Replimune Group, Inc. (NASDAQ: REPL), a clinical stage
biotechnology company pioneering the development of a novel
portfolio of oncolytic immunotherapies, today announced results
from the primary analysis of the CERPASS trial evaluating RP1 in
combination with cemiplimab for the treatment of locally advanced
or metastatic cutaneous squamous cell carcinoma (CSCC) and provided
initial data for all patients in the anti-PD1 failed melanoma
cohort of the IGNYTE clinical trial. The company also shared a new
data snapshot from the IGNYTE cohort of anti-PD1 failed
non-melanoma skin cancer (NMSC) patients and data from the ARTACUS
trial evaluating RP1 as monotherapy for skin cancer in patients who
have had solid organ or hematopoietic cell transplants.
“Data from across our skin cancer program clearly show that RP1
is an active agent both as monotherapy and in combination with
anti-PD1 therapy in multiple settings, giving us further confidence
in the potential of RP1 to be an important treatment option for
skin cancer patients,” said Philip Astley-Sparke, CEO of Replimune.
“The overall data from the CERPASS study indicate that treatment
with RP1 in combination with cemiplimab led to clinically
meaningful activity with a higher rate of complete responses and
favorable duration of response versus cemiplimab alone. Further,
the positive data from the full 140 patient anti-PD1 failed
melanoma cohort in the IGNYTE trial shows approximately 1 in 3
patients treated with RP1 in combination with nivolumab achieved a
durable response which we believe is supportive of our planned
submission of a BLA in 2H 2024 for this high unmet need patient
population.”
Results from the CERPASS Trial in CSCCThe
CERPASS clinical trial was a global, randomized study enrolling 211
patients randomized 2 to 1 to receive RP1 plus cemiplimab versus
cemiplimab standard of care for patients with locally advanced or
metastatic CSCC. The CERPASS study was conducted under a Master
Clinical Trial Collaboration and Supply Agreement with Regeneron
Pharmaceuticals.
The study did not meet either of the two primary endpoints of
complete response rate (CRR) or overall response rate (ORR) as
assessed by blinded independent central review. RP1 in combination
with cemiplimab increased the CRR versus cemiplimab alone (38.1%
vs. 25%, p=0.040), which was just short of the required threshold
for statistical significance in this study (p<0.025). Notably,
among the 83 patients with locally advanced disease, the complete
response rate in the RP1 plus cemiplimab group was 48.1% versus
22.6% in the cemiplimab only group. The ORR was comparable between
the two study groups (52.5% for RP1 plus cemiplimab vs. 51.4% for
cemiplimab alone, p=0.692). Importantly, RP1 in combination with
cemiplimab also increased duration of response (DOR) as compared to
cemiplimab alone (hazard ratio 0.45), however, these data are
immature and further follow up is required. Of note, RP1 plus
cemiplimab provided particularly meaningful clinical activity for
many patients with difficult to treat, disfiguring tumors that
typically have the greatest impact on quality of life, given their
size and location.
There was also an imbalance in baseline tumor burden across the
treatment groups which may have impacted the number of responses
seen. A significantly greater number of patients with high baseline
tumor burden (larger than 10 cm in total diameter) were treated in
the RP1 plus cemiplimab group as compared to the cemiplimab alone
group (23% of RP1 plus cemiplimab treated patients had high
baseline tumor burden vs. 12.5% of cemiplimab only patients). In a
pre-specified analysis, patients with total tumor burden less than
or equal to 10 cm had a CRR of 43% in the RP1 plus cemiplimab group
versus 27% in the cemiplimab only group. For those patients with
tumor burden greater than 10 cm, CRR was 21.9% in the RP1 plus
cemiplimab group versus 11.1% in the cemiplimab only group.
The trial will continue as planned to assess DOR, progression
free survival (PFS) and overall survival (OS) with greater
maturity.
Treatment-related adverse events associated with RP1 plus
cemiplimab were predominantly transient Grade 1-2 “flu-like”
symptoms being seen as compared to cemiplimab alone, including
fatigue, pyrexia, pruritis, nausea, hypothyroidism, chills,
diarrhea, asthenia, infusion-related reaction, rash, rash
maculo-popular, and vomiting. There was a range of Grade 3 events
occurring in one patient each in the RP1 plus cemiplimab arm
(16.5%), except for fatigue, rash maculo-popular, and
immune-mediated hepatitis which occurred in 2 patients each. Grade
4 events were one each of immune-mediated myocarditis and
myocarditis. There were no Grade 5 treatment-related adverse
events.
