Replimune Group (REPL) Study Result summary

Study design and patient population

• IGNITE/IGNYTE is a global Phase I/II trial of RP1 plus nivolumab in anti-PD-1 failed melanoma, enrolling 156 patients with stringent eligibility and real-world resistance subtypes, all with at least 12 months of follow-up.

• Nearly half of patients had visceral disease, half had failed both anti-PD-1 and anti-CTLA-4, two-thirds had primary refractory disease, and one-third had high LDH, reflecting a difficult-to-treat population.

• Median follow-up was 15.4 months, with a data cutoff of March 8, 2024.

• All patients had confirmed progression on prior anti-PD-1 therapy and were followed for at least 12 months.

• The primary endpoint was overall response rate (ORR) by independent central review, with additional analyses by investigator assessment and RECIST 1.1 as requested by the FDA.

Efficacy results

• Central review showed an ORR of 33.6% by mRECIST 1.1 and 32.9% by RECIST 1.1, consistent with investigator-assessed ORR of 32.1%.

• Median duration of response exceeded 36 months, with all responses lasting over 6 months.

• Responses were observed in both injected and non-injected lesions, including visceral and bone metastases, indicating systemic activity.

• 1 in 3 patients achieved an objective response, with 55% experiencing clinical benefit (CR + PR + SD).

• Target lesions were reduced in over 50% of patients.

Safety and tolerability

• RP1 plus nivolumab was generally well tolerated, with most adverse events being grade 1 or 2 and constitutional in nature.

• Low incidence of grade 3/4 events; no grade 5 events reported.

• Most common side effects included chills, fatigue, pyrexia, and nausea.

• Grade 4 events were rare and included single cases of specific lab abnormalities and organ events.