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© 2026 Revolution Medicines, Inc. On Target to Outsmart CancerFebruary 2026
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2Legal DisclaimerThis 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 financial position, business strategy, prospective products, availability of funding, ability to manage existing collaborations and establish new strategic collaborations, licensing or other arrangements, the scope, progress, results and costs of developing our product candidates or any other future product candidates, conducting clinical trials, the potential market size and size of the potential patient populations for our product candidates, the timing and likelihood of success of obtaining product approvals, plans and objectives of management for future operations, the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates, future results of anticipated products and the impact of global events and other macroeconomic conditions on our business are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. The information included in these materials is provided as of February 25, 2026, unless specified elsewhere herein, and is qualified as such. Except as required by applicable law, we undertake no obligation to update any forward-looking statements or other information contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Revolution Medicines in general, see Revolution Medicines’ Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 25, 2026, and its future periodic reports to be filed with the Securities and Exchange Commission. This presentation concerns product candidates that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA) or any other regulatory authority. These product candidates are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated.This presentation includes certain information regarding publicly available results from clinical trials by third parties evaluating other product candidates. Such trials were not head-to-head trials with any of Revolution Medicines' product candidates and include differences in study protocols, patient populations and reporting standards, and caution should be exercised when comparing data across trials. All copyrights and trademarks used herein are the property of their respective owners.
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3Our Mission | Revolutionize Treatment Globally for Patients with RAS-Addicted Cancers through the Discovery, Development and Delivery of Innovative, Targeted Medicines 2500+ patientstreated with one or more of our RAS(ON) inhibitors8 randomized Phase 3 registrational trials • active and planned for 2026+ extensive Phase 1/2 trials4 clinical-stage investigational drugs •daraxonrasib | zoldonrasib | elironrasib | RMC-5127+ preclinical pipeline 3 common RAS-addicted cancerspancreatic | non-small cell lung | colorectal As of January 2026
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4Uniquely Positioned | Aiming to Change Global Standards of Care for Patients with Common RAS-Addicted Cancers (1) Estimated using tumor mutation frequencies from FoundationCORE March 2022. * Preclinical assets. •>90% are RAS-driven(1)Pancreatic ductal adenocarcinoma Non-small cell lung cancer •~30% are RAS-driven(1)•RAS-targeted therapies exist for G12C only, no full approvals to-date •~50% are RAS-driven(1)•Challenging genetically heterogeneous disease with limited treatment options Colorectal cancer Daraxonrasib(multi-selective) Zoldonrasib RMC-5127 Elironrasib RMC-0708* (Q61H)RMC-8839*(G13C) G12D G12CG13XQ61XG12 other Product Pipeline Targets RAS Variants Among RAS Mutant Solid Tumors G12V Disease progression often associated with reactivation of RAS pathway signaling
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5 Proprietary tri-complex discovery platform targeting the oncogenic (or “ON”) state of RAS Robust clinical development programs and expertise to maximize impact for patientsExpanding commercialization and operational capabilities to ensure delivery of successful launches and change global standards of care Industry-Leading Capabilities | Advancing Targeted Treatment Regimens Based on RAS(ON) Inhibitors Virtuous cycle of innovation driven by bench, bedside and commercial insights
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© 2023 Revolution Medicines Confidential 6
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7COMPOUNDFOCUSSTUDY DETAILSEARL Y CLIN. DEVELOPMENTREGISTRATIONAL TRIAL Daraxonrasib(MUL TI) PDAC 2L metastatic1L metastaticAdjuvant in resectableNSCLC2L/3L metastatic1L metastaticPlanning ongoingSolid tumors+ SOC, RAS(ON) inhibitor doublets or other investigational agents Zoldonrasib (G12D)PDAC 1L metastatic1L metastaticPhase 3 initiation plannedNSCLC 1L metastaticPhase 3 initiation plannedSolid tumors+ SOC, RAS(ON) inhibitor doublets or other investigational agentsElironrasib (G12C)Solid tumorsMonotherapy+ SOC, RAS(ON) inhibitor doublets or other investigational agentsRMC-5127(G12V)Solid tumorsMonotherapy Pipeline Led by Four Pioneering, Clinical-Stage, RAS(ON) Inhibitors Additional clinical development opportunities include RAS(ON) mutant-selective inhibitors RMC-0708 (Q61H) and RMC-8839 (G13C) and additional novel targeted approaches for patients with RAS-addicted cancers.
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8Pancreatic Cancer | Registrational Trials to Maximize Potential Across Early- to Late-Stage Disease Settings Daraxonrasib | MUL TI•2L metastatic (RASolute 302): daraxonrasib monotherapy vs. chemo Enrollment completed •1L metastatic (RASolute 303): daraxonrasib monotherapy, or daraxonrasib + GnP vs GnP alone Initiated •Adjuvant (RASolute 304): daraxonrasib vs. observation Ongoing Zoldonrasib | G12D•1L metastatic (RASolute 305): zoldonrasib + chemo vs. chemo Initiated•1L metastatic (RASolute 309): zoldonrasib + daraxonrasib vs. chemo Start-up activities ongoing Registrational Trials Daraxonrasib | MUL TI•Unprecedented clinical profile across treatment lines, RAS mutations and regimenso2L metastatic: compelling monotherapy antitumor activity with acceptable safety/tolerability profile; encouraging PFS and OS estimates relative to standard of care in 1L PDACo1L metastatic: encouraging monotherapy and combination antitumor activity with acceptable safety/tolerability profileZoldonrasib | G12D•Encouraging antitumor activity with highly differentiated safety/tolerability oClinical profile attractive for monotherapy and combination approaches Clinical Evidence 1L, first line; 2L, second line; PDAC, pancreatic ductal adenocarcinoma; PFS, progression-free survival; OS, overall survival; GnP, gemcitabine nab-paclitaxel.
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9Pancreatic Cancer | Registrational Trials Maximize Potential Across Early- to Late-Stage Disease Settings RASolute 302: Urgent need, fastest entry point into PDAC, opportunity to establish OS benefit and new SOC in 2L patientsRASolute 303: Opportunity to test two hypotheses and provides optionality, including chemo-free in 1L; opportunity to establish new SOC in 1L patientsRASolute 304: Moving into early-stage disease, ensuring all patients have a RAS inhibitor option; potential to improve disease-free survival and establish new SOC RASolute 305 and RASolute 309: Parallel development to test two hypotheses; pioneering RAS(ON) inhibitor doublet with compelling clinical and biologic rationale; zoldonrasib’s differentiated safety/tolerability profile enables broad range of combinations Strategic Drivers Registrational Trials Daraxonrasib | MUL TI•2L metastatic (RASolute 302): daraxonrasib monotherapy vs. chemo Enrollment completed •1L metastatic (RASolute 303): daraxonrasib monotherapy, or daraxonrasib + GnP vs GnP alone Initiated •Adjuvant (RASolute 304): daraxonrasib vs. observation Ongoing Zoldonrasib | G12D•1L metastatic (RASolute 305): zoldonrasib + chemo vs. chemo Initiated•1L metastatic (RASolute 309): zoldonrasib + daraxonrasib vs. chemo Start-up activities ongoing 1L, first line; 2L, second line; GnP, gemcitabine nab-paclitaxel; PDAC, pancreatic ductal adenocarcinoma; SOC, standard of care.
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10Advancing Zoldonrasib in 1L PDAC | Encouraging Initial Results in Combination with FOLFIRINOX Median follow up: 3.9 months (range 2.7, 8.0). The waterfall plot includes all treated subjects who received first dose of zoldonrasib at least 10 weeks prior to data cutoff date (to allow 1 potential scan). 1 mFFX = oxaliplatin IV at 85 mg/m2, leucovorin IV at 400 mg/m2, irinotecan IV at 150 mg/m2, 5-fluorouracil IV at 2,400 mg/m2 (over 46-hour) given Q2W. 2 Objective response rate (ORR) (per RECIST v 1.1) includes partial responses that were confirmed (PR) or still had the potential to confirm (PR*). 3 Disease control rate (DCR) includes complete responses (CR), PR and stable disease (SD). PD, progressive disease. •Initial safety and tolerability profile of the combination was largely consistent with the well-known profile of modified FOLFIRINOX alone •High zoldonrasib dose intensity maintained with mFOLFIRINOX regimen Safety/Tolerability Summary Zoldonrasib 1200 mg + mFFX1 (N=19)% (95% CI)ORR2 63% (38, 84)DCR3 95% (74, 100) Data cutoff: December 1, 2025
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11Non-Small Cell Lung Cancer | Broad Potential Across Lines of Therapy with Multi- and Mutant-Selective ApproachesDaraxonrasib | MUL TI•Compelling monotherapy clinical results in previously treated patients, including ORR, PFS and OS•Demonstrated combinability in 1L with pembrolizumab +/- chemotherapy with encouraging safety/tolerability and antitumor activity Zoldonrasib | G12D•Initial safety/tolerability and antitumor activity supports continued evaluation as monotherapy and combinationElironrasib | G12C•Differentiated clinical profile, including safety/tolerability and clinical activity observed in both G12C-naïve and G12C-previously treated patients •2L/3L metastatic (RASolve 301) Ongoing•1L metastaticPlanning ongoing •1L metastatic (RASolve 308) Advanced planning •Studying as monotherapy and in combinations informing potential registrational trials Clinical EvidenceRegistrational Trials ORR, objective response rate; PFS, progression-free survival; OS, overall survival; 1L, first line; 2L, second line; 3L, third line.
