Cogent to present preclinical data from pipeline programs at AACR meeting

Cogent Biosciences (COGT) announced preclinical data from four pipeline programs during poster sessions at the American Association for Cancer Research 2025 Annual Meeting taking place in Chicago. Title: Identification of a potent KRAS (ON) inhibitor with selectivity for mutant KRAS over HRAS and NRAS: 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 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 PI3Kalpha H1047R mutant-selective inhibitor: Cogent is developing a potential best-in-class, wild-type-sparing, PI3Kalpha inhibitor that provides coverage for the both the H1047R mutation as well as E542K and E545K helical mutants. The phosphoinositide 3-kinase 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 PI3Kalpha. 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 and MCF-7 breast cancer TGI models. Title: The Reversible and Selective FGFR2/3 inhibitor CGT4859 has superior target coverage of resistance mutations missed by leading FGFR 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. 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 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 greater than2.5 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 penetration: Cogent’s potential best-in-class EGFR-sparing, brain-penetrant ErbB2 inhibitor includes potent coverage of key mutations 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.