– DCC-3116 Shown to Inhibit EGFR and EGFR
Family Inhibitor-induced Autophagy in Multiple EGFR-mutant
Non-Small Cell Lung Cancer Cell Lines and Decrease Tumor Burden in
Combination with Osimertinib and Afatinib in EGFR Mutant Xenograft
Model –
Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a
commercial-stage biopharmaceutical company developing innovative
medicines to improve the lives of people with cancer, today
announced the presentation of preclinical data from the Company’s
first-in-class selective ULK kinase inhibitor, DCC-3116, in
combination with EGFR inhibitors in non-small cell lung cancer
(NSCLC) models at the AACR-NCI-EORTC International Conference on
Molecular Targets and Cancer Therapeutics.
“The data presented today show that DCC-3116 inhibits the
autophagy that develops as a resistance mechanism after treatment
with EGFR inhibitors in multiple EGFR-mutant NSCLC cell lines and
that DCC-3116 decreases tumor burden when combined with EGFR
inhibitors. These findings are particularly important as EGFR is
mutated in approximately 30% of NSCLC patients, the vast majority
of whom develop resistance to EGFR inhibitors,” said Matthew L.
Sherman, M.D., Chief Medical Officer of Deciphera. “These results
reinforce the broad potential of autophagy inhibition as a
mechanism to address the challenge of drug resistance in the
treatment of cancer.”
Results from the study, presented in a poster titled “DCC-3116,
a first-in-class selective inhibitor of ULK1/2 kinases and
autophagy, synergizes with EGFR inhibitors osimertinib and afatinib
in NSCLC preclinical models” are summarized below. The poster
presentation is available on-demand via the meeting website and on
the Company’s website at
www.deciphera.com/presentations-publications.
In Vitro Data Show Ability of DCC-3116 to Reduce Autophagy
that Develops as a Resistance Mechanism after Treatment with EGFR
Inhibitors in NSCLC Cell Lines
– EGFR inhibitors gefitinib, erlotinib and
osimertinib, and the ErbB-family inhibitor, afatinib, activated
autophagy three to four-fold over basal levels as measured by
pATG13, a cellular substrate of autophagy-initiating kinases
ULK1/2, in the EGFR exon 19-deleted HCC827 NSCLC cell line.
DCC-3116, a potent inhibitor of ULK1 and ULK2, was shown to inhibit
both basal and EGFR-induced phosphorylation of pATG13.
– Treatment of the EGFR T790M-mutated NSCLC
cell line H1975 with osimertinib or afatinib, which inhibit the
T790M mutation, induced autophagy three-fold over basal levels
while treatment with gefitinib or erlotinib, which are not able to
inhibit the T790M mutation, did not induce ULK-mediated ATG13
phosphorylation. DCC-3116 potently inhibited osimertinib and
afatinib-induced phosphorylation of ATG13 and inhibited the
increase in autophagosomes induced by these agents.
In Vivo Data Show that Combination of DCC-3116 with EGFR
Inhibitors Resulted in Significantly Greater Tumor Responses in
NSCLC Xenograft Model
– The combination of DCC-3116 with
osimertinib or afatinib resulted in significantly greater tumor
responses than single agent treatments in the H1975 EGFR-mutant
xenograft model.
The clinical development plan for DCC-3116 will initially focus
on documented RAS and RAF cancer mutations, which utilize autophagy
for tumor growth and survival. DCC-3116 is currently being
investigated in a Phase 1, multicenter, open-label, first-in-human
study designed to evaluate the safety, tolerability, clinical
activity, pharmacokinetics, and pharmacodynamics of DCC-3116 as a
single agent and in combination with trametinib, a commercially
available MEK inhibitor, in patients with advanced or metastatic
tumors with a mutant RAS or RAF gene. Following the dose escalation
phase, combination expansion cohorts are currently planned in
patients with advanced or metastatic pancreatic ductal
adenocarcinoma with KRAS or BRAF mutations, non-small cell lung
cancer (NSCLC) with KRAS, NRAS, or BRAF mutations, colorectal
cancer with KRAS, NRAS, or BRAF mutations, and melanoma with NRAS
or BRAF mutations. Combination expansion cohorts are planned to
evaluate DCC-3116 in combination with trametinib. Initial data from
the Phase 1 dose escalation cohorts is expected in 2022.