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12Colorectal Cancer | Exploring Combinations to Maximize Clinical Impact in Genetically Heterogeneous Disease Zoldonrasib | G12D and Elironrasib | G12C•Actively exploring range of clinical combinations Evaluating multiple potential combinations to optimize potential clinical impact:•RAS(ON) inhibitor doublets•SOC chemotherapies•EGFR antibodies•Other novel approaches (bi-specifics, etc.) Daraxonrasib | MUL TI•Evaluating daraxonrasib in combination with RAS(ON) mutant-selective inhibitors as part of RAS(ON) doublet combinationsoElironrasib plus daraxonrasib doublet has demonstrated encouraging antitumor activity in patients with late-line CRC Clinical EvidenceEnabling Registrational Trials CRC, colorectal cancer; SOC, standard of care.
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© 2023 Revolution Medicines Confidential 13
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14Discover | Continuous Innovation Through Unique Platform and Insights to Sustain Leadership Position and Impact Highly productive, industry leading drug discovery capabilitiesContinuing investment leveraging proprietary platform and clinical/translational insights from broad data sets to advance potentially ground-breaking approaches Singular focus on creating novel targeted therapies for patients with RAS-addicted cancers has created differentiated expertise and know-how
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15Daraxonrasib Demonstrates Encouraging Durability in RAS Mutant PDAC in Clinical and Preclinical Settings OSMedian, Months (95% CI)RAS G12X13.1 (10.9, NE)RAS Mutant15.6 (10.9, NE) Preclinical Models of RAS G12X PDAC2L PDAC Patients – Overall Survival ! "! #! $! ! %& &! D& (!! F*+,-./-012*P42/P 5-064.1, T1.812,,9./:;122 !"#$%&'(')# !"#$%&'&*+',"%-."# Clinical Kaplan-Meier: Median (range) follow-up is 16.7 (10.3, 24.6)monthsand 17.4 (10.3, 24.6) months for RAS G12X and RAS Mutant, respectively. Preclinical Kaplan-Meier: daraxonrasib dosed at 25 mg/kg po qd; n=1-10/group; Progression defined as tumor doubling from baseline; Responses assigned according to mRECIST. Jiang et al., Cancer Disc 2024.2L, second line; PDAC, pancreatic ductal adenocarcinoma; OS, overall survival; CI, confidence interval; NE, not estimable.Data cutoff: June 30, 2025
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16 Standard Models ! "! #! $! ! %!! &!!! &%!! D!!! ()*+,-.,+/M1* 23).,/M4-5,6-7M43,844"9 ! "! #! $! ! %!! &!!! &%!! D!!! ()*+,-.,+/M1* 23).,/M4-5,6-7M43,844"9 ! "! #! $! ! %!! &!!! &%!! D!!! ()*+,-.,+/M1* 23).,/M4-5,6-7M43,844"9 !"#A%"C D(%()"#%(*+, -./MNN -O34RS78+#9+,+A"%8:";,C<A ! "! #! $! ! %!! &!!! &%!! D!!! ()*+,-.,+/M1* 23).,/M4-5,6-7M43,844"9 ! Post-Progression Treatment(NSCLC, KRAS G12C)2 Innovative New Class of RAS(ON) Inhibitors Designed to Overcome RAS-Driven Drug Resistance and Extend Clinical Benefit; FIH in 2026Resistant Models3 ! "! #! $! ! %!! &!!! &%!! D!!! ()*+,-.,+/M1* 23).,/M4-5,6-7M43,844"9 ! "! #! $! ! %!! &!! #!! D!! ()*+,-.,+/M1* 23).,/M4-5,6-7M43,844"9 RM-055 Daraxonrasib NSCLC (KRAS G12C)2 PDAC (KRAS G12D)1 First-in-human (FIH) study initiation planned for 2026. Standard models: 1HPAF-II (PDAC, KRASG12D Amp/WT) n=7 per group; 2LUN055 (NSCLC, KRASG12C Amp/WT) n=2-3 per group. 3Resistant models: HPAF-II (PDAC, KRASG12D Amp/WT) with acquired resistance to RMC-7977 (RAS(ON) multi-selective tool compound) n=9 per group. Reduced sensitivity to daraxonrasib inhibition is a function of reactivation of downstream RAS signaling. LUN055 (NSCLC, KRASG12C Amp/WT) with acquired resistance to daraxonrasib n=3 per group. Resistance to daraxonrasib inhibition is a function of increase in KRAS G12C copy number. Daraxonrasib 25 mg/kg po qd; RM-055 10 mg/kg po qd. PDAC, pancreatic ductal adenocarcinoma; NSCLC, non-small cell lung cancer.
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© 2023 Revolution Medicines Confidential 17
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18Deliver | Building State-of-the-Art Organization and Capabilities to Enable Successful Commercialization Scaling the commercialization organization in preparation for daraxonrasib launch readiness Experienced leadership team with a strong track record of success in broad range of oncology builds and launches Core capabilities established in the US and building underway in priority international regions Deep cross-functional talent across medical affairs, market access, marketing, sales and enabling functions
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Confidential 19Creating Industry-Leading Global Targeted Medicines Franchise for Patients with RAS-Addicted CancersStrong financial position enables broad execution across compelling opportunities to serve unmet needs $2.0 billionin cash and investments as of December 31, 2025+$1.75 billion in additional committed capital(1) Financial Guidance$1.6 – $1.7 billion2026 GAAP Operating Expenses(2)(1) $2.0 billion in total flexible committed capital from agreement with Royalty Pharma, of which $250 million has been received as of December 31, 2025 (2) includes $180 to $200 million in non-cash stock-based compensation expense.
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20Tracking Expected Impact •Readout for RASolute 302 (daraxonrasib) 2L registrational trial 1H 2026•Update on daraxonrasib 1L mono + combination data 1H 2026üInitiate RASolute 305 (zoldonrasib + chemo combination) 1L registrational trial 1H 2026•Initiate RASolute 309 (daraxonrasib + zoldonrasib doublet) 1L registrational trial 2H 2026 •Initiate RASolve 308 (zoldonrasib combination) 1L registrational trial 1H 2026•Share plans to advance daraxonrasib combination in 1L2026•Update on elironrasib registrational strategy 2026•Substantially complete enrollment in RASolve 301 (daraxonrasib) 2L+ registrational trial 2026 •Update on combination CRC data 2026üInitiate Phase 1 combination trial with PD-1/VEGF bispecificQ1 2026 Pancreatic Cancer Program Colorectal Cancer & RVMD-Led CollaborationsNon-Small Cell Lung Cancer Program 1H, first half; 1L, first line; CRC, colorectal cancer; RP2D, recommended Phase 2 dose. Early-Stage Programs•Identify candidate RP2D for RMC-51272H 2026•Initiate Phase 1 trial with innovative new class of RAS(ON) inhibitors Q4 2026
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Confidential 21 Our Why | Building on Strong Pillars for Growing Transformative Patient ImpactRAS-addicted cancers are among the most common and difficult-to-treat cancers in need of new targeted medicinesExtensive clinical evidence has shown that RAS(ON) inhibitors have the potential to improve outcomes and change global standards of care for patients living with such cancersCompelling opportunities for further advancement through drug combinations and continuing product innovationPublished: February 28, 2025Published: November 5, 2025
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22 On Target to Outsmart Cancer®
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© 2023 Revolution Medicines Confidential 23 Appendix
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© 2023 Revolution Medicines Confidential 24 Reference Data Tables for Current Therapies Across PDAC, NSCLC and CRC