Initial Data from All Patients in the IGNYTE Cohort of
RP1 in Anti-PD1 Failed MelanomaThe registration directed
anti-PD1 failed melanoma cohort from the IGNYTE clinical trial
includes 140 patients and completed enrollment earlier this year.
Data are also included for 16 patients from the initial cohort
representing a total of 156 patients in this treatment setting.
In the RP1 plus nivolumab group (n=156), the ORR was 31.4% with
a CR rate of 12% showing activity consistent with the prior
snapshot of 91 anti-PD1 failed melanoma patients. As of this
report, there are 5 patients still on study with the opportunity
for response. In the full population, almost half of patients
failed combination therapy with ipilimumab plus nivolumab as
compared to the earlier snapshot where approximately a third were
ipilimumab and nivolumab failures. Approximately 50% of patients
experienced clinical benefit, defined as CR, PR, or stable disease
(SD). Of responders, 100% are ongoing at more than six months with
78% of responses still ongoing as of November 6, 2023. Responses
reported for this snapshot were investigator-assessed. RP1 combined
with nivolumab continues to be well-tolerated, with mainly Grade
1-2 “on target” side effects, observed.
In this cohort, responses were seen across disease stages,
including complete responses in patients with stage IVM1b/c
disease. Responses are highly durable with median DOR greater than
24 months, and often deepening over time. Preliminary OS data are
promising. The primary analysis by independent central review will
be triggered once all patients have had at least 12 months of
follow up in March 2024.
Treatment-related adverse events associated with RP1 in
combination with nivolumab in this cohort were predominantly Grade
1-2 constitutional type events (> 5% of patients), including
fatigue, chills, pyrexia, nausea, influenza-like illness, pruritis,
diarrhea, injection site pain, vomiting, headache, rash, myalgia,
asthenia, decreased appetite, and injection site reaction, with a
low incidence of Grade 3-5 events. Grade 4 events were one each of
lipase increased, cytokine release syndrome, myocarditis and
hepatic cytosis and the Grade 5 treatment-related adverse event was
one event of immune mediated myocarditis, which was attributed to
nivolumab and is an expected immune mediated adverse event for
nivolumab.
IGNYTE Regulatory UpdateThe company recently
participated in a Type C meeting with the U.S. Food and Drug
Administration (FDA). During the discussion, the FDA acknowledged
that the anti-PD1 failed melanoma population is one of unmet need.
The FDA agreed with an anti-PD1 failed melanoma confirmatory study
design concept consisting of a 2-arm randomized trial with
physician’s choice of treatment as a comparator arm in the study
population. Full protocol development is currently underway. The
proposed Phase 3 confirmatory trial should be initiated by the time
of an application under the accelerated approval pathway. After
following all patients for at least 12 months and pending central
review by RECIST v1.1, BLA submission for RP1 in combination with
nivolumab is planned for 2H 2022.
Data Overview from Phase 1/2 ARTACUS Clinical Trial of
RP1 MonotherapyAs previously presented, treatment with RP1
monotherapy in the Phase 1/2 ARTACUS clinical trial in skin cancer
patients who have had solid organ or hematopoietic cell transplants
led to an ORR of 34.8% (8 of 23 evaluable patients, including 5 CRs
and 3 partial responses). These patients are generally not eligible
for anti-PD1 therapy which could precipitate transplant rejection.
Most responses were ongoing as of the data cutoff date of September
18, 2023. There was no evidence of allograft rejection. RP1
monotherapy was well tolerated, and the safety profile was similar
to that observed in non-immunocompromised patients with advanced
skin cancers.
Initial Data Snapshot from the IGNYTE Cohort of RP1 in
Anti-PD1 Failed NMSCThe NMSC data reported from the IGNYTE
trial is from the first 30 patients enrolled in the cohort, all
with at least 6 months of follow up, including patients with CSCC,
MCC, basal cell carcinoma, and angiosarcoma. The data show that
treatment with RP1 in combination with nivolumab led to an ORR of
30% (9 of 30 patients) which is consistent with data from the
anti-PD1 failed melanoma cohort with approximately a third of
patients responding and 60% demonstrating clinical benefit. The
combination of RP1 and nivolumab was well tolerated in this patient
population with a safety profile consistent with the overall
experience seen with this treatment regimen to date in skin
cancer.