About DCC-3116
DCC-3116 is an investigational first-in-class small molecule
designed to inhibit cancer autophagy, a key tumor survival
mechanism, by inhibiting the ULK kinase. DCC-3116 is currently
being studied in a Phase 1, multicenter, open-label, first-in-human
study as a single agent and in combination with trametinib, a
commercially available MEK inhibitor, in patients with advanced or
metastatic tumors with a mutant RAS or RAF gene.
About Deciphera Pharmaceuticals
Deciphera is a biopharmaceutical company focused on discovering,
developing, and commercializing important new medicines to improve
the lives of people with cancer. We are leveraging our proprietary
switch-control kinase inhibitor platform and deep expertise in
kinase biology to develop a broad portfolio of innovative
medicines. In addition to advancing multiple product candidates
from our platform in clinical studies, QINLOCK® is Deciphera’s
switch control inhibitor for the treatment of fourth-line GIST.
QINLOCK is approved in Australia, Canada, China, Hong Kong, Taiwan,
and the United States. For more information, visit
www.deciphera.com and follow us on LinkedIn and Twitter
(@Deciphera).
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, without limitation, our expectations
regarding the broad potential of autophagy inhibition as a
mechanism to address the challenge of drug resistance in the
treatment of cancer, ULK kinase inhibition’s potential to represent
a new treatment for cancers caused by RAS or RAF cancers, and our
planned expansion cohorts.. The words “may,” “will,” “could,”
“would,” “should,” “expect,” “plan,” “anticipate,” “intend,”
“believe,” “estimate,” “predict,” “project,” “potential,”
“continue,” “seek,” “target” and similar expressions are intended
to identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements in this press release are based on
management’s current expectations and beliefs and are subject to a
number of risks, uncertainties and important factors that may cause
actual events or results to differ materially from those expressed
or implied by any forward-looking statements contained in this
press release, including, without limitation, risks and
uncertainties related to the severity and duration of the impact of
COVID-19 on our business and operations, our ability to
successfully demonstrate the efficacy and safety of our drug
candidates and in additional indications for our existing drug, the
preclinical or clinical results for our product candidates, which
may not support further development of such product candidates, our
ability to manage our reliance on sole-source third parties such as
our third party drug substance and drug product contract
manufacturers, comments, feedback and actions of regulatory
agencies, our ability to commercialize QINLOCK and execute on our
marketing plans for any drugs or indications that may be approved
in the future, our ability to build and scale our operations to
support growth in additional geographies, the inherent uncertainty
in estimates of patient populations, competition from other
products, our ability to obtain and maintain reimbursement for any
approved product and the extent to which patient assistance
programs are utilized, our ability to comply with healthcare
regulations and laws, our ability to obtain, maintain and enforce
our intellectual property rights, any or all of which may affect
the initiation, timing and progress of clinical studies and the
timing of and our ability to obtain additional regulatory
approvals, and other risks identified in our Securities and
Exchange Commission (SEC) filings, including our Quarterly Report
on Form 10-Q for the quarter ended June 30, 2021, and subsequent
filings with the SEC. We caution you not to place undue reliance on
any forward-looking statements, which speak only as of the date
they are made. We disclaim any obligation to publicly update or
revise any such statements to reflect any change in expectations or
in events, conditions or circumstances on which any such statements
may be based, or that may affect the likelihood that actual results
will differ from those set forth in the forward-looking statements.
Any forward-looking statements contained in this press release
represent our views only as of the date hereof and should not be
relied upon as representing our views as of any subsequent date. We
explicitly disclaim any obligation to update any forward-looking
statements.
Deciphera, the Deciphera logo, QINLOCK, and the QINLOCK logo are
registered trademarks of Deciphera Pharmaceuticals, LLC.
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version on businesswire.com: https://www.businesswire.com/news/home/20211007005295/en/
Investor Relations: Jen Robinson Deciphera
Pharmaceuticals, Inc. jrobinson@deciphera.com 781-906-1112
Media: David Rosen Argot Partners
David.Rosen@argotpartners.com 212-600-1902
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