Bezuclastinib

WALTHAM, Mass. and BOULDER, Colo., April 25, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced preclinical data from four pipeline programs during poster sessions at the American Association for Cancer Research (AACR) 2025 Annual Meeting taking place in Chicago. “We welcome the opportunity to present updated results from these programs that represent our exciting pipeline of potential best-in-class targeted therapies,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “These data demonstrate Cogent’s ability to discover and advance novel therapies for rare disease populations with high unmet medical need, and we look forward to continuing to advance these candidates.” Poster Details Title: Identification of a potent KRAS (ON) inhibitor with selectivity for mutant KRAS over HRAS and NRASSession Category: ChemistrySession Title: Lead Identification and OptimizationSession Date and Time: April 30, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 25Poster Board Number: 3Published Abstract Number: 6974 Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. The poster presented today describes Cogent’s internally-developed pan KRAS(ON) inhibitor program with selectivity over HRAS and NRAS and picomolar (pM) activity across KRAS mutations. In response to our 30mg/kg oral dose we observed robust PD including 90% tumor growth inhibition in a mouse TGI model. Lead optimization of this series is ongoing. Title: Preclinical characterization of CGT6297, a novel PI3Kα H1047R mutant-selective inhibitorSession Category: Experimental and Molecular TherapeuticsSession Title: Kinase and Phosphatase Inhibitors 2Session Date and Time: April 28, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 20Poster Board Number: 5Published Abstract Number: 3004 Cogent is developing a potential best-in-class, wild-type-sparing, PI3Kα inhibitor that provides coverage for the both the H1047R mutation as well as E542K and E545K helical mutants. The phosphoinositide 3-kinase (PI3K) pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. The approved agents for these patients often lead to dose limitations, resulting from activity against wild-type PI3Kα. In the poster being presented today, Cogent’s preclinical candidate CGT6297 demonstrates broad cellular panel profiling across multiple resistant and mutated cell lines, including, for the first time, efficacy against PI3K helical mutations. The poster also showcases the activity of CGT6297 in both ST1056 (H1047R mutant) and MCF-7 (E545K mutant) breast cancer TGI models. Title: The Reversible and Selective FGFR2/3 inhibitor CGT4859 has superior target coverage of resistance mutations missed by leading FGFR inhibitorsSession Category: Clinical ResearchSession Title: Targeted Therapies and Combinations 2Session Date and Time: April 29, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 34Poster Board Number: 27Published Abstract Number: 4729 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. The poster presented today describes Cogent’s internally-developed FGFR2/3 inhibitor which maintains potency on FGFR2 mutations and is selective against the entire kinome and a broad panel of channels and receptors. Exploratory pharmacokinetics (PK) studies conducted across species showed CGT4859 to be a low-clearance compound with high oral bioavailability. Further, in an AN3 CA model, CGT4859 demonstrated dose-responsive tumor growth inhibition with complete regressions at >2.5 mg/kg QD or BID and was well-tolerated. Cogent is currently enrolling patients in an ongoing Phase 1 trial with CGT4859 in patients with confirmed FGFR2 or FGFR3 mutations, including patients with advanced cholangiocarcinoma. The trial is designed to explore the safety, tolerability and clinical activity of escalating doses with the goal of selecting an active and well tolerated dose for further clinical investigation. Title: Identification of CGT4255 an EGFR-sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetrationSession Category: Experimental and Molecular TherapeuticsSession Title: Novel Antitumor Agents 3Session Date and Time: April 29, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 21Poster Board Number: 1Published Abstract Number: 5623 Cogent’s potential best-in-class EGFR-sparing, brain-penetrant ErbB2 inhibitor includes potent coverage of key mutations (YVMA, S310F, V842I, L755S) inadequately addressed by currently approved therapies. Activating mutations in the ErbB2 gene have been identified in multiple cancers and demonstrate a tumorigenic role similar to that of ErbB2 amplification. New data presented on this compound describes CGT4255’s exceptional stability in human whole blood and liver cytosol fractions and high oral bioavailability and low clearance across preclinical species. In addition, CGT4255 is expected to have equivalent brain to plasma exposure suggesting potential best-in class properties. All posters will be available on the ‘Posters and Publications’ page of Cogent’s website. New Leadership AppointmentsCogent also announced today that Ray Frost has joined Cogent as Senior Vice President, Market