GFH375 (VS-7375), a potential
best-in-class oral KRAS G12D (ON/OFF) inhibitor, demonstrated
potent anti-tumor activity in pancreatic and colorectal cancer
models; Partner GenFleet plans to submit IND in H1 2024
Preclinical data demonstrate strong anti-tumor
activity of avutometinib with FAK inhibitor combination with
standard-of-care chemotherapy in pancreatic cancer models; supports
the scientific rationale for ongoing RAMP 205 Phase 1/2 trial
Avutometinib with FAK inhibitor combination
overcomes resistance to BRAF and MEK inhibitors and to
immunotherapy in patient-derived melanoma models
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients, today announced
that preclinical data will be presented in five posters at the
American Association for Cancer Research (AACR) Annual Meeting 2024
to be held on April 5-10 in San Diego, California. The
presentations will highlight anti-tumor efficacy of GFH375
(VS-7375), a potent and selective orally bioavailable KRAS G12D
(ON/OFF) inhibitor, and will also show data of RAF/MEK clamp plus
FAK inhibition in pancreatic ductal adenocarcinoma (PDAC) models
supporting the ongoing RAMP 205 trial. Additional presentations
will support the use of avutometinib and FAK inhibitor combination
in cutaneous melanoma models to overcome resistance to BRAF and MEK
inhibitors, resistance to immunotherapy, and brain metastasis.
“For the first time, GenFleet and Verastem will present potency,
selectivity, anti-tumor efficacy, and bioavailability data on
GFH375 (VS-7375), a potential best-in-class orally active KRAS G12D
(ON/OFF) inhibitor. We look forward to an IND submission by
GenFleet in China in H1 2024,” said Jonathan Pachter, Ph.D., chief
scientific officer of Verastem Oncology. “Additionally, preclinical
data will be presented demonstrating that the combination of
avutometinib and a FAK inhibitor with standard-of-care chemotherapy
can induce tumor regressions in pancreatic cancer models, providing
the scientific rationale for the ongoing RAMP 205 Phase 1/2 study
evaluating the combination of avutometinib, defactinib,
gemcitabine, and nab-paclitaxel in first-line metastatic pancreatic
ductal adenocarcinoma. Collectively, these data from the five
posters build on our desire to advance treatments that target the
RAS/MAPK pathway and provide new options for patients with RAS/MAPK
driven cancers.”
Key Data Presentations:
- Title: GFH375 (VS-7375): An oral, selective KRAS G12D
(ON/OFF) inhibitor with potent anti-tumor efficacy
- Abstract #: 3318
- Date/Time: Monday, April 8, 2024, 1:30 – 5:00 p.m.
PDT
- Sponsor: GenFleet Therapeutics
- Title: Combined inhibition of RAF, MEK and FAK increases
PDAC responsiveness to cytotoxic- and immune therapy
- Abstract #: 2899
- Date/Time: Monday, April 8, 2024, 1:30 – 5:00 p.m.
PDT
- Institution: Siteman Cancer Center, Department of
Medicine, Washington University School of Medicine
- Title: Combined Inhibition of RAF, MEK, and FAK
attenuates melanoma brain metastases and prolongs survival in
preclinical models
- Abstract #: 4127
- Date/Time: Tuesday, April 9, 2024, 9:00 a.m. – 12:30
p.m. PDT
- Institution: Huntsman Cancer Institute, Department of
Surgery, University of Utah School of Medicine
- Title: A novel combination therapy targeting RAF, MEK,
and FAK to overcome skin cutaneous melanoma treatment
resistance
- Abstract #: 4745
- Date/Time: Tuesday, April 9, 2024, 9:00 a.m. – 12:30
p.m. PDT
- Institution: Moores Cancer Center-Department of
Pharmacology, University of California San Diego
- Title: The SOS1 Inhibitor MRTX0902 Demonstrates Activity
Across Cancer Models with Mutations in Proximal Components of the
RAS-MAPK pathway
- Abstract #: 7268
- Date/Time: Wednesday, April 10, 2024, 9:00 a.m. – 12:30
p.m. PDT
- Sponsor: Mirati Therapeutics, Inc.
The accepted abstracts are available on the AACR conference
website:
https://www.aacr.org/meeting/aacr-annual-meeting-2024/.
About GFH375 (VS-7375)
GFH375 (VS-7375) is a potential best-in-class, potent and
selective oral KRAS G12D (ON/OFF) inhibitor, identified as the lead
program from the Verastem Oncology discovery and development
collaboration with GenFleet Therapeutics. GenFleet plans to submit
an IND in China for GFH375 (VS-7375) in the first half of 2024, and
upon approval GenFleet is expected to initiate a Phase 1 trial in
China in the second half of 2024. The collaboration includes three
discovery programs, the first being the KRAS G12D inhibitor, and
will provide Verastem Oncology with exclusive options to obtain
licenses to each of the three compounds in the collaboration after
successful completion of pre-determined milestones in Phase 1
trials. The licenses would give Verastem Oncology development and
commercialization rights outside of the GenFleet markets of
mainland China, Hong Kong, Macau, and Taiwan.
