Replimune Group Inc. (NASDAQ: REPL), a biotechnology company
developing oncolytic immuno-gene therapies derived from its
Immulytic™ platform, today announced that the first patient has
been enrolled in its registration-directed, randomized, controlled
Phase 2 clinical trial of RP1 in combination with Regeneron and
Sanofi’s Libtayo® (cemiplimab-rwlc) compared to Libtayo alone in
patients with cutaneous squamous cell carcinoma (CSCC). The Company
also announced plans to initiate a new clinical trial of RP1 as
monotherapy in organ transplant recipients with CSCC in early 2020.
“We are pleased to announce the initiation of our first
registration-directed clinical trial for which we believe the data
generated to date for RP1 in CSCC is strongly supportive," said
Robert Coffin, Ph.D., President and CEO of Replimune. “Having
reviewed the initial data in CSCC, we also intend to initiate
a new clinical trial of single agent RP1 in organ transplant
recipients with CSCC, which we expect to begin enrolling
early next year.”
The registration-directed Phase 2 clinical trial in CSCC is a
multi-center, randomized, controlled clinical trial intended to
enroll approximately 240 patients. The study’s primary objective is
to compare the response rate following treatment with RP1 in
combination with Libtayo to the response rate achieved with Libtayo
alone. Libtayo is an anti-PD-1 therapy developed by Regeneron and
Sanofi, which was approved by the U.S. Food and Drug Administration
(FDA) last year for the treatment of patients with metastatic CSCC
or locally-advanced CSCC who are not candidates for curative
surgery or curative radiation. This clinical trial is being
conducted under the Company’s collaboration agreement with
Regeneron. The first patient in the trial has now been enrolled,
and multiple clinical trial sites in the U.S. and Australia are
open for enrollment. Additional clinical trial sites in these and
other countries will be added, with recruitment expected to take
approximately 18 to 24 months.
New Clinical Trial Planned of RP1 as Monotherapy in
Organ Transplant Recipients with CSCC
Replimune intends to initiate a new Phase 1b clinical trial of
single agent RP1 in organ transplant recipients with CSCC, for
which the clinical trial protocol has been accepted by the FDA
under the Company’s Investigational New Drug application. This
clinical trial is intended to enroll approximately 30 patients and
assess the safety and efficacy of RP1 in liver and kidney
transplant recipients with recurrent CSCC, and is expected to
initiate in the first quarter of 2020.
“CSCC is a significant unmet medical need in organ transplant
recipients, where it is the most prevalent tumor type in an
immunosuppressed population already at higher risk for malignancy
in general, and where anti-PD1 therapy provides a significant risk
of rejection of the transplanted organ,” said Howard Kaufman, MD,
Chief Medical Officer of Replimune. “We believe that single agent
RP1 has the potential to address a significant unmet need for these
patients.”
Initial Clinical Data with RP1 Strongly Supports the
Company’s Programs in CSCC
The Phase 1 part of Replimune’s Phase 1/2 clinical trial of RP1
enrolled 36 patients with advanced heavily pre-treated cancers who
have failed available therapy, evaluating treatment with RP1 alone
given up to five times, and RP1 given up to eight times in
combination with Opdivo® (nivolumab) from the second RP1 dose.
Following completion of the Phase 1 part of the clinical trial, the
Company opened enrollment for Phase 2 cohorts of 30 patients each
in patients with melanoma, non-melanoma skin cancers, bladder
cancer, and MSI-H tumors. Five patients with CSCC have been
enrolled and treated with RP1 combined with Opdivo in this clinical
trial, including one from the Phase 1 expansion in combination with
Opdivo, and four from the Phase 2 non-melanoma skin cancer cohort.
Initial results in these CSCC patients showed:
- The first patient achieved a biopsy-confirmed complete response
(CR) of extensive disease of the scalp. Clear tumor flattening was
observed after the first dose of RP1 and prior to the first dose of
Opdivo, prior to the patient ultimately achieving a CR. PD-L1 and
CD8 T cell levels were also substantially increased post-treatment
as compared to baseline (this data remains pending for the other
patients).
- The second patient achieved a partial response (PR) of bulky
bi-lateral disease in the neck, with substantial reduction observed
after the first dose of RP1 and prior to the first dose of Opdivo,
including of the uninjected tumor contralateral to the injection
site.
- The third patient had extensive and rapidly progressing
metastatic disease and died from disease progression within 6 weeks
of starting therapy.
- The fourth patient, also with bulky disease in the neck, had a
substantial reduction after the first RP1 dose, which continued to
reduce following the introduction of Opdivo.
- The fifth patient, with recurrent bone invasive CSCC of the
cheek, had substantial flattening after the first RP1 dose and has
recently initiated the combination therapy phase with RP1 and
Opdivo.
