Replimune Group, Inc. announced an initial data snapshot from the first 75 patients from the anti-PD1 failed cutaneous melanoma cohort of the IGNYTE clinical. The IGNYTE clinical trial is evaluating RP1 (vusolimogene oderparepvec) in combination with nivolumab, with the anti-PD1 failed melanoma cohort being conducted with registrational intent. The Company also provided new data from the ongoing Phase 1 clinical trials evaluating RP2 and RP3, as well as a detailed overview of its RP2/3 Phase 2 development plans.

A virtual investor event will be held at 8:00 a.m. ET to discuss the new data. IGNYTE is Replimune's multi-cohort clinical trial evaluating RP1 combined with nivolumab in multiple tumor type specific cohorts. The Company is presenting new data from the first 75 patients from the 125 patient anti-PD1 failed melanoma cohort, which has registrational intent.

The IGNYTE clinical trial is being conducted under a collaboration and supply agreement with Bristol-Myers Squibb, with the anti-PD1 failed melanoma cohort expected to complete enrollment by around the end of this year. The ORR in the first 75 patients from the anti-PD1 failed melanoma cohort was 36%, consistent with that observed in the prior Phase 2 cohort (N=16) presented in June 2022 where an ORR of 37.5% was seen. The complete response (CR) rate was 20.0%, compared to 12.5% shown in the prior 16 patients presented in June 2022.

Further patients remain on study from the first 75 patients who have the opportunity for response, and current responses continue to deepen. The data demonstrates that RP1 combined with nivolumab shows clinically meaningful durable activity across the range of anti-PD1 failed cutaneous melanoma presentations, including in patients with moderate to high tumor burden, with 85% of responses ongoing. The data clearly demonstrate systemic activity, with both injected and in un-injected lesions responding, including in un-injected visceral disease.

Most responses seen were in patients who did not respond to prior anti-PD1 therapy (i.e. did not previously achieve a PR or CR). Safety data with RP1 in combination with nivolumab assessed across all skin cancer patients treated with RP1 combined with nivolumab (N=187), including the new 75 patients, continues to demonstrate an attractive safety profile, with predominantly ‘on target' Grade 1-2 side effects indicative of systemic immune activation. Overall, Replimune believes that RP1 in combination with nivolumab has the potential to become a go-to treatment option for melanoma patients after progressing on or after anti-PD1 therapy, including on adjuvant therapy or on or after a first- or second-line anti-PD1-containing regimen, including in combination with anti-CTLA-4. The data snapshot from the first 75 patients was investigator assessed as compared to the primary endpoint of ORR for all patients in the cohort which is to be assessed by central review.

RP2 leverages the Company's platform to express an anti-CTLA-4 antibody, in addition to the GALV-GP R- and GM-CSF expressed by RP1. RP3 further expresses CD40L and 4-1BBL in addition to anti-CTLA-4 and GALV-GP R-, but does not express GM-CSF, and is intended to induce a broad and potent anti-tumor immune response. The Company is pursuing a Phase 2 development plan for RP2 and RP3 targeting tumor types in large and underserved markets, including where liver metastases are common, as well as patients with primary liver cancer, and patients with earlier disease where the objective of treatment would be to achieve a cure.

This includes the development of RP2/3 in combination with the current standard of care (SOC), including immunotherapy, chemotherapy and radiation, and in settings following the current SOC. The Company is presenting updated data in uveal melanoma patients from the Phase 1 clinical trial evaluating RP2 in combination with nivolumab which the Company believes provides a proxy for the treatment for a range of intractable tumor types that metastasize to the liver. Seventeen patients have been treated with RP2 as monotherapy (N=4) or in combination with nivolumab (N=13) to date, with enrollment of uveal melanoma patients into this clinical trial now being complete.

Four of the 14 patients which are so far evaluable have responded to treatment (28.6%), including metastatic tumors in the liver and bone. The final three of 17 patients remain on treatment, but currently have insufficient follow-up data to determine response outcome as of the cut-off date. Three of the four responses are ongoing at 9, 12 and 21 months, with the fourth patient having progressed at 15 months.

The Company is also presenting data from a Phase 1 clinical trial of RP3 in combination with nivolumab, in patients with soft tissue sarcomas. Five patients have been treated with RP3 combined with nivolumab in patients with multiple soft tissue sarcomas including in leiyomyosacoma, osteosarcoma, chondrosarcoma, and epithelioid sarcomas who have all have failed standard of care (chemotherapy and other therapies). At the data cut-off date, 3 of 5 patients have sufficient follow up for response assessment, and all three are responding to therapy in settings with no viable alternative treatment option, indicating the potential utility of RP3 in treating this difficult to treat tumor type.

Overall, RP2/3 continues to demonstrate promising early signals that could unlock additional opportunities in hard to treat cancers. The Company is providing further details on its Phase 2 development plans with RP2/3, and is also separately announced a clinical collaboration with Roche in colorectal cancer (CRC) and hepatocellular carcinoma (HCC), which will both utilize Roche's atezolizumab and bevacizumab. Three Phase 2 clinical trials are to be conducted with RP2/3, each initiating in the first half of 2023.

Squamous cell carcinoma of the head and neck (SCCHN): A two cohort clinical trial with RP3 will be conducted, with the first cohort of 100 patients with locally advanced disease being randomized to receive either SOC chemotherapy combined with radiation or RP3 combined with chemotherapy and radiation followed by adjuvant nivolumab therapy.