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25PDAC is an Aggressive Disease - Cytotoxic Chemotherapy is Global Standard of Care Across Lines of Therapy Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC9618512/; mPDAC Treatment Rates Flatiron EMR Jan 1, 2014 – June 20, 2021, (N=11,410); CancerMPact® Patient Metrics, Oracle Life Sciences. Available from cancermpact.lsapps.oracle.com. Accessed 30 July 2025. PDAC, pancreatic ductal adenocarcinoma; 1L, first line; 2L, second line. 2L chemotherapy No treatment (eligibility or choice) Surgery and adjuvant chemotherapy Chemotherapy Metastatic disease ResectableLocally advanced 56,000 new diagnoses annually (US) 1L chemotherapy Death during treatment ~ 40% No treatment(eligibility or choice)~ 60% PDAC
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26Adjuvant: High Unmet Need for Patients with Resectable PDAC (1) https://pmc.ncbi.nlm.nih.gov/articles/PMC9618512/. (2) mPDACTreatment Rates Flatiron EMR Jan 1, 2014 – June 20, 2021, (N=11,410);CancerMPact® Patient Metrics, Oracle Life Sciences. Available fromcancermpact.lsapps.oracle.com. (3) Cancers 2021, 13(18), 4724; https://doi.org/10.3390/cancers13184724. (4) PRODIGE 24, NEJM (2018) 379: 2395-2406. (5) ESPAC-4, Lancet (2017) 389: 1011-1024. PDAC, pancreatic ductal adenocarcinoma; DFS, disease-free survival. OS, overall survival. PDAC Resectable and borderline resectable disease accounts for ~15-25% of newly diagnosed patients with pancreatic cancer in the US.(1,2) While surgery with perioperative chemotherapy offers the possibility of a cure, ~80% advance to metastatic disease.(3) 5FU- and gemcitabine-based regimens are the most common perioperative treatmentsStudyRegimenTreatment lineNo. of patientsMedian DFS (months)3-year DFS(%)PRODIGE 24(4)FOLFIRINOXAdjuvant24721.639.7ESPAC-4(5)Gemcitabine + capecitabineAdjuvant36413.920.9 Reported Efficacy
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271L PDAC: Significant Need for Improved Treatment(s) Gemcitabine-basedGemcitabine/nab-Paclitaxel5FU-basedmFOLFIRINOX or NALIRIFOXEfficacy (1-7)ORR (%)*23-4332-42DCR (%) 50-7662-70mPFS (mo)5.5-7.16.4-8.0mOS (mo) 8.5-11.711.1-11.7Safety (4)G3+ TRAE Rate (%)~70~70Dose Reduction due to TRAE (%)~50~50Dose Discontinuation due to TRAE (%)~25~25 (1) PRODIGE4, NEJM (2011) 364: 1817-1825. (2) AVENGER 500, JCO (2024) 42:3692-3701. (3) NAPOLI-3, Lancet (2023) 402: 1272-1281. (4) MPACT, NEJM (2013) 369: 1691-1703. (5) HALO, JCO (2020) 38: 3185-3194. (6) RESOLVE, Ann Oncol (2021) 32: 600-608. (7) CanStem111P, eClinicalMedicine (2023) 58: 101897. * ORR range includes a mix of confirmed and unconfirmed responses.PDAC, pancreatic ductal adenocarcinoma; ORR, objective response rate; DCR, disease control rate; mPFS, median progression-free survival; mOS, median overall survival; G3+, Grade 3 +; TRAE, treatment-related adverse event; 5-FU, 5-fluorouracil. Reported Efficacy and Safety PDAC
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282L+ PDAC: Significant Need for Improved Treatment(s) StudyRegimenTreatment lineNo. of patientsORR (%)Median PFS (months)Median OS (months)NAPOLI 1(1)5-FU+LV+Nal-IRI2L+11783.16.1SWOG S1513(2)FOLFIRI2L58102.96.5SWOG S1115(3)FOLFOX2L6272.06.7SEQUOIA(4)FOLFOX2L28462.16.3QUILT-3.010(5)Gemcitabine + nab-paclitaxel2L4032.76.6Trybeca-1(6)Gemcitabine + nab-paclitaxel2L148NA3.56.9GEMPAX(7)Gemcitabine + paclitaxel2L140173.16.4Gupta et al.(8)5-FU+LV+Nal-IRI3L+3031.95.0Enzler et al.(9)CBP501+cisplatin+nivolumab3L+3661.95.1 (1) Onivyde USPI; (2) Chiorean EG, et al. Clin Cancer Res 2021:27:6314–33; (3) Chung V, et al. JAMA Oncol 2017;3:516–22; (4) Hecht JR, et al. J Clin Oncol 2021;39:1108–18; (5) Huffman BM, et al. JAMA Network Open 2023;6:e2249720. (6) Hammel P, et al. ASCO GI 2022; (7) Fouchardiere C, et al. J Clin Oncol 2024;42:1055-1066; (8) Gupta A, et al. Frontiers Oncol 2023: 13:1250136; (9) Enzler T, et al. Eur J Cancer 2024: 113950, means of median PFS and median OS from four experimental regimens providedPDAC, pancreatic ductal adenocarcinoma; ORR, objective response rate; PFS, progression-free survival; OS, overall survival; NA, not available. •5-FU/LV/Nal-IRI dose interruptions required in 62% of patients, dose reductions in 33%, and discontinuations in 11%(1)•Gemcitabine + nab-paclitaxel dose modifications required in 63%(6) Reported Efficacy Reported Safety and Dose Modifications PDAC
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292L+ NSCLC: Significant Need for Improved Treatment(s) (1) Garon EB, et al. Lancet 2014;384:665-673. (2)Borghaei H, et al. N Engl J Med 2015; 373:1627-1639. (3) Rittmeyer A, et al. Lancet 2017;389:255-265. (4)Fehrenbacher L, et al. Lancet 2016;387:1837-1846. (5) de Langen AJ, et al. Lancet 2023;401:733-746. (6) Ahn MJ, J Clin Oncol. 2024 Sep 9:JCO2401544. doi: 10.1200/JCO-24-01544. (7) Mok TS, J Clin Oncol. 2024;42(17_suppl):LBA8509.NSCLC, non-small cell lung cancer; CPI, check point inhibitor; 2L, second line; ORR, objective response rate; PFS, progression-free survival; OS, overall survival. Reported EfficacyStudyTiming relative to CPI approval in 1LTreatment armNo. of patientsORR (%)Median PFS (months)Median OS (months)REVEL(1) priorDocetaxel, 2L+62514%3.09.1CheckMate 057(2) priorDocetaxel, 2L+29012%4.29.4OAK(3) priorDocetaxel, 2L+42513%4.09.6POPLAR(4) priorDocetaxel, 2L+14314.7%3.09.7CodeBreak 200(5) afterDocetaxel, 2L+17413.2%4.511.3TROPION-Lung-01(6) afterDocetaxel, 2L+30513%3.711.8KRYSTAL-12(7) afterDocetaxel, 2L+1529.2%3.8NACodeBreak 200(5) afterSotorasib, 2L+17128%5.610.6KRYSTAL-12(7) afterAdagrasib, 2L+30132%5.5NA NSCLC
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30Later Line CRC: Significant Need for Improved Treatment(s) StudyRegimenTreatment lineNo. of patientsORR (%)DCR (%)Median PFS (months)Median OS (months)RECOURSE(1)Trifluridine/tipiracil3L+5342%44%2.0 (1.9–2.1)7.1 (6.5–7.8)SUNLIGHT(2)Trifluridine/tipiracil + Bevacizumab3L2466%77%5.6 (4.5–5.9)10.8 (9.4–11.8)CORRECT(3)Regorafenib2L+5051%41%2.0 (1.9–2.3)6.4 (5.8–7.3) (1) Mayer R, et al. N Engl J Med 2015;372:1909-19; Lonsurf USPI. (2) Prager GW, et al. N Engl J Med 2023;388:1657-67; Lonsurf USPI. (3) Grothey A, et al. Lancet 2013;381:303–12; STIVARGA USPI.CRC, colorectal cancer; ORR, objective response rate; DCR, disease control rate; PFS, progression-free survival; OS, overall survival; 3L, third line; 2L, second line. Reported Efficacy CRC
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© 2023 Revolution Medicines Confidential 31 DaraxonrasibRAS(ON) Multi-Selective InhibitorActive against: •Diverse RAS driver mutations•Multiple drug resistance mechanisms, including secondary RAS mutations and wild-type RASFDA granted:•Commissioner’s National Priority Voucher •Orphan Drug Designation•Breakthrough Therapy Designation
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© 2023 Revolution Medicines Confidential 32 Daraxonrasib Clinical Data
