On Target to Outsmart CancerTM 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

On Target to Outsmart CancerTM

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 financial position, business strategy, prospective

products, availability of funding, ability to maintain existing collaborations, including with Sanofi, 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, 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 the COVID-19 pandemic 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 part of an oral presentation on January 11, 2022 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 10, 2021, 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). 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 is being investigated.

On Target to Outsmart Cancer HIGH UNMET NEED IN RAS-ADDICTED CANCERS

RAS proteins drive 30% of human cancers(1), and are largely unserved by targeted therapeutics STRONG CLINICAL VALIDATION OF RAS AS CANCER DRIVER Proof-of-principle from first-gen KRASG12C inhibitors(2) predicts favorable impact of targeted inhibitors across numerous RAS cancer drivers DEEP SCIENCE-DRIVEN PIPELINE Comprehensive collection of groundbreaking RAS(ON) Inhibitors with best-in-class preclinical profiles and/or first-in-class potential covering RAS space broadly;

first candidates planned to enter clinic in 2022 Leading RAS Companion Inhibitors in clinic designed for combination treatment strategies to counter resistance to RAS targeted therapies (1) Prior et al., Cancer Research 2020 (2) Lumakras

approved by the FDA in May 2021

Excessive RAS(ON) Signaling Drives 30% of Human Cancers = RAS(OFF)

RAS-Addicted Cancers = RAS(ON) Normal RAS Cancer Mutations New patients per year (U.S.)(1) 230,000 All Cell Membrane 67,000 Lung cancer Tightly regulated Excessive control RAS(ON) cell proteins growth RAS(ON)

uncontrolled signaling cell growth drives 79,000 Colorectal cancer Exemplary G12C, G12D, G12V, G12R mutations in G13C, G13D 49,000 KRAS, HRAS Pancreatic cancer and/or NRAS Q61H, Q61K, Q61L (1) Estimated using tumor mutation frequencies from

Foundation Medicine Insights August 2020 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2020 (see appendix for additional detail); lung cancer = non-small cell

RAS Deep -Addicted Science- Cancers Driven Pipeline of Targeted Therapies for RAS(ON) Inhibitors RAS Companion

Inhibitors 2 Drug expected Candidates to enter 2 Clinical-stage Drug Candidates clinic in 2022 RAS COOPERATING 2 expected Drug Candidates to file RAS(ON) TARGETS 1 IND-ready CANCER Drug Candidate INDs in 2023

DRIVERS 4+ programs Pipeline expansion

RAS(ON) Inhibitors Induce Rapid, Deep Suppression and Sustained of Drivers RAS(ON) Cancer RASMULTI KRASG12C RMC-6236 RMC-6291 RAS(ON) DRIVERS CANCER KRASG12D KRASG13C RMC-9805 RMC-8839

Engine Distinctive Targets RAS Oncogenic Drug Discovery: RAS(ON) Innovation Proteins ) Inhibitory Tri-Complexes Selected compounds Cyclophilin A Binary complex Non-covalent Covalent RAS(ON) Inhibitors Deep and Diverse Collection Highly potent and selective

Oral and drug-like Rapid, deep and sustained suppression of RAS(ON) signaling

RMC-6236: First-in-Class RASMULTI(ON) Inhibitor with Broad Potential Against RAS-Addicted Cancers Colorectal 32% Highly Potent and Selective RAS(ON) Inhibitor Inhibits

canonical RAS family members, suppressing Pancreatic the mutant cancer driver and cooperating wild-type 32% RAS proteins 137,000 Robust Anti-tumor Activity in Cancer Models New KRASG12X patients (1) Deep and sustained inhibition drives

durable per year (U.S.) anti-tumor activity in tumors with common RAS variants including KRASG12D, KRASG12V, KRASG12R and KRASG12C 30% Lung Attractive PK/ADME Profile Other 6% Favorable in vivo oral bioavailability, clearance and

concentration in tumors for effective target coverage in RAS-addicted cancer cells KRASG12X includes KRASG12D, KRASG12V, KRASG12R and KRASG12C 8 (1) Calculated using tumor mutation frequencies from Foundation

