Revolution Medicines, Inc. · NASDAQ:RVMD
Revolution Medicines — Investor Presentation (January 2023)
32 slides from Revolution Medicines's investor presentation, Jan 10, 2023
Slide 1: On Target to Outsmart Cancer
On Target to Outsmart Cancer TM January 10, 2023
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: RAS Companion Inhibitors and RAS(ON) Inhibitors Overview
RAS Companion Inhibitors Class-leading drug candidates to counter treatment resistance RAS(ON) Inhibitors Groundbreaking class of drug candidates for robust cancer suppression HIGH UNMET NEED IN RAS-ADDICTED CANCERS 30% of human cancers(1), largely unserved by targeted therapeutics STRONG CLINICAL V
Slide 4: Excessive RAS(ON) Signaling Drives 30% of Human Cancers
Excessive RAS(ON) Signaling Drives 30% of Human Cancers, Targeted by Our Pipeline Strategy RAS-Addicted Cancers New patients per year (U.S.)(1) Normal RAS Cancer Mutations Cell Membrane Tightly regulated RAS(ON) proteins control cell growth Excessive RAS(ON) signaling drives uncontrolled cell growth
Slide 5: Deep, Science-Driven Clinical and Preclinical Pipeline of Targeted Therapies
Deep, Science-Driven Clinical and Preclinical Pipeline of Targeted Therapies for RAS-Addicted Cancers RAS Companion Inhibitors RAS(ON) Inhibitors RAS(ON) Cancer Drivers RAS Cooperating Targets Multiple pipeline expansion programs + Clinical-stage Drug Candidates 2 IND-ready Drug Candidate 1 Clinical
Slide 6: RAS(ON) Inhibitors Bind Near RAS Cancer Mutation Hotspots
a Groundbreaking RAS(ON) Inhibitors Bind Near RAS Cancer Mutation Hotspots and Suppress Cancer Signaling Potent, selective, oral and drug-like inhibitors Deep and sustained suppression of RAS(ON) cancer signaling RAS-Q61 RAS-G13 RAS-G12 Oncogenic RAS(ON) RAS(ON) Inhibitor Inhibited RAS(ON) RAS(ON) I
Slide 7: Current Portfolio of RAS(ON) Inhibitors Targets Every RAS Mutation Hotspot
Current Portfolio of RAS(ON) Inhibitors Targets Every RAS Cancer Mutation Hotspot (1) Calculated 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 (see appendix for addi
Slide 8: RMC-6236: First-in-Class RASMULTI(ON) Inhibitor
RMC-6236: First-in-Class RASMULTI(ON) Inhibitor with Broad Potential Against RAS-Addicted Cancers KRASG12X includes KRASG12D, KRASG12V, KRASG12R and KRASG12C 137,000 New KRASG12X patients per year (U.S.)(1) Pancreatic 32% Other 6% Colorectal 32% Lung 30% Characterization above is based on RVMD precl
Slide 9: RMC-6236: Highly Active with Durable Benefit Across in Vivo Models
RMC-6236: Highly Active with Durable Benefit Across in Vivo Models of Major Human Cancers with KRASG12X Drivers RVMD preclinical research as of 06/01/22 RMC-6236 dosed at 25 mg/kg po qd; n=1-10/group Progression defined as tumor doubling from baseline NSCLC = non-small cell lung cancer; PDAC = pancr
Slide 10: RMC-6236 Phase 1/1b Trial
RMC-6236 Phase 1/1b Trial: Clinical Translation of Preclinical Single Agent Profile and Initial Platform Validation (1) Long-term in mouse models defined as up to 90 days of treatment (2) Ongoing study - ClinicalTrials.gov Identifier: NCT05379985 https://clinicaltrials.gov/ct2/show/NCT05379985?term=
Slide 11: 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 29,000 New KRASG12C patients per year (U.S.)(1) Pancreatic 3% Other 3% Colorectal 18% Lung 76% Highly Potent and Selective RAS(ON) Inhibitor Highly active against KRASG12C Covalent for irreversible inhibit
Slide 12: RMC-6291: Superior Response Rates and Durability in Mouse Clinical Trial