Portfolio UpdateAs previously shared, the
company presented strong data with RP2 in uveal melanoma during a
plenary session at the 20th International Congress of the Society
for Melanoma Research in November. Based on the data in this
population, planning is underway for a randomized controlled
clinical trial of RP2 in second line (2L) uveal melanoma with the
company intending to investigate other rare cancer opportunities as
target indications.
To focus on near term priority studies, including the RP1 Phase
3 confirmatory study in anti-PD1 failed melanoma and the RP2
registrational study in uveal melanoma, RP2/3 development in
squamous cell carcinoma of the head and neck (SCCHN) and colorectal
cancer (CRC) is being discontinued. The 2L hepatocellular carcinoma
(HCC) trial will continue with RP2 only. At this time, development
of RP3 will be discontinued.
As of September 30, 2023, cash and investments total $496.8M. We
expect that the reprioritization of the portfolio will extend the
cash runway into early 2026.
Conference Call DetailsReplimune will host a
conference call and webcast today at 8:00 a.m. ET. Listeners can
register for the conference call via this link. Analysts
wishing to participate in the question and answer session should
use this link. The webcast and slides of the presentation can
be accessed in the Investors section of Replimune’s website
at www.replimune.com. A replay of the webcast will be
available on Replimune’s investor website approximately two hours
after the call's conclusion. Those who plan on participating are
advised to join 15 minutes prior to the start time.
About Replimune Replimune
Group, Inc., headquartered in Woburn, MA, was founded in 2015
with the mission to transform cancer treatment by pioneering the
development of a novel portfolio of oncolytic immunotherapies.
Replimune’s proprietary RPx platform is based on a potent HSV-1
backbone intended to maximize immunogenic cell death and the
induction of a systemic anti-tumor immune response. The RPx
platform is designed to have a unique dual local and systemic
mechanism of action (MOA) consisting of direct selective
virus-mediated killing of the tumor resulting in the release of
tumor derived antigens and altering of the tumor microenvironment
to ignite a strong and durable systemic response. This MOA is
expected to be synergistic with most established and experimental
cancer treatment modalities, leading to the versatility to be
developed alone or combined with a variety of other treatment
options. For more information, please
visit www.replimune.com.
Forward Looking StatementsThis press release
contains forward looking statements within the meaning of
Section 27A of the Securities Act of 1933, as amended, and
Section 21E of the Securities Exchange Act of 1934, as
amended, including statements regarding our expectations about our
cash runway, the design and advancement of our clinical trials, the
timing and sufficiency of our clinical trial outcomes to support
potential approval of any of our product candidates, our goals to
develop and commercialize our product candidates and the likelihood
of the benefit of our product candidates to patients, patient
enrollments in our existing and planned clinical trials and the
timing thereof, our belief that RP1 can be an important treatment
option for skin cancer patients, the timing of a submission of a
BLA for our IGNYTE cohort, if any, and other statements identified
by words such as “could,” “expects,” “intends,” “may,” “plans,”
“potential,” “should,” “will,” “would,” or similar expressions and
the negatives of those terms. Forward-looking statements are not
promises or guarantees of future performance, and are subject to a
variety of risks and uncertainties, many of which are beyond our
control, and which could cause actual results to differ materially
from those contemplated in such forward-looking statements. These
factors include risks related to our limited operating history, our
ability to generate positive clinical trial results for our product
candidates, the costs and timing of operating our in-house
manufacturing facility, the timing and scope of regulatory
approvals, changes in laws and regulations to which we are subject,
competitive pressures, our ability to identify additional product
candidates, political and global macro factors and related public
health issues, the affects of the discontinuation of certain of our
trials and our development of RP3, and other risks as may be
detailed from time to time in our Annual Reports on Form 10-K
and Quarterly Reports on Form 10-Q and other reports we file
with the Securities and Exchange Commission. Our actual results
could differ materially from the results described in or implied by
such forward-looking statements. Forward-looking statements speak
only as of the date hereof, and, except as required by law, we
undertake no obligation to update or revise these forward-looking
statements.
Investor InquiriesChris BrinzeyICR
Westwicke339.970.2843chris.brinzey@westwicke.com
Media InquiriesArleen
GoldenbergReplimune917.548.1582media@replimune.com
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