Medicine Insights August 2020 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2020 (see appendix for additional detail); lung cancer = non-small cell lung

cancer Characterization above is based on RVMD preclinical research

RMC-6236: Highly Active in Vivo Across Cancer Models with KRASG12X

Drivers NSCLC PDAC CRC 62% ORR (8/13) 57% ORR (8/14) 38% ORR (5/13) 200 100% DCR (13/13) 200 86% DCR (12/14) 200 54% DCR (7/13) mPD 100 mPD Baseline 100 100 Volume From mPD Tumor 0 mSD 0 0 Mean Change mSD mSD % mPR mPR mPR mCR mCR mCR -100 -100 100

- 2 4 1903 2393 1955 2803 H441 1358 H358 KP HPAC GP2D H2122 H2030 SW620 SW403 CTG LUN352 NCI LUN232 CTG CTG NCI CTG NCI CTG LUN020 NCI LUN137 PAN022 PAN038 PAN1001 PAN026 PAN020 PAN003 Capan PAN010 PAN031

PAN039 PAN029 PAN009 CRC007 CRC043 CRC078 CRC060 CRC1018 CRC047 CRC051 CRC044 CRC039 CRC1005 KRASG12C KRASG12D KRASG12R KRASG12V Deep Tumor Regressions and Complete Responses Observed Across Cancer Models

RMC-6236 RVMD preclinical dosed research, at 25 mg/kg as po of 10/12/21 qd; n = 3-10/group 9 NSCLC = non-small cell lung cancer;

PDAC = pancreatic ductal adenocarcinoma; CRC = colorectal cancer Responses assigned according to mRECIST (see appendix) ORR = objective response rate; DCR = disease control rate

RMC-6236: Diverse RAS Highly Drivers Active in Vivo Across Cancer

Models with 100 KRASG12X Tumors 75 RMC-6236 Median not reached Control % Tumors for either active Progression- 50 treatment group RAS Pathway Mutant Tumors Median = 9 days Free for both RMC-6236 25 control groups Control 0 0 10 20 30 Days on Treatment Durable Anti-Tumor Benefit Observed in KRASG12X Cancer Models and Beyond RVMD RMC-6236 preclinical dosed

research, at 25 mg/kg as po of 10/12/21 qd 10 Progression defined as tumor doubling from baseline over 28 days p<0.0001 by Log-rank test (control vs RMC-6236

treatment) See appendix for composition of KRASG12X Tumors and RAS Pathway Mutant Tumors

RMC with -Checkpoint 6236: Anti-Tumor Inhibitor Immunity in Vivo and Strong Additivity Favorable Transformation

of Durable Complete Responses Tumor Immune Microenvironment with Checkpoint Inhibitor Combination CD8+ T Cells M2 M mMDSCs ) Control RMC-6236 + Anti-PD1

(mm 3 CD45+ Volume of % Tumor 10/10 CR Mean Control RMC-6236 Modulation of the Tumor Microenvironment Primes for Anti-Tumor Immunity in Cancer Models RVMD preclinical research, as of 09/10/2021 Syngeneic tumor

model with CT26 cell line engineered to express KRASG12C 11 RMC-6236 dosed at 25 mg/kg po qd; Anti-PD1 dosed at 10 mg/kg ip biw; n = 10/group M2 M = M2

macrophages; mMDSCs = Monocytic myeloid derived suppressor cells

RMC-6236: Clinical Priorities to Pursue

First-in-Class Activity Against KRASG12X Tumors 2022 Further development Submit IND Define RP2DS Initiate single agent dose escalation in

patients Single agent expansion cohorts in KRASG12X with cancers with KRASG12X mutations (focused tumors (NSCLC, pancreatic cancer and CRC) on NSCLC, pancreatic cancer and CRC) G12X Activities Combinations in KRAS tumors (NSCLC,

Include below MTD expansion cohorts in pancreatic cancer and CRC) select populations during dose escalation Aims Evidence of first-in-class single agent

activity against KRASG12X tumors See Milestones table KRASG12X may include KRASG12D, KRASG12V, KRASG12R and/or KRASG12C 12 RP2DS = Recommended Phase 2 dose and schedule MTD = maximum tolerated dose NSCLC =

non-small cell lung cancer; CRC = colorectal cancer

RMC-6291: Mutant-Selective RAS(ON) Inhibitor with Best-in-Class Potential for KRASG12C Cancers Highly Potent and Selective RAS(ON) Inhibitor Lung 76% Highly active against KRASG12C Covalent for irreversible

inhibition Low off-target risk and acceptable safety profile 29,000 Robust Anti-tumor Activity in Cancer Models New KRASG12C patients Rapid, deep and sustained inhibition drives durable per year

