Replimune Group (REPL) Investor presentation summary

Unmet need and current treatment landscape

• Advanced melanoma has significant unmet need, with 50% of patients progressing within 12 months and a 5-year overall survival of only 35%.

• Limited options exist after progression on immune checkpoint inhibitors, with lifileucel (AMTAGVI) as the only FDA-approved agent for anti-PD-1 failed melanoma, but it involves complex, multi-component therapy and notable toxicity.

• Retreatment with anti-PD-1 therapies yields low response rates (5-7%), and other combinations have modest efficacy and high toxicity.

Proposed therapy and mechanism of action

• Vusolimogene oderparepvec (TUDRIQEV) is an HSV-1 based oncolytic viral immunotherapy expressing GM-CSF and a fusogenic glycoprotein, combined with nivolumab.

• The dual mechanism drives both local tumor lysis and systemic immune activation, enhancing T cell infiltration and antitumor response in both injected and non-injected lesions.

• Preclinical and biomarker data show increased CD8+ T cells and PD-L1 expression, supporting biological plausibility.

Clinical efficacy and safety (IGNYTE study)

• In anti-PD-1 refractory melanoma (n=140), the combination achieved an ORR of 33.6% (95% CI: 25.8, 42.0), with a median duration of response of 24.8 months.

• Responses were observed across all clinically relevant subgroups, including those with high tumor burden and both primary and secondary resistance.

• The 3-year overall survival rate was 47.8%, with a median OS of 32.9 months.

• Safety profile was favorable, with most adverse events being Grade 1 or 2; Grade 3+ events occurred in 31.4% of patients, and no treatment-related Grade 5 events were reported.