Replimune (REPL) Provides Data Update from its RP1 and RP2 Programs and Announces Plans to Expand the Development of RP2/3 Beyond Phase 1

Replimune Group, Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic® platform, today announced updated interim data from the Phase 2 skin cancer cohorts combining RP1 (vusolimogene oderparepvec) with Opdivo®* (nivolumab) and data from RP2 alone and in combination with Opdivo that continues to provide strong support for development in its lead indications. Additionally, Replimune announced plans to initiate a Phase 2 clinical trial program in tumor types that metastasize to the liver. A virtual investor event will be held today at 8:00 a.m. ET to discuss the updated data.

“As our data matures there are some clear themes emerging,” said Philip Astley-Sparke CEO of Replimune. “In our longest-running clinical trial of RP1 combined with Opdivo in melanoma and in non-melanoma skin cancers including cutaneous squamous cell carcinoma (CSCC), we are seeing a clear trend that partial responses tend to convert to complete responses over time, providing many patients with the potential for a cure while also having a transformative long-term impact on quality of life. Our updated data further support our two registration-directed studies in skin cancers. We look forward to seeing if we can replicate the data we have seen with RP1 in skin cancers in anti-PD1/L1 failed non-small cell lung cancer (NSCLC), where we recently dosed our first patient. The signal with RP1 in patients who have failed anti-PD1 is continuing with RP2 and reinforces the potential utility of our platform for treating patients who have failed prior immune checkpoint therapy. Finally, the signal with RP1 indicating the potential to treat patients with liver metastases, who in general have a very poor prognosis, has been further confirmed with RP2, where we are now planning to move into Phase 2 development with RP2/3 in tumor types that commonly metastasize to the liver, including colon cancer, lung cancer and breast cancer.”

Updated clinical data from the Phase 2 cohort with RP1 in combination with Opdivo in patients with CSCC and other non-melanoma skin cancers continues to support the CERPASS registration-directed clinical trial of RP1 in combination with Libtayo®* (cemiplimab) in CSCC

The data continues to demonstrate that RP1 in combination with Opdivo is well tolerated and that it drives deep and durable responses in patients with CSCC with the number of complete responses (CRs), a dual independent primary endpoint in the CERPASS study, continuing to increase. At the current data cut off (n=15), seven of the nine responses are complete responses with a current CR rate of 46% and overall response rate (ORR) of 60%. Another potentially eighth complete response will require biopsy confirmation. The Company believes this data provides clear differentiation versus anti-PD1 therapy alone and provides strong validation of Replimune’s current registration-directed clinical development plan, with the initial readout of the CERPASS study expected in 2022.

Updated clinical data evaluating RP1 in combination with Opdivo in anti-PD1 failed melanoma patients continues to strongly support the Company’s registration-directed cohort in the IGNYTE clinical trial

Sixteen anti-PD1 failed cutaneous melanoma patients were enrolled into the previously reported 30 patient cohort in melanoma (which included anti-PD1 naïve cutaneous melanoma, mucosal and uveal melanoma, in addition to anti-PD1 failed cutaneous melanoma). The status of the anti-PD1 failed melanoma patients is as follows:

• Five of these patients have so far met the formal criteria for response; four of which had previously failed both anti-PD1 and anti-CTLA-4 therapies, with a current ORR of 31%.
• Of two further patients on study one remains a surgical complete response at 18 months from the start of treatment (classified as stable disease according to the study protocol) and the second patient with local progression following an extended period of stable disease has reinitiated RP1 treatment and is responding to therapy.

Despite improvements in therapy, many melanoma patients treated with anti-PD1 therapy have primary resistance or acquire resistance to immune checkpoint blockade following initial response. The clear activity of RP1 in combination with Opdivo in anti-PD1 failed patients, including in patients with extensive visceral disease, represents a new potential therapeutic option for these patients. Based on the initial data with RP1 in melanoma, the Company initiated a registration-directed 125-patient cohort of anti-PD1 failed melanoma which is expected to read out in 2022. The signal with RP1 in anti-PD1 failed melanoma indicating that the Replimune series of product candidates may provide an effective therapy for these patients has also been further confirmed with RP2 (see below), although there are no current plans to independently develop RP2 in cutaneous melanoma.