(U.S.)(1) anti-tumor effects across multiple KRASG12C tumor types, with complete responses in some models Colorectal 18% Attractive PK/ADME Profile Favorable in vivo oral bioavailability and clearance Pancreatic for effective target coverage

in KRASG12C-addicted 3% Other 3% cancer cells 13 (1) Calculated using tumor mutation frequencies from Foundation Medicine Insights August 2020 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2020 (see

appendix for additional detail); lung cancer = non-small cell lung cancer Characterization above is based on RVMD preclinical research

RMC-6291: Superior Outcomes in Mouse Clinical Trial with KRASG12C NSCLC

Models RMC-6291 Adagrasib 72% (18/25) ORR 52% (13/25) ORR 92% (23/25) DCR 72% (18/25) DCR mPD mPD mSD mSD mPR mPR mCR mCR

Best-in-Class Potential in KRASG12C NSCLC RVMD preclinical research as of 10/21/21 Adagrasib NSCLC = Non-small dosed at cell 100

lung mg/kg cancer po qd; RMC-6291 dosed at 200 mg/kg po qd; n = 3 to 10/group 14 Responses assigned according to mRECIST (see appendix)

RMC-6291 May Improve on KRASG12C (OFF) Inhibitor Class Across

Three Outcome Measures in NSCLC Increased Rate Of Response(a) Increased Depth Of Response(b) Increased Duration Of Response(c) Volume Tumor in Change % Control RMC-6291 Adagrasib

Best-in-Class Potential in KRASG12C NSCLC RVMD preclinical research as of 07/28/21 RMC NSCLC -6291 = Non dosed -small at cell 200 lung mg/kg cancer po qd; Adagrasib

dosed at 100 mg/kg po qd 15 PDX Models: (a) LUN055; (b) LXFA-983; (c) CTG-0828 Nichols. Targeting KRASG12C(ON) and Potential Application to Overcoming Drug

Resistance in RAS-Addicted Tumors. RAS-Targeted Drug Development Summit. Sept. 22, 2021.

RMC-6291: Clinical Priorities to Pursue

Best-in-Class Activity Against KRASG12C Tumors 2022 Further development Submit IND Define RP2DS Initiate single agent dose escalation in

Single agent expansion cohorts in KRASG12C KRASG12C tumors NSCLC and pancreatic cancer (RAS inhibitor na ve +/- failure) Activities Include below MTD expansion cohorts in select populations (e.g., NSCLC) during dose

Combinations in KRASG12C NSCLC & CRC escalation Aims Preliminary evidence of superior activity against KRASG12C tumors See Milestones table RP2DS = Recommended Phase 2 dose and schedule 16 NSCLC MTD = maximum = non-small tolerated cell lung dose cancer; CRC = colorectal cancer

RMC-9805: Mutant-Selective RAS(ON) Inhibitor with Best-in-Class Potential for KRASG12D Cancers Highly Potent and Selective RAS(ON) Inhibitor Pancreatic Colorectal 38% 40% Highly active against KRASG12D Covalent

for irreversible inhibition Low off-target risk and acceptable safety profile 55,000 Robust Anti-tumor Activity in Cancer Models New KRASG12D patients Rapid, deep and sustained inhibition drives

durable per year (U.S.)(1) regressions in KRASG12D lung, pancreatic and colorectal cancers Attractive PK/ADME Profile Lung Favorable in vivo oral bioavailability and clearance Other 14% for effective target coverage in KRASG12D-addicted 8%

cancer cells 17 (1) Calculated using tumor mutation frequencies from Foundation Medicine Insights August 2020 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2020 (see appendix for additional detail);

lung cancer = non-small cell lung cancer Characterization above is based on RVMD preclinical research

RMC-9805: Selective, Covalent and Orally Active with Sustained

Inhibition of KRASG12D in Vivo Selective Covalent Single Dose PK/PD Modification of KRASG12D HPAC CDX (PDAC, KRASG12D/WT) PD: Tumor DUSP6 (%) KRAS: WT G12D G13D G12C G13C PK: Unbound plasma conc. (nM) X-linked

KRAS 100 KRAS H/NRAS mRNA 100 control 10 to Unbound Potent Inhibition of KRASG12D DUSP6 50 1 Concentration Cancer Cell Growth 125 Tumor relative 0.1 (nM) Plasma 100 % 0 0.5 1 2 4 8 24 48 0.01 %Control) 75 Time point (h) Proliferation 50

