Cogent Biosciences

This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).

This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of bezuclastinib (CGT9486) plus best supportive care (BSC) with placebo plus BSC in patients with nonadvanced systemic mastocytosis (NonAdvSM), including indolent systemic mastocytosis and smoldering systemic mastocytosis, whose symptoms are not adequately controlled by BSC. This study will be conducted in three parts. Patients in Parts 1a, 1b and 2 will receive bezuclastinib or placebo, and may roll over onto Part 3 to receive treatment with bezuclastinib. Additionally, a substudy of subjects will investigate the efficacy, safety, and tolerability of bezuclastinib in patients who are experiencing inadequate symptom control with avapritinib.Show more

This is an open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (what the body does to the drug), pharmacodynamic (what the drug does to the body), and antitumor activity of CGT4859 in adult participants with intrahepatic cholangiocarcinoma (iCCA) or other advanced solid tumors with FGFR2 and/or FGFR3 genetic alternations.Show more

This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib.

Cogent Biosciences is a Waltham, Massachusetts biotech, with a second research site in Boulder, Colorado, that is on the verge of its first approvals. The company began life in 2014 as Unum Therapeutics, a cell therapy company that went public in 2018 and struggled. In July 2020 it acquired Kiq, a private company holding the rights to a KIT inhibitor originally discovered at Plexxikon, renamed itself Cogent Biosciences that October under CEO Andrew Robbins, and wound down the cell therapy work. Everything since has been built around that one molecule, bezuclastinib, and Cogent trades on Nasdaq as COGT.

Bezuclastinib is a pill designed to block a specific mutant form of the KIT protein, KIT D816V, which drives roughly 90 to 95% of systemic mastocytosis, a rare disease in which abnormal mast cells accumulate in the bone marrow, skin, and organs. What sets it apart from earlier KIT drugs is selectivity: it is built to hit the mutant protein while largely sparing related enzymes, and it was designed to stay out of the brain, which is meant to avoid the cognitive side effects seen with avapritinib (Ayvakit), the only approved targeted therapy in this space. In the placebo-controlled SUMMIT trial in non-advanced systemic mastocytosis, reported in July 2025, patients on bezuclastinib had a significantly larger drop in total symptom score at 24 weeks than patients on placebo, and 87% saw their serum tryptase fall by at least half, compared with none on placebo. The most common side effects were hair color change and altered taste, with liver enzyme elevations in about one in five patients. The FDA accepted the application with a decision date of December 30, 2026. In the single-arm APEX trial in advanced systemic mastocytosis, a more aggressive form that often overlaps with blood cancers, 65% of evaluable patients responded, and Cogent submitted that application on June 30, 2026.

The third indication is gastrointestinal stromal tumor (GIST), another cancer driven by KIT mutations. In the Phase 3 PEAK trial, reported in November 2025 and presented at ASCO in 2026, adding bezuclastinib to sunitinib in patients whose GIST had progressed on imatinib cut the risk of progression or death in half, extending median progression-free survival from 9.2 to 16.5 months, the first positive Phase 3 result in second-line GIST in more than two decades. The FDA granted priority review with a decision date of November 30, 2026. Cogent has hired its full commercial field team, signed a long-term manufacturing agreement in September 2026, and offers expanded access programs in both systemic mastocytosis and GIST for patients who cannot join a trial. Behind bezuclastinib, the company has three early-stage precision cancer drugs in Phase 1: CGT4859 for FGFR2 and FGFR3-driven tumors including bile duct cancer, CGT4255 for HER2-mutant cancers, and CGT6297 for PIK3CA-mutant breast and endometrial cancers, plus preclinical programs against pan-KRAS and the JAK2 V617F mutation behind polycythemia vera and other myeloproliferative neoplasms. With $866 million in cash on a pro forma basis at mid-2026, Cogent says it is funded into late 2028.

None as of October 2026. Cogent Biosciences has no FDA-approved drug yet; its programs are still in trials.

Most advanced: Bezuclastinib (Phase 3).

Where to watch: the FDA calendar lists any Cogent Biosciences application once a decision date is public, and the trials list on this page shows what is recruiting now.