Replimune : JP Morgan Healthcare Conference 2025 Presentation

REPL

Igniting a systemic immune response to cancer with oncolytic immunotherapy

JP Morgan Healthcare Conference January 13, 2025

3 Clinical Assets with >700 Patients Treated

7 Ongoing Clinical Trials

Establishing a Skin

RP1

Cancer Franchise

Lead Indication: Anti-PD-1 Failed Melanoma

Additional Data: Anti-PD-1 Failed NMSC and Solid Organ Transplant (SoT)

Expanding RPx

RP2

RP3

Opportunities

Uveal Melanoma

HepatocellularCarcinoma (HCC)

Additional Signals

Positioned for Successful RP1 Independent Commercial Launch in 2H 2025

*modified RECIST; ORR=overall response rate; ^Trial being conducted under collaboration and supply agreement with Roche; #Trial being conducted under

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collaboration and supply agreement with BMS; H&N=head and neck; NMSC = Non melanoma skin cancers, COGs=cost of goods; SoT = solid organ

© 2025 Replimune Group Inc.

transplant, LA = locally advanced, CSCC = cutaneous squamous cell carcinoma; BCC = basal cell carcinoma; MCC = Merkel cell carcinoma

Oncolytic Immunotherapy Designed to Activate a Dual Local and Systemic Anti-Tumor Response

Oncolytic Immunotherapy - New clinical isolate of HSV-1 modified to express a fusogenic glycoprotein and immune stimulating proteins

Intact host antiviral response: Normal tissue remains undamaged

Injected Local

1

Non-Injected Systemic

Response

2

Immune Response

M E C H A N I S M

M E C H A N I S M

Dysregulated host antiviral response allows robust virus replication and tumor lysis

Dendritic cell T cell

Healthy tissue

Bommareddy PK et al AJCD. 2016

Tumor cell death and

Enhanced T cell

release of tumor

priming and

antigens

activation

Release

Local

T cell infiltration and

of virus progeny

Inflammation

killing of distant,

non-injected tumors

Generating a strong

Infection of more

Altering of tumor

and durable systemic

tumor cells

microenvironment

anti-tumor immune

response

Tumor tissue

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© 2025 Replimune Group Inc.

Igniting a Systemic Immune Response via RPx Intra-tumoral (IT) Delivery

Expressed Payloads

(Immune Stimulating)

GM-CSF (intended to mature antigen presenting cells, & activate the immune system against cancer)

GALV-GP R- (intended to cause cell fusion and immunogenic cell death, to enhance direct tumor killing & the adaptive and innate immune responses)

Anti-CTLA-4 (antibody intended to prevent immune blockade at the APC

Therapeutic Objective

Robust local and distant / systemic anti-tumor response

Limitadverse events and toxicities

Combinability and Rx synergy e.g., I-O, targeted therapies

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RP1: Delivering on the Promise of Oncolytic Immunotherapy

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Significant Unmet Need for Melanoma Patients that

Progress on PD-1 Containing Regimens

~50% of patients on

Current

first line therapy

Few treatment

Limited response

treatments have

progress within 6

options available3,4

rates/durability5,6

toxicity

months1,2

concerns7,8,9

Sources: . 1. Wolchok JD, et al. N Engl J Med. 2024. 2. Tawbi HA, et al. J Clin Oncol. 2024;42:16 suppl. 3. Mooradian MJ, et al. Oncology. 2019;33(4):141-8. 4. National Comprehensive Cancer Network. NCCN Clinical Practice

Guidelines in Oncology (NCCN Guidelines®). Melanoma: Cutaneous. Version 2. 2024. 5. Dixon-Douglas JR, et al. Curr Oncol Rep. 2022;24(8):1071-9. 6. Ascierto PA, et al. J Clin Oncol. 2023;41(15)2724-35. 7. Chesney J, et al. J Immunother Cancer. 2022;10(12):e005755. 8. US Food and Drug Administration. BLA clinical review and evaluation - AMTAGVI. BLA 125773. Updated February 6, 2024. Accessed May 31, 2024. https://www.fda.gov/media/176951/download. 9. Sarnaik AA, et al. J Clin Oncol. 2021;39(24):2656-66.

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© 2025 Replimune Group Inc.

RP1 + Nivolumab Delivers Consistent Responses

Across Anti-PD-1 Failed Melanoma Subgroups

Prior single-

Prior anti-

Prior anti-

Prior anti-

Stage

Stage

Primary

Secondary

PD-1

BOR

All patients

agent

PD-1/

PD-1

IIIb-IVa

IVb-IVd

resistance

resistance

not

n (%)

(N = 140)

anti-PD-1

CTLA-4

adjuvant

(n = 72)

(n = 68)

(n = 92)

(n = 48a)

adjuvant

(n = 75)

(n = 65)

(n = 36)

(n = 104)

CR

21 (15.0)

16

(21.3)

5 (7.7)

17 (23.6)

4 (5.9)

16 (17.4)

5

(10.4)

11 (30.6)

10 (9.6)

PR

26 (18.6)

13

(17.3)

13 (20.0)

12 (16.7)

14 (20.6)

17 (18.5)

9

(18.8)

5 (13.9)

21

(20.2)

SD

41 (29.3)

20

(26.7)

21 (32.3)

24 (33.3)

17 (25.0)

22 (23.9)

19

(39.6)

10 (27.8)

31

(29.8)

PD

43 (30.7)

24

(32.0)

19 (29.2)

18 (25.0)

25 (36.8)

31 (33.7)

12

(25.0)

9 (25.0)

34 (32.7)

ORR

47 (33.6)

29 (38.7)

18 (27.7)

29 (40.3)

18 (26.5)

33 (35.9)

14 (29.2)

16 (44.4)

31

(29.8)

Data presented at ESMO 2024, SITC 2024

aIncludes one patient with unknown resistance status.