- All patients other than the third patient continue on
treatment.
The data from these patients can be found in the presentation
linked here.
“I have been highly impressed by the initial clinical data in
patients with CSCC treated with RP1,” said Professor
Kevin Harrington, PhD, of The Royal Marsden Hospital in the UK
who has treated the majority of CSCC patients in the trial. “The
clear demonstration of clinical activity in CSCC, particularly the
early and rapid tumor reductions seen in patients with advanced
disease including prior to the addition of Opdivo, combined with
the emerging safety profile, is very encouraging.”
The full Phase 1 safety, clinical efficacy and biomarker data
from this clinical trial, which Replimune believes further supports
the overall clinical development strategy for RP1, is scheduled to
be presented at The Society For Immunotherapy of Cancer Annual
Meeting in National Harbor, Maryland. on November 8, 2019.
About CSCC
CSCC is the second most common form of skin cancer and is
responsible for an estimated 7,000 deaths each year in the U.S. It
currently accounts for approximately 20% of all skin cancers in the
U.S., with the number of newly diagnosed cases expected to rise
annually. When CSCC invades deeper layers of the skin or adjacent
tissues, it is categorized as locally advanced. Once it spreads to
other distant parts of the body, it is considered metastatic.
Libtayoâ is the only approved therapy in the United States and
Brazil, and conditionally approved therapy in the European Union
and Canada, for the treatment of locally advanced or metastatic
CSCC.
About CSCC in the Organ Transplant
Population
The risk of developing cancer following solid organ transplant
has been reported to be between 2- and 4-fold higher than in the
general population. This includes increased rates of skin cancer,
Hodgkin and non-Hodgkin lymphoma, Kaposi sarcoma, and liver, lung,
and thyroid cancers. The cumulative incidence of skin cancers, such
as CSCC, increases with time from transplantation, with rates as
high as 70% after 20 years. When compared with the general
population, organ transplant recipients have a 65- to 250-fold
increased risk of developing CSCC and a 2- to 8-fold risk of
developing melanoma. In the clinical trials in which immune
checkpoint blockade drugs have been investigated, organ transplant
patients were excluded due to the potential risk of transplanted
organ rejection, and as a result, safety and efficacy has not been
formally studied. Safety and efficacy of immune checkpoint blockade
drugs in organ transplant recipients has, however, recently been
obtained from literature reports including 57 organ
transplant patients (Fisher et al 2019 J. Am. Acad. Dermatol. Jul
11 Epub ahead of print). Kidney allograft was the most commonly
reported transplant (n = 32), followed by liver (n = 20) and heart
(n = 5). While the efficacy of immune checkpoint blockade drugs was
consistent with that in the general population, 37% of cases
resulted in graft rejection and 14% resulted in death due to
rejection of the graft. The highest rate of rejection was seen in
patients with kidney transplant (41%), followed by liver (35%) and
heart (20%).
About RP1
RP1 is Replimune’s lead Immulytic™ product candidate and is
based on a proprietary new strain of herpes simplex virus
engineered to maximize tumor killing potency, the immunogenicity of
tumor cell death and the activation of a systemic anti-tumor immune
response.
About Replimune
Replimune Group Inc., headquartered in Woburn, MA, was founded
in 2015 to develop the next generation of oncolytic immune-gene
therapies for the treatment of cancer. Replimune is developing
novel, proprietary therapeutics intended to improve the direct
cancer-killing effects of selective virus replication and the
potency of the immune response to the tumor antigens released. The
Company’s Immulytic™ platform is designed to maximize systemic
immune activation, in particular to tumor neoantigens, through
robust viral-mediated immunogenic tumor cell killing and the
delivery of optimal combinations of immune-activating proteins to
the tumor and draining lymph nodes. The approach is expected to be
highly synergistic with immune checkpoint blockade and other
approaches to cancer treatment. Replimune intends to progress these
therapies rapidly through clinical development in combination with
other immuno-oncology products with complementary mechanisms of
action. For more information, please visit
www.replimune.com.
Forward Looking Statements
This 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 advancement
of our clinical trials, our plans to initiate new clinical trials,
our goals to develop and commercialize our product candidates, our
proposed scientific presentations, 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 establishing, equipping, and
operating our planned 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, and other risks set forth
under the heading “Risk Factors” of our Quarterly Report on Form
10-Q for the quarterended June 30, 2019. 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 Inquiries Chris BrinzeyWestwicke, an
ICR Company339.970.2843chris.brinzey@westwicke.com
Media InquiriesArleen Goldenberg Verge
Scientific
Communications917.548.1582agoldenberg@vergescientific.com
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