Cascadian Therapeutics Highlights Preclinical Program Presentations at the American Association for Cancer Research Annual Me...
April 05 2017 - 8:00AM
Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage
biopharmaceutical company, today announced data highlights from
presentations of preclinical data for the Company’s investigational
orally bioavailable, potent and selective checkpoint kinase 1
(Chk1) inhibitor known as CASC-578. An additional abstract
highlights data from the first public presentation on the Company’s
preclinical antibody program targeting the immune checkpoint
receptor TIGIT. These data were presented at the American
Association for Cancer Research (AACR) Annual Meeting 2017 in
Washington, DC from April 1-5, 2017.
“The research presented at AACR illustrates why we believe
CASC-578 is well positioned for IND-enabling studies,” said Scott
Peterson, Ph.D., Chief Scientific Officer of Cascadian
Therapeutics. “CASC-578 has demonstrated anti-tumor activity as a
single agent or in combination with a Wee1 inhibitor in preclinical
models of acute leukemia, mantle cell lymphoma and non-small cell
lung cancer. Furthermore, a recent GLP safety pharmacology study
indicated CASC-578 has an acceptable safety profile with no
apparent effects on QTc interval or cardiac contractility.”
Dr. Peterson added, “Our TIGIT antibody program presentation
profiles the discovery of highly potent, fully human TIGIT
antibodies, which are active as a single agent in a mouse tumor
model that is resistant to PD-1 antibody blockade.”
A summary of data highlights presented at AACR follows. To
access these poster presentations, please visit
www.cascadianrx.com.
CASC-578, a novel Chk1 inhibitor, is
active as a single agent in solid tumors and displays synergistic
anti-tumor activity in combination with Wee1 inhibition (Abstract
#295)
CASC-578 is a highly selective, picomolar inhibitor of Chk1 that
is active as a single agent and in combination with
chemotherapeutic agents in a variety of solid tumor and
hematological tumor derived cell lines. Chk1 is a protein kinase
that regulates cell cycle progression in response to DNA damage
response (DDR) signaling.
- CASC-578 is active as a single agent in non-small cell lung
cancer (NSCLC) tumor models and has shown enhanced activity with
Wee1 inhibitor in vitro and in NSCLC tumor xenograft.
The novel orally available sub-nanomolar potent and
selective checkpoint kinase 1 inhibitor CASC-578 is highly active
in mantle cell lymphoma as a single agent and in combination with
Wee1 inhibition (Abstract #297)
- Targeting the DNA Damage Response (DDR) axis with CASC-578,
alone or in combination with Wee-1 inhibition, presents a promising
therapeutic approach to treating mantle cell lymphoma and other
hematological cancers.
- CASC-478 showed compelling single agent activity on mantle cell
lymphoma cell lines – both in vitro and in vivo, including complete
tumor regression in a Jeko-1 xenograft model.
Preclinical pharmacokinetics of CASC-578, a novel
selective potent and orally bioavailable small molecule checkpoint
kinase 1 inhibitor (Abstract #4090)
- CASC-578 has desirable drug-like properties, including good
oral availability and ADME/PK properties, sub-nanomolar Chk1
inhibition, limited off-target kinase activity (>1000x selective
vs. Chk2) and balanced pharmacokinetics, potency and in vivo
efficacy.
Discovery and characterization of novel antagonistic
antibodies that bind with high affinity to human, cynomolgus and
murine TIGIT, an immune checkpoint receptor (Abstract
#578)
TIGIT is an emerging immune checkpoint target that regulates the
induction of adaptive (T cell) and innate (natural killer or NK)
cells. CASC-TIGIT antibodies represent a potentially attractive
approach to immune checkpoint inhibition.
- Novel, high-affinity, fully human antibodies have been
identified that block TIGIT function.
- Lead antibody binds with sub-nM affinity to human, cynomolgus
monkey and mouse TIGIT and blocks ligand interactions and signaling
in T cells
- Potent single-agent activity in mouse model that is resistant
to PD-1 antibody.
About Cascadian Therapeutics
Cascadian Therapeutics is a clinical-stage biopharmaceutical
company dedicated to developing innovative product candidates for
the treatment of cancer. Its lead product candidate, tucatinib, is
an investigational oral, selective small molecule HER2 inhibitor.
Cascadian Therapeutics is conducting a randomized, double-blind,
controlled pivotal clinical trial called HER2CLIMB, which is
comparing tucatinib vs. placebo, each in combination with
capecitabine and trastuzumab, in patients with locally advanced or
metastatic HER2-positive breast cancer with and without brain
metastases, who have previously been treated with a taxane,
trastuzumab, pertuzumab and T-DM1. Additional details on
HER2CLIMB can be found at www.HER2CLIMB.com or
www.clinicaltrials.gov. For more information, please
visit www.cascadianrx.com.
Forward-Looking Statements
In order to provide Cascadian Therapeutics' investors with an
understanding of its current results and future prospects, this
release contains statements that are forward-looking. Any
statements contained in this press release that are not statements
of historical fact may be deemed to be forward-looking statements.
Words such as "believes," "anticipates," "plans," "expects,"
"will," "intends," "potential," "possible" and similar expressions
are intended to identify forward-looking statements. These
forward-looking statements include Cascadian Therapeutics'
expectations regarding clinical development activities, and the
potential benefits of CASC-578 and CASC-TIGIT antibodies.
Forward-looking statements involve risks and uncertainties related
to Cascadian Therapeutics' business and the general economic
environment, many of which are beyond its control. These risks,
uncertainties and other factors could cause Cascadian Therapeutics'
actual results to differ materially from those projected in
forward-looking statements, including the risks associated with the
costs and expenses of developing its product candidates, the
adequacy of financing and cash, cash equivalents and investments,
changes in general accounting policies, general economic factors,
achievement of the results it anticipates from its preclinical
development and clinical trials of its product candidates and its
ability to adequately obtain and protect its intellectual property
rights. Although Cascadian Therapeutics believes that the
forward-looking statements contained herein are reasonable as of
the date hereof, it can give no assurance that its expectations are
correct. All forward-looking statements are expressly qualified in
their entirety by this cautionary statement. For a detailed
description of Cascadian Therapeutics' risks and uncertainties, you
should review the documents filed by Cascadian Therapeutics with
the securities regulators in the United States on EDGAR and in
Canada on SEDAR. Cascadian Therapeutics does not undertake any
obligation to publicly update its forward-looking statements based
on events or circumstances after the date hereof, except to the
extent required by law.
Investor and Media Contact:
Monique Greer
Cascadian Therapeutics
206-801-2107
mgreer@cascadianrx.com
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