SAN DIEGO, April 10, 2021 /PRNewswire/ -- Mirati
Therapeutics, Inc. (NASDAQ: MRTX), a late-stage targeted oncology
company, today announced initial preclinical results evaluating its
investigational synthetic lethal PRMT5 inhibitor in
methylthioadenosine phosphorylase (MTAP)-deleted cancer
models. Mirati's internally discovered PRMT5 compound is the first
to specifically target the PRMT5/methylthioadenosine (MTA) complex.
This approach is designed to leverage elevated levels of MTA in
cancers exhibiting an MTAP deletion and to selectively kill
cancer cells harboring this genetic alteration. The results were
presented today during a late-breaking minisymposium at the 2021
American Association for Cancer Research (AACR) Virtual Annual
Meeting [Abstract # LB003].
Preclinical results showed that the Mirati PRMT5 compound bound
selectively to the PRMT5/MTA complex and demonstrated a greater
than 100-fold selectivity for MTAP-deleted cells compared
with cells that do not exhibit this genetic defect in both
proliferation and mechanistic assays. This selectivity for the
PRMT5/MTA complex and MTAP-deleted cancer cells allows for
the selective targeting of cancer cells while sparing healthy
cells, which are also dependent on PRMT5 for cell growth and
survival. In addition, treatment of MTAP-deleted tumor
xenograft-bearing mice with the Mirati PRMT5 compound resulted in
halted tumor growth and near complete reduction of symmetric
dimethylarginine (SDMA), a biomarker of PRMT5 activity, at
well-tolerated dose levels.
"We are proud to have a potential first-in-class therapeutic
agent to specifically target the PRMT5/MTA complex in
MTAP-deleted cancer cells," said James Christensen, Ph.D., executive vice
president and chief scientific officer, Mirati Therapeutics, Inc.
"Based on discoveries made by Mirati scientists, we have designed a
novel approach to specifically bind to and inhibit PRMT5 in complex
with MTA. With this approach, we are able to target
MTAP-deleted tumors, which should result in an improved
therapeutic index relative to known PRMT5 and MAT2A
inhibitors."
About PRMT5 Inhibition in MTAP-deleted Cancers
PRMT5 is an enzyme critical to the survival of both healthy and
cancer cells and is partially inhibited by MTA, which accumulates
in MTAP-deleted cancers. The MTAP deletion is present
in approximately 10 percent of all cancers and is the most
frequently observed gene deletion event (MTAP/CDKN2A) across
several cancer types. Cancers with an MTAP deletion, such as
pancreatic, lung, and bladder cancers, are associated with a poor
prognosis, representing a significant unmet medical need.
Activated PRMT5 is crucial for the regulation of cellular
processes essential for cell survival, including regulation of RNA
splicing, gene expression and protein translation. In
MTAP-deleted cancer cells, the inhibitory cofactor MTA
accumulates and binds to PRMT5. Mirati's PRMT5 compound
selectively targets the PRMT5/MTA complex in MTAP-deleted
cancer cells while sparing healthy cells. The Mirati PRMT5 compound
is advancing toward an Investigational New Drug (IND) filing in the
first half of 2022.
About Mirati Therapeutics
Mirati Therapeutics is a late-stage biotechnology company whose
mission is to discover, design and deliver breakthrough therapies
to transform the lives of patients with cancer and their loved
ones. The company is relentlessly focused on bringing forward
therapies that address areas of high unmet need, including lung
cancer, and advancing a pipeline of novel therapeutics targeting
the genetic and immunological drivers of cancer. Mirati is using
its scientific expertise to develop novel solutions in two
registration-enabling programs: adagrasib (MRTX849), an
investigational small molecule, potent and selective KRAS G12C
inhibitor, as monotherapy and in combination with other agents, and
sitravatinib, an investigational spectrum-selective inhibitor of
receptor tyrosine kinases in combination with checkpoint inhibitor
therapies. Mirati is also advancing its differentiated preclinical
portfolio, including MRTX1133, an investigational KRAS G12D
inhibitor, and other oncology discovery programs. Unified for
patients, Mirati's vision is to unlock the science behind the
promise of a life beyond cancer.
For more information about Mirati Therapeutics, visit us at
Mirati.com or follow us on Twitter and LinkedIn.
Forward Looking Statements
This press release contains forward-looking statements regarding
the business of Mirati Therapeutics, Inc. ("Mirati"). Any statement
describing Mirati's goals, expectations, financial or other
projections, intentions or beliefs, development plans and the
commercial potential of Mirati's drug development pipeline,
including without limitation adagrasib (MRTX849), sitravatinib and
MRTX1133, is a forward-looking statement and should be considered
an at-risk statement. Such statements are subject to risks and
uncertainties, particularly those challenges inherent in the
process of discovering, developing and commercialization of new
drug products that are safe and effective for use as human
therapeutics, and in the endeavor of building a business around
such drugs.
Mirati's forward-looking statements also involve assumptions
that, if they never materialize or prove correct, could cause its
results to differ materially from those expressed or implied by
such forward-looking statements. Although Mirati's forward-looking
statements reflect the good faith judgment of its management, these
statements are based only on facts and factors currently known by
Mirati. As a result, you are cautioned not to rely on these
forward-looking statements. These and other risks concerning
Mirati's programs are described in additional detail in Mirati's
quarterly reports on Form 10-Q and annual reports on Form 10-K,
which are on file with the U.S. Securities and Exchange Commission
(the "SEC") available at the SEC's Internet site
(www.sec.gov).These forward-looking statements are made as of the
date of this press release, and Mirati assumes no obligation to
update the forward-looking statements, or to update the reasons why
actual results could differ from those projected in the
forward-looking statements, except as required by law.
Mirati Contacts
Investor Relations
Temre Johnson
(858) 332-3562
ir@mirati.com
Media Relations
Priyanka Shah
(908) 447-6134
media@mirati.com
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