Based on the emerging data indicating that RP1 can be safely administered to tumors in the lung and the evidence of clinical activity in patients with lung metastases from other tumor types, including in patients with anti-PD1 failed disease, the Company has commenced dosing into a 30 patient cohort of patients with anti-PD1/L1 failed NSCLC.

Updated RP2 monotherapy data continues to show compelling durability of response and new data in combination with Opdivo provides initial additional evidence of the clinical utility of RP2 in patients with hard-to-treat cancers

RP2 leverages Replimune’s platform to express an anti-CTLA-4 antibody, in addition to GALV-GP R- and GM-CSF expressed by RP1. After fully enrolling patients in the RP2 monotherapy cohort (n=9) in the Phase 1 clinical trial with RP2, 27 of the target number of 30 patients have now been enrolled in the cohort evaluating RP2 in combination with Opdivo. With limited follow up available, initial data shows:

• The data with RP2 combined with Opdivo in anti-PD1 failed cutaneous melanoma has further confirmed the signal previously seen with RP1 in this setting. Of the nine anti-PD1 failed cutaneous melanoma patients enrolled, four have so far achieved a partial response.
• The signal in uveal melanoma with RP1 combined with Opdivo and with single-agent RP2 has been further confirmed with RP2 combined with Opdivo, with clear evidence of anti-tumor activity.
• Signals of activity with RP2 combined with Opdivo have also been seen in patients with other tumor types beyond melanoma and uveal melanoma, including a partial response in anti-PD1 failed squamous cell head and neck cancer. RP2 single-agent activity had also previously been reported in a patient with anti-PD1 failed esophageal cancer and in a patient with salivary gland cancer where partial and complete responses respectively remain ongoing at 18 and 15 months from treatment initiation.

Replimune plans to conduct clinical trials with RP2/3 in patients with liver metastases from a range of tumor types

• Based on the observation of clinical responses in patients with liver metastases following treatment with both RP1 and with RP2, and the fact that treating liver metastases is a considerable unmet need in patients with advanced cancer, Replimune plans to initiate a clinical development program with RP2 and/or RP3 specifically in patients with liver metastases from various cancer types.
• The intended program includes:
  • Expanding the Phase 1/2 study with RP2 to provide further signal confirmation for the treatment of patients with liver metastases from various cancer types.
  • Plans to initiate a Phase 2 clinical trial program with RP2 and/or RP3 with cohorts of patients with liver metastases from a range of solid tumor types in the first half of 2022.
• Details of the clinical trial design will be announced at a later time and is intended to include a range of tumor types where metastasis to the liver are common. This includes highly prevalent tumors such as colorectal and other gastrointestinal cancers, lung cancer and breast cancer.
• Whether RP2 or RP3 is used for particular tumor types will depend on the clinical data as it continues to emerge.

“Patients with liver metastases across tumor types have a poorer prognosis than those without, and their treatment presents a considerable clinical challenge. Liver metastases across tumor types are also associated with systemic resistance to immune checkpoint blockade,” commented Professor Mark Middleton, Professor of Experimental Cancer Medicine in the Department of Oncology, consultant Medical Oncologist at the Oxford Cancer and Haematology Centre and Head of the Department of Oncology at the University of Oxford, who will also present the latest data with RP1 and RP2 at today’s investor event. “Treatment of patients with liver metastases with RP1 or RP2, including patients with anti-PD1/L1 failed disease, has resulted in durable and systemic clinical benefit and offers the potential to provide a new standard of care for this large patient group.”

The data from this clinical update and an overview of the rationale and development strategy for patients with liver metastases can be found in the presentation for today’s investor event, linked here.

Investor event and webcast information

Replimune will host a virtual investor event today, Thursday, June 3, 2021 at 8:00 a.m. ET. The webcast and slides will be accessible live under “Events & Presentations” on the Investors page of the Company’s website at www.replimune.com or by clicking here. A replay of the event will be available on Replimune’s website.

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