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33 2L PDAC: Daraxonrasib (300 mg) Demonstrated Compelling Clinical Activity in Patients with RAS Mutations Median (range) follow-up is 16.7 (10.3, 24.6) monthsand 17.4 (10.3, 24.6) months for RAS G12X and RAS Mutant, respectively.Median duration of response (95% confidence interval) is 8.2 months (3.8, NE) and 8.2 months (3.8, 8.8), respectively. (1) Objective response rate (ORR) (per RECIST v 1.1) includes complete (CR) and partial responses (PR) that were confirmed or still had the potential to confirm. (2) Disease control rate (DCR) includes CR, PR and stable disease (SD). (3) One patient included in the denominator for ORR and DCR calculations is not displayed on waterfall and treated as a non-responder for purposes of the ORR and DCR calculations due to lack of post-baseline target lesion assessment. (4) RAS Mutant or RAS Other defined as patients with G12X, G13X or Q61X PDAC.2L, second line; PDAC, pancreatic ductal adenocarcinoma; PR*, unconfirmed partial response; RECIST, response evaluation criteria in solid tumors.Data cutoff: June 30, 2025 RAS G12XN=26RAS Mutant(4)N=38(3) ORR(1), % (n)35% (9)29% (11)DCR(2), % (n)92% (24)95% (36) PDAC (4)
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34 2L PDAC: Daraxonrasib (300 mg) Demonstrated Encouraging Progression-Free Survival and Overall Survival Median (range) follow-up is 16.7 (10.3, 24.6)months and 17.4 (10.3, 24.6) months for RAS G12X and RAS Mutant, respectively. 2L, second line; PDAC, pancreatic ductal adenocarcinoma; PFS, progression-free survival; OS, overall survival; CI, confidence interval; NE, not estimable. PFS Probability OS Probability Median PFS, Months (95% CI)RAS G12X8.5 (6.7, 10.5)RAS Mutant8.1 (5.9, 10.1) Median OS, Months (95% CI)RAS G12X13.1 (10.9, NE)RAS Mutant15.6 (10.9, NE) Data cutoff: June 30, 2025 PDAC
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352L+ PDAC: Daraxonrasib at 300 mg Daily Generally Well Tolerated N=83Any GradeGrade ≥3Patients with Any TRAE, N (%) 80 (96%)28 (34%)TRAEs occurring in ≥15% of patients, N (%)Rash* 75 (90%)6 (7%)Stomatitis/mucositis*45 (54%)3 (4%)Diarrhea 43 (52%)3 (4%)Nausea 32 (39%)0Vomiting 30 (36%)0Paronychia 15 (18%)0Fatigue 14 (17%)1 (1%)Other select TRAEs, N (%) Platelet count decreased8 (10%)3 (4%)AST increased 8 (10%)3 (4%)Anemia 7 (8%)6 (7%)ALT increased 6 (7%)2 (2%)Neutrophil count decreased5 (6%)3 (4%) Data cutoff: June 30, 2025*Bundled term comprising multiple MedDRA preferred terms (PTs).2L+. second line and beyond; PDAC, pancreatic ductal adenocarcinoma; TRAE, treatment-related adverse event; ALT, alanine transaminase.; AST, aspartate transaminase. PDAC
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362L+ PDAC: Acceptable Dose Modification and Dose Intensity Achieved in Patients Receiving Daraxonrasib at 300 mg Daily N=83Patients with dose modification due to TRAEs, N (%)40 (48%)Dose interruption 36 (43%)Dose reduction 25 (30%)Patients with dose discontinuation due to TRAEs, N (%)0Mean dose intensity86% 2L+, second line and beyond; PDAC, pancreatic ductal adenocarcinoma; TRAE, treatment-related adverse event.Data cutoff: June 30, 2025 PDAC
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37 1L PDAC: Daraxonrasib (300 mg) Monotherapy Demonstrated Promising Initial Antitumor Activity in Patients with RAS Mutations Data cutoff: July 28, 2025 N=38(1,4) ORR(2), % (n)47% (18)DCR(3), % (n)89% (34) Two treatment-naïve patients who are included in the safety analysis are excluded from the waterfall and ORR/DCR analysis because they do not meet the definition of 1L metastatic PDAC: one patient had locally advanced disease and the other had a synchronous neuroendocrine tumor. Median (range) follow-up is 9.3 (4.8, 11.5) months. (1) All patients received a first dose 300 mg QD of daraxonrasib at least 14 weeks prior to data cutoff date. (2) Objective response rate (ORR) (per RECIST v 1.1) includes complete (CR) and partial responses (PR) that were confirmed or still had the potential to confirm. (3) Disease control rate (DCR) includes CR, PR and stable disease (SD). (4) Four patients included in the denominator for ORR and DCR calculations are not displayed on waterfall and treated as non-responders for purposes of the ORR and DCR calculations due to lack of post-baseline target lesion assessment. RAS mutations defined as patients with G12X, G13X or Q61X PDAC. 1L, first line; PDAC, pancreatic ductal adenocarcinoma; PR*, unconfirmed partial response; QD, once daily; RECIST, response evaluation criteria in solid tumors, SOD, sum of diameters. PDAC
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381L PDAC: Daraxonrasib (300 mg) Monotherapy Generally Well ToleratedN=40Any GradeGrade ≥3Patients with any TRAE, N (%)38 (95%)14 (35%)TRAEs occurring in ≥15% of patients, N (%)Rash* 35 (88%)3 (8%)Diarrhea 23 (58%)4 (10%)Stomatitis/mucositis*23 (58%)3 (8%)Nausea 20 (50%)1 (3%)Vomiting 20 (50%)2 (5%)Fatigue 14 (35%)1 (3%)Constipation6 (15%)0Decreased appetite6 (15%)0Other select TRAEs, N (%) ALT increased3 (8%)0AST increased3 (8%)0Platelet count decreased3 (8%)0Anemia 2 (5%)1 (3%)Neutrophil count decreased0 0*Bundled term comprising multiple MedDRA preferred terms (PTs). Two treatment-naïve patients are included in this safety analysis but are excluded from the waterfall and ORR/DCR analysis because they do not meet the definition of 1L metastatic PDAC: one patient had locally advanced disease and the other had a synchronous neuroendocrine tumor. 1L, first line; PDAC, pancreatic ductal adenocarcinoma; TRAE, treatment-related adverse event; ALT, alanine transaminase; AST, aspartate transferase.Data cutoff: July 28, 2025 PDAC
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391L PDAC: Daraxonrasib (300 mg) Monotherapy Demonstrated Acceptable Rate of Dose Modification and Favorable Dose IntensityN=40Patients with dose modification due to TRAEs, N (%)25 (63%)Dose interruption 21 (53%)Dose reduction 13 (33%)Patients with dose discontinuation due to TRAEs, N (%)4 (10%)Mean dose intensity85% 1L, first line; PDAC, pancreatic ductal adenocarcinoma; TRAE, treatment-related adverse event. Data cutoff: July 28, 2025 PDAC
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40Daraxonrasib Combination with GnP Demonstrated Improved Depth and Durability of Responses in Preclinical Models of PDACCapan-1 (PDAC, KRAS G12V / G12V) **p< 0.01***p<0.001, 2-way repeated measures ANOVA ! "! #! $! %! &! D! (! )! *! ! &! "!! +,-./01/234,25412 6T8503./930:34..;01<=344 !"#$%&'(')# !"#$%&'('*+,+# -- --- --- --- --- (1) 7 KRASG12X, 3 KRASWT PDAC xenograft models, n=46 per groupProgression defined as tumor doubling from baseline** Adjusted p<0.01 *** Adjusted p<0.001 by Log-rank test 10 PDAC Xenograft Models1 25 mg/kg translates to a clinical dose range of approximately 200-300 mg. Dose used in GnP arms translates to clinical dose of GnP, gemcitabine 50 mg/kg ip q3d + nab-paclitaxel 250 mg/kg iv qw; PDAC, pancreatic ductal adenocarcinoma. ! "! #! $! %! &!! ! D!! &!!! &D!! ()*+,-.,+/M1* 23).,/M4-5,6-7M43,8449: !"#$%& #D()D ** *** ***! "! #! $! %! &! D! (! )! *! ! &! "!! +,-./01/234,25412 6T8503./930:34..;01<=344 !"#A%"C D(%()"#%(G+,-K/-M12P1-4"-RS T#8 D(%()"#%(G+,-9-T#8 WX-8D<!-M"S=CG->?-@A<BTWKCa-b-@A<BFde I=S+(#-g-?S I=S+(#-g-K/i/S MM MMM MMM MMM MMM ! "! #! $! %! &! D! (! )! *! ! &! "!! +,-./01/234,25412 6T8503./930:34..;01<=344 !"#A%"C D(%()"#%(G+,-K/-M12P1-4"-RS T#8 D(%()"#%(G+,-9-T#8 WX-8D<!-M"S=CG->?-@A<BTWKCa-b-@A<BFde I=S+(#-g-?S I=S+(#-g-K/i/S MM MMM MMM MMM MMM PDAC
