., dexamethasone) drives enzalutamide resistance in vitro; ORIC-101 r
Slide 20: ORIC-101 Overcomes GR-Driven Chemotherapy Resistance Across Cell Lines
ORIC-101 Overcomes GR-Driven Chemotherapy Resistance Across a Wide Range of Human Cancer Cell Lines Ovarian Cancer GR Positive TNBC GR Positive NSCLC GR Positive Ovarian Cancer GR Negative (Control) Chemo + GR agonist Chemo + GR agonist + ORIC-101 Chemo Vehicle Green = Tumor cell colony % = Percenta
Slide 21: ORIC-101 Overcomes GR-Driven Resistance to Chemotherapy In Vivo
ORIC-101 Overcomes GR-Driven Resistance to Chemotherapy In Vivo TNBC Xenograft Model Comparable activity demonstrated in xenograft models of ovarian cancer, TNBC and in combination with other classes of chemotherapy Source: ORIC data. Note: HCC1806 tumor growth curves. Mice were treated with paclita
Slide 22: ORIC-101 Is Currently Being Studied in Two Phase 1b Studies
ORIC-101 Is Currently Being Studied in Two Phase 1b Studies Phase 1a: Single Agent PK, PD, and Safety (Complete) Phase 1b: Multiple Indications and Combinations Phase 1a Normal healthy volunteer single ascending dose Phase 1b Prostate cancer ORIC-101 + enzalutamide Phase 1b Advanced solid tumors ORI
Slide 23: ORIC-101 Demonstrated a Favorable Safety and Tolerability Profile in Phase 1a
ORIC-101 Demonstrated a Favorable Safety and Tolerability Profile in Phase 1a All adverse events observed across Phase 1a studies were limited to Grade 1; higher rate of GI events at 350 mg attributed, at least in part, to pill burden of the early clinical formulation (7 capsules) Treatment-Emergent
Slide 24: Phase 1b Trial of ORIC-101 with Enzalutamide in Metastatic Prostate Cancer
Phase 1b Trial of ORIC-101 in Combination with Enzalutamide in Patients with Metastatic Prostate Cancer Patients: Chemo-naïve metastatic prostate cancer with evidence of disease progression on enzalutamide Patients will enroll while remaining on enzalutamide (i.e., no treatment-free period) Exclusio
Slide 25: Multiple Pathways Exist for Future Development of ORIC-101 in Prostate Cancer
Multiple Pathways Exist for Future Development of ORIC-101 in Prostate Cancer Illustrative Prostate Cancer Treatment Landscape YR 1 2 DIAGNOSIS DEATH Metastatic (M1) Non-metastatic (M0) Asymptomatic Symptoms Biochemical Recurrence (PSA) Dx Pre-Chemo Chemo PSA=0 Lupron XTANDI ERLEADA NUBEQA CASODEX X
Slide 26: Expansion Portion of Phase 1b Trial of ORIC-101 with Abraxane
Expansion Portion of Phase 1b Trial of ORIC-101 in Combination with Abraxane in Advanced Solid Tumors Ongoing Dose Level 1 ORIC-101 + nab-pac Dose Level 2 ORIC-101 + nab-pac Dose Level 3 ORIC-101 + nab-pac Patients: Part I (dose escalation): Advanced solid tumors completed Part II (dose expansion):
Slide 27: ORIC Expects to Broadly Explore Predictive Biomarkers and PD Activity
ORIC Expects to Broadly Explore Predictive Biomarkers and PD Activity to Determine Patient Selection and Confirm Target Engagement in Phase 1b Physiologic biomarkers to assess GR pathway modulation (e.g., cortisol levels in plasma) Protein expression of GR to stratify patient population (e.g., expre
Slide 28: ORIC-533 Oral CD73 Inhibitor
ORIC-533 Oral CD73 Inhibitor
Slide 29: CD73, a Cell Surface Enzyme in the Adenosine Pathway, Linked to Therapy Resistance
CD73, a Cell Surface Enzyme in the Adenosine Pathway, Has Been Linked to Therapy Resistance Overexpressed across cancer types driving local elevation of adenosine Expression is correlated with poor prognosis Mediates immunosuppression and chemoresistance via adenosine production Upregulated in respo
Slide 30: ORIC Oral CD73 Inhibitors Demonstrate Potent Adenosine Inhibition
