Full Press Release Details
New Clinical Data, Broad Program Update and Future Development Strategy for its Tumor-Directed Oncolytic Immunotherapies
with Opdivo (nivolumab) continues to demonstrate deep and durable responses in patients with melanoma and non-melanoma skin cancers
(NMSC); new positive initial data in patients with anti-PD1 failed NMSC
shows clinical activity with RP1 monotherapy in solid organ transplant recipients with cutaneous squamous cell carcinoma (CSCC)
development planned for RP2/RP3 in hard-to-treat tumor types
event to be held today at 8:00 am ET
Woburn, MA, March 30, 2022
- Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel class
of tumor-directed oncolytic immunotherapies, today announced updated data from completed cohorts of the Phase 2 part of the IGNYTE clinical
trial in non-melanoma skin cancer (NMSC) and melanoma. Additionally, the Company announced new data from the ongoing clinical trial in
anti-PD1 failed NMSC and from the ARTACUS clinical trial, a Phase 1b/2 trial of RP1 (vusolimogene oderparepvec) as monotherapy in solid
organ transplant recipients with skin cancer. The Company also provided a detailed overview of its RP2/3 Phase 2 development plans. A
virtual investor event will be held today at 8:00 a.m. ET to discuss the updated data.
"Today we are pleased to provide
a comprehensive clinical update across our pipeline that continues to demonstrate the potential of our oncolytic immunotherapy platform
to address a broad range of cancers," said Philip Astley-Sparke CEO of Replimune. "Updated data from our IGNYTE cohorts in
anti-PD1 na ve cutaneous squamous cell carcinoma (CSCC) and anti-PD1 failed melanoma continue to support our two registration-directed
studies in these settings. New data presented today also supports our ambition to establish a broad franchise with RP1 in skin cancer,
with activity demonstrated in a variety of anti-PD-1/L1 failed non-melanoma skin cancers as well initial data demonstrating utility of
RP1 as a monotherapy in solid organ transplant recipient patients where anti-PD1 is contra-indicated. We have seen strong initial data
with RP2 monotherapy and in combination with Opdivo which supports the advancement of RP2/3 into new and difficult to treat
tumor types. As a result, we are announcing a broad RP2/3 Phase 2 development plan including new clinical trials in advanced/metastatic
squamous cell carcinoma of the head and neck (SCCHN), hepatocellular carcinoma (HCC), and colorectal cancer (CRC). We look forward to
initiating our clinical trials in these large and underserved markets and delivering meaningful new therapies to patients."
The Company is pursuing the development
of RP1 for the treatment of multiple skin cancers alone and in combination with anti-PD1 therapy. The Company is today presenting updated
data from the Phase 2 part of the IGNYTE clinical trial combined with Opdivo.
"The frequency, depth and durability
of responses seen across a range of skin cancers with RP1 alone and combined with Opdivo, including in anti-PD1 failed disease,
suggests broad utility of the approach," said Professor Kevin Harrington of The Institute of Cancer Research, London and The Royal
Marsden NHS Foundation Trust, who will today present the new RP1 data. "Based on this data, I look forward to seeing the results
of the registration-directed studies in CSCC and anti-PD1 failed melanoma and the potential provision of a new treatment paradigm for
RP2/3 Development Strategy
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. The Company will review data from the
Phase 1 clinical trial of RP2 alone and in combination with Opdivo and announce its development strategy for the Phase 2 clinical
development of RP2/3. After fully enrolling patients in the RP2 monotherapy (n=9) and combination with Opdivo (n=30) cohorts in
the Phase 1 clinical trial with RP2 (data presented in Nov 2020 and Nov 2021), a further cohort of Phase 1 patients with tumor types
of particular interest (gastro-intestinal [GI] cancers, breast cancer, lung cancer, head and neck cancer and uveal melanoma) was recently
opened, with the first patients having been enrolled and from which initial data is expected later in the year.
RP3 further expresses CD40L and 4-1BBL
in addition to anti-CTLA-4 and GALV-GP R-, is intended to induce a broad and potent anti-tumor immune response, and for which a Phase
1 clinical trial is also underway. As monotherapy the Company has dosed three patients at a low dose and three at a high dose in a variety
of hard-to-treat salvage therapy patients with injections of RP3 into both superficial and deep tumors, including injections into the
lung and liver. The higher dose level has been confirmed as the recommended Phase 2 dose (RP2D). A seventh patient has also recently
been enrolled such that three HSV seronegative patients in total have been treated at the RP2D. The first six patients enrolled in this
Phase 1 clinical trial had heavily pre-treated advanced sarcoma, esophageal cancer, colorectal cancer, head and neck cancer and melanoma.