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41 TreatmentTarget RangesRASolute 303 Combination ArmRationale for SelectionDose: 160–300 mg Schedule:QD Dose: 200 mg Schedule:QD •Highly active and generally well tolerated in 2L PDAC•Optimize risk/benefit in combination with GnPDose: G – 1000 mg/m2 nP – 125 mg/m2Schedule (28-day):(1, 2)Days 1, 15 or Days 1, 8, 15 Dose: G – 1000 mg/m2 nP – 125 mg/m2Schedule (28-day):Days 1, 15 •Schedules commonly used with comparable outcomes •D1, 15 shows less severe bone marrow toxicity and neurotoxicity Highly Active Regimens of Daraxonrasib and GnP to be Deployed in Combination Arm of RASolute 303 Phase 3 1L PDAC Trial (1) J Gastrointest Oncol (2016) 7:469-478. (2) Ther Adv Med Oncol (2017) 9: 75-82. GnP, gemcitabine nab-paclitaxel; 1L, first line; PDAC, pancreatic ductal adenocarcinoma; QD, once daily; 2L second line. Daraxonrasib GnP(Gemcitabine nab-Paclitaxel) Objectives for Combination ArmContinuous suppression of RAS signaling | Additive antitumor mechanisms | Safety and tolerability PDAC
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42 1L PDAC: Daraxonrasib + GnP Demonstrated Encouraging Initial Antitumor Activity in Patients with RAS Mutations Median (range) follow-up is 6.9 (4.3, 9.7) months. (1) All treated 1L PDACpatients received a first dose 200 mg QD of daraxonrasib and GnP Q2W at least 18 weeks prior to data cutoff date. (2) Objective response rate (ORR) (per RECIST v 1.1) includes complete (CR) and partial responses that were confirmed (PR) or still had the potential to confirm. (3) Disease control rate (DCR) includes CR, PR and stable disease (SD). (4) Onepatient included in the denominator for ORR and DCR calculations is not displayed on waterfall and treated as a non-responder for purposes of the ORR and DCR calculations due to lack of post-baseline target lesion assessment.1L, first line; PDAC, pancreatic ductal adenocarcinoma; GnP, gemcitabine nab-paclitaxel; QD, once daily; Q2W, once every two weeks; PR*, unconfirmed partial response; RECIST, response evaluation criteria in solid tumors. N=31(1,4) ORR(2), % (n)55% (17)DCR(3), % (n)90% (28) Data cutoff: July 28, 2025 PDAC
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43 (N=40)Any GradeGrade ≥3Patients with any TRAE, N (%)39 (98%)23 (58%)TRAEs occurring in ≥30% of Patients, N (%)Rash* 34 (85%)5 (13%)Fatigue 27 (68%)5 (13%)Diarrhea 27 (68%)5 (13%)Nausea 25 (63%)2 (5%)Vomiting 19 (48%)0Anemia 17 (43%)9 (23%)Stomatitis/mucositis*17 (43%)3 (8%)Edema peripheral16 (40%)0Neutrophil count decreased15 (38%)6 (15%)Platelet count decreased14 (35%)2 (5%)Alopecia 13 (33%)0Other select TRAEs, N (%) ALT increased10 (25%)2 (5%)AST increased9 (23%)1 (3%) 1L PDAC: Daraxonrasib + GnP Demonstrated Acceptable Safety/Tolerability *Bundled term comprising multiple MedDRA preferred terms (PTs) 1L, first line; PDAC, pancreatic ductal adenocarcinoma; GnP, gemcitabine nab-paclitaxel; TRAE, treatment-related adverse event; ALT, alanine transaminase; AST, aspartate transferase. Data cutoff: July 28, 2025 PDAC
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441L PDAC: Daraxonrasib + GnP Demonstrated Acceptable Rate of Dose Modification and Favorable Dose Intensity for Daraxonrasib(N=40)DaraxonrasibGnPPatients with dose modification due to TRAEs, N (%)21 (53%)22 (55%)Dose interruption 21 (53%)15 (38%)Dose reduction 9 (23%)17 (43%)Patients with dose discontinuation due to TRAEs, N (%)2 (5%)3 (8%) Mean dose intensity81%63% 1L, first line; PDAC, pancreatic ductal adenocarcinoma; GnP, gemcitabine nab-paclitaxel; TRAE, treatment-related adverse event.Data cutoff: July 28, 2025 PDAC
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45 2L/3L NSCLC: Encouraging Durability in Patients with RAS G12X Mutations Treated with Daraxonrasib at 120-220 mg Daily RMC-6236-001: 2L/3L patients with RAS G12X NSCLC treated with daraxonrasib at 120-220 mg daily. Population includes patients with RAS G12X mutant NSCLC who have received 1 or 2 prior lines of therapy which must include prior immunotherapy and platinum chemotherapy administered either concurrently or sequentially, and have not received docetaxel previously. Adjuvant therapy or multimodal therapy with curative intent is considered prior therapy ifdisease progression occurred ortreatment completion was within 6 months of first dose of daraxonrasib. Median follow-up is 10.8months. 2L, second line; 3L, third line; NSCLC, non-small cell lung cancer; PFS, progression-free survival; OS, overall survival; CI, confidence interval; NE, not estimable. Median PFS, Months(95% CI)9.8 (6, 12.3) NSCLC Data cutoff: Sep 30, 2024 Median OS, Months(95% CI)17.7 (13.7, NE)
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462L/3L NSCLC: Daraxonrasib Generally Well Tolerated in Patients Treated at 120-220 mg Daily (1) Includes preferred terms of rash pustular, Rash papular, Rash maculopapular, Rash macular, Rash, Erythema, Dermatitis acneiform. Multiple types of rash may have occurred in the same patient.TRAE, treatment-related adverse event; NSCLC, non-small cell lung cancer; ALT, alanine transaminase; AST, aspartate transferase. •One Grade 4 pneumonitis (possibly related) observed at 300 mg dose level in patient with concomitant pneumocystis pneumonia•No other Grade 4 TRAEs. No Grade 5 TRAEs 120-300 mg120-220 mg300 mg(N=124)(N=73)(N=51)Any Grade Grade ≥3Any GradeGrade ≥3Any GradeGrade ≥3Any TRAE121 (98%)33 (27%)71 (97%)12 (16%)50 (98%)21 (41%)TRAEs in ≥ 10% of patients, n (%)Rash(1) 110 (89%)9 (7%)66 (90%)5 (7%)44 (86%)4 (8%)Diarrhea87 (70%)10 (8%)46 (63%)1 (1%)41 (80%)9 (18%)Nausea68 (55%)0 (0%)36 (49%)0 (0%)32 (63%)0 (0%)Vomiting55 (44%)3 (2%)29 (40%)2 (3%)26 (51%)1 (2%)Stomatitis47 (38%)3 (2%)25 (34%)0 (0%)22 (43%)3 (6%)Paronychia26 (21%)0 (0%)14 (19%)0 (0%)12 (24%)0 (0%)Fatigue20 (16%)0 (0%)8 (11%)0 (0%)12 (24%)0 (0%)Dry skin19 (15%)0 (0%)9 (12%)0 (0%)10 (20%)0 (0%)AST increased17 (14%)2 (2%)11 (15%)0 (0%)6 (12%)2 (4%)ALT increased15 (12%)3 (2%)10 (14%)0 (0%)5 (10%)3 (6%)Decreased appetite14 (11%)0 (0%)4 (6%)0 (0%)10 (20%)0 (0%)Dysgeusia12 (10%)0 (0%)3 (4%)0 (0%)9 (18%)0 (0%)Other select TRAEs, n (%)Anemia9 (7%)3 (2%)4 (6%)2 (3%)5 (10%)1 (2%) Data cutoff: Sept 30, 2024 NSCLC
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472L/3L NSCLC: Daraxonrasib Favorable Dose Intensity Maintained at 120-220 mg120-300 mg(N=124)120-220 mg(N=73)300 mg(N=51)TRAEs leading to dose modification, n (%)64 (52%)30 (41%)34 (67%)Dose interruption59 (48%)25 (34%)34 (67%)Dose reduction34 (27%)15 (21%)19 (37%)TRAEs leading to dose discontinuation, n (%)7 (6%)3 (4%)4 (8%)TRAEs leading to dose reductions in ≥ 10% patientsDiarrhea 12 (10%)4 (6%)8 (16%)Rash(1) 13 (11%)6 (8%)7 (14%)Mucositis/stomatitis 6 (5%)1 (1%)5 (10%)Mean dose intensity(2) 86%91%78% (1) Includes preferred terms of Rash pustular, Rash maculopapular, Rash, Dermatitis acneiform. Multiple types of rash may have occurred in the same patient. (2) Mean dose intensity figures were updated on March 14, 2025 to correct for a programming error. Previously, the mean dose intensity was represented as 81% at the 120-300 mg dose range, 88% at the 120-220 mg dose range and 72% at the 300 mg dose. NSCLC, non-small cell lung cancer; TRAE, treatment-related adverse event. •For the 120-220 mg cohort, median treatment duration was 5.5 months •Median cumulative duration of dose interruption was 8.5 daysData cutoff: Sept 30, 2024 NSCLC
