RVMD 44th Annual J.P.… Presentation

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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 January 12, 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’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 5, 2025, 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 commercial 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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7Pancreatic Cancer | Registrational Trials to Maximize Potential Across Early- to Late-Stage Disease Settings Daraxonrasib | MULTI•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 Initiated Zoldonrasib | G12D•1L metastatic (RASolute 305): zoldonrasib + chemo vs. chemo Start-up activities ongoing •1L metastatic (RASolute 309): zoldonrasib + daraxonrasib vs. chemo Start-up activities ongoing Registrational Trials Daraxonrasib | MULTI•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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8Pancreatic 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 | MULTI•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 Initiated Zoldonrasib | G12D•1L metastatic (RASolute 305): zoldonrasib + chemo vs. chemo Start-up activities ongoing •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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9Advancing Zoldonrasib in 1L PDAC | Encouraging Initial Results in Combination with FOLFIRINOX Median follow up: 3.9 months (range 2.7, 8.0). Waterfall plot includes all treated subjects with >=1 post-baseline target tumor assessments, died or had clinical progression prior to the first postbaseline tumor assessment. 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. •Zoldonrasib monotherapy significantly differentiated from chemo allowing for continuous RAS suppression with few severe toxicities and minimal dose modifications •Initial safety profile of zoldonrasib + mFOLFIRINOX combination largely consistent with mFOLFIRINOX alone•Favorable zoldonrasib dose intensity maintained with full dose 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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10Non-Small Cell Lung Cancer | Broad Potential Across Lines of Therapy with Multi- and Mutant-Selective ApproachesDaraxonrasib | MULTI•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 metastatic Advanced planning •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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11Colorectal 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 | MULTI•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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13Discover | 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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14Daraxonrasib 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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15 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 Acquired 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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17Deliver | 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 18Creating Industry-Leading Global Targeted Medicines Franchise for Patients with RAS-Addicted Cancers Strong financial position enables broad execution across compelling opportunities to serve unmet needs $1.9 billionin cash and investments as of September 30, 2025+$1.75 billion in additional committed capital(1) (1) $2.0 billion in total flexible committed capital from agreement with Royalty Pharma, of which $250 million has been received as of September 30, 2025

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19Tracking Expected Impact •Readout for RASolute 302 (daraxonrasib) 2L registrational trial 1H 2026•Update on daraxonrasib 1L mono + combination data 1H 2026•Initiate 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•Initiate (daraxonrasib combination) 1L registrational trial 2H 2026•Update on elironrasib registrational strategy 2026•Substantially complete enrollment in RASolve 301 (daraxonrasib) 2L+ registrational trial 2026 •Update on combination CRC data 2026•Initiate 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 20 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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21 On Target to Outsmart Cancer®

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