Revolution Medicines, Inc. · NASDAQ:RVMD
Revolution Medicines — Investor Presentation (January 2022)
33 slides from Revolution Medicines's investor presentation, Jan 11, 2022
Slide 1: On Target to Outsmart Cancer
On Target to Outsmart CancerTM
Slide 2: Legal Disclaimer
Legal Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and fina
Slide 3: On Target to Outsmart Cancer
On Target to Outsmart Cancer HIGH UNMET NEED IN RAS-ADDICTED CANCERS RAS proteins drive 30% of human cancers(1), and are largely unserved by targeted therapeutics STRONG CLINICAL VALIDATION OF RAS AS CANCER DRIVER Proof-of-principle from first-gen KRASG12C inhibitors(2) predicts favorable impact of
Slide 4: Excessive RAS(ON) Signaling Drives 30% of Human Cancers
Excessive RAS(ON) Signaling Drives 30% of Human Cancers = RAS(OFF) RAS-Addicted Cancers = RAS(ON) Normal RAS Cancer Mutations New patients per year (U.S.)(1) 230,000 All Cell Membrane 67,000 Lung cancer Tightly regulated Excessive control RAS(ON) cell proteins growth RAS(ON) uncontrolled signaling c
Slide 5: Deep Science-Driven Pipeline of Targeted Therapies for RAS-Addicted Cancers
RAS Deep -Addicted Science- Cancers Driven Pipeline of Targeted Therapies for RAS(ON) Inhibitors RAS Companion Inhibitors 2 Drug expected Candidates to enter 2 Clinical-stage Drug Candidates clinic in 2022 RAS COOPERATING 2 expected Drug Candidates to file RAS(ON) TARGETS 1 IND-ready CANCER Drug Can
Slide 6: RAS(ON) Inhibitors Induce Rapid, Deep and Sustained Suppression of Cancer Drivers
RAS(ON) Inhibitors Induce Rapid, Deep Suppression and Sustained of Drivers RAS(ON) Cancer RASMULTI KRASG12C RMC-6236 RMC-6291 RAS(ON) DRIVERS CANCER KRASG12D KRASG13C RMC-9805 RMC-8839
Slide 7: RAS(ON) Drug Discovery Engine: Distinctive Innovation Targets Oncogenic RAS Proteins
Engine Distinctive Targets RAS Oncogenic Drug Discovery: RAS(ON) Innovation Proteins ) Inhibitory Tri-Complexes Selected compounds Cyclophilin A Binary complex Non-covalent Covalent RAS(ON) Inhibitors Deep and Diverse Collection • Highly potent and selective • Oral and drug-like • Rapid, deep and su
Slide 8: RMC-6236: First-in-Class RAS-MULTI(ON) Inhibitor
RMC-6236: First-in-Class RASMULTI(ON) Inhibitor with Broad Potential Against RAS-Addicted Cancers Colorectal 32% Highly Potent and Selective RAS(ON) Inhibitor • Inhibits canonical RAS family members, suppressing Pancreatic the mutant cancer driver and cooperating wild-type 32% RAS proteins 137,000 R
Slide 9: RMC-6236: Highly Active in Vivo Across Cancer Models with KRASG12X Drivers
RMC-6236: Highly Active in Vivo Across Cancer Models with KRASG12X Drivers NSCLC PDAC CRC 62% ORR (8/13) 57% ORR (8/14) 38% ORR (5/13) 200 100% DCR (13/13) 200 86% DCR (12/14) 200 54% DCR (7/13) mPD 100 mPD Baseline 100 100 Volume From mPD Tumor 0 mSD 0 0 Mean Change mSD mSD % mPR mPR mPR mCR mCR mC
Slide 10: RMC-6236: Durable Anti-Tumor Benefit in KRASG12X Models
RMC-6236: Diverse RAS Highly Drivers Active in Vivo Across Cancer Models with 100 KRASG12X Tumors 75 RMC-6236 Median not reached Control % Tumors for either active Progression- 50 treatment group RAS Pathway Mutant Tumors Median = 9 days Free for both RMC-6236 25 control groups Control 0 0 10 20 30
Slide 11: RMC-6236: Anti-Tumor Immunity and Additivity with Checkpoint Inhibitor
RMC with -Checkpoint 6236: Anti-Tumor Inhibitor Immunity in Vivo and Strong Additivity Favorable Transformation of Durable Complete Responses Tumor Immune Microenvironment with Checkpoint Inhibitor Combination CD8+ T Cells M2 M𛉠mMDSCs ) Control RMC-6236 + Anti-PD1 (mm 3 CD45+ Volume of % Tumor 10
Slide 12: RMC-6236: Clinical Priorities to Pursue First-in-Class Activity
RMC-6236: Clinical Priorities to Pursue First-in-Class Activity Against KRASG12X Tumors 2022 Further development • Submit IND^ • Define RP2DS • Initiate single agent dose escalation in patients • Single agent expansion cohorts in KRASG12X with cancers with KRASG12X mutations (focused tumors (NSCLC,
