Repare Therapeutics : Corporate Presentation

Insight that enriches. Precision that empowers.

Corporate Presentation

June 2024

Disclaimer

Statements contained in this presentation regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "anticipates," "believes," "expects," "intends," "plans," "potential," "projects," "would" and "future" or similar expressions are intended to identify forward-looking statements. Each of these forward-looking statements involves substantial risks and uncertainties that could cause actual results to differ significantly from those expressed or implied by such forward-looking statements. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding the initiation, timing, progress and results of our current and future preclinical studies and clinical trials, including specifically our clinical trials of lunresertib, camonsertib, RP-1664, and preclinical studies of RP-3467; the expected timing of program updates and data disclosures; the timing of filing INDs and other regulatory documents; the timing and likelihood of seeking regulatory approval for our product candidates; the competitive landscape for our product candidates; our ability to identify and develop additional product candidates using our SNIPRx platform; and our estimates regarding expenses, future revenue, capital requirements, cash runway and needs for additional financing.

These forward-looking statements reflect our current beliefs and expectations. Many factors may cause differences between current expectations and actual results, including the duration and impact of the COVID-19 pandemic on our business and market volatility, unexpected safety or efficacy data observed during preclinical or clinical studies, clinical site activation rates or clinical trial enrollment rates that are lower than expected, changes in expected or existing competition, changes in the

regulatory environment, and unexpected litigation or other disputes. These and other risks are described more fully in our filings with the Securities and Exchange Commission ("SEC"), including the "Risk Factors" section of our Annual Report on Form 10-Q filed with the SEC on May 7, 2024, and other documents we subsequently filed with or furnished to the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Except as required by law, we assume no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Neither we nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such data after the date of this presentation. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.

Solely for convenience, the trademarks and trade names in this presentation may be referred to without the ® and symbols, but such references should not be construed as any indicator that their respective owners will not assert their rights thereto.

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Developing

Next-Generation

Precision

Oncology

Medicines

Differentiated, proprietary

clinical pipeline

• Lunresertib: First-in-class oral PKMYT1 inhibitor (Phase 1/2)
• Camonsertib: ATR inhibitor (Phase 1/2)
• RP-1664:First-in-class selective PLK4 inhibitor (Phase 1)

Proprietary CRISPR-

enabled SNIPRx platform

• Focused on genomic instability and DNA damage repair
• Clinical trials enriched for patients with tumors carrying a network of synthetic lethal alterations (STEP2)

Multiple clinical catalysts

expected in 2024

• Key readouts from ongoing trials
• New clinical entries (PLK4 and Polθ ATPase inhibitors)

Strong balance sheet

• Cash and investments of ~$237M1 fund operations to mid-2026
• Multiple clinical catalysts in that timeframe

3	1 As of March 31, 2024.
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Targeting the untargetable through synthetic lethality

Precision oncology last 20 years:

Targetable gain of function (e.g., EGFR)

~29%

~17%
Focused on 71% untapped
	target space, conventionally
	untargetable

 Gain of function (e.g.,

~54%		CCNE1, 17%)
	Loss of function (no known

driver; e.g., BRCA1, 54%)

Specifically targeting and disrupting genes essential for cancer cell survival

SNIPRx identifies and targets necessary genes to induce synthetic lethality

• Highly targeted & tumor-type agnostic approach
• Exploiting cancer cell genomic instability, including DNA damage repair

Platform validated with established and expanding clinical-stage pipeline

4

Expanding pipeline of precision oncology therapeutics

	PROGRAM	TUMOR LESION	DRUG TARGET	PRECLINICAL	PHASE 1	PHASE 2	PHASE 3	RIGHTS
				Camonsertib Combination
	Lunresertib	CCNE1,	PKMYT1	Chemotherapy Combinations (FOLFIRI/Gemcitabine)
	(RP-6306)1	FBXW7 + others
				Debio 0123 Wee1i Combination
	Camonsertib	ATM + 16		Monotherapy NSCLC Expansion
	STEP2	ATR
	(RP-3500)
	lesions		Other Combinations (PARP Inhibitors/Gemcitabine)
	RP-1664	TRIM37-high	PLK4	Monotherapy
	RP-3467	BRCA1/2	Polθ ATPase
	SNIPRx®	Additional SL targets in advanced stages of development
	Platform	Discovery and validation of new SL precision oncology targets

5	1 Excludes ISTs.

