Press Release Details

New bezuclastinib nonclinical data demonstrate superior selectivity against closely related kinases, as well as minimal brain penetration, compared with other KIT inhibitors 

Building a pipeline of multiple small molecule inhibitors targeting genetically defined diseases, including next generation FGFR2 inhibitors and novel ErbB2 mutant selective program

Continuing enrollment in APEX, SUMMIT and PEAK trials; on-track to report initial APEX data in 1H 2022

CAMBRIDGE, Mass. and BOULDER, Colo., April 11, 2022 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, presented two poster presentations at the American Association of Cancer Research (AACR) annual meeting taking place April 8-13, 2022. The first included updated nonclinical bezuclastinib data reinforcing its potential to be a differentiated, best-in-class KIT mutant inhibitor. The second focused on nonclinical data from Cogent’s next-generation fibroblast growth factor receptor 2 (FGFR2) research program, designed to spare FGFR1 while potently covering all gatekeeper and molecular brake mutations. Finally, the company shared additional details at an R&D Investor Event, on its portfolio expansion plans by highlighting its early efforts to develop an ErbB2 mutant selective inhibitor for patients with non-exon 20 mutations.

“We continue to make significant progress establishing Cogent as an emerging leader in precision medicines for genetically defined diseases,” said Andrew Robbins, President and Chief Executive Officer of Cogent Biosciences. “This weekend we presented updated nonclinical data adding to a growing body of evidence supporting bezuclastinib as a potential best-in-class KIT mutant inhibitor for systemic mastocytosis and gastrointestinal stromal tumor (GIST) patients. Separately, we introduced two novel programs from the Cogent Research Team which highlighted our growing portfolio of novel, small-molecule targeted therapies for patients fighting genetically driven diseases. We continue to enroll patients into our APEX, SUMMIT and PEAK trials and look forward to sharing initial clinical results from the APEX study later this quarter.”  

Bezuclastinib Nonclinical Data
Bezuclastinib is a tyrosine kinase inhibitor that is active against KIT mutations relevant to both systemic mastocytosis (SM) and gastrointestinal stromal tumors (GIST). New nonclinical data, presented at AACR, demonstrates that bezuclastinib potently inhibits A loop-mutations exquisitely selective against other closely related kinases, and differentiates bezuclastinib by its lack of brain penetration. These data support that bezuclastinib inhibits KIT downstream signaling and is able to drive tumor regressions at clinically achievable doses.

“Currently approved KIT inhibitors are limited by off-target toxicities related to broad-spectrum kinase inhibition, secondary activation loop mutations, CNS-related adverse events, and sub-optimal clinical dosing,” said Jessica Sachs, MD, Cogent’s Chief Medical Officer. “With KIT mutations serving as driver mutations in up to 80% of GIST and over 90% of systemic mastocytosis, we’re excited with the growing validation of bezuclastinib as a highly potent and selective inhibitor of KIT D816V and remain focused on advancing our ongoing clinical trials.”

Growing Pipeline of Small Molecule Inhibitors
Cogent’s research team is also building a pipeline of small molecule inhibitors. FGFR inhibitors are well-established oncogenic drivers in multiple diseases, but approved medicines fail to capture the full landscape of FGFR altered tumor types, with FGFR1-mediated hyperphosphatemia serving as the most common dose-limiting toxicity for pan-FGFR inhibitors. Based on preclinical data presented, the Company’s FGFR program has the potential to both spare FGFR1 inhibition, avoiding related toxicity, as well as potently cover the relevant molecular brake and gatekeeper mutations associated with this target. Cogent is advancing a potent, selective FGFR2 inhibitor program toward candidate selection later this year and expects to file this first internally developed Investigational New Drug application (IND) in the second half of 2023.

The Company also shared an early look at a novel, non-exon 20 ErbB2 mutant program. ErbB2 is a tyrosine kinase receptor that belongs to a family of four receptors, which are also known as HER1, HER2, HER3 and HER4, respectively. A significant unmet need remains for patients with non-exon 20 ErbB2 mutations. Activating mutations in the ErbB2 gene have been identified in multiple cancers and demonstrate a tumorigenic role similar to that of ErbB2 amplification.

“We’ve made tremendous progress moving our programs from early discovery into lead generation,” said John Robinson, PhD, Cogent’s Chief Scientific Officer. “We are pleased to share the latest developments which highlight the ability of our team to discover new treatment candidates in genetically defined diseases with high unmet need, and we look forward to discussing additional programs in the future, including potential first-to-market opportunities.”

About Cogent Biosciences, Inc.
Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting FGFR2 and ErbB2. Cogent Biosciences is based in Cambridge, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: Twitter and LinkedIn. Information that may be important to investors will be routinely posted on our website and Twitter.

Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the potential for bezuclastinib to be a best-in-class KIT mutant inhibitor, the company’s plans to present initial clinical results from APEX later this quarter, the potential of the company’s FGFR2 and ErbB2 research programs, and the company’s plan to file an IND for a FGFR2 candidate in the 2^nd half of 2023.The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof.

Investor Contact:
Christi Waarich
Senior Director, Investor Relations
christi.waarich@cogentbio.com

Media contact:
Amanda Sellers
asellers@vergescientific.com
301.332.5574