Revolution Medicines, Inc. · NASDAQ:RVMD
Revolution Medicines — Corporate Update (January 2024)
33 slides from Revolution Medicines's corporate update, Jan 9, 2024
Slide 1: On Target to Outsmart Cancer
Exhibit 99.1 On Target to Outsmart Cancer January 9, 2024 © 2024 Revolution Medicines, Inc.
Slide 2: Legal Disclaimer
2 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 fi
Slide 3: Mission: to revolutionize treatment for patients with RAS-addicted cancers
3 Mission: to revolutionize treatment for patients with RAS-addicted cancers through the discovery, development and delivery of innovative, targeted medicines. • Pioneering class of RAS(ON) inhibitor drug candidates targeting oncogenic drivers of common, life-threatening cancers • Unprecedented RAS(
Slide 4: Portfolio of RAS(ON) Inhibitors Designed to Target 30% of Human Cancers
4 Portfolio of RAS(ON) Inhibitors Designed to Target 30% of Human Cancers RAS-Mutant Cancers (1) Normal New patients per year (U.S.) RAS Cancer Mutations >200,000 including Cell 60,000 Membrane Lung cancer (29% of NSCLC) Excessive Tightly regulated RAS(ON) signaling drives = RAS(OFF) RAS(ON) protein
Slide 5: Pioneering Tri-complex RAS(ON) Inhibitors Designed to Deliver Robust and Durable Anti-tumor Activity
5 Pioneering Tri-complex RAS(ON) Inhibitors Designed to Deliver Robust and Durable Anti- tumor Activity • Direct inhibition of RAS(ON) cancer Oncogenic RAS(ON) Inhibited RAS(ON) drivers RAS(ON) Inhibitor • Deep and durable suppression of RAS GTP cancer signaling designed to defy common drug resistan
Slide 6: Initial Clinical Profiles of RAS(ON) Inhibitors Support Broad Set of Potential Opportunities
6 Initial Clinical Profiles of RAS(ON) Inhibitors Support Broad Set of Potential Opportunities to Treat RAS-Addicted Cancers Target Multi-Selective Genotypes G12X and RMC-6236 Clinical validation in NSCLC and PDAC (1) expansion Mutant-Selective Evidence of differentiated clinical activity in RMC-629
Slide 7: 2024 Capital Allocation Priorities to Advance Pioneering RAS(ON) Inhibitor Pipeline
7 2024 Capital Allocation Priorities to Advance Pioneering RAS(ON) Inhibitor Pipeline … … driving to Industry-Leading Propel RMC-6236 Targeted into first pivotal trial(s) Expand reach Qualify mutant-selective Medicines of RMC-6236 inhibitors by clinically assessing led by RMC-6291 and Franchise for
Slide 8: RAS(ON) Multi-Selective Inhibitor RMC-6236
8 RAS(ON) Multi-Selective Inhibitor RMC-6236 © 2023 Revolution Medicines Confidential
Slide 9: RMC-6236-001 Phase 1 Study Design
9 RMC-6236-001 Phase 1 Study Design Key Eligibility Criteria Dose Escalation RMC-6236 administered orally QD • Advanced solid tumors (1) with KRAS G12X mutations (initially excluding KRAS G12C) 400 mg • Received prior standard therapy 300 mg Dose Optimization appropriate for tumor type and (2) 220 m
Slide 10: RMC-6236-001: Summary of Treatment-Related Adverse Events
10 RMC-6236-001: Summary of Treatment-Related Adverse Events Total (n=131) Maximum severity of TRAEs Grade 1 Grade 2 Grade 3 Grade 4 Any Grade TRAEs occurring in ≥10% of patients, n (%) * Rash 57 (44) 29 (22) 6 (5) 0 92 (70) Nausea 41 (31) 14 (11) 0 0 55 (42) Diarrhea 32 (24) 9 (7) 1 (1) 0 42 (32) V
Slide 11: KRAS G12X NSCLC: Best Overall Response to RMC-6236
11 KRAS G12X NSCLC: Best Overall Response to RMC-6236 (1) Evaluable for Efficacy (n=40) RMC-6236-001: Clinical Activity in KRAS (2) G12X NSCLC Best overall response, n (%) Complete response 1 (3) Partial response 14 (35) Stable disease 19 (48) Progressive disease 5 (13) (3) Not evaluable 1 (3) ORR,
Slide 12: KRAS G12X PDAC: Best Overall Response to RMC-6236
