Replimune : Primary Analysis of the IGNYTE Registrational Cohort Presentation June 2024

Primary Analysis of the IGNYTE

Registrational Cohort in Anti-PD1

Failed Melanoma

June 6, 2024

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Safe Harbor

Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding the advancement, timing and sufficiency of our clinical trials, patient enrollments in our existing and planned clinical trials and the timing thereof, the results of our clinical trials, the timing and release of our clinical data, statements regarding our expectations about our cash runway, our goals to develop and commercialize our product candidates, our expectations regarding the size of the patient populations for our product candidates if approved for commercial use and other statements identified by words such as "could," "expects," "intends," "may," "plans," "potential," "should," "will," "would," or similar expressions and the negatives of those terms. Forward-looking statements are not promises or guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to generate positive clinical trial results for our product candidates, the costs and timing of operating our in-house manufacturing facility, the timing and scope of regulatory approvals, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, political and global macro factors including the impact of global pandemics and related public health issues, the ongoing military conflicts between Russia-Ukraine and Israel-Hamas and the impact on the global economy and related governmental imposed sanctions, and other risks as may be detailed from time to time in our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, and other reports we file with the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward-looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements.

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Today's Speakers/Q&A Panel

SUSHIL PATEL

CEO

Replimune

MICHAEL WONG

Professor

Melanoma Medical Oncology, University of

Texas MD Anderson Cancer Center

KOSTAS XYNOS	ROBERT COFFIN
Chief Medical Officer	Founder and Chief Scientist
Replimune
Replimune

CAROLINE ROBERT

Professor

Head of Dermatology Unit, Institute Gustave Roussy and Co-

Director Melanoma Research Unit INSERM, Paris-Sud University.

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Today's Agenda

• Data Summary
• ASCO 2024 Recap: IGNYTE 12-monthInvestigator-assessed Data
• Topline IGNYTE Primary Analysis by Independent Central Review
• Progress to BLA
• Q&A

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Data Summary

• Strong primary analysis data: ORR of 33.6% (mRECIST 1.1) and 32.9% (RECIST 1.1) by independent central review
• • Improvement versus investigator-assessed ORR of 32.1% (mRECIST 1.1)
• Median DOR >35 months; 100% of responses last >6 months (from baseline)
• • DOR by independent central review consistent with investigator assessment
• Phase 3 confirmatory study (IGNYTE-3) with first patient expected to be enrolled in Q3 2024; BLA submission planned for 2H 2024

*N=140	IGNYTE Investor Event (6/6/24)	5

ASCO Recap: Anti-PD1 Failed Melanoma Patients from the IGNYTE Clinical Trial

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Options are Limited in Melanoma Following

Progression on Anti-PD1 Therapy

• Further single agent anti-PD1 for patients having confirmed PD on prior anti-PD1 gives a response rate of 6-7%1,2
• Nivolumab + ipilimumab is a potential option3, but toxicity is high4-5
• Anti-LAG3plus anti-PD1 has not demonstrated meaningful efficacy in the anti-PD1 failed setting6
• For BRAF mutant tumors, BRAF-targeted therapy responses are generally transient7
• T-VEC+ pembrolizumab has limited activity outside of the adjuvant setting, with no responses seen in patients with visceral disease8-9
• TIL therapy for select patients gives response rates of ~30%, but comes with toxicity (nearly all patients have grade 4 toxicity)10

CTLA-4, cytotoxic T-lymphocyte an6gen 4; LAG3, lymphocyte-ac6va6on gene 3; PD-1, programmed cell death protein 1; TIL, tumor infiltra6ng lymphocyte

1. Mooradian MJ, et al. Oncology. 2019;33(4):141-8. 2. Beaver JA, et al. Lancet Oncol. 2018;19(2):229-39. 3. Na6onal Comprehensive Cancer Network. NCCN Clinical Prac6ce Guidelines in Oncology (NCCN Guidelines®). Melanoma: Cutaneous. Version 2.2024. 4. Pires da Silva I, et al. Lancet Oncol. 2021;22(6):836-47. 5. VanderWalde AM, et al. Presented at the American Associa6on of Cancer Research Annual Mee6ng 2022. New Orleans. 6. Ascierto PA, et al. J Clin Oncol. 2023;41(15)2724-35. 7. Dixon-Douglas JR, et al. Curr Oncol Rep. 2022;24(8):1071-9. 8. Gastman B, et al. J Clin Oncol. 2022;40(16_suppl):9518. 9. Hu-Lieskovan S, et al. Cancer Res. 2023;83(7_suppl):3275. 10. US Food and Drug Administra6on. BLA clinical review and evalua6on - AMTAGVI. BLA 125773. Updated February 6, 2024. Accessed May 31, 2024].hcps://www.fda.gov/media/176951/download.

