Press Release Details
Deciphera Pharmaceuticals, Inc. Expands Pipeline with Potential First-in-Class Autophagy Inhibitor to Treat Mutant RAS Cancers
-DCC-3116 Selectively Targets ULK Kinase, an Initiating Protein that Activates Autophagy -
- Company to Host a Webcast on
Based on pre-clinical studies, DCC-3116 selectively inhibits ULK kinase, believed to be the initiating factor that activates autophagy. Autophagy is a cell survival pathway in which cells respond to stress by recycling their own components and/or clearing damaged organelles and proteins from the cell. Mutant RAS cancers, including KRAS, NRAS, and HRAS cancers, are reported to have high basal levels of autophagy, which they use to maintain nutrient supply, regulate cancer cell metabolism, and mitochondria surveillance.1 In multiple in vitro and in vivo models of mutant RAS cancers, autophagy inhibition combined with inhibition of MAPK signaling using MEK inhibitors or ERK inhibitors has demonstrated synergistic anti-tumor effects.2,3 When used in pre-clinical in vitro and in vivo studies in combination with inhibitors of the MAPK pathway, DCC-3116 synergized with these inhibitors to inhibit mutant RAS cancer growth. Cellular studies in mutant RAS cancers have demonstrated that MAPK pathway inhibitors further activate autophagy as a compensatory survival mechanism. Such activation of autophagy is seen with RAF, MEK, and ERK inhibitors as well as with direct inhibitors of mutant KRAS G12C. As an inhibitor of ULK, DCC-3116 is designed to address mutant RAS cancers by inhibiting the basal and compensatory autophagy that mutant RAS cancer cells use for their survival.
“We are very excited to announce our new development candidate,
DCC-3116, a potential first-in-class agent aimed at treating mutant RAS
cancers through the inhibition of autophagy,” said
“Our new clinical candidate, DCC-3116, is a potent and selective
inhibitor of ULK kinase generated using our proprietary switch control
inhibitor platform. Inhibition of ULK has potential application in a
very wide range of cancers and is an exciting addition to our pipeline,”
Deciphera is currently conducting IND-enabling studies for DCC-3116 and, pending favorable results, expects to file an IND in mid-2020.
DCC-3116 Event and Webcast Information
Deciphera will host a live event and webcast to discuss the new program
A live audio webcast of the event and accompanying slides may be accessed through the Investors section of Deciphera’s website at www.deciphera.com. A replay of the webcast will be available for 30 days following the event.
Investors and others should note that
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, statements regarding our
DCC-3116 program, our expectations for and the possibility of our
DCC-3116 candidate to inhibit ULK and autophagy and possibly treat or
provide therapeutic benefit for a wide range of cancers, and the timing
of and our plans to conduct IND-enabling studies, file an IND and
develop DCC-3116 for mutant RAS cancers. The words “may,” “will,”
“could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,”
“believe,” “estimate,” “predict,” “project,” “potential,” “continue,”
“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 designation of DCC-3116 as a new
clinical candidate, the expected benefits and development of DCC-3116,
delay of any current or planned pre-clinical, IND-enabling and/or
clinical studies or the development of our drug candidates, including
ripretinib, rebastinib, DCC-3014 and DCC-3116, our advancement of
multiple early-stage and later-stage efforts, our ability to
successfully demonstrate the efficacy and safety of our drug candidates
including in later-stage studies, the preclinical and clinical results
for our drug candidates, which may not support further development of
such drug candidates, our efforts to scale up and manage drug product
manufacturing, our ability to implement commercial readiness, actions of
regulatory agencies, any or all of which may affect the initiation,
timing and progress of clinical studies and other risks identified in
1.Guo, Jessie Yanxiang et al. “Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis.” Genes & Development 2011; 25: 460-470.
2. Bryant, Kirsten L. et al. “Combination of ERK and autophagy inhibition as treatment approach for pancreatic cancer.” Nature Medicine 2019; 25: 628-640.
3. Kinsey, Conan G. et al. “Protective autophagy elicted by RAF → MEK → ERK inhibition suggests a treatment strategy for RAS-driven cancers.” Nature Medicine 2019; 25: 620-627.
Deciphera Pharmaceuticals, Inc.
Gina Nugent, The Yates Network