Slide 13: RMC-6291: Mutant-Selective RAS(ON) Inhibitor for KRASG12C Cancers
RMC-6291: Mutant-Selective RAS(ON) Inhibitor with Best-in-Class Potential for KRASG12C Cancers Highly Potent and Selective RAS(ON) Inhibitor Lung 76% • Highly active against KRASG12C • Covalent for irreversible inhibition • Low off-target risk and acceptable safety profile 29,000 Robust Anti-tumor A
Slide 14: RMC-6291: Superior Outcomes in Mouse Clinical Trial with KRASG12C NSCLC Models
RMC-6291: Superior Outcomes in Mouse Clinical Trial with KRASG12C NSCLC Models RMC-6291 Adagrasib 72% (18/25) ORR 52% (13/25) ORR 92% (23/25) DCR 72% (18/25) DCR mPD mPD mSD mSD mPR mPR mCR mCR Best-in-Class Potential in KRASG12C NSCLC RVMD preclinical research as of 10/21/21 Adagrasib NSCLC = Non-s
Slide 15: RMC-6291 May Improve on KRASG12C(OFF) Inhibitor Class in NSCLC
RMC-6291 May Improve on KRASG12C (OFF) Inhibitor Class Across Three Outcome Measures in NSCLC Increased Rate Of Response(a) Increased Depth Of Response(b) Increased Duration Of Response(c) Volume Tumor in Change % Control RMC-6291 Adagrasib Best-in-Class Potential in KRASG12C NSCLC RVMD preclinical
Slide 16: RMC-6291: Clinical Priorities to Pursue Best-in-Class Activity
RMC-6291: Clinical Priorities to Pursue Best-in-Class Activity Against KRASG12C Tumors 2022 Further development • Submit IND^ • Define RP2DS • Initiate single agent dose escalation in • Single agent expansion cohorts in KRASG12C KRASG12C tumors NSCLC and pancreatic cancer (RAS inhibitor naïve +/- fa
Slide 17: RMC-9805: Mutant-Selective RAS(ON) Inhibitor for KRASG12D Cancers
RMC-9805: Mutant-Selective RAS(ON) Inhibitor with Best-in-Class Potential for KRASG12D Cancers Highly Potent and Selective RAS(ON) Inhibitor Pancreatic Colorectal 38% 40% • Highly active against KRASG12D • Covalent for irreversible inhibition • Low off-target risk and acceptable safety profile 55,00
Slide 18: RMC-9805: Selective, Covalent and Orally Active with Sustained Inhibition of KRASG12D
RMC-9805: Selective, Covalent and Orally Active with Sustained Inhibition of KRASG12D in Vivo Selective Covalent Single Dose PK/PD Modification of KRASG12D HPAC CDX (PDAC, KRASG12D/WT) PD: Tumor DUSP6 (%) KRAS: WT G12D G13D G12C G13C PK: Unbound plasma conc. (nM) X-linked KRAS 100 KRAS H/NRAS mRNA 1
Slide 19: RMC-9805: Tumor Regressions in Models of KRASG12D Cancers
RMC-9805: Regressions Tumor in Models of KRASG12D Cancers • First-in-class mutant-selective covalent inhibitor of KRASG12D • Deep and durable anti-tumor responses in vivo in pancreatic and colorectal cancer models • Oral dosing, well tolerated HPAC CDX (PDAC, KRASG12D/WT) 3 ) (mm 3000 Control RMC-98
Slide 20: RMC-8839: First-in-Class Mutant-Selective RAS(ON) Inhibitor for KRASG13C Cancers
RMC-8839: First-in-Class Mutant-Selective RAS(ON) Inhibitor for KRASG13C Cancers Lung 70% Highly Potent and Selective RAS(ON) Inhibitor • Highly active against KRASG13C • Covalent for irreversible inhibition • Low off-target risk and acceptable safety profile 3,000 Robust Anti-tumor Activity in Canc
Slide 21: RMC-8839: Selective, Covalent and Orally Active with Sustained Inhibition of KRASG13C
RMC-8839: Selective, Covalent and Orally Active with Sustained Inhibition of KRASG13C in Vivo Selective Covalent Single Dose PK/PD Modification of KRASG13C NCI-H1734 (NSCLC CDX, KRASG13C) KRAS: WT G12C G13C PD: Tumor DUSP6 (%) PK: Unbound plasma conc. (nM) X-linked KRAS KRAS H/NRAS Potent Inhibition
Slide 22: RMC-8839: Tumor Regressions in Models of KRASG13C Cancers
RMC-8839: Regressions Tumor in Models of KRASG13C Cancers • First-in-class mutant-selective covalent inhibitor of KRASG13C • Deep anti-tumor responses in vivo in non-small cell lung cancer models • Oral dosing, well tolerated NCI-H1734 CDX (NSCLC, KRASG13C/WT) Control RMC-8839 ST2822B PDX (NSCLC, KR
