Combination of Defactinib and CH5126766
Shows Promise in Treating KRAS Mutant Solid Tumors in Clinical
Trial
Clinical Data Presentation and Regulatory
Discussions Planned for 1H 2020
Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology
or the Company), a biopharmaceutical company focused on developing
and commercializing medicines seeking to improve the survival and
quality of life of cancer patients, today announced a global
licensing agreement with Chugai Pharmaceutical Co., Ltd., (Chugai)
whereby Verastem Oncology is obtaining worldwide development and
commercialization rights to the RAF/MEK inhibitor CH5126766 (CKI27)
from Chugai currently under development for the treatment of KRAS
mutant solid tumors. The Company will host an investor call to
discuss the opportunity and a development update today (details
below).
CH5126766 in combination with Verastem Oncology’s focal adhesion
kinase (FAK) inhibitor, defactinib, is currently the subject of a
clinical study (Phase I followed by expansion cohorts) with the
expansion cohorts now ongoing in patients with KRAS mutant advanced
solid tumors, including low grade serous ovarian cancer (LGSOC),
non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).1
This clinical study of the defactinib/CH5126766 combination is
supported by the single-agent Phase 2 studies of defactinib in KRAS
mutant NSCLC2 and CH5126766 in KRAS mutant NSCLC and LGSOC.3
“Based on the single-agent defactinib results in KRAS mutant
NSCLC, we conducted an internal pre-clinical effort to identify
drug classes that were synergistic with defactinib and saw the
highest level of synergy in combination with MEK inhibitors and,
specifically, with CH5126766,” said Dan Paterson, President and
Chief Operating Officer of Verastem Oncology. “The exciting early
clinical results led to our decision to enter into a partnership
with Chugai for CH5126766 and accelerate the combination
development program for patients with KRAS mutant cancers, which
are highly aggressive and recurrent. We plan to initiate
discussions with regulatory authorities about our development plans
and to define the registration path early this year.”
“We found that MEK blockade activates FAK signaling as a
potential escape mechanism,” stated Professor Udai Banerji,
Professor of Molecular Cancer Pharmacology at The Institute of
Cancer Research and Honorary Consultant in Medical Oncology, MBBS,
MD, DNB, PhD, FRCP at The Royal Marsden NHS Foundation Trust,
London, England, and lead investigator of the clinical study.
“Based on the synergy between FAK and MEK inhibitors observed in
preclinical KRAS mutant models, we have been assessing the
combination of defactinib and CH5126766 for treatment of patients
with KRAS mutant cancers. The results to date have been encouraging
and we look forward to sharing our clinical findings, including the
response rate in an upcoming scientific presentation.”
“CH5126766 is a unique and particularly promising inhibitor of
the RAS/RAF/MEK signaling pathway,” noted Neal Rosen, MD, PhD,
Memorial Sloan Kettering Cancer Center, NY, NY. “In contrast to
other MEK inhibitors in development, CH5126766 blocks both MEK
kinase activity and the ability of RAF to phosphorylate MEK. This
unique mechanism allows CH5126766 to block MEK signaling without
the compensatory activation of MEK that appears to limit the
efficacy of other inhibitors. The clinical data with the
combination of defactinib and CH5126766 are striking and suggest
promise for patients with KRAS mutant solid tumors.”
Under the terms of the agreement, Verastem Oncology is
responsible for the development and worldwide commercialization of
CH5126766. The Company will make an upfront payment of $3M and pay
royalties to Chugai. Given the potential of the opportunity, the
Company will be evaluating various partnering strategies.
Conference Call and Webcast Information
The Verastem Oncology management team will host a conference
call and webcast on Wednesday, January 8, 2020, at 4:00 PM (ET).
The call can be accessed by dialing (877) 341-5660 (U.S. and
Canada) or (315) 625-3226 (international), five minutes prior to
the start of the call and providing the passcode 3756707 and web
PIN 1655.
The live, listen-only webcast of the conference call can be
accessed by visiting the investors section of the Company's website
at https://investor.verastem.com/events. A replay of the webcast
will be archived on the Company's website for 90 days following the
call.
About Defactinib
Defactinib is an oral small molecule inhibitor of FAK and PYK2
that is currently being evaluated as a potential combination
therapy for various solid tumors. The Company has received orphan
drug designation for defactinib in ovarian cancer and mesothelioma
in the US, EU and Australia. Preclinical research by Verastem
Oncology scientists and collaborators at world-renowned research
institutions has described the effect of FAK inhibition to enhance
immune response by decreasing immuno-suppressive cells, increasing
cytotoxic T cells, and reducing stromal density, which allows
tumor-killing immune cells to enter the tumor.4,5 A Phase 1/2
clinical trial of defactinib in combination with CH5126766 in
patients with KRAS mutant advanced solid tumors, including low
grade serous ovarian cancer (LGSOC), non-small cell lung cancer
(NSCLC) and colorectal cancer (CRC) is underway.1 The
defactinib/CH5126766 combination is supported by the single-agent
Phase 2 studies of defactinib in KRAS mutant NSCLC2 and CH5126766
in KRAS mutant NSCLC and LGSOC.3 Defactinib is also in clinical
testing in combination with pembrolizumab for treatment of patients
with pancreatic cancer, NSCLC and mesothelioma.6
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a commercial
biopharmaceutical company committed to the development and
commercialization of medicines to improve the lives of patients
diagnosed with cancer. We are driven by the strength, tenacity and
courage of those battling cancer – single-minded in our resolve to
deliver new therapies that not only keep cancer at bay, but improve
the lives of patients diagnosed with cancer. Because for us, it’s
personal.
