WALTHAM, Mass .– (COMMERCIAL THREAD) – Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a commercial-stage biopharmaceutical company developing innovative drugs to improve the lives of people with cancer, today announced the presentation of preclinical data for the first selective kinase Company’s ULK 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 Therapeutics Against the cancer.
“Data presented today show that DCC-3116 inhibits autophagy which develops as a resistance mechanism after treatment with EGFR inhibitors in several EGFR mutant NSCLC cell lines and that DCC-3116 decreases the tumor burden when combined with EGFR inhibitors. These results are particularly important because EGFR is mutated in approximately 30% of patients with NSCLC, the vast majority of which develop resistance to EGFR inhibitors, âsaid Matthew L. Sherman, MD, medical director of Deciphera. “These findings reinforce the large potential of autophagy inhibition as a mechanism to address the challenge of drug resistance in cancer treatment.
The results of the study, presented in a poster titled “DCC-3116, a first-order selective inhibitor of ULK1 / 2 kinases and autophagy, acts synergistically with EGFR inhibitors, osimertinib and afatinib in preclinical models of NSCLC âare summarized below. below. The poster presentation is available upon request through the meeting website and on the Company’s website at www.deciphera.com/presentations-publications.
In vitro Data show the ability of DCC-3116 to reduce autophagy that develops as a resistance mechanism after treatment with EGFR inhibitors in NSCLC cell lines
– The EGFR inhibitors gefitinib, erlotinib and osimertinib, and the ErbB family inhibitor, afatinib, activated autophagy three to four times over basal levels measured by pATG13, a cell substrate of kinases initiating ULK1 / 2 autophagy, in exon 19 of EGFR-HCC827 NSCLC cell line deleted. DCC-3116, a potent inhibitor of ULK1 and ULK2, has been 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 inhibits the T790M mutation, induced three-fold autophagy compared to basal levels whereas treatment with gefitinib or erlotinib, which are not able to inhibit the mutation induce ULK-mediated phosphorylation of ATG13. DCC-3116 strongly inhibited the phosphorylation of ATG13 induced by osimertinib and afatinib and inhibited the increase in autophagosomes induced by these agents.
In Vivo Data show that the combination of DCC-3116 with EGFR inhibitors resulted in significantly greater tumor responses in the NSCLC xenograft model
– The combination of DCC-3116 with osimertinib or afatinib resulted in significantly higher tumor responses than monotherapy treatments in the EGFR H1975 mutant xenograft model.
The clinical development plan for DCC-3116 will initially focus on documented RAS and RAF cancer mutations, which use autophagy for tumor growth and survival. DCC-3116 is currently in a phase 1, multicenter, open-label study, the first human study designed to assess the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of DCC- 3116 as monotherapy 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 extension 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 extension cohorts are planned to evaluate DCC-3116 in combination with trametinib. The first data from the phase 1 dose escalation cohorts are expected in 2022.
DCC-3116 is a first-class experimental small molecule designed to inhibit cancer autophagy, a key tumor survival mechanism, by inhibiting ULK kinase. DCC-3116 is currently under investigation in a phase 1, multicenter, open label, first in humans study as monotherapy and in combination with the commercially available MEK inhibitor trametinib in patients with advanced or metastatic tumors with a RAS or RAF Gene mutant.
About Deciphera Pharmaceuticals
Deciphera is a biopharmaceutical company focused on the discovery, development and commercialization of important new drugs to improve the lives of people with cancer. We are leveraging our proprietary switch-controlled kinase inhibitor platform and our deep expertise in kinase biology to develop a broad portfolio of innovative drugs. In addition to advancing several product candidates from our clinical studies platform, QINLOCKÂ® is Deciphera’s switch control inhibitor for the treatment of fourth-line GISTs. 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).
Caution 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 large potential of autophagy inhibition as a mechanism to address the challenge of drug resistance in the treatment of cancer, the potential of ULK kinase inhibition to represent a novel treatment for cancers caused by RAS or RAF cancers, and our planned expansion cohorts. “Predict”, “plan”, “anticipate”, “intend”, “believe”, “estimate”, “foresee”, “project”, “potential”, “continue”, “seek”, “target” âAnd similar phrases are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All forward-looking statements contained in this press release are based on the current expectations and beliefs of management and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to occur. differ materially from those expressed or implied by any forward-looking statement. statements in this press release, including, without limitation, the risks and uncertainties relating to the severity and duration of the impact of COVID-19 on our business and operations, our ability to successfully demonstrate effectiveness and the safety of our drug candidates and in other indications for our existing drug, the preclinical or clinical results of our product candidates, which may not support the further development of these product candidates, our ability to manage our dependence on it. ” with regard to single-source third parties such as our drug substance and third-party drug product manufacturer’s contract, comments, feedback and actions of regulatory agencies, our ability to market IQ NLOCK and execute our marketing plans for all drugs or indications that may be approved in the future, our ability to develop and evolve our operations to support the growth this in other geographies, the inherent uncertainty in patient population estimates, competition from other products, our ability to obtain and maintain reimbursement for any approved product, and the extent to which patient assistance programs patients are used, our ability to comply with healthcare regulations and laws, our ability to obtain, maintain and enforce our intellectual property rights, all or part of which may affect the launch, timing and progress clinical studies and timing and our ability to obtain additional regulatory approvals, and other risks identified in our Securities and Exchange Commission (SEC) files, including our quarterly report on Form 10-Q for the quarter ended June 30, 2021 and subsequent SEC filings. We caution you not to place undue reliance on forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise such statements to reflect any change in expectations or in the events, conditions or circumstances on which such statements may be based, or which may affect the likelihood that actual results will differ from those set forth in forward-looking statements. All forward-looking statements contained in this press release represent our views only as of the date hereof and should not be construed as representing our views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements.
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