12 KRAS G12X PDAC: Best Overall Response to RMC-6236 (1) Evaluable for Efficacy (n=46) RMC-6236-001: Clinical Activity in KRAS (2) G12X PDAC Best overall response, n (%) Partial response 9 (20) Stable disease 31 (67) Progressive disease 3 (7) (3) Not evaluable 3 (7) ORR, n (%) 9 (20) Confirmed, n 5
Slide 13: Zeroing In on RMC-6236 Monotherapy Dose Selection
13 Zeroing In on RMC-6236 Monotherapy Dose Selection Mean Steady-State Blood PK Profiles Individual Steady-State Blood AUC 10000 400 mg 300 mg 8000 200/220 mg 160 mg 6000 Exposure in mice at 25 120 mg mg/kg* 80 mg 4000 40 mg 20 mg Exposure in mice at 10 2000 10 mg mg/kg* 0 Time (Hours) Dose Level •
Slide 14: Key RMC-6236-001 Monotherapy Expansion Cohorts Underway
14 Key RMC-6236-001 Monotherapy Expansion Cohorts Underway Patients Cohort Purpose Enrolled NSCLC G12X dose optimization (300 mg and below) Dose selection for pivotal trial ✔ RAS G13X and Q61X expansion (300 mg) Pivotal trial design ✔ PDAC G12X dose optimization (300 mg and below) Dose selection for
Slide 15: Proposed Global Randomized Phase 3 Trial in Previously-Treated RAS Mutant NSCLC
15 Proposed Global Randomized Phase 3 Trial in Patients with Previously-Treated RAS Mutant NSCLC (1) (1,2) Trial Design Potential Patient Populations RMC-6236 Endpoints PFS R G12X-C 13% Core Population: OS G12X Patients Docetaxel Patient Reported Outcomes • N > 400 patients • Prior therapies: Anti-P
Slide 16: Potential Global Randomized Phase 3 Trial of RMC-6236 in Previously-Treated PDAC
16 Potential Global Randomized Phase 3 Trial of RMC-6236 in Patients with Previously-Treated PDAC (1) (1,2) Trial Design Potential Patient Populations Endpoints RMC-6236 R PFS Physician’s choice: OS e.g., GnP or mFOLFIRINOX Patient Reported Outcomes G12X - 85% Core Population: G12X Patients • N > 50
Slide 17: Complementary RAS(ON) Inhibitors Designed for Monotherapy and Combination Strategies
17 Complementary RAS(ON) Inhibitors Designed for Monotherapy and Combination Strategies Against RAS-Addicted Cancers RAS Multi-Selective RAS Mutant-Selective • Monotherapy with broad potential • Alternative monotherapy for RAS-addicted cancers approaches • Backbone of RAS(ON) inhibitor • Complementa
Slide 18: RAS(ON) G12C-Selective Inhibitor RMC-6291
18 RAS(ON) G12C-Selective Inhibitor RMC-6291 © 2023 Revolution Medicines Confidential
Slide 19: RMC-6291-001 Phase 1 Study Design
19 RMC-6291-001 Phase 1 Study Design Key Eligibility Criteria Dose Escalation RMC-6291 administered orally QD or BID • Advanced solid tumors G12C with KRAS mutations 400 mg BID • Received prior standard therapy including treatment with 300 mg BID G12C KRAS (OFF) inhibitors 200 mg BID • ECOG PS 0–1 D
Slide 20: RMC-6291-001: Summary of Treatment-Related Adverse Events
20 RMC-6291-001: Summary of Treatment-Related Adverse Events Total (n=63) Maximum Severity of TRAEs Grade 3 Any Grade Grade 1 Grade 2 TRAEs occurring in ≥10% of patients, n (%) Diarrhea 1 (2) 18 (29) 10 (16) 7 (11) Nausea 0 17 (27) 14 (22) 3 (5) ECG QT prolonged 7 (11) 16 (25) 8 (13) 1 (2) –– – QTcF
Slide 21: KRAS G12C NSCLC: Best Overall Response to RMC-6291
21 G12C G12C KRAS NSCLC Previously Treated with or Naïve to a KRAS (OFF) Inhibitor: Best Overall Response to RMC-6291 (1) Evaluable for Efficacy* (n=17) RMC-6291-001: Clinical Activity in KRAS G12C (2) NSCLC Prior Naïve to Best overall response, G12Ci G12Ci n (%) (n=10) (n=7) (3) Partial response 5
Slide 22: KRAS G12C CRC: Best Overall Response to RMC-6291
22 G12C G12C KRAS CRC Naïve to KRAS (OFF) Inhibitor: Best Overall Response to RMC-6291 (1) Evaluable for Efficacy* (n=19) RMC-6291-001: Clinical Activity in KRAS G12C (2) CRC † Best overall response, n (%) n=20 (3) Partial response 8 (40) Stable disease 8 (40) (4) Progressive disease 4 (20) ORR, n (