RMC-6291: Superior Response Rates and Durability in Mouse Clinical Trial with 25 KRASG12C NSCLC Models RMC-6291 (n=108, 25 models) Adagrasib (n=118, 25 models) Control (n=114, 25 models) RMC-6291 – Median not reached Adagrasib – Median not reached Control – Median 9 days PFS RVMD preclinical researc
Slide 13: RMC-6291 Phase 1/1b Trial
RMC-6291 Phase 1/1b Trial: Clinical Translation of Preclinical Single Agent Profile and Initial Platform Validation (1) Long-term in mouse models defined as up to 90 days of treatment (2) Ongoing study - ClinicalTrials.gov Identifier: NCT05462717 https://www.clinicaltrials.gov/ct2/show/NCT05462717?t
Slide 14: RMC-9805: First-in-Class Mutant-Selective RAS(ON) Inhibitor for KRASG12D Cancers
RMC-9805: First-in-Class Mutant-Selective RAS(ON) Inhibitor for KRASG12D Cancers 55,000 New KRASG12D patients per year (U.S.)(1) Pancreatic 38% Other 8% Colorectal 40% Lung 14% Highly Potent and Selective RAS(ON) Inhibitor Highly active against KRASG12D Covalent for irreversible inhibition Low off-t
Slide 15: RMC-9805: Selective, Covalent Binding and Inhibition of KRASG12D(ON)
Drug Exposure and Pathway Suppression after Oral Dosing(1) RMC-9805: Selective, Covalent Binding and Inhibition of KRASG12D(ON) with Apoptosis Induction in Vivo Control RMC-9805 RAS signaling (pERK) Apoptosis (cleaved caspase 3) RVMD preclinical research RMC-9805 dosed at 100 mg/kg po in HPAC subcut
Slide 16: RMC-9805 Drives Tumor Regressions in Pancreatic Cancer and Brain Metastasis
RMC-9805 Drives Deep and Durable Tumor Regressions in Models of Pancreatic Cancer and Brain Metastasis Control RMC-9805 HPAC (KRASG12D) - Brain Xenograft(2) HPAC (KRASG12D) - Pancreas Xenograft(1) RVMD preclinical research RMC-9805 dosed at 100 mg/kg po qd (1) HPAC pancreas orthotopic xenograft mode
Slide 17: RMC-9805: Highly Active in Vivo Across Diverse KRASG12D Models
RMC-9805: Highly Active in Vivo Across Diverse KRASG12D Cancer Models RVMD preclinical research as of 11/02/22 RMC-9805 dosed at 100 mg/kg po qd; n=2-8/group NSCLC = non-small cell lung cancer; PDAC = pancreatic ductal adenocarcinoma; CRC = colorectal cancer Responses assigned according to mRECIST (
Slide 18: RAS(ON) Inhibitors Induce Anti-Tumor Immunity
RAS(ON) Inhibitors Induce Anti-Tumor Immunity via Multiple Mechanisms in Immunocompetent Models Additive Benefit Supports Clinical Combination Strategies with Immune Therapies % Tumors progression-free Control Anti-PD1 RMC-6236 Combination Control Anti-PD1 RMC-6291 Combination Control Anti-PD1 RMC-9
Slide 19: RMC-0708: First-in-Class Mutant-Selective RAS(ON) Inhibitor for KRASQ61H Cancers
RMC-0708: First-in-Class Mutant-Selective RAS(ON) Inhibitor for KRASQ61H Cancers Highly Potent and Selective RAS(ON) Inhibitor Highly active against KRASQ61H Non-covalent, highly selective over wild-type RAS Low off-target risk and acceptable safety profile Robust Anti-tumor Activity in Cancer Model
Slide 20: RMC-0708: Sustained Pathway Inhibition and Tumor Regressions
NSCLC(2) RMC-0708: Sustained Pathway Inhibition in Vivo and Tumor Regressions in KRASQ61H Cancer Models RVMD preclinical research RMC-0708 dosed at 30 mg/kg po qd (1) PK/PD data collected at indicated timepoints after a single dose (2) HCC2108 subcutaneous xenograft model (NSCLC, KRASQ61H/Q61H) (3)
Slide 21: On Target to Outsmart Pancreatic Cancer