Slide 23: Pancreatic Cancer: Devastating Disease Driven by KRAS Mutations
On Pancreatic Target to Cancer Outsmart G12D RMC-6236 Devastating disease 36% RMC-9805 >90% driven by KRAS mutations 49,000 G12V RMC-6236 26% New KRASMUTANT pancreatic cancer patients per year (US)(1) G12R RMC-6236 13% RMC-6291 Dismal survival rates G12C No approved targeted therapies 2% RMC-6236 Ot
Slide 24: RAS Companion Inhibitors Suppress Cooperating Targets and Pathways
RAS Inhibitors Companion Suppress Cooperating Targets and Sustain Pathways RAS-Addicted that Cancers RMC-4630 SHP2 RMC-5552 RAS (ON) mTORC1 CANCER DRIVERS IMMUNE CHECKPOINTS
Slide 25: RMC-4630: Ongoing and Planned Clinical Combination Studies
RMC-4630: Ongoing and Planned Clinical Combination Studies COMBINED STUDY SPONSOR WITH INDICATION(S) STATUS CodeBreaK 2L+ KRASG12C Amgen sotorasib Ongoing (Phase 1b/2) 101c (U.S.) solid tumors RMC-4630-03 2L+ KRASG12C RevMed sotorasib Ongoing (Phase 2) (Global) NSCLC TCD16210 2L+ KRASG12C Sanofi ada
Slide 26: RMC-4630: Clinical Priorities to Pursue Best-in-Class Combination Activity
RMC-4630: Clinical Priorities to Pursue Best-in-Class Combination Activity in KRASG12C Tumors 2022 Further development • Registration study in combination with KRASG12C(OFF) inhibitor in KRASG12C NSCLC • Complete enrollment in RMC-4630-03 and • Combination study(ies) with KRASG12C(OFF) preliminary e
Slide 27: RMC-5552 Clinical Opportunity
Opportunity RMC-5552 Clinical • Potent, selective inhibitor of hyperactivated mTORC1 to reactivate the tumor suppressor 4EBP1 • Designed for combination with RAS(ON) inhibitors in patients with cancers harboring RAS/mTOR pathway co-mutations(1) • >30,000 new patients per year across lung, colorectal
Slide 28: RMC-5552: Clinical Priorities to Pursue Best-in-Class Combination Activity
RMC-5552: Clinical Priorities to Pursue Best-in-Class Combination Activity in RASMUTANT/mTORC1-Activated Tumors 2022 Further development • Define single agent RP2DS • Complete single agent dose-escalation • Complete single agent expansion cohorts • Initiate single agent expansion cohorts in • Combin
Slide 29: Deep Pipeline of Targeted Therapies for Majority of RAS-Addicted Cancers
Deep Pipeline of Targeted Therapies for Majority of RAS-Addicted Cancers PRECLINICAL IND-ENABLING CLINICAL PHASE 1 CLINICAL PHASE 2 CLINICAL PHASE 3 RAS(ON) INHIBITORS RMC-6236 RASMULTI RMC-6291 KRASG12C RMC-9805 KRASG12D RMC-8839 KRASG13C Additional G12R, G12V, G13D, Q61X, other RAS COMPANION INHIB
Slide 30: Anticipated Milestones
Anticipated Milestones PROGRAM MILESTONE (EXPECTED TIMING) RAS(ON) INHIBITORS RMC-6236 (RASMULTI) Submit IND (1H22); Provide evidence of first-in-class single agent activity (2023) RMC-6291 (KRASG12C) Submit IND (1H22); Provide preliminary evidence of superior activity (2023) RMC-9805 (KRASG12D) Sub
Slide 31: Financial Information
Financial Information Financial Position Cash, cash equivalents and $608.7 million(1) marketable securities @ 9/30/2021 2021 Financial Guidance 2021 GAAP net loss of $170 million to $190 million(2) (1) Expected to fund planned operations to end of 2023 (2) Includes non-cash stock-based compensation
Slide 32: Focused on serving high unmet needs across numerous RAS-driven cancers
Focused on serving high unmet needs across numerous cancers driven by diverse RAS mutations Targeted RAS(ON) Inhibitors with compelling preclinical profiles expected to begin entering clinic in 2022 Targeted RAS Companion Inhibitors designed to counter drug resistance have shown initial clinical act
Slide 33: Appendix
Appendix RAS cancer epidemiology statistics are estimated using tumor mutation frequencies from Foundation Medicine Insights August 2020 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2020: RAS mutations include: KRAS G12(A,C,D,R,S,V), KRAS G13(C,D),
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