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481L NSCLC: Daraxonrasib + Pembrolizumab +/- Chemotherapy Demonstrated Encouraging Preliminary Antitumor Activity Data cutoff: Feb 10, 2025 RAS mutations includes G12D, G12V, G12A, G12F, and Q61H. The patient described as not evaluable per RECIST v1.1 (NE) on the waterfall figure discontinued study after 1 cycle of treatment but achieved an unconfirmed stable disease. (1) Tumor proportion score (TPS) is based on local testing. (2) Includes efficacy evaluable patients defined as those who had one post-baseline scan or who died or had clinical progression prior to the first post-baseline response assessment. (3) Patients treated in the daraxonrasib + pembrolizumab in TPS ≥ 50% were not evaluated at the 100 mg dose. (4) Objective response rate (ORR) (per RECIST v 1.1) includes partial responses that were confirmed (PR) or still had the potential to confirm (PR*). (5) Disease control rate (DCR) includes complete responses (CR), PR and stable disease (SD). Chemotherapy = cisplatin/carboplatin plus pemetrexed. NSCLC, non-small cell lung cancer; SOD, sum of diameters; NE, not evaluable; RECIST; response evaluation criteria in solid tumors; SOD, sum of diameters; 1L, first line. # Post 1 1 3 1 2 1 3 3 1 1 Baseline Scans TPS Subgroup1Daraxonrasib 100-200 mg +Pembrolizumab + Chemotherapy (N=10)2 TPS < 50%ORR4, % (n)60% (6)DCR5, % (n)90% (9) TPS Subgroup1 Daraxonrasib 200 mg + Pembrolizumab (N=7)2,3 TPS ≥ 50%ORR4, % (n)86% (6)DCR5, % (n)100% (7) # Post 1 3 1 1 1 1 1 Baseline Scans NSCLC
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491L NSCLC: Daraxonrasib + Pembrolizumab +/- Chemotherapy Generally Well Tolerated Data cutoff: Feb 10, 2025 Daraxonrasib 200 mg + Pembrolizumab (N=10)Daraxonrasib (100-200 mg) + Pembrolizumab + Chemotherapy (N=13)Median follow-up, mo (range)2.3 (0.9, 6.2)2.6 (0.7, 5.6)Preferred TermAny GradeGrade ≥ 3Any GradeGrade ≥ 3Any TRAE, ≥ 25% in any subset9 (90%)2 (20%)12 (92%)6 (46%)Rash(1) 8 (80%)05 (39%)0Nausea 5 (50%)1 (10%)6 (46%)0Diarrhea 6 (60%)07 (54%)1 (8%)Vomiting 5 (50%)04 (31%)0Stomatitis/mucositis(2) 3 (30%)1 (10%)6 (46%)0Fatigue 2 (20%)05 (39%)0Neutrophil count decreased0 06 (46%)3 (23%)Anemia 1 (10%)05 (39%)3 (23%)Thrombocytopenia(3) 1 (10%)06 (46%)2 (15%)Select TRAEs AST increased1 (10%)01 (8%)0ALT increased1 (10%)02 (15%)0Pneumonitis1 (10%)01 (8%)0Colitis 0 0 0 0(1) Includes dermatitis acneiform, rash, rash maculo-papular, rash erythematous, and rash pustular.(2) Includes mucosal inflammation and stomatitis. (3) Includes thrombocytopenia, platelet count decreased. Any treatment-related AE, including those considered related only to chemotherapy (cisplatin/carboplatin and pemetrexed) or pembrolizumab. 1L, first line; NSCLC, non-small cell lung cancer; TRAE, treatment-related adverse event; ALT, alanine transaminase; AST, aspartate transferase. NSCLC
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501L NSCLC: Daraxonrasib + Pembrolizumab +/- Chemotherapy Combination Supports Favorable Dose IntensityDaraxonrasib 200 mg + Pembrolizumab (N=10)Daraxonrasib (100-200 mg) + Pembrolizumab + Chemotherapy (N=13)Daraxonrasib-related AEs:Leading to daraxonrasib dose reduction1 (10%)1 (8%)Leading to daraxonrasib discontinuation0(1) 1 (8%)Pembrolizumab-related AEs:Leading to pembrolizumab discontinuation0 1 (8%)Chemotherapy-related AEs:Leading to chemotherapy dose reduction- 5 (38%)Leading to chemotherapy discontinuation- 1 (8%)Daraxonrasib mean relative dose intensity93% 90% (1) Data shown are investigator corrected from EDC.Chemotherapy = carboplatin or cisplatin + pemetrexed; NSCLC, non-small cell lung cancer; 1L, first line; AE, adverse event.Data cutoff: Feb 10, 2025 NSCLC
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© 2023 Revolution Medicines Confidential 51 Daraxonrasib Registrational Study Designs
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52 2L Metastatic PDAC: Design of RASolute 302 Trial Key Eligibility Criteria•Confirmed PDAC•1 prior line of therapy in the metastatic setting•ECOG PS 0-1 R1:1 Daraxonrasib 300 mg PO QD (N=230)Investigator’s Choice SOC Chemotherapy(1)(N=230) N = 460 •PFS, OS •PFS, OS•ORR, DOR•QoL Primary Endpoints(RAS G12X) Secondary Endpoints(All Patients)NCT06625320 (1) SOC chemotherapy options: Gemcitabine + nab-paclitaxel, modified FOLFIRINOX, NAL-IRI+5-FU+LV, or FOLFOX. 2L, second line. PDAC, pancreatic ductal adenocarcinoma; ECOG PS, Eastern Cooperative Oncology Group Performance Status; R, randomized; PO, oral administration; QD, once daily; SOC, standard of care; PFS, progression-free survival; OS, overall survival; ORR, objective response rate; DOR, duration of response; QoL, quality of life. PDAC Breakthrough Therapy Designation granted by the U.S. FDA to daraxonrasib for previously treated metastatic PDAC in patients with KRAS G12 mutations
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531L Metastatic PDAC: Design of RASolute 303 Trial N ~ 900 Key Eligibility Criteria•Confirmed metastatic PDAC, regardless of RAS status•No prior systemic therapy for metastatic disease•ECOG PS 0 or 1•RAS mutation status (required for stratification) R1:1:1 Daraxonrasib (300 mg) GnP(2) •PFS, OS •ORR, DOR•Safety Primary Endpoints Secondary EndpointsDaraxonrasib (200 mg) + GnP(1)Daraxonrasib (300 mg) Treatment until disease progression or intolerance for all three arms. (1) Daraxonrasib (200 mg) + GnP (1000 mg/m2 and 125 mg/m2) given on Days 1, 15 in a 28-day cycle for up to 6 months, followed by daraxonrasib monotherapy (300 mg). (2) GnP (1000 mg/m2 and 125 mg/m2) on Days 1, 8, and 15 in a 28-day cycle. 1L, first line; PDAC, pancreatic ductal adenocarcinoma; ECOG PS, Eastern Cooperative Oncology Group Performance Status; R, randomized; GnP, gemcitabine nab-paclitaxel; PFS, progression-free survival; OS, overall survival; ORR, objective response rate; DOR, duration of response. PDAC
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54Adjuvant Therapy in Resectable PDAC: Design of RASolute 304 Trial Key Eligibility Criteria•Confirmed PDAC•R0 or R1 resection*•ECOG PS 0 or 1•≥4 months of perioperative therapy •DFSPrimary Endpoint •OS•Safety Secondary Endpoints Surgery+Perioperative chemotherapy per local SOC Daraxonrasib 300 mg PO QD Duration 2 yearsNo radiologic evidence of disease Observation R1:1 N=500 PDAC *R0 resection: No macroscopic residual tumor. No residual tumor at >1 mm of the surgical margins. R1 resection: No macroscopic residual tumor. Microscopic residual tumor at ≤1 mm of the surgical margins.PDAC, pancreatic ductal adenocarcinoma; SOC, standard of care; ECOG PS, Eastern Cooperative Oncology Group Performance Status; R, randomized; PO, oral; QD, once daily; DFS, disease-free survival; OS, overall survival.