CTG, Cell (3D 25 0 -11 -10 -9 -8 -7 -6 -5 Log M [RMC-9805] RVMD RMC-9805 preclinical dosed research, at 100 mg/kg as of po 10/13/2021 18 PDAC = pancreatic ductal

RMC-9805: Regressions Tumor in Models of KRASG12D Cancers First-in-class mutant-selective covalent inhibitor of KRASG12D Deep and durable anti-tumor responses in vivo in pancreatic and colorectal cancer models Oral

dosing, well tolerated HPAC CDX (PDAC, KRASG12D/WT) 3 ) (mm 3000 Control RMC-9805 Volume 2000 Dosing Tumor 1000 start Mean 0 10 20 30 40 50 Days post-implant Gp2D CDX (CRC, KRASG12D/WT) 3 ) (mm Control RMC-9805 Volume 2000 Dosing 1000 Tumor start Mean 0 10 20 30 40 50 Days post-implant RVMD preclinical research, as of 11/05/2021 RMC-9805 dosed at 100 mg/kg pd qd; n =

10/group (top), 6/group (bottom); PDAC = pancreatic ductal adenocarcinoma; CRC = colorectal cancer

RMC-8839: First-in-Class Mutant-Selective RAS(ON) Inhibitor for KRASG13C Cancers Lung 70% Highly Potent and Selective RAS(ON) Inhibitor Highly active against KRASG13C Covalent for irreversible inhibition

Low off-target risk and acceptable safety profile 3,000 Robust Anti-tumor Activity in Cancer Models New KRASG13C patients Rapid, deep and sustained inhibition drives durable Colorectal

(1) G13C 21% per year (U.S.) regressions in KRAS lung cancers Attractive PK/ADME Profile Favorable in vivo oral bioavailability and clearance Pancreatic for effective target coverage in KRASG13C-addicted 2% Other cancer cells 7% 20 (1)

Calculated using tumor mutation frequencies from Foundation Medicine Insights August 2020 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2020 (see appendix for additional detail); lung cancer = non-small cell lung cancer Characterization above is based on RVMD preclinical research

RMC-8839: Selective, Covalent and Orally Active with Sustained

Inhibition of KRASG13C in Vivo Selective Covalent Single Dose PK/PD Modification of KRASG13C NCI-H1734 (NSCLC CDX, KRASG13C) KRAS: WT G12C G13C PD: Tumor DUSP6 (%) PK: Unbound plasma conc. (nM) X-linked KRAS KRAS H/NRAS Potent Inhibition of KRASG13C Cancer Cell Growth 125 No PD data at 0.5 and 1 hr 100 %Control) 75 Proliferation 50 Cell (CTG, 25 0 -11 -10 -9 -8 -7 Log M [RMC-8839] RVMD RMC-8839 preclinical

dosed research, at 100 mg/kg as of po 12/22/2021 21 NSCLC = non-small cell lung cancer

RMC-8839: Regressions Tumor in Models of KRASG13C Cancers First-in-class mutant-selective covalent inhibitor of KRASG13C Deep anti-tumor responses in vivo in non-small cell lung cancer

models Oral dosing, well tolerated NCI-H1734 CDX (NSCLC, KRASG13C/WT) Control RMC-8839 ST2822B PDX (NSCLC, KRASG13C/WT) Control

RMC-8839 RMC-8839 dosed at 100 mg/kg pd qd; n = 5/group; RVMD preclinical NSCLC = research, Non-small as cell of lung 11/17/2021

On Pancreatic Target to Cancer Outsmart G12D RMC-6236 Devastating

disease 36% RMC-9805 >90% driven by KRAS mutations 49,000 G12V RMC-6236 26% New KRASMUTANT pancreatic cancer patients per year (US)(1) G12R RMC-6236 13% RMC-6291 Dismal survival rates G12C No approved targeted therapies 2% RMC-6236 Other

RMC-6236 23% 23 (1) numbers Calculated using using cancer tumor incidence mutation from frequencies ACS Cancer from Facts Foundation and Figures Medicine 2020 (see Insights appendix August for additional 2020

and detail) scaled to estimated patient Our development-stage RAS(ON) Inhibitors Inhibit >90% of pancreatic cancer drivers (1) in cancer models Exhibit strong anti-tumor activity in preclinical models of pancreatic cancer

RAS Inhibitors Companion Suppress Cooperating Targets and Sustain Pathways