ORIC Oral CD73 Inhibitors Demonstrate Potent Adenosine Inhibition with Enhanced Activity Over an Antibody-Based Approach ORIC-533 Analogue Suppresses Adenosine Production In Vitro Oral Administration of ORIC-533 Analogue Maintains Exposure and Reduces Adenosine in Tumors In Vivo Source: ORIC data. I
Slide 31: Preliminary Evidence of ORIC-533 Differentiation versus Competitor Compounds
Preliminary Evidence of ORIC-533 Differentiation versus Competitor Small Molecule Compounds ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression high AMP environment ORIC-533 Potently Blocks Adenosine Production from AMP ORIC-533 Rescues CD8+ T Cells in 1m
Slide 32: ORIC-533 Demonstrates Single Agent Inhibition of Tumor Growth
CD73 Inhibitor ORIC-533 Demonstrates Significant Single Agent Inhibition of Tumor Growth and Reverts Intratumor Immunosuppression with Oral Dosing In Vivo ORIC-533 IND filing expected in 1H 2021, after which a single agent clinical development path will be pursued in an undisclosed tumor type Source
Slide 33: ORIC-944 Allosteric PRC2 Inhibitor
ORIC-944 Allosteric PRC2 Inhibitor
Slide 34: PRC2 Plays Pivotal Role in Transcriptional Regulation and Cancer
PRC2 Plays Pivotal Role in Transcriptional Regulation and Cancer PRC2 is a validated oncogenic target across several cancers with promising therapeutic potential in prostate cancer, among other indications Note: EZH1, enhance of zeste homolog 1. EZH2, enhance of zeste homolog 2. EED, embryonic ectod
Slide 35: ORIC-944 Targets the EED Subunit with Strong Single-Agent Activity
ORIC-944 Targets the EED Subunit and Has Demonstrated Strong Single-Agent Activity in Enzalutamide-Resistant Prostate Cancer Models 86% tumor growth inhibition **** Vehicle Enzalutamide ORIC-944 In vivo efficacy with ORIC-944 observed in multiple prostate cancer models; Along with improved drug prop
Slide 36: ORIC-114 Brain Penetrant EGFR/HER2 Exon Inhibitor
ORIC-114 Brain Penetrant EGFR/HER2 Exon 20 Inhibitor
Slide 37: ORIC-114 Designed to Selectively Target EGFR and HER2
ORIC-114 Was Designed to Selectively Target EGFR and HER2 with High Potency Against Exon 20 Insertion Mutations Head-to-Head Kinome Selectivity Profiling Poziotinib TAK-788 CLN-081 ORIC-114 vs. Source: Data on file. Note: All kinome selectivity screens conducted in 468 kinases at 1µM. Top 10% shown.
Slide 38: ORIC-114 Demonstrates Potent In Vivo Activity
ORIC-114 Demonstrates Potent In Vivo Activity in an EGFR Exon 20 Insertion Model and Intracranial EGFR Mutant Model Source: Data on file. Patil et al. Clin Lung (2020). Note: Left graph shows a NSCLC EGFR exon 20 insertion in vivo model in NPH variant. Right graph shows an intracranial NSCLC EGFR ex
Slide 39: Multiple Potential Areas for Development with ORIC-114
There Are Multiple Potential Areas for Development with ORIC-114 Exon 20 Insertions EGFR NSCLC (with and w/o brain mets) Tumor Agnostic (with brain mets) Tumor Agnostic (with and w/o brain mets) NSCLC (with and w/o brain mets) Tumor Agnostic (with and w/o brain mets) Other Alterations HER2 Initial F
Slide 40: Broad Pipeline Targeting Multiple Resistance Mechanisms
Broad Pipeline Targeting Multiple Resistance Mechanisms Program Target ID / Validation Lead Identification Lead Optimization Preclinical Phase 1 Phase 2 Phase 3 Indication Type of Resistance Prostate cancer Solid tumors Solid tumors PRODUCT CANDIDATES DISCOVERY RESEARCH PROGRAMS Multiple programs ta
Slide 41: ORIC Vision: Become a Leading Oncology Company Overcoming Resistance in Cancer
ORIC Vision: Become a Leading Oncology Company at the Forefront of Overcoming Resistance In Cancer Experienced Leadership Lead Program Targeting Multiple Large Indications Broad Pipeline Strong Financial Foundation Multiple Upcoming Catalysts Heritage of discovering and developing multiple approved
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