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55Previously Treated NSCLC: Design of RASolve 301 Trial Key Eligibility Criteria•Locally advanced or metastatic NSCLC•RAS genotypes: RAS G12X-C (core population), G12C, G13X or Q61X •Prior therapies: 1 or 2 prior lines of therapy which must include immunotherapy and platinum chemotherapy administered concurrently or sequentially; no prior docetaxel or RAS inhibitor•ECOG PS 0-1 R1:1 Daraxonrasib 200 mg PO QD (N=210)Docetaxel75 mg/m2 IV Q3W(N=210) N=420 •PFS, OS •PFS, OS•ORR, DOR•QoL Primary Endpoints(RAS G12X-C)(1) Secondary Endpoints(All RAS Mutant Patients(1) (1) Nested trial design to enable hierarchical evaluation of Core and Core + Expanded populations.NSCLC, non-small cell lung cancer; ECOG PS, Eastern Cooperative Oncology Group Performance Status; R, randomized; PO, oral administration; QD, once daily; Q3W, once every three weeks; PFS, progression-free survival; OS, overall survival; ORR, objective response rate; DOR, duration of response; QoL, quality of life. NCT06881784 NSCLC
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© 2023 Revolution Medicines Confidential 56 ElironrasibRAS(ON) G12C-Selective Covalent Inhibitor Active against •Primary RAS G12C mutation•Tumors in patients naïve to, or previously treated with, first-generation KRAS(OFF) inhibitorsFDA granted:•Breakthrough Therapy Designation
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© 2023 Revolution Medicines Confidential 57 Elironrasib Clinical Data
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58 Elironrasib Monotherapy: Encouraging Antitumor Activity and Durability in Patients with Previously Treated RAS G12C NSCLC Data includes patients with previously treated NSCLC who have been treated with both immunotherapy and chemotherapy but have not received a G12C(OFF) inhibitor. (1) Objective response rate (ORR) (per RECIST v 1.1) includes partial responses that were confirmed (PR) or still had the potential to confirm (PR*). (2) Disease control rate (DCR) includes CR, PR, and stable disease (SD). NSCLC, non-small cell lung cancer; BID, twice daily; PFS, progression-free survival; CI, confidence interval; NE, not evaluable; SOD, sum of diameters; RECIST; response evaluation criteria in solid tumors; PD, progressive disease.Data cutoff: Apr 7, 2025 Elironrasib (200 mg BID) (N=36)ORR1, % (n)56% (20) DCR2, % (n)94% (34) Elironrasib (200 mg BID) (N=36)Median PFS 9.9 (6.2, NE)Months (95% CI) on treatment NSCLC # PostBaseline Scans
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59Elironrasib Monotherapy: Encouraging Antitumor Activity in Patients with RAS G12C NSCLC Previously Treated with a G12C(OFF) Inhibitor Elironrasib (200 mg BID) (N=24)ORR1, % (n)42% (10)DCR2, % (n)79% (19) Data Cutoff: August 4, 2025 Median (range) follow-up is 17.6 (10.3, 24.6) monthsand 17.4 (14, 28.5) months.Median duration of response (95% confidence interval) is 11.2 mo (5.9-NE). (1) Objective response rate (ORR) (per RECIST v 1.1) includes complete (CR) and partial responses (PR) that were confirmed. (2) Disease control rate (DCR) includes CR, PR and stable disease (SD). (3) One patient included in the denominator for ORR and DCR calculations is not displayed on waterfall and treated as a non-responder for purposes of the ORR and DCR calculations due to lack of post-baseline target lesion assessment. NSCLC, non-small cell lung cancer; PR*, unconfirmed partial response; RECIST, response evaluation criteria in solid tumors; PD, progressive disease. NSCLC
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60Elironrasib Monotherapy: Encouraging Durability in Patients with RAS G12C NSCLC Previously Treated with a G12C(OFF) Inhibitor NSCLC NSCLC, non-small cell lung cancer; mo, month; NE, not evaluable; OS, overall survival; PFS, progression free survival; CI, confidence interval: RECIST, response evaluation criteria in solid tumors. PFS, mo (CI)6.2mo (4.0, 10.3)6-mo PFS rate, % (CI)53% (31-71)Median OS, mo (CI)NE (6.7, NE)12-mo OS rate, % (CI)62% (40-78) PFS Probability OS Probability Data Cutoff: August 4, 2025
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61Elironrasib Monotherapy: Generally Well Tolerated in Patients with Previously Treated RAS G12C NSCLCElironrasib 200 mg BID (N=36)Maximum Severity of Treatment-Related AEs Any GradeGrade ≥3Any TRAE 28 (78%)7 (19%)TRAEs in ≥ 15% of patients, n (%)Diarrhea 11 (31%)2 (6%)Nausea 8 (22%)0Electrocardiogram QT prolonged 8 (22%)1 (3%)Other select TRAEs, n (%)ALT increased 2 (6%)1 (3%)AST increased 3 (8%)1 (3%)TRAEs leading to dose modification, n (%)10 (28%)6 (17%)Dose interruption 8 (22%)5 (14%)Dose reduction 7 (19%)5 (14%)TRAEs leading to treatment discontinuation, n (%)1 (3%)1 (3%)Mean dose intensity94% Data cutoff: Apr 7, 2025Included NSCLC patients who have previously been treated with both immunotherapy and chemotherapy but have not received a G12C(OFF) inhibitor. Median time on treatment was 9.0 months (range: 0.0–16.7) NSCLC, non-small cell lung cancer; BID, twice daily; AE, adverse event; ALT, alanine transaminase; AST, aspartate transferase; TRAE, treatment-related adverse event. NSCLC No treatment-related Grade 4 or 5 AEs or SAEs have been reported
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62Elironrasib + Pembrolizumab: Promising Preliminary Antitumor Activity in Patients with 1L RAS G12C NSCLCElironrasib 200 mg BID + Pembrolizumab in TPS1 ≥ 50% (N=5)2ORR3, % (n)100% (5) DCR4, % (n)100% (5) Data cutoff: Feb 10, 2025 (1) Tumor proportion score (TPS) is based on local testing. (2) Includes efficacy evaluable patients defined as those who had one post-baseline scan or who died or had clinical progression prior to the first post-baseline response assessment. (3) Objective response rate (ORR) (per RECIST v 1.1) includes partial responses that were confirmed (PR) or still had the potential to confirm (PR*). (4) Disease control rate (DCR) includes complete responses (CR), PR and stable disease (SD). NSCLC, non-small cell lung cancer; BID, twice daily; SOD, sum of diameters; 1L, first line. # Post 1 2 1 1 2Baseline Scans on treatment NSCLC
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63Elironrasib + Pembrolizumab: Generally Well Tolerated with Favorable Dose Intensity in Patients with 1L RAS G12C NSCLC Data cutoff: Feb 10, 2025 Elironrasib 200 mg BID + Pembrolizumab(N=8)Median time on treatment, mo (range)2.7 (0.7-3.2)Any GradeGrade ≥3Any TRAE 6 (75%)2 (25%)TRAEs in ≥ 15% of patients, n (%)Nausea 2 (25%)0Diarrhea 2 (25%)0Electrocardiogram QT prolonged 2 (25%)1 (13%)Other select TRAEs, n (%)ALT elevated 2 (25%)(1) 0AST elevated 1 (13%)(1) 1 (13%)(1) TRAEs, n (%)Leading to elironrasib dose reduction2 (25%)Leading to elironrasib dose discontinuation0Leading to pembrolizumab dose discontinuation 1 (13%)Elironrasib mean dose intensity85% (1) Increases in AST or ALT were reported to the sponsor under the term hepatic cytolysis.1L, first line; NSCLC, non-small cell lung cancer; BID, twice daily; TRAE, treatment-related adverse event; ALT, alanine transaminase; AST, aspartate transferase. NSCLC
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© 2023 Revolution Medicines Confidential 64 Elironrasib + DaraxonrasibRAS(ON) Inhibitor Doublet Background
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65 0 20 40 60 0 20 40 60 80 100 Days On Study % Tumors progression-free Elironrasib + Daraxonrasib Elironrasib Daraxonrasib Control Left Chart: KPAR (NSCLC KRAS G12C/G12C), elironrasib (100 mg/kg, PO QD), daraxonrasib (25 mg/kg PO QD)). Dashed line represents treatment stop. Days on study represent days on treatment. Right Chart: e3LL (T cell excluded NSCLC, KRAS G12C/G12C, NRASKO), elironrasib (30 mg/kg, PO QD), daraxonrasib (25 mg/kg PO QD)). Anti-PD-1 clone RMP1-14 CP151 (10 mg/kg IP BIW) in all graphs. Days on study represent days post tumor implant. NSCLC, non-small cell lung cancer; QD, once daily; BIW, twice-weekly. Interim data: April 20, 2025 Elironrasib and Daraxonrasib Show Combination Benefit and Synergize with Anti-PD-1 in Preclinical NSCLC ModelsRAS(ON) Inhibitor Doublet SensitizesImmune-Refractory NSCLCtoAnti-PD-1Elironrasib and Daraxonrasib Show Combination Benefit in a NSCLC Model Anti-PD-1 Control Elironrasib+anti-PD-1 Daraxonrasib+anti-PD-1 Elironrasib+Daraxonrasib+Anti-PD-1 NSCLC
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66 Data cutoff: Feb 10, 2025 Elironrasib + Daraxonrasib(N=26)(1)ORR(2), % (n)62% (16)DCR(3), % (n)92% (24) # Post Baseline Scans NSCLC The combination arm includes patients treated at elironrasib 200 mg BID + daraxonrasib (100-200 mg QD). (1) Includes efficacy evaluable patients defined as those who had one post-baseline scan or who died or had clinical progression prior to the first post-baseline response assessment. (2) Objective response rate (ORR) (per RECIST v 1.1) includes partial responses that were confirmed (PR) or still had the potential to confirm (PR*). Some patients may not appear in the waterfall due to either missing tumor assessment for 1 or more tumor lesions or discontinuing study drug prior to firsttumor assessment. (3) Disease control rate (DCR) includes complete response (CR), partial response (PR) and stable disease (SD). NSCLC, non-small cell lung cancer; SOD, sum of diameters, PD, progressive disease; RECIST; response evaluation criteria in solid tumors; 2L, second line. Elironrasib + Daraxonrasib: Doublet Shows Encouraging Antitumor Activity in Patients with 2L+ NSCLC Previously Treated with KRAS(OFF) G12C Inhibitor