Three of the six patients (with melanoma and colorectal cancer) died due to disease progression approximately two to four months from
initiating the study, indicating the advanced nature of disease of the patients enrolled. Two other patients also had rapid progressive
disease, and one patient with esophageal cancer had stable disease out to one year. Thus, while no new safety signals having been observed
as compared to RP1 or RP2, based on the patients enrolled it is too early to draw any conclusions as to efficacy. Enrollment into the
cohort of patients dosed with RP3 combined with Opdivo has also recently commenced. This cohort will focus on enrolling patients
with GI cancers, breast cancer, lung cancer and head and neck cancer. Initial data for the combination cohort is expected towards the
end of the year. Additional patients will also be dosed as monotherapy.
RP2/3 Phase 2 Clinical Development
The Phase 2 development plan for RP2
and RP3 is intended to target tumor types in large underserved markets, including where liver metastases are common, as well as patients
with primary liver cancer, and patients with early disease where the objective of treatment would be to achieve 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 following indications for signal
finding single arm Phase 2 clinical trials have been identified which meet these criteria:
Replimune has a clinical trial collaboration
and supply agreement with BMS for the supply of Opdivo in its clinical trial program with RP2/3.
The RP2/3 phase 2 program is expected
to initiate around the year end.
The Company believes that development
in this combination of clinical indications provides a risk balanced approach to delivering substantial value across a range of underserved
tumor types with early to later stage disease, each with clear unmet need, and in combination with a range of other anti-cancer approaches
where clinical synergy may reasonably be expected to be seen. The decision as to whether RP2 or RP3 will be used in these clinical trials
will be made later in the year, following generation and analysis of further clinical data with RP2 and RP3 in their respective ongoing
Phase 1 clinical trials.
"RP2 and RP3 represent an exciting
new potential approach to treating a range of difficult to treat tumor types, including head and neck cancer, gastro-intestinal cancer
and HCC patients who are underserved by current treatment approaches," said Dr. Muneeb Ahmed, Chief of Vascular and Interventional
Radiology at Beth Israel Deaconess Medical Center and Associate Professor at Harvard Medical School. "I look forward to participating
in the planned Phase 2 program as we explore the breadth of clinical activity with RP2/3 across a range of early to later stage disease
The data from this clinical update and
an overview of the rationale and the RP2/3 development strategy can be found in the presentation for today's investor event, linked
Opdivo is a trademark of
Bristol-Myers Squibb Company.
Investor event and webcast information
Replimune will host a virtual investor
event today, Wednesday, March 30, 2022 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.
CERPASS is Replimune's registration-directed
randomized, global Phase 2 clinical study to compare the effects of Libtayo alone versus a combination of Libtayo and Replimune's
investigational oncolytic immunotherapy RP1. The clinical trial is enrolling 180 patients with locally advanced or metastatic cutaneous
squamous cell carcinoma (CSCC) who are na ve to anti-PD1 therapy. The clinical trial will evaluate complete response (CR) rate and
overall response rate (ORR) as its two primary efficacy endpoints as assessed by independent review, as well as duration of response,
progression-free survival (PFS), and overall survival (OS) as secondary endpoints. The study is being conducted under a clinical trial
collaboration agreement with Regeneron in which the costs of the trial are shared and full commercial rights retained by Replimune. Libtayo
is being jointly developed by Regeneron and Sanofi. Libtayo is a registered trademark of Regeneron.
IGNYTE is Replimune's multi-cohort
Phase 1/2 trial of RP1 plus Opdivo . There are 4 tumor specific cohorts currently enrolling in this clinical trial including
a 125-patient cohort in anti-PD1 failed cutaneous melanoma. This cohort was initiated after completing enrollment in a prior Phase 2
cohort in the same clinical trial of approximately 30 patients with melanoma. The additional cohorts are in non-melanoma skin cancers
which includes both na ve and anti-PD1 failed CSCC, in anti-PD1 failed microsatellite instability high, or MSI-H/dMMR tumors and
anti-PD(L)-1 failed non-small cell lung cancer (NSCLC). This trial is being conducted under a collaboration and supply agreement with