On Target to Outsmart Pancreatic Cancer: RAS(ON) Inhibitors Covering All KRASMUTANT Drivers(1) RMC-6236 & RMC-9805 RMC-6236 RMC-6236 RMC-6236 G12D G12V G12R G12C Other(1) 49,000 New KRASMUTANT pancreatic cancer patients per year (U.S.)(1) Dismal survival rates No approved targeted therapies Devastat
Slide 22: RAS Companion Inhibitors Suppress Cooperating Targets and Pathways
RAS(ON) Cancer Drivers SHP2 WT RAS RAS Companion Inhibitors Suppress Cooperating Targets and Pathways that Sustain RAS-Addicted Cancers RMC-4630 RMC-5552 mTORC1 RMC-6236
Slide 23: Evaluation of RMC-4630 in Combination with Sotorasib
Evaluation of RMC-4630 in Combination with Sotorasib in KRASG12C Cancer Patients (1) Ongoing study - ClinicalTrials.gov Identifier: NCT03634982 https://clinicaltrials.gov/ct2/show/NCT03634982?term=RMC-4630&draw=2&rank=1 (2) Ongoing study - ClinicalTrials.gov Identifier: NCT04185883 https://clinicalt
Slide 24: RMC-5552: First-in-Class Bi-steric mTORC1-Selective Inhibitor
AKT Toxicity and resistance RMC-5552: First-in-Class Bi-steric mTORC1-Selective Inhibitor for Cancers with Hyperactive mTOR Signaling Characterization above is based on RVMD preclinical research mTORC2 substrate mTOR active site inhibitors Rapalogs RMC-5552 mTORC1 substrates Highly Potent and Select
Slide 25: RMC-5552: Profile as RAS Companion Inhibitor
RMC-5552: Compelling Profile as RAS Companion Inhibitor Preliminary radiologic and molecular evidence of activity at tolerated doses: Disease control across diverse tumors, including durable stable disease Objective response and regressions Favorable changes in surrogate markers 3 of 6 patients with
Slide 26: RMC-5552 Phase 1/1b Trial
RMC-5552 Phase 1/1b Trial: Clinical Optimization of Single Agent Profile for Combination with RAS(ON) Inhibitor Portfolio (1) Ongoing study - ClinicalTrials.gov Identifier: NCT04774952 https://clinicaltrials.gov/ct2/show/NCT04774952?term=rmc-5552&draw=2&rank=1 MTD = maximum tolerated dose; RP2DS = r
Slide 27: Overcoming Resistance: RMC-6291 + RMC-6236 Combination
Overcoming Resistance: RMC-6291 + RMC-6236 Combination Induces Regressions in KRASG12C NSCLC Model RASMULTI(ON) Inhibitor Deployed as a RAS Companion Inhibitor RVMD preclinical research NCI-H2122 subcutaneous xenograft model (NSCLC, KRASG12C/G12C) RMC-6291 dosed at 100 mg/kg po qd; RMC-6236 dosed at
Slide 28: Deep Pipeline of Targeted Therapies for 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-0708 KRASQ61H RMC-8839 KRASG13C Pipeline Expansion G12R, G12V, G13D, Q61X,
Slide 29: Anticipated Milestones
Anticipated Milestones MILESTONE (EXPECTED TIMING) RAS(ON) INHIBITORS RMC-6236 (RASMULTI) Provide evidence of first-in-class single agent activity (mid-2023) RMC-6291 (KRASG12C) Provide preliminary evidence of superior profile (2H2023) RMC-9805 (KRASG12D) Announce dosing of first patient (mid-2023)
Slide 30: Financial Information
Financial Information Financial Position Cash, cash equivalents and marketable securities as of September 30, 2022 $655.0 million(1) With current cash, cash equivalents and marketable securities the company projects it can fund planned operations through 2024. (2) Includes non-cash stock-based compe
Slide 31: 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 entered clinic in 2022 Targeted RAS Companion Inhibitors designed to counter drug resistance have shown initial clinical activity and evaluatio
Slide 32: 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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