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
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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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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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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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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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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)
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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.