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IGNYTE Study Design

Anti-PD1 Failed Melanoma Cohort

Screening	28	RP1	2 we ks	2 weeks	2 weeks	Nivolumab
28 days	2 weeks RP1+nivolumaba	2 weeks Nivolumab
Anti-PD1 failed
melanoma cohort
(140 pts; 16 pts		Cycle 1	Cycles 2-8	Cycle 9		Cycles 10-30b
treated in prior
cohorts: Total=156)

Primary objectives

• Safety and tolerability
• Efficacy as assessed by ORR using modified RECIST 1.1 criteria

Secondary objective

DOR, CR rate, DCR, PFS, by central & investigator review, ORR by investigator review, and 1-year and 2-year OS

Key eligibility criteria

Confirmed progressionwhile onprior anti-PD1 therapyc

At least 8 weeks of prior anti-PD1,confirmed progressionwhile onanti- PD1; anti-PD1 must be the last therapy before clinical trial. Patients on prior adjuvant therapy must have progressed while on prior adjuvant treatment.

Primary analysis to be conducted when all patients have ≥ 12 months follow up

aDosing with nivolumab begins at dose 2 of RP1 (C2D15). bOp?on to reini?ate RP1 for 8 cycles if criteria are met. c. Non-neurological solid tumors	CR, complete response; CT, computed tomography; DCR, disease control
rate; DOR, dura?on of response; ECOG, Eastern Coopera?ve Oncology Group; LD, longest diameter; ORR, objec?ve response rate; OS, overall survival; PD-1, programmed cell death protein 1; PFS, progression-free	IGNYTE Investor Event (6/6/24)	8
survival; pfu, plaque-forming unit; Q4W, every 4 weeks; RECIST, Response Evalua?on Criteria in Solid Tumors.

Baseline Clinical Characteristics

A 'real world' anti-PD1 failed melanoma population was enrolled

• Good representation of each of the sub-groups of patients who progress on prior anti-PD1 therapy

Patients, n (%)	All patients		Patients, n (%)	All patients
	(N = 156)			(N = 156)

	Age (median [range])	62 (21-91)
	Sex
	Female	52 (33.3)
	Male	104 (66.7)
	Stage
	IIIb/IIIc/IVM1a	75 (48.1)
	IVM1b/c/d	81 (51.9)
	Prior therapy
	Anti-PD1 only as adjuvant therapy	39 (25.0)
	Anti-PD1 not as adjuvant therapy	117 (75.0)
	Anti-PD1 & anti-CTLA-4	74 (47.4)
	Received BRAF-directed therapy	17 (10.9)

Other disease characteristics

	Primary resistance to prior anti-PD1a	105 (67.3)
	Secondary resistance to prior anti-PD1b,c	51 (32.7)
	BRAF wt	103 (66.0)
	BRAF mutant		53	(34.0)
	LDH ≤ULN	105 (67.3)
	LDH >ULN		50	(32.1)
	LDH unknown	1	(0.6)

Median follow up

is 15.4 months (range 0.5-55.5)

Data cutoff: March 8th 2024. aPrimary resistance: Progressed within 6 months of star6ng the immediate prior course of an6-PD-1 therapy; bSecondary resistance: Progressed ager 6 months of treatment on the immediate prior course of an6-PD-	IGNYTE Investor Event (6/6/24)	9
1 therapy; cIncludes 2 pt unknown resistance status. CTLA-4, cytotoxic T-lymphocyte an6gen 4; LDH, lactate dehydrogenase; PD-1, programmed cell death protein 1; ULN, upper limit of normal; wt, wild-type.

Efficacy

Investigator assessed data with all patients having at least 12 months follow up

All patients enrolled in IGNYTE

BOR	All patients
n (%)	(n = 156)
CR	23 (14.7)
PR	28 (17.9)
SD	34 (21.8)
PD	63 (40.4)
ORR	51 (32.7c)

Prior single-

agent anti-PD1

(n = 82)

18 (22.0)

1. (15.9)

1. (22.0)

1. (37.8)

31 (37.8)

Prior anti- PD1/CTLA-4 (n = 74)a

5 (6.8)

1. (20.3)
2. (21.6)

1. (43.2)

20 (27.0)

Stage IIIb-	Stage IVM1b-d
IVM1a	(n = 81)
(n = 75)
18 (24.0)	5	(6.2)
13 (17.3)	15	(18.5)
19 (25.3)	15	(18.5)
24 (32.0)	39	(48.1)
31 (41.3)	20 (24.7)

1o resistance to	2o resistance to
anti-PD1	anti-PD1
(n = 105)	(n = 51)b
18 (17.1)	5	(9.8)
18 (17.1)	10	(19.6)
17 (16.2)	17	(33.3)
47 (44.8)	16 (31.4)
36 (34.3)	15 (29.4)

aEight pa)ents were treated with sequen)al an)-CTLA-4 and an)-PD1 (ORR for prior combined an)-CTLA-4/an)-PD1 was 25.8%). bIncludes one pa)ent with unknown resistance status. cORR for the 140-pa)ent registra)on intended cohort was 32.1%

• 1 in 3 patients achieved an objective response (32.7%)
• Consistent ORR across subgroups, including:

1. 27% ORR in patients who had prior anti-PD1 & anti-CTLA-4

1. 34% ORR in patients who are primary resistant to their prior anti-PD1 therapy

Data cutoff: March 8th 2024. BOR, best overall response; CR, complete response; CTLA-4, cytotoxic T-lymphocyte an6gen 4; PD-1, programmed cell death protein 1; PD, progressive disease; PR, par6al response; ORR, objec6ve response rate; SD, stable disease. IGNYTE Investor Event (6/6/24)

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