Slide 23: RAS(ON) G12D-Selective Inhibitor RMC-9805
23 RAS(ON) G12D-Selective Inhibitor RMC-9805 © 2023 Revolution Medicines Confidential
Slide 24: RMC-9805: Clinical Stage, RAS(ON) Mutant-Selective, Covalent Inhibitor for RAS G12D Cancers
24 RMC-9805: Clinical Stage, RAS(ON) Mutant-Selective, Covalent Inhibitor for RAS G12D Cancers Selective Covalent Binding to KRAS G12D WT G12D G13D G12C G13C KRAS: X-linked KRAS KRAS H/NRAS In Vivo Anti-Tumor Activity across KRAS G12D Cancer Models 200 61,000 CRC 150 NSCLC New KRAS G12D patients mPD
Slide 25: Phase 1b Combo: RMC-6236 + RMC-6291 Doublet
25 Phase 1b Combo: RMC-6236 + RMC-6291 Doublet Designed to Overcome Resistance and Prolong Durability in KRAS G12C NSCLC (1) (2) Preclinical Validation RMC-6291-101 Clinical Trial 100 Objectives: evaluate safety, tolerability and preliminary activity of RMC-6236 combined with RMC-6291 75 Patient Pop
Slide 26: Phase 1b Combos: RAS(ON) Inhibitor Combinations with Pembrolizumab
26 Phase 1b Combos: RAS(ON) Inhibitor Combinations with Pembrolizumab to Inform Potential Evaluation in 1L NSCLC (1) (2) Preclinical Validation RMC-LUNG-101 Clinical Trial: Pembrolizumab Objectives: evaluate safety, tolerability and preliminary activity of RMC-6236 and RMC-6291 each combined with Co
Slide 27: Key RAS(ON) Inhibitor Combination Cohorts
27 Key RAS(ON) Inhibitor Combination Cohorts Cohort Status Purpose (1) NSCLC RMC-6236 + pembrolizumab +/- chemotherapy recruiting qualification for potential 1L RMC-6291 + pembrolizumab +/- chemotherapy recruiting qualification for potential 1L (2) Solid tumors RMC-6236 + RMC-6291 qualification for
Slide 28: Highlights of 2H-2023
28 Highlights of 2H-2023 RAS(ON) Multi-Selective Inhibitor • Encouraging initial RMC-6236 monotherapy safety, tolerability and antitumor activity profiles in both NSCLC and PDAC reported in October • Favorable safety and response trends continue to build, including in 300 mg daily cohort • Favorable
Slide 29: Broad Clinical Validation Across RAS Genotypes and Tumor Types in 2023 Driving Late-Stage Development in 2024
29 Broad Clinical Validation Across RAS Genotypes and Tumor Types in 2023 Driving Late-Stage Development in 2024 Expand reach Qualify mutant-selective inhibitors of RMC-6236 led by RMC-6291 and by clinically assessing RMC-9805 for Propel RMC-6236 opportunities late-stage development into first pivot
Slide 30: Deep Pipeline of Targeted Therapies for Majority of RAS-Addicted Cancers
30 Deep Pipeline of Targeted Therapies for Majority of RAS-Addicted Cancers PRECLINICAL IND-ENABLING PHASE 1 PHASE 2 PHASE 3 RAS(ON) INHIBITORS MULTI RMC-6236 G12C RMC-6291 RMC-9805 G12D RMC-5127 G12V Q61H RMC-0708 (1) G13C RMC-8839 Pipeline G12R, G13D, other Expansion RAS COMPANION INHIBITORS (1) S
Slide 31: Financial Information
31 Financial Information Financial Position Preliminary estimate of cash, cash equivalents and marketable securities as (1,2) $1.85 billion of December 31, 2023 (unaudited) 2023 Financial Guidance (3) 2023 net loss of $385 million to $415 million (1) Includes cash, cash equivalents and marketable se
Slide 32: On Target to Outsmart Cancer
32 On Target to TM Outsmart Cancer
Slide 33: Appendix
33 Appendix • All RAS cancer epidemiology statistics are estimated using tumor mutation frequencies from Foundation Medicine Insights March 2022 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2023: • RAS mutations include: KRAS G12(A,C,D,F,L,R,S,V),
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