BOR, best overall response; CR, complete response; CTLA-4, cytotoxic T-lymphocyte antigen 4; mRECIST, modified response evaluation criteria in solid tumors; PD-1, programmed cell death protein 1; PD, progressive disease; PR, partial response; ORR, objective response rate; SD, stable disease.

Centrally reviewed mRECIST v1.1 responses (per protocol); all patients have ≥12 months follow up

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© 2025 Replimune Group Inc.

Durable Responses and Promising Overall Survival

Median Duration of Response - 21.6 months*

Overall Survival - Not Reached

Probability of Ongoing Response

1

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

RP1 + Nivolumab Censored

Median (95% CI) 21.62 [14.52, NR]

+

1

Survival

0.9

75.3%

Median (95% CI)

NR [26.18, NR]

0.8

63.3%

0.7

Overall

0.6

54.8%

0.5

of

0.4

Probability

0.3

0.2

0.1

RP1 + Nivolumab

0

Censored

+

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42

Time (Months)

Number of subjects at risk:

RP1 + Nivo 47

46

39

31

23

18

16

13

10

8

6

4

1

1

1

Data presented at ESMO 2024, SITC 2024

0

3

6

9

12

15

18

21

24

27

30

33

36

39

42

45

48

Time (Months)

Number of subjects at risk:

RP1 + Nivo 140

127

116

104

95

73

63

52

43

35

29

17

9

6

5

3

0

*From response initiation; range (1.2+ to 43.5+ months)

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© 2025 Replimune Group Inc.

Systemic Benefit with Deep Responses in Visceral Lesions

Anti-tumor effect on non-injected visceral

Responses in injected and non-injected

lesions*

lesions*

Location of

n

Any

>0% to

≥30% to

visceral

100%

(Lesions)

Reduction

<30%

<100%

lesions

Lung

29

28 (96.6%)

7 (24.1%)

9 (31%)

12 (41.4%)

Liver

15

15 (100%)

4 (26.7%)

5 (33.3%)

6 (40%)

Adrenal

3

1 (33.3%)

0

0

1 (33.3%)

Ovary

1

1 (100%)

0

0

1 (100%)

Spleen

6

5 (83.3%)

5 (83.3%)

0

0

Pleura

2

2 (100%)

0

1 (50%)

1 (50%)

Brain

3

1 (33.3%)

1 (33.3%)

0

0

Pancreas

1

0

0

0

0

TOTAL

60

53 (88.3%)

17 (28.3%)

15 (25%)

21 (35%)

Data presented at SITC 2024

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*in responding patients (N=47)

© 2025 Replimune Group Inc.

Favorable Safety Profile of RP1 + Nivolumab

TRAEs occurring in ≥5% of patients

Preferred term, n (%)

(N = 141)

All Grades

Grade 3-4

≥1 TRAE

126 (89.4)

18

(12.8)

Fatigue

46 (32.6)

1 (0.7)

Chills

45 (31.9)

0

(0.0)

Pyrexia

43 (30.5)

0

(0.0)

Nausea

31 (22.0)

0

(0.0)

Influenza-like illness

25 (17.7)

0

(0.0)

Injection-site pain

21 (14.9)

0

(0.0)

Diarrhoea

20 (14.2)

1 (0.7)

Vomiting

19 (13.5)

0

(0.0)

Headache

18 (12.8)

0 (0.0)

Pruritus

18 (12.8)

0

(0.0)

Asthenia

14 (9.9)

1 (0.7)

Arthralgia

10 (7.1)

1 (0.7)

Decreased appetite

9 (6.4)

1 (0.7)

Myalgia

9 (6.4)

0

(0.0)

Cough

8 (5.7)

0

(0.0)

Rash

8 (5.7)

0

(0.0)

Injection-site reaction

7 (5.0)

0

(0.0)

Vitiligo

7 (5.0)

0 (0.0)

Data presented at ESMO 2024, SITC 2024

Predominantly grade 1 and 2 constitutional-type side effects

Low incidence of grade 3 events (none occurring in >5% of patients); five grade 4 events in total

No grade 5 events

Additional grade 3/4 TRAEs (grade 4 italicized):

Two events each (1.4%): Hypophysitis, rash maculo-popular

One event each (0.7%): Abdominal pain, acute left ventricular failure, amylase increased, cancer pain, cytokine release syndrome, eczema, enterocolitis, extranodal marginal zone B-cell lymphoma (MALT type), hepatic cytolysis, hyponatraemia, immune-mediated enterocolitis, infusion-related reaction, left ventricular dysfunction, lipase increased, memory impairment, meningitis aseptic, muscular weakness, myocarditis, palmar-plantar erythrodysaesthesia syndrome, paraesthesia, peripheral sensory neuropathy, radiculitis brachial, sinus arrhythmia, splenic rupture, tricuspid valve incompetence, tumor pain, type 1 diabetes mellitus

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Disclaimer

Replimune Group Inc. published this content on January 14, 2025, and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on January 14, 2025 at 05:17:01.490.