Revolution Medicines : RVMD Corporate Presentation

On Target to Outsmart Cancer

May 8, 2024

© 2024 Revolution Medicines, Inc.

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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 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 the impact of global events and other macroeconomic conditions on our business, and the expected benefits of the transaction with EQRx, Inc. 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 May 8, 2024 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 May 8, 2024, 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.

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Mission: to revolutionize treatment for patients with RAS-addicted cancers through the discovery, development and delivery of innovative, targeted medicines.

• Pioneering class of RAS(ON) inhibitor drug candidates targeting oncogenic drivers of common, life-threatening cancers
• Unprecedented RAS(ON) multi-selectiveinhibitor (RMC-6236)and RAS(ON) G12C-selectiveinhibitor (RMC-6291) show promising and highly differentiated initial clinical profiles
• On track toward late-stagedevelopment of RMC-6236 and advancement of mutant-selective inhibitors led by RMC-6291 and RMC-9805

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Portfolio of RAS(ON) Inhibitors Designed to Target 30% of Human Cancers

RAS-Mutant Cancers

Normal

Cell

Membrane

Tightly regulated

= RAS(OFF)RAS(ON) proteins control cell growth

• RAS(ON)

RAS Cancer Mutations

Excessive

RAS(ON) signaling drives uncontrolled cell growth

Oncogenic mutations in KRAS, NRAS or HRAS are common at positions

G12, G13 and Q61

New patients per year (U.S.)(1)

>200,000

including

60,000

Lung cancer

(29% of NSCLC)

75,000

Colorectal cancer

(49% of CRC)

53,000

Pancreatic cancer

(92% of PDAC)

1. Estimated using tumor mutation frequencies from Foundation Medicine Insights March 2022 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2023 (see appendix for additional detail); NSCLC = non-small cell lung cancer; CRC = colorectal cancer; PDAC = pancreatic ductal adenocarcinoma

Pioneering Tri-complex RAS(ON) Inhibitors Designed to Deliver Robust and Durable Anti-tumor Activity

Oncogenic RAS(ON)	Inhibited RAS(ON)

RAS(ON)

Inhibitor

GTP

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• Direct inhibition of RAS(ON) cancer drivers
• Deep and durable suppression of RAS cancer signaling designed to defy common drug resistance mechanisms
• Clinical validation of first two RAS(ON) Inhibitors studied as single agents

Cell	Cyclophilin A
Membrane

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Initial Clinical Profiles of RAS(ON) Inhibitors Support Broad Set of Potential Opportunities to Treat RAS-Addicted Cancers

		Target
Multi-Selective	Genotypes
RMC-6236 Clinical validation in NSCLC and PDAC	G12X and
expansion(1)
Mutant-Selective
RMC-6291	Evidence of differentiated clinical	G12C
activity in NSCLC and CRC
RMC-9805 Dose escalation ongoing	G12D

1. KRAS G12X initially defined as mutation at codon 12 which encodes glycine (G) to X where X = A, D, R, S, or V. RMC-6236-001 protocol amended in August 2023 to broaden enrollment, now allowing patients with tumors bearing mutations in any of the three hotspots (G12X/G13X/Q61X) in any of the three major RAS isoforms (KRAS/NRAS/HRAS); G12X broadened to include G12C.

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2024 Capital Allocation Priorities to Advance
Pioneering RAS(ON) Inhibitor Pipeline …	… driving to

Expand reach of RMC-6236

by clinically assessing

opportunities

(1L, types, mutations)

Propel RMC-6236

into first pivotal trial(s)

Qualify mutant-

selective inhibitors led by RMC-6291and RMC-9805for late-stagedevelopment

Industry-Leading

Targeted

Medicines

Franchise for RAS-Addicted Cancers

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RAS(ON) Multi-Selective Inhibitor

RMC-6236

RMC-6236-001 Phase 1 Study Design

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Key Eligibility Criteria

• Advanced solid tumors with KRAS G12X mutations(1) (initially excluding KRAS G12C)
• Received prior standard therapy appropriate for tumor type and stage
• ECOG PS 0-1
• No active brain metastases

Key Endpoints

• Safety and tolerability
• Pharmacokinetics
• Anti-tumoractivity

Dose Escalation

RMC-6236 administered orally QD

400 mg

300 mg

220 mg(2)

160 mg	Lowest dose/exposure
120 mg
range projected to drive
80 mg	tumor regressions in
humans based on
40 mg	preclinical models

20 mg

10 mg

Additional patients with PDAC or NSCLC were enrolled at dose levels that cleared DLT evaluation

Dose Optimization

+

RAS Genotype and

Tumor Type Expansion

RMC-6236-001Clinical Trial: https://clinicaltrials.gov/study/NCT05379985

1. KRAS G12X initially defined as mutation at codon 12 which encodes glycine (G) to X where X = A, D, R, S, or V.
2. 220 mg cleared DLT evaluation and a dose of 200 mg was selected for further expansion/optimization.

DLT, dose-limiting toxicity; ECOG PS, Eastern Cooperative Oncology Group Performance Status; QD, once daily.

Data Extracted 11 Sep 2023.

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RMC-6236-001: Summary of Treatment-Related Adverse Events

	Total (n=131)
Maximum severity of TRAEs	Grade 1	Grade 2	Grade 3	Grade 4	Any Grade
TRAEs occurring in ≥10% of patients, n (%)
Rash*	57 (44)	29	(22)	6	(5)	0	92 (70)
Nausea	41	(31)	14 (11)		0	0	55	(42)
Diarrhea	32	(24)	9	(7)	1	(1)	0	42	(32)
Vomiting	27 (21)	9	(7)	0	0	36	(28)
Stomatitis	10 (8)	9	(7)	2	(2)	0	21	(16)
Fatigue	12 (9)	4	(3)		0	0	16	(12)
Other select TRAEs, n (%)
ALT elevation	6	(5)	1	(1)	1 (1)‡	0	8	(6)
AST elevation	6	(5)		0	1 (1)‡	0	7	(5)
Electrocardiogram QT prolonged	1	(1)		0		0	0	1	(1)
TRAEs leading to dose reduction† , n (%)		0	9	(7)	2	(2)	0	11 (8)
TRAEs leading to treatment discontinuation, n (%)		0		0		0	1 (1)	1 (1)

• Median duration of treatment at the time of data extraction was 2.27 months (range: 0.2-14)
• One Grade 4 TRAE occurred in a patient with PDAC treated at 80 mg who had a large intestine perforation at the site of an invasive tumor that reduced in size while on treatment (TRAE leading to treatment discontinuation)
• No fatal TRAEs were observed. Two patients discontinued study treatment due to death: one patient with PDAC (120 mg) died

due to PD; one patient with NSCLC (200 mg) died due to unknown cause reported as unrelated to RMC-6236

• Post-dataextraction, the Grade 3 ALT and AST elevations were associated with biliary obstruction and reported as unrelated to RMC-6236

*Includes preferred terms of dermatitis acneiform, rash maculopapular, rash, rash pustular, dermatitis psoriasiform, erythema, rash erythematous; multiple types of rash may have occurred in the same patient; † The most common TRAE leading to dose reduction was rash (acneiform or maculopapular); there were no reductions at doses ≤80 mg. AE, adverse event; ALT, alanine transaminase; AST, aspartate transferase; PD, progressive disease; TRAEs, treatment-related adverse events.