Revolution Medicines, Inc. · NASDAQ:RVMD
Revolution Medicines — AACR Annual Meeting 2025
18 slides from Revolution Medicines's conference presentation, April 2025
Slide 1: Preliminary Safety and Antitumor Activity of Zoldonrasib (RMC-9805) in KRAS G12D NSCLC
Preliminary Safety and Antitumor Activity of Zoldonrasib (RMC-9805), an Oral, RAS(ON) G12D-Selective, Tri-Complex Inhibitor in Patients with KRAS G12D Non- Small Cell Lung Cancer (NSCLC) from a Phase 1 Study in Advanced Solid Tumors Kathryn C Arbour1, Tanvetyanon Tawee, Rona Yaeger, Aparna R Parikh,
Slide 2: Disclosure Information
Disclosure Information Kathryn C Arbour I have the following relevant financial relationships to disclose: Advisory Board: Bristol Myers Squibb, Revolution Medicines, Merck, Amgen, Regeneron, AstraZeneca, G1 Therapeutics, Novartis Grant/Research support: Revolution Medicines, Bristol Myers Squibb, M
Slide 3: Large Unmet Need in RAS G12D Mutant Cancers
Large Unmet Need in RAS G12D Mutant Cancers Uncontrolled RAS(ON) Signaling Drives Cells to an Oncogenic State1-3 RAS G12D Cancers are Common NSCLC Normal RAS Cancer Mutations 14% PDAC CRC 38% Other 61,000 11% New RAS G12D CRC Cell patients per year Membrane 4 (U.S.) NSCLC Tightly regulated Excessive
Slide 4: Zoldonrasib is an Oral, Mutant-Selective Covalent Inhibitor Targeting the ON State of RAS G12D
Zoldonrasib is an Oral, Mutant-Selective Covalent Inhibitor Targeting the ON (Active, GTP-bound) State of RAS G12D Multiple Approaches to Target RAS G12D Zoldonrasib Mechanism of Action in the GTP-bound or ON State Daraxonrasib (RMC-6236) Zoldonrasib RAS(ON) Multi-Selective • Noncovalent, multi-sele
Slide 5: Zoldonrasib Drives Deep and Durable Regressions in Preclinical Models in Vivo
Zoldonrasib Drives Deep and Durable Regressions in KRAS G12D NSCLC Preclinical Models in Vivo Deep Responses in NSCLC KRAS G12D Durable Responses in NSCLC KRAS G12D Preclinical Xenograft Models Preclinical Xenograft Models 200 % Progression-Free Survival 70% ORR (7/10) 100 % Change from Baseline 80%
Slide 6: RMC-9805-001 Phase 1 Study Design Arm A: Zoldonrasib Monotherapy
RMC-9805-001 Phase 1 Study Design Arm A: Zoldonrasib Monotherapy Key Eligibility Criteria Part 1: Dose Escalation • Advanced solid tumors with KRAS Zoldonrasib administered orally QD or BID, G12D mutations 21-day treatment cycle • Received prior standard therapy appropriate for tumor type and 1200 m
Slide 7: Demographics and Baseline Characteristics for Patients Treated with Zoldonrasib
Demographics and Baseline Characteristics for Patients Treated with Zoldonrasib All Doses 1200 mg QD (N = 211) (N = 90) Age, median (range), years 62 (25-86) 62 (25-86) Male, n (%) 116 (55%) 51 (57%) ECOG PS 1, n (%) 148 (70%) 64 (71%) Tumor type, n (%) NSCLC 30 (14%) 28 (31%) PDAC 115 (55%) 42 (47%
Slide 8: Exposure Showed Dose-Dependent Increases and Achieved Levels Predicted to Induce Tumor Regressions
Exposure Showed Dose-Dependent Increases and Achieved Levels Predicted to Induce Tumor Regressions Mean Steady-State Blood PK Profiles Individual Steady-State Blood AUC1 10000 30000 Steady-State Whole Blood Steady-State Whole Blood 1000 Concentration (nM) AUC (nM x h) 20000 100 10 10000 Exposure in
Slide 9: Treatment Related Adverse Events (TRAEs) for Patients Receiving Zoldonrasib
Treatment Related Adverse Events (TRAEs) for Patients Receiving Zoldonrasib All Patients Treated with Zoldonrasib (N = 211)1 Maximum Severity of Treatment-Related AEs Grade 1 Grade 2 Grade 3 Any Grade Any TRAE 109 (52%) 32 (15%) 2 (1%) 143 (68%) TRAEs occurring in ≥10% of patients, n (%) Nausea 61 (