About the Avutometinib and Defactinib Combination
Avutometinib is a RAF/MEK clamp that induces inactive complexes
of MEK with ARAF, BRAF and CRAF potentially creating a more
complete and durable anti-tumor response through maximal RAS/MAPK
pathway inhibition. In contrast to currently available MEK-only
inhibitors, avutometinib blocks both MEK kinase activity and the
ability of RAF to phosphorylate MEK. This unique mechanism allows
avutometinib to block MEK signaling without the compensatory
activation of MEK that appears to limit the efficacy of other
MEK-only inhibitors. The U.S. Food and Drug Administration (FDA)
granted Breakthrough Therapy designation for the combination of
Verastem Oncology’s investigational RAF/MEK clamp avutometinib,
with defactinib, a selective FAK inhibitor, for the treatment of
all patients with recurrent low-grade serous ovarian cancer (LGSOC)
regardless of KRAS status after one or more prior lines of therapy,
including platinum-based chemotherapy.
Verastem Oncology is currently conducting clinical trials with
its RAF/MEK clamp avutometinib in RAS/MAPK driven tumors as part of
its (Raf And Mek Program). RAMP 301
(NCT06072781) is a Phase 3 confirmatory trial evaluating the
combination of avutometinib and defactinib versus standard
chemotherapy or hormonal therapy for the treatment of recurrent
LGSOC. RAMP 201 (NCT04625270) is a Phase 2 registration-directed
trial of avutometinib in combination with defactinib in patients
with recurrent LGSOC and has completed enrollment in the dose
optimization, expansion phase, and low-dose evaluation cohorts.
Verastem Oncology has established clinical collaborations with
Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) and KRAZATI™
(adagrasib) in combination with avutometinib in KRAS G12C mutant
NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204
(NCT05375994) trials, respectively. Supported by the “Therapeutic
Accelerator Award” Verastem Oncology received from PanCAN, the
Company is conducting RAMP 205 (NCT05669482), a Phase 1b/2 clinical
trial evaluating avutometinib and defactinib with
gemcitabine/nab-paclitaxel in patients with front-line metastatic
pancreatic cancer.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a late-stage development
biopharmaceutical company committed to the development and
commercialization of new medicines to improve the lives of patients
diagnosed with cancer. Our pipeline is focused on novel small
molecule drugs that inhibit critical signaling pathways in cancer
that promote cancer cell survival and tumor growth, including
RAF/MEK inhibition and FAK inhibition. For more information, please
visit www.verastem.com and follow us on LinkedIn.
Forward-Looking Statements Notice
This press release includes forward-looking statements about
Verastem Oncology’s strategy, future plans and prospects, including
statements related to the expected outcome and benefits of the
collaboration with GenFleet, Amgen and Mirati, the potential
clinical value of various of its clinical trials, the timing of
commencing and completing trials, including topline data reports,
interactions with regulators and the potential for and timing of
commercialization of product candidates. The words "anticipate,"
"believe," "estimate," "expect," "intend," "may," "plan,"
"predict," "project," "target," "potential," "will," "would,"
"could," "should," "continue," “can,” “promising” 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 avutometinib in combination with other
compounds, including defactinib, LUMAKRAS™ and others; the
uncertainties inherent in research and development, such as
negative or unexpected results of clinical trials, the occurrence
or timing of applications for our product candidates that may be
filed with regulatory authorities in any jurisdictions; whether and
when regulatory authorities in any jurisdictions may approve any
such applications that may be filed for our product candidates,
and, if approved, whether our product candidates will be
commercially successful in such jurisdictions; 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 trial design, labeling and other matters that
could affect the timing, 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 cause adverse safety events and/or unexpected
concerns may arise from additional data or analysis, or result in
unmanageable safety profiles as compared to their levels of
efficacy; that our product candidates may experience manufacturing
or supply interruptions or failures; that any of our third party
contract research organizations, contract manufacturing
organizations, clinical sites, or contractors, among others, who we
rely on fail to fully perform; that we face substantial
competition, which may result in others developing or
commercializing products before or more successfully than we do
which could result in reduced market share or market potential for
our product candidates; 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, including as a result of conducting
additional studies; that we may not have sufficient cash to fund
our contemplated operations; that we may not attract and retain
high quality personnel; that we or Chugai Pharmaceutical Co., Ltd.
will fail to fully perform under the avutometinib license
agreement; that our target market for our product candidates might
be smaller than we are presently estimating; that Secura Bio, Inc.
will fail to fully perform under the asset purchase agreement with
Secura Bio, Inc., including in relation to milestone payments; that
we will not see a return on investment on the payments we have and
may continue to make pursuant to the collaboration and option
agreement with GenFleet or that GenFleet will fail to fully perform
under the agreement; that we may be unable to obtain adequate
financing in the future through product licensing, co-promotional
arrangements, public or private equity, debt financing or
otherwise; 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 Annual Report on Form 10-K
for the year ended December 31, 2022 as filed with the Securities
and Exchange Commission (SEC) on March 14, 2023 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20240305290262/en/
For Investor and Media Inquiries: Julissa Viana Vice
President, Corporate Communications and Investor Relations
investors@verastem.com or media@verastem.com
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