Our first FDA approved product is now available for the
treatment of patients with certain types of indolent non-Hodgkin’s
lymphoma (iNHL). Our pipeline comprises product candidates that
seek to treat cancer by modulating the local tumor
microenvironment. For more information, please visit
www.verastem.com.
Forward looking statements notice
This press release includes forward-looking statements about
Verastem Oncology’s strategy, future plans and prospects, including
statements regarding the development and activity of Verastem
Oncology’s FAK inhibitor defactinib in combination with CH5126766 ,
and the potential commercial success of the combination therapy in
patients with KRAS mutant cancers. The words "anticipate,"
"believe," "estimate," "expect," "intend," "may," "plan,"
"predict," "project," "target," "potential," "will," "would,"
"could," "should," "continue," and similar expressions are intended
to identify forward-looking statements, although not all
forward-looking statements contain these identifying words.
Each forward-looking statement is subject to risks and
uncertainties that could cause actual results to differ materially
from those expressed or implied in such statement. Applicable risks
and uncertainties include the risks and uncertainties, among other
things, regarding: the success in the development and potential
commercialization of our product candidates, including defactinib
in combination with CH5126766; the occurrence of adverse safety
events and/or unexpected concerns that may arise from additional
data or analysis or result in unmanageable safety profiles as
compared to their levels of efficacy; our ability to obtain,
maintain and enforce patent and other intellectual property
protection for our product candidates; the scope, timing, and
outcome of any legal proceedings; decisions by regulatory
authorities regarding labeling and other matters that could affect
the availability or commercial potential of our product candidates;
whether preclinical testing of our product candidates and
preliminary or interim data from clinical trials will be predictive
of the results or success of ongoing or later clinical trials; that
the timing, scope and rate of reimbursement for our product
candidates is uncertain; that third-party payors (including
government agencies) may not reimburse; that there may be
competitive developments affecting our product candidates; that
data may not be available when expected; that enrollment of
clinical trials may take longer than expected; that our product
candidates will experience manufacturing or supply interruptions or
failures; that we will be unable to successfully initiate or
complete the clinical development and eventual commercialization of
our product candidates; that the development and commercialization
of our product candidates will take longer or cost more than
planned; that we or Chugai Pharmaceutical Co., Ltd. will fail to
fully perform under the CH5126766 license agreement; that we may
not have sufficient cash to fund our contemplated operations; that
we may be unable to make additional draws under our debt facility
or obtain adequate financing in the future through product
licensing, co-promotional arrangements, public or private equity,
debt financing or otherwise; that we will be unable to execute on
our partnering strategies for defactinib in combination with
CH5126766; that we will not pursue or submit regulatory filings for
our product candidates, and that our product candidates will not
receive regulatory approval, become commercially successful
products, or result in new treatment options being offered to
patients.
Other risks and uncertainties include those identified under the
heading "Risk Factors" in the Company’s Quarterly Report on Form
10-Q for the quarterly period ended September 30, 2019, as filed
with the Securities and Exchange Commission (SEC) on October 30,
2019, its Annual Report on Form 10-K for the year ended December
31, 2018 as filed with the SEC on March 12, 2019 and in any
subsequent filings with the SEC. The forward-looking statements
contained in this press release reflect Verastem Oncology’s views
as of the date hereof, and the Company does not assume and
specifically disclaims any obligation to update any forward-looking
statements whether as a result of new information, future events or
otherwise, except as required by law.
References
1 https://clinicaltrials.gov/, NCT03875820
2 Gerber D. et al. Phase 2 study of the focal adhesion kinase
inhibitor defactinib (VS-6063) in previously treated advanced KRAS
mutant non-small cell lung cancer. Lung Cancer 2020: 139:60-67.
3 Chénard-Poirier, M. et al. Results from the biomarker-driven
basket trial of RO5126766 (CH5127566), a potent RAF/MEK inhibitor,
in RAS- or RAF-mutated malignancies including multiple myeloma.
Journal of Clinical Oncology 2017: 35.
10.1200/JCO.2017.35.15_suppl.2506.
4 Jiang H et al. Targeting focal adhesion kinase renders
pancreatic cancers responsive to checkpoint immunotherapy. Nat Med
2016: Aug 22(8) 851-60.
5 Sulzmaier F.J. et al. FAK in cancer: mechanistic findings and
clinical applications. Nature Rev Cancer. 2014 14: 598-610.
6 www.clinicaltrials.gov, NCT02758587
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version on businesswire.com: https://www.businesswire.com/news/home/20200108005086/en/
Investors: John Doyle Vice President, Investor Relations &
Finance +1 781-469-1546 jdoyle@verastem.com
Media: Lisa Buffington Corporate Communications +1 781-292-4205
lbuffington@verastem.com
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