Slide 10: Treatment Related Adverse Events (TRAEs) for Patients Receiving Zoldonrasib 1200 mg QD
Treatment Related Adverse Events (TRAEs) for Patients Receiving Zoldonrasib 1200 mg QD Patients Treated with 1200 mg QD Zoldonrasib (N = 90)1 Maximum Severity of Treatment-Related AEs Grade 1 Grade 2 Grade 3 Any Grade Any TRAE 49 (54%) 16 (18%) 2 (2%) 67 (74%) TRAEs occurring in ≥10% of patients, n
Slide 11: Demographics and Baseline Characteristics for Patients with NSCLC Treated with 1200 mg QD Zoldonrasib
Demographics and Baseline Characteristics for Patients with NSCLC Treated with 1200 mg QD Zoldonrasib Patients with NSCLC Treated with 1200 mg QD Zoldonrasib (N = 28) Age, years, median (range) 64 (36-86) Male, n (%) 14 (50%) ECOG PS 1, n (%) 18 (64%) Smoking Status Current 1 (4%) Past 12 (43%) Neve
Slide 12: ORR and DCR in Patients with NSCLC Treated with 1200 mg QD Zoldonrasib
ORR and DCR in Patients with KRAS G12D NSCLC Treated with 1200 mg QD Zoldonrasib 100 Tumor Response for Patients with NSCLC Treated with 1200 mg QD (N = 18)1 Best % Change in SOD from Baseline ORR2, % (n) 61% (11) DCR (CR+PR+SD), % (n) 89% (16) 50 in Target Tumor Burden 1 per RECIST v1.1 2 Includes
Slide 13: Duration of Treatment and Responses in Patients with KRAS G12D NSCLC
Duration of Treatment and Responses in Patients with KRAS G12D NSCLC Treated with 1200 mg QD Zoldonrasib NSCLC KRAS G12D patients (N = 18) Median (range) time to response: 1.4 months (1.2–2.8) Median (range) time on treatment: 2.6 months (1.3–8.0) Treatment Ongoing Initial Response Death 0 1 2 3 4 5
Slide 14: ctDNA Clearance in Patients with NSCLC Treated with 1200 mg QD Zoldonrasib
ctDNA Clearance in Patients with KRAS G12D NSCLC Treated with 1200 mg QD Zoldonrasib NSCLC KRAS G12D patients (N = 9) 100 • 9 patients with NSCLC treated at 1200 mg QD zoldonrasib had detectable KRAS G12D at baseline and were evaluable for changes in KRAS G12D 10 VAF on treatment1 KRAS G12D VAF • Ma
Slide 15: Case Report: Patient with KRAS G12D NSCLC
Case Report: Patient with KRAS G12D NSCLC Baseline CT Demographics and Baseline Characteristics • 70-year-old Caucasian woman • Initially diagnosed with KRAS G12D NSCLC (Stage IIIA) in February 2018; Metastatic progression: May 2022 • Past-smoker • Concurrent TP53 and MGA mutations; TMB low (7.9 mut
Slide 16: Case Report: Patient with KRAS G12D NSCLC
Case Report: Patient with KRAS G12D NSCLC Baseline CT Demographics and Baseline Characteristics • 36-year-old Asian woman, with no PMH • Initially diagnosed with KRAS G12D NSCLC (Stage IIIA disease, T4N0) in Sept 2022; Metastatic progression: Nov 2023 Disappearance of extensive • Non-smoker lung and
Slide 17: Conclusions
Conclusions • Zoldonrasib is a potent, mutant-selective, covalent inhibitor of RAS(ON) G12D • Zoldonrasib is orally bioavailable and demonstrates dose-dependent blood PK reaching exposures consistent with those inducing tumor regressions in preclinical KRAS G12D NSCLC models • Zoldonrasib is well to
Slide 18: Acknowledgements
Acknowledgements • We thank all patients who participated in this study, their families who supported them, and the clinical investigators and research staff who cared for them • Revolution Medicines Research and Development team • The RMC-9805-001 study is sponsored by Revolution Medicines, Inc. (C