Replimune Group, Inc. used its annual report for the fiscal year ended March 31, 2026, to update investors on a pivotal and unresolved regulatory effort for RP1, or vusolimogene oderparepvec, its lead oncolytic immunotherapy candidate. The company’s most consequential recent action is the continued pursuit of U.S. accelerated approval for RP1 in combination with Bristol Myers Squibb’s anti-PD-1 therapy nivolumab for adult patients with advanced melanoma who previously received an anti-PD-1-containing regimen. The regulatory timeline has become the central issue for Replimune. The company submitted its first Biologics License Application, or BLA, for RP1 plus nivolumab in November 2024, and the FDA granted Breakthrough Therapy designation in the same treatment setting. The agency accepted the application for priority review and set a July 22, 2025, PDUFA target date. However, on July 21, 2025, the FDA issued a Complete Response Letter, or CRL, saying it could not approve the application in its present form. According to Replimune, the FDA stated that the IGNYTE trial was not considered an adequate and well-controlled clinical investigation providing substantial evidence of effectiveness, including contribution of components, and that the trial could not be adequately interpreted because of heterogeneity in the patient population. Replimune then sought to address the agency’s concerns through a Type A meeting process. The company announced on September 2, 2025, that a Type A meeting had been scheduled after it submitted a briefing book responding to the CRL, including prior agreements on patient population, criteria for PD-1 resistance, use of literature to support contribution of components, additional analyses from the BLA data, and comments on the Phase 3 confirmatory trial design. The Type A meeting occurred on September 16, 2025. Replimune said on September 18, 2025, that it was evaluating FDA feedback and that a path forward under accelerated approval had not yet been determined. After reviewing the feedback and meeting minutes, the company resubmitted the BLA on October 9, 2025. The FDA accepted the resubmission on October 20, 2025, deemed it a complete response to the first CRL, and set an April 10, 2026, target action date under a Class 2 resubmission timeline. On April 10, 2026, the FDA issued a second CRL for the RP1 BLA. Replimune said the second CRL reiterated points from the first CRL that the company believed had been addressed through the accepted resubmission, and also reversed positions the company understood the FDA to have taken during the September 2025 Type A meeting. The company later announced on May 29, 2026, that, after collaborative communications with the FDA, it and the agency had aligned on a path forward for resubmission and reconsideration of the BLA. On June 26, 2026, Replimune said the FDA had accepted the latest BLA resubmission as a Class 1 resubmission, with a new action date of August 2, 2026. The FDA also stated that it would convene an advisory committee meeting in late July 2026. The filing makes clear that this regulatory outcome is strategically important for Replimune. The company warns that without accelerated approval of RP1 plus nivolumab from the resubmitted BLA, it may not be able to continue development of RP1 in this indication, or potentially at all, and may need to implement a restructuring plan and review priorities across its RPx portfolio and the company as a whole. The application is supported by the IGNYTE trial, a multi-cohort clinical study conducted in collaboration with Bristol Myers Squibb. Under that collaboration, BMS granted Replimune a non-exclusive, royalty-free license to nivolumab and is supplying the drug at no cost for use in combination with RP1. The key registration-directed Phase 2 expansion cohort enrolled 140 patients with anti-PD-1-failed cutaneous melanoma. Replimune reported that 48.6% of patients had stage IVM1b/c/d disease, 65.7% had primary anti-PD-1 resistance, 56.4% were PD-L1 negative, and 46.4% had previously received both anti-PD-1 and anti-CTLA-4 therapy. The confirmed overall response rate was 32.9%, including a 15.0% complete response rate. Median duration of response was 33.7 months, and overall survival rates at one and two years were 75.3% and 63.3%, respectively. Replimune also highlighted longer-term data presented in May 2026 at the American Society of Clinical Oncology annual meeting. In a three-year landmark overall survival analysis from IGNYTE, RP1 plus nivolumab achieved median overall survival of 32.9 months in patients with anti-PD-1-failed advanced melanoma. At three years, 47.8% of all treated patients remained alive, and survival rose to 83.5% among responders. The company said the combination continued to show a favorable and manageable safety profile, with predominantly Grade 1–2 constitutional side effects, no Grade 5 events, and no new safety signals. Beyond the BLA, Replimune reported that it continues to enroll patients in IGNYTE-3, or I-3, a two-arm randomized Phase 3 trial in anti-PD-1-failed melanoma. The trial uses physician’s choice of treatment as the comparator arm. The company said the FDA had previously indicated in September 2025 Type A meeting minutes that nivolumab plus relatlimab, marketed as Opdualag, may be an acceptable comparator, but Replimune believes the agency reverted from that position in the second CRL. The company said it plans to continue working with the FDA on the path forward for the I-3 trial. The annual report also updates other RP1 development programs. In non-melanoma skin cancer cohorts of IGNY.