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67Elironrasib + Daraxonrasib: Generally Well Tolerated in 2L+ NSCLC Patients Previously Treated with G12C(OFF) Inhibitor Included NSCLC patients who have previously been treated with immunotherapy, chemotherapy and a G12C(OFF) inhibitor. (1) Includes preferred terms of rash pustular, rash papular, rash maculopapular, rash macular, rash, erythema, dermatitis acneiform, dermatitis bullous. Multiple types of rash may have occurred in the same patient. (2) Includes preferred terms of stomatitis and mucosal inflammation.TRAE, treatment-related adverse event (to any drug); 2L+, second line and beyond; NSCLC, non-small cell lung cancer; ALT, alanine transaminase; AST, aspartate transferase.Data cutoff: Feb 10, 2025 Elironrasib 200 mg BID + Daraxonrasib 100-200 mg QD(N=33)Median time on treatment, mo (range) 3.61 (0.20-8.67)Any GradeGrade ≥3Any TRAE 31 (94%)15 (43%)TRAEs in ≥ 20% of patients, n (%)Rash(1) 22 (67%)4 (12%)Diarrhea 19 (58%)2 (6%)Stomatitis/mucositis(2) 17 (52%)3 (9%)NauseaVomitingAnemia 15 (46%)11 (33%)7 (21%)000Other select TRAEs, n (%)ALT increased5 (15%)0AST increased5 (15%)0Electrocardiogram QT prolonged 2 (6%)1 (3%)TRAEs leading to dose modification, n (%)19 (58%)12 (36%)Dose interruption of any drug17 (52%)12 (36%)Dose reduction of any drug5 (15%)0Dose discontinuation of any drug0 0Mean dose intensity of elironrasib95%Mean dose intensity of daraxonrasib85% NSCLC
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68Limited Monotherapy Activity of Either Daraxonrasib in RAS Mutant CRC or Elironrasib in CRC Previously Treated with KRAS G12C(OFF) Inhibitor (1) KRAS G12X-C; all patients treated at 300 mg QD. (2) Elironrasib 200 mg BID (RP2D). (3) ORR (by RECISTv1.1) includes confirmed CRs/PRs. The analysis is based on patients who received first dose of daraxonrasib at least 14 weeks prior to data cutoff date (to allow 2 potential scans). CRC, colorectal cancer; ORR, objective response rate; QD, once daily; BID, twice daily; RECIST; response evaluation criteria in solid tumors. Elironrasib data cutoff: Oct 28, 2024Daraxonrasib data cutoff: Sep 30, 2024 RAS InhibitorPopulationORRn/N (%)Daraxonrasib in RAS Mutant CRC(1,3)300 mg QD RAS inhibitor naive2/22 (9%)Elironrasib in KRAS G12C Mutant CRC(2)200 mg BID Previously treated with a G12C(OFF) Inhibitor 0/6 CRC
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69 Data cutoff: Oct 28, 2024 CRC Analyses include all patients who received first dose of study drug(s) at least 8 weeks prior to data cutoff date (to allow 1 potential scan). (1) The combination arm includes patients treated at elironrasib 100 or 200 mg BID + daraxonrasib (100-200 mg QD). (2) Objective response rate (ORR) (per RECIST v 1.1) includes partial responses that were confirmed (PR) or still had the potential to confirm (PR*). Some patients do not appear in the waterfall due to either missing tumor assessment for 1 or more tumor lesions or discontinuing study drug prior to firsttumor assessment. One patient with CR* has confirmed PR. (3) Disease control rate (DCR) includes complete response (CR), partial response (PR) and stable disease (SD). CRC, colorectal cancer; SOD, sum of diameters; RECIST; response evaluation criteria in solid tumors. # PostBaseline Scans Elironrasib + Daraxonrasib(1) (N=12)ORR(2), % (n)25% (3) DCR(3), % (n)92% (11) Elironrasib + Daraxonrasib: Doublet Shows Encouraging Antitumor Activity in Patients with CRC Previously Treated with KRAS(OFF) G12C Inhibitor
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© 2023 Revolution Medicines Confidential 70 ZoldonrasibRAS(ON) G12D-Selective Covalent Inhibitor Active against: •Primary RAS G12D mutation•Most common RAS driver in RAS-addicted solid tumorsFDA granted:•Breakthrough Therapy Designation
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© 2023 Revolution Medicines Confidential 71 Zoldonrasib Clinical Data
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72 Encouraging Initial Activity of Zoldonrasib Monotherapy in Previously Treated Patients with KRAS G12D PDACTumor Response for PDAC Patients Treated with 1200 mg Daily Dose (QD, N=20 or BID, N=20)1 ORR2, % (n)30% (12) DCR3, % (n)80% (32) David S. Hong et al., Preliminary Safety, Pharmacokinetics, and Antitumor Activity of RMC-9805, an Oral, RAS(ON) G12D-Selective, Tri-Complex Inhibitor in Patients with KRAS G12D Pancreatic Ductal Adenocarcinoma (PDAC) from a Phase 1 Study in Advanced Solid Tumors, ENA 2024. (1) All treated patients with PDAC who received a first daily dose at least 14 weeks prior to data cutoff date (applies to waterfall plot and ORR table). (2) Objective response rate (ORR) (per RECIST v 1.1) includes partial responses that were confirmed (PR) or still had the potential to confirm (PR*). (3) Disease control rate (DCR) includes complete response (CR), PR and stable disease (SD). Some patients do not appear in the waterfall due to either missing tumor assessment for 1 or more tumor lesions or discontinuing study drug prior to firsttumor assessment. PDAC, pancreatic ductal adenocarcinoma; QD, once daily; BID, twice daily; PD, progressive disease; NE, not evaluable; RECIST, response evaluation criteria in solid tumors. PDAC Data cutoff: Sep 2, 2024 PDAC
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73 All patients with NSCLC who received first dose of zoldonrasib at least 8 weeks prior to data cutoff date (applies to waterfall plot and ORR table). Two patients treated with 1200 mg QD are not displayed on the waterfall plot (but are included in the denominator for ORR/DCR) due to death prior to the first scan (1 patient: unrelated adverse event) or due to unevaluable scan (1 patient).(1) per RECIST v1.1. (2) Objective response rate (ORR) (per RECIST v1.1.) includes partial responses that were confirmed (PR) or still had the potential to confirm (PR*). Some patients do not appear in the waterfall due to either missing tumor assessment for 1 or more tumor lesions or discontinuing study drug prior to firsttumor assessment. (3) Disease control rate (DCR) includes complete responses (CR), PR and stable disease (SD). NSCLC, non-small cell lung cancer; QD, once daily; RECIST, response evaluation criteria in solid tumors.Data cutoff: Dec 2, 2024 Encouraging Initial Activity of Zoldonrasib Monotherapy in Previously Treated Patients with KRAS G12D NSCLCTumor Response for Patients with NSCLC Treated with 1200 mg QD (N=18)1 ORR2, % (n)61% (11) DCR3, % (n)89% (16) NSCLC # Post Baseline Scans
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74Zoldonrasib Monotherapy: Generally Well Tolerated Across Indications Data cutoff: Dec 2, 2024(1) Includes all tumor types (PDAC, NSCLC, CRC, and other types). (2) Includes preferred terms of Dermatitis acneiform, Rash, Rash maculo-papular. (3) Includes preferred terms of stomatitis and mucosal inflammation; Median time on treatment was 2.89 months (range: 0.03–9.66). AE, adverse event; ALT, alanine transaminase; AST, aspartate transferase; QD, once daily; TRAE, treatment-related adverse event. Patients Treated with 1200 mg QD Zoldonrasib (N=90)(1)Maximum Severity of Treatment-Related AEs Grade 1Grade 2Grade 3Any GradeAny TRAE49 (54%)16 (18%)2 (2%)67 (74%) TRAEs occurring in ≥10% of patients, n (%) Nausea 30 (33%)5 (6%)035 (39%)Diarrhea 18 (20%)3 (3%)1 (1%)22 (24%)Vomiting 12 (13%)4 (4%)016 (18%)Rash(2) 11 (12%)0011 (12%) Other select TRAEs, n (%)AST increased5 (6%)2 (2%)07 (8%) ALT increased4 (4%)1 (1%)1 (1%)6 (7%) Stomatitis/mucositis(3) 1 (1%)001 (1%)TRAEs leading to dose reduction, n (%)2 (2%)2 (2%)04 (4%) TRAEs leading to dose interruption, n (%)3 (3%)3 (3%)2 (2%)8 (9%) TRAEs leading to treatment discontinuation, n (%)1 (1%)001 (1%)Mean dose intensity98%No treatment-related Grade 4 or 5 AEs or SAEs have been reported
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© 2023 Revolution Medicines Confidential 75 Royalty Pharma Partnership
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76Royalty Pharma Partnership Bolsters Already Strong Financial Position by Providing $2 Billion in Flexible Committed Capital$2 Billion Committed SyntheticRoyalty($1.25 B)Term Debt($0.75 B) 5 Tranches3 Tranches Received positive readout approval Market-competitive interest rate linked to SOFR $250 million trancheUp to $250 million tranche* Future tranches can be drawn at RVMD’s discretion subject to the satisfaction of the applicable development or commercial trigger. RVMD discretion*Scheduled* RVMD discretion*Scheduled* $250 million trancheUp to $250 million tranche Downward tiered, single-digit royalty rates on revenue, decreasing by tranche