Proven experience in drug discovery and development

Leadership Team

Lloyd M. Segal	Steve Forte, CPA
President & CEO	Chief Financial Officer

Michael Zinda, PhD	Maria Koehler MD, PhD
Chief Scientific Officer	Chief Medical Officer

Cameron Black, PhD	Philip Herman
Head of Discovery	Chief Commercial, Portfolio
	Development Officer

Kim A. Seth, PhD	Daniel Bélanger
Chief Business Officer	Head of Human Resources

Scientific Founders

Daniel Durocher, PhD

• Developed CRISPR SL platform
• Deep DNA repair knowledge
• Lunenfeld-TanenbaumResearch Institute (LTRI) & professor at University of Toronto

Agnel Sfeir, PhD

• DDR and cancer pathway investigator
• Pioneer in Polθ, genome instability
• Professor, MSKCC

Frank Sicheri, PhD

• Globally recognized structural biologist, expert in eukaryotic cell signaling, drug mechanism of action
• LTRI & professor at University of Toronto

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Lunresertib (RP-6306)

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Lunresertib:

First-in-class, oral, small molecule,

Large, genomically

defined potential addressable

patient population of ~90k

• 50% RECIST response in camonsertib combination in gynecological tumors

Anti-tumor activity

observed

• Across multiple tumor types and genotypes
• POC in patients established
• FDA agreed with RP2D; safe and well tolerated

PKMYT1 inhibitor

Repare discovered synthetic lethality of PKMYT1 inhibition

• Initially identified CCNE1 amplification
• STEP2 screen identified additional genes
• • FBXW7 and PPP2R1A
  • • First and currently the only PKMYT1 inhibitor in clinical trials

Supported preclinical

synergy hypothesis and patient selection approach from proprietary SNIPRx platform

88	POC, proof of concept; RP2D, recommended Phase 2 dose.

Large, genomically defined potential patient population

~90K addressable patients including ~65K among top tumors with genetic alterations largely mutually exclusive

Top New Advanced Tumor Cases (US+UK/EU4)

Tumor Type

Uterine

Ovarian

Stomach

Colorectal

Bladder

Cervical

Esophageal

Sarcoma1

Lung Squamous2

Prevalence of Genes of Interest

3.8%								12.9%							7.6%
																								20.0%
										19.0%
																				17.7%
10.2%								6.4%
																		14.7%
	13.1%
															12.2%
5.8%								6.3%
														11.8%
		9.1%
													11.5%
7.1%							3.3%
										7.8%
7.1%
										7.6%
4.7%

4.7%

CCNE1

FBXW7

PPP2R1A

Multiple

Eligible Patients

28.9%7,000

6,300

9,000

24,500

6,200

1,300

4,500

1,200

5,300

• Based on estimated number of pts US+UK/EU4 treated in 1st line, advanced setting for diagnosed and new recurrent patients (CancerMPact®, Treatment Architecture, United States, 2021; accessed 5/19/23) and lesion prevalence (TCGA). 1 Soft Tissue Sarcoma only; 2 Squamous subtype of Non-Small Cell Lung Cancer only

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Evolving broad trial program: sponsored and collaborative

Lunresertib Combination Therapy

Future Opportunities

Key inclusion

Selected tumors with amplified

Ovarian, Lung,

Esophageal /

criteria:

Recurrent solid

tumors

CCNE1

amplification or

PPP2R1A

FBXW7

inactivating

mutations

MAGNETIC: + Gemcitabine

MYTHIC: + Camonsertib;

+ Debio 0123 (Wee1 inhibitor)

MINOTAUR: + FOLFIRI

Multiple Investigator Sponsored Trials

(CCTG1, Carbo/paclitaxel2)

Determine RP2D dose / schedule

Progress to late-stage trials

CCNE1

Selected tumors with FBXW7 loss

Tumors with high rate of sensitivity genes

Basket trial

Gastric

CRC,

Other GI,

Pan Tumor

Endometrial,

Bladder

Breast,

Sarcoma, Bile Duct

1. Canadian Clinical Trial Group (CCTG) collaborations include NCT05605509 and NCT05601440.
2. Standard of care ("SOC") for 1st line ovarian cancer is carbo/paclitaxel (6 cycles) + PARPi maintenance therapy or carbo/paclitaxel with bevacizumab + bev maintenance therapy; this IST supports future

10 potential 1st line combination studies as triplet therapy in patients with CCNE1 amplified tumors.