Access and Adam Boyd, Ph.D. has joined Cogent as Senior Vice President, Corporate Strategy. Mr. Frost joins Cogent with over 20 years of industry experience. Previously he served as Vice President Market Access at Ono Pharma USA and Zealand Pharma (Zealand). While at Zealand he played an integral part in building the commercial infrastructure to support the launch of their first product. Prior to Zealand he held roles of increasing responsibility in Market Access and Health Policy at Melinta Therapeutics, The Medicines Company, Bayer Healthcare, Eisai and MGI PHARMA. Mr. Frost is a graduate of Hofstra University. Dr. Boyd joins Cogent with nearly 25 years of industry experience building and leading global teams across Development functions including Biostatistics, Clinical Pharmacology, Clinical Operations, and Data Management. In these roles, he was instrumental in bringing several products to market, including Mektovi® (binimetinib), Braftovi® (encorafenib), Jakafi® (ruxolitinib), and Folotyn® (pralatrexate). Prior to joining Cogent, Dr. Boyd was Vice President, Biometrics at Intellia Therapeutics, and prior to that, held various roles of increasing responsibility at Pfizer, Array BioPharma, Novartis, and Allos Therapeutics. Dr. Boyd earned his Ph.D. in Biostatistics from the University of Colorado, where he is currently a member of the Colorado School of Public Health’s Dean’s Advisory Board. Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that, on April 14, 2025, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of “inducement” equity awards to five new employees, including Mr. Frost and Dr. Boyd, under the company’s 2020 Inducement Plan with a grant date of April 21, 2025. The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, nonqualified options to purchase 446,000 shares of Cogent common stock. Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date. 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. The company also has an ongoing Phase 1 study of its novel internally discovered FGFR2 inhibitor. In addition, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases targeting mutations in ErbB2, PI3Kα and KRAS. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward-Looking StatementsThis 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 best-in-class therapeutic potential of the company’s pre-clinical pipeline candidates. 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 WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

WALTHAM, Mass. and BOULDER, Colo., March 25, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced four preclinical poster presentations at the upcoming 2025 AACR Annual Meeting being held in Chicago, IL April 25-30, 2025. Poster Details Title: Identification of a potent KRAS (ON) inhibitor with selectivity for mutant KRAS over HRAS and NRASSession Category: ChemistrySession Title: Lead Identification and OptimizationSession Date and Time: April 30, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 25Poster Board Number: 3Published Abstract Number: 6974 Title: Preclinical characterization of CGT6297, a novel PI3Kα H1047R mutant-selective inhibitorSession Category: Experimental and Molecular TherapeuticsSession Title: Kinase and Phosphatase Inhibitors 2Session Date and Time: April 28, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 20Poster Board Number: 5Published Abstract Number: 3004 Title: The Reversible and Selective FGFR2/3 inhibitor CGT4859 has superior target coverage of resistance mutations missed by leading FGFR inhibitorsSession Category: Clinical ResearchSession Title: Targeted Therapies and Combinations 2Session Start: April 29, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 34Poster Board Number: 27Published Abstract Number: 4729 Title: Identification of CGT4255 an EGFR sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetrationSession Category: Experimental and Molecular TherapeuticsSession Title: Novel Antitumor Agents 3Session Start: April 29, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 21Poster Board Number: 1Published Abstract Number: 5623 Inducement Grant Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grant of an “inducement” equity award on March 21, 2025 to one new employee under the company’s 2020 Inducement Plan. The award was approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employee received a nonqualified option to purchase 9,700 shares of Cogent common stock. The option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date. 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. The company also has an ongoing Phase 1 study of its novel internally discovered FGFR2 inhibitor. In addition, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases targeting mutations in ErbB2, PI3Kα and KRAS. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward-Looking StatementsThis 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 clinical development plans and timelines and the potential of the company’s pipeline programs. 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 WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com