CAMBRIDGE, Mass., Dec. 22, 2020 /PRNewswire/ -- Leap Therapeutics,
Inc. (Nasdaq:LPTX), a biotechnology company focused on developing
targeted and immuno-oncology therapeutics, today announced the
publication in Molecular Cancer Research of preclinical
results from studies of human and murine versions of DKN-01, a
humanized monoclonal antibody that binds to and blocks the activity
of the Dickkopf-1 (DKK1)
protein. The article, entitled "mDKN-01, a Novel
Anti-DKK1 Monoclonal Antibody,
Enhances Innate Immune Responses in the Tumor Microenvironment," is
available online. The studies characterized a murine version of
DKN-01 (mDKN-01) in order to better understand the mechanism of
action (MOA) of DKK1 inhibition in
two mouse cancer models.
"In the current studies, we demonstrated that the inhibition of
DKK1 with a monoclonal antibody in a
syngeneic melanoma model led to tumor growth inhibition (TGI)
requiring host NK1.1 cells, but not T or B cells, and provided
enhanced efficacy when combined with a PD-1 inhibitor. In a second
model, the antibody was a potent inhibitor of breast cancer
metastases to lung," said Walter
Newman, Ph.D., Senior Research Fellow of Leap. "These
results show the innate immune system effects of mDKN-01 and
support further exploration as to how DKN-01 results in the
activation of NK cells and mitigation of metastatic spread."
DKK1, a secreted modulator of
Wnt/Beta-catenin and CKAP4/PI3K/AKT signaling, is overexpressed in
many cancers, is associated with worse clinical outcomes, and has
been shown to have immunosuppressive effects. To better understand
the DKN-01 MOA, Leap engineered a murine framework for the DKN-01
CDR domains and examined the efficacy of mDKN-01 in a mouse model
of melanoma. These studies show that targeting DKK1 suppresses tumor growth, reduces
intra-tumoral myeloid-derived suppressor cells (MDSC) in the tumor
and spleen, activates NK cells, and up-regulates PD-L1 expression
on MDSC. Tumor cell signaling analysis in these studies indicates
that mDKN-01 is not acting as a Wnt/B-catenin pathway agonist, but
is inducing a collection of favorable immune changes in the tumor
microenvironment.
In the animal model studied, mDKN-01 and an anti-PD-1 antibody
demonstrated additive TGI effects. A clinical trial of DKN-01 plus
pembrolizumab, an anti-PD-1 antibody, has recently been completed
in esophagogastric cancer patients with promising results in
patients whose tumors express high levels of DKK1. Leap has recently initiated a trial of
DKN-01 in combination with BeiGene's tislelizumab, an anti-PD-1
antibody, in DKK1-high second line
gastroesophageal junction and gastric cancer (GEJ/GC) patients and
in combination with tislelizumab, capecitabine, and oxaliplatin in
first-line GEJ/GC patients.
About DKN-01
DKN-01 is a humanized monoclonal antibody that binds to and
specifically blocks the activity of the Dickkopf-1 (DKK1) protein, a modulator of Wnt/Beta-catenin
and CKAP4/PI3K/AKT signaling pathways, frequently implicated in
tumorigenesis. The U.S. Food and Drug Administration has
granted Orphan Drug Designation for the treatment of gastric and
gastroesophageal junction cancer and Fast Track Designation in
combination with tislelizumab for the treatment of patients with
gastric and gastroesophageal junction adenocarcinoma whose tumors
express high DKK1 protein, following disease progression
on or after prior fluoropyrimidine- and platinum- containing
chemotherapy and if appropriate, human epidermal receptor growth
factor (HER2)/neu-targeted therapy.
About Leap Therapeutics
Leap Therapeutics (Nasdaq:LPTX) is focused on developing
targeted and immuno-oncology therapeutics. Leap's most advanced
clinical candidate, DKN-01, is a humanized monoclonal antibody
targeting the Dickkopf-1 (DKK1)
protein. DKN-01 is in clinical trials in patients with
esophagogastric, hepatobiliary, gynecologic, and prostate cancers.
Leap has entered into a strategic partnership with BeiGene, Ltd.
for the rights to develop DKN-01 in Asia (excluding Japan), Australia, and New
Zealand. For more information about Leap Therapeutics, visit
http://www.leaptx.com or view our public filings with the SEC that
are available via EDGAR at http://www.sec.gov or via
https://investors.leaptx.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, Section 21E of the Securities Exchange Act of 1934, as
amended, and the Private Securities Litigation Reform Act of 1995,
which involve risks and uncertainties. These statements include
Leap's expectations with respect to the development and advancement
of DKN-01, including the initiation, timing and design of future
studies, enrollment in future studies, potential for the receipt of
future option exercise, milestones or royalty payments from
BeiGene, and other future expectations, plans and prospects.
Although Leap believes that the expectations reflected in such
forward-looking statements are reasonable as of the date made,
forward-looking statements are subject to known and unknown risks,
uncertainties and other factors that could cause actual results to
differ materially from our expectations. Such risks and
uncertainties include, but are not limited to: that the initiation,
conduct, and completion of clinical trials, laboratory operations,
manufacturing campaigns, and other studies may be delayed,
adversely affected, or impacted by COVID-19 related issues; the
accuracy of our estimates regarding expenses, future revenues,
capital requirements and needs for financing; the outcome, cost,
and timing of our product development activities and clinical
trials; the uncertain clinical development process, including the
risk that clinical trials may not have an effective design or
generate positive results; our ability to obtain and maintain
regulatory approval of our drug product candidates; the size and
growth potential of the markets for our drug product candidates;
our ability to continue obtaining and maintaining intellectual
property protection for our drug product candidates; and other
risks. Detailed information regarding factors that may cause actual
results to differ materially will be included in Leap Therapeutics'
periodic filings with the SEC, including Leap's Annual Report on
Form 10-K for the fiscal year ended December
31, 2019, as filed with the SEC on March 16, 2020 and as may be updated by Leap's
Quarterly Reports on Form 10-Q and the other reports Leap files
from time to time with the SEC. Any forward-looking statements
contained in this release speak only as of its date. Leap
undertakes no obligation to update any forward-looking statements
contained in this release to reflect events or circumstances
occurring after its date or to reflect the occurrence of
unanticipated events.
CONTACT:
Douglas E. Onsi
President & Chief Executive Officer
Leap Therapeutics, Inc.
617-714-0360
donsi@leaptx.com
Heather Savelle
Investor Relations
Argot Partners
212-600-1902
heather@argotpartners.com
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SOURCE Leap Therapeutics, Inc.