Replimune Group, Inc. reported a pivotal regulatory update in its annual filing for the fiscal year ended March 31, 2026, centered on its lead oncolytic immunotherapy candidate, RP1, also known as vusolimogene oderparepvec. The company said the U.S. Food and Drug Administration has accepted its latest resubmission of the Biologics License Application for RP1 in combination with Bristol Myers Squibb’s nivolumab for the treatment of advanced melanoma in patients who progressed on an anti-PD-1-containing regimen. The most recent action occurred on June 26, 2026, when Replimune announced that the FDA accepted the BLA resubmission as a Class 1 resubmission and assigned an action date of August 2, 2026. The FDA also indicated that it would convene an advisory committee meeting in late July 2026. This followed a difficult regulatory path: Replimune originally submitted the BLA in November 2024 under the accelerated approval pathway after receiving Breakthrough Therapy designation for RP1 plus nivolumab in the same setting. The FDA accepted the application and granted priority review with a July 22, 2025 PDUFA date, but issued a complete response letter on July 21, 2025. The first CRL stated that the FDA could not approve the application in its then-current form, citing concerns that the IGNYTE trial was not an adequate and well-controlled clinical investigation providing substantial evidence of effectiveness, including contribution of components, and that the patient population was too heterogeneous to adequately interpret the trial. Replimune held a Type A meeting with the FDA on September 16, 2025, resubmitted the BLA on October 9, 2025, and on October 20, 2025 announced that the FDA had accepted that resubmission as a complete response to the first CRL, setting an April 10, 2026 action date under a Class 2 resubmission timeline. On April 10, 2026, however, the FDA issued a second CRL. Replimune said the second CRL reiterated points from the first CRL and, in the company’s view, reversed certain positions the FDA had taken during the September 2025 Type A meeting. The company later announced on May 29, 2026, that after collaborative communications with the FDA, the parties had aligned on a path forward for another resubmission and reconsideration of the BLA. Replimune said the FDA indicated it would treat the new resubmission as urgent and prioritize review given the unmet need in advanced melanoma. The regulatory stakes are significant. Replimune warned that without accelerated approval of RP1 plus nivolumab from the resubmitted BLA, it may be unable to continue development of RP1 for this indication, or potentially at all, and could be required to implement a restructuring plan and review priorities across its RPx portfolio and the broader company. The BLA is supported by Replimune’s IGNYTE trial, a multi-cohort study conducted in collaboration with Bristol Myers Squibb, which granted Replimune a non-exclusive, royalty-free license to nivolumab and supplies the drug at no cost for use with RP1. The registration-directed Phase 2 expansion cohort in anti-PD-1-failed cutaneous melanoma enrolled 140 patients treated with RP1 plus nivolumab. According to data cited in the filing, 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 trial produced a confirmed overall response rate of 32.9%, including a 15.0% complete response rate. Responses occurred with similar frequency, depth, duration and kinetics in injected and non-injected lesions, including visceral lesions. Median duration of response was 33.7 months, while overall survival rates at one and two years were 75.3% and 63.3%, respectively. Replimune also reported a three-year landmark overall survival analysis presented at the 2026 American Society of Clinical Oncology annual meeting in May 2026, showing median overall survival of 32.9 months. At three years, 47.8% of all treated patients remained alive, rising to 83.5% among responders. The company said safety remained favorable and manageable, with mostly Grade 1–2 constitutional side effects, no Grade 5 events and no new safety signals. Replimune is also continuing the IGNYTE-3 trial, or I-3, a randomized Phase 3 study in anti-PD-1-failed melanoma. The company dosed the first patient in August 2024. The study is designed as a two-arm randomized trial using physician’s choice of treatment as the comparator. Replimune noted that the FDA had previously indicated in September 2025 meeting minutes that nivolumab plus relatlimab, marketed as Opdualag, could be an acceptable comparator, but the company believes the FDA changed its position in the second CRL. Replimune said it continues enrolling patients and plans to keep working with the FDA on the trial’s path forward. Beyond melanoma, Replimune reported clinical activity for RP1 in non-melanoma skin cancers. In the IGNYTE non-melanoma skin cancer cohort, updated data presented in 2025 showed responses across tumor types including cutaneous squamous cell carcinoma, Merkel cell carcinoma, basal cell carcinoma and angiosarcoma. Among anti-PD-1-naïve patients, reported overall response rates were 100.0% in Merkel cell carcinoma, based on four patients; 33.3% in basal cell carcinoma, based on three patients; 66.7% in angiosarcoma, based on six patients; and 56.3% in cutaneous squamous cell carcinoma, based on 16 patients. Among anti-PD-1-failed patients, response rates were 26.3%.