Revolution Medicines : RVMD Corporate Presentation

On Target to Outsmart Cancer

November 6, 2023

© 2023 Revolution Medicines

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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, the expected timing of closing of the proposed transaction with EQRx, Inc. (EQRx) and the expected benefits of the proposed transaction 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 November 6, 2023 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 6, 2023, 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.

All copyrights and trademarks used herein are the property of their respective owners.

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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 drug candidates designed to serve RAS-addicted cancer patients by targeting oncogenic RAS(ON) drivers of common, life-threatening cancers
• Unprecedented RASMULTI inhibitor (RMC-6236)and RASG12C-selectiveinhibitor (RMC-6291) show highly differentiated and promising initial clinical profiles
• Innovative single agent and combination development strategies aim to deliver durable clinical benefit broadly to patients with RAS-addicted cancers

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Excessive RAS(ON) Signaling Drives 30% of Human Cancers, Targeted by Our RAS(ON) Inhibitors

• RAS(OFF)

RAS-Mutant Cancers

Normal

• RAS(ON)

Cell

Membrane

Tightly regulated

RAS(ON) proteins control cell growth

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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Development-Stage RAS(ON) Inhibitor Portfolio Designed to Treat Nearly All Patients with RAS-Addicted Cancers

MULTI

RAS Selectivity

>200,000

new patients

per year (U.S.)(1)

RMC-6236clinical

Mutant-Selective

RMC-6291clinical

RMC-9805clinical

RMC-5127IND-enabling

RMC-0708IND-enabling

multiple mutations

(initial focus on G12X) and WT

G12C

G12D

G12V

Q61H

G12C

G12D

G12V

G12

other

G12X

G13X

RMC-8839IND-enabling

G13C

Q61X

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).

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Complementary RAS(ON) Inhibitors Designed for Monotherapy and Combination Strategies Against RAS-Addicted Cancers

RASMULTI

• Monotherapy with broad potential for RAS-addicted cancers
• Backbone of RAS(ON) Inhibitor doublets with mutant-selective RAS(ON) Inhibitors
• Targeted agent for SOC combinations, including immunotherapies

RAS Mutant-Selective

• Alternative monotherapy approaches
• Complementary to RASMULTI Inhibitor in RAS(ON) Inhibitor doublets
• Differentiated targeted agent profiles for SOC combinations, including immunotherapies

SOC = standard of care

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RMC-6236:First-in-Class, RASMULTI(ON) Inhibitor with Broad Potential Against RAS-Addicted Cancers

166,000

New KRASG12X patients

per year (U.S.)(1)

• Highly selective for RAS(ON) proteins with broad and deep anti-tumor activity in preclinical models
• Orally bioavailable and generally well-tolerated in patients at active doses
• Unprecedented clinical profile with anti-tumor activity observed across diverse RAS cancer mutations; multiple potential monotherapy registrational paths
• Profound combinatorial activity with mutant- selective RAS(ON) Inhibitors in preclinical models; potential for targeted RAS(ON) Inhibitor doublets in patients

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

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RMC-6236:Dose-DependentAnti-Tumor Activity at Low Doses in RAS-Addicted NSCLC Model

		Control
	3000	RMC-6236 1 mg/kg
	RMC-6236 10 mg/kg
)
	RMC-6236 25 mg/kg
3
(mm
Tumor Volume	2000
1000	Dosing
Mean		start
	0	20	30	40	50

Days on Study

End of Study Responses

	500	Control
Volume	400	RMC-6236 1 mg/kg
RMC-6236 10 mg/kg
	RMC-6236 25 mg/kg
300
Tumor
200
in
Change	100	8/10 R	10/10 CR
0
%
	-100

RVMD preclinical research

NSCLC = non-small cell lung cancer

NCI-H441 CDX (NSCLC, KRASG12V/WT); All doses given orally, once daily

R = number of regressions >10% from initial; CR = number of regressions ≥80% from initial Each animal represented as a separate bar in waterfall plot

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RMC-6236: Highly Active with Durable Responses Across Models of Major Human Cancers with RASG12X Drivers

NSCLC	PDAC	CRC
53% ORR (8/15)	61% ORR (11/18)	44% ORR (8/18)
100% DCR (15/15)	89% DCR (16/18)	56% DCR (10/18)

PFS

RMC-6236 - Median not reached Control - Median 9 days

Mean Tumor Volume % Change From Baseline

300

200

100

0

-100

LUN352

NCI-H2122

CTG-1903

LUN232

CTG-0743

CTG-1955

CTG-2393

CTG-1612

NCI-H2030

CTG-2803

NCI-H441

CTG-1358

NCI-H358

LUN020

LUN137

300

200

100

0

-100

KP-4

PAN022

PAN026

PAN1001

PAN038

PAN020

PAN003

PAN010

PAN014

PAN039

Capan-2

PAN001

PAN045

PAN031

PAN028

HPAC

PAN043

PAN009

300

200

mPD

100

0

mSD

mPR

-100

mCR

CRC007

CRC043

CRC078

CRC022

CRC060

CRC1018

CRC050

CRC047

CRC044

CRC058

GP2D

CRC051

CRC039

CRC012

SW620

CRC1009

SW403

CRC1005

	Progression-Free	100
Tumors%	75
50
		25
		0
		0			20	40		60		80	100

Days on Treatment

RMC-6236 (n=191, 51 models)

Control (n=215, 51 models)

RVMD preclinical research as of 06/01/22

NSCLC = non-small cell lung cancer; PDAC = pancreatic ductal adenocarcinoma; CRC = colorectal cancer RMC-6236 dosed at 25 mg/kg po qd; n=1-10/group

Progression defined as tumor doubling from baseline; Responses assigned according to mRECIST:

mPD = progressive disease; mSD = stable disease; mPR = partial response; mCR = complete response; ORR = objective response rate; DCR = disease control rate; PFS = progression-free survival