Cogent Biosciences, Inc. reported positive initial data from the Company?s ongoing Phase 2 SUMMIT trial evaluating bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM) at the 65th American Society of Hematology (ASH 2023) Annual Meeting & Exposition taking place December 9-12, 2023 in San Diego, CA. Patient Demographics SUMMIT is a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 clinical trial of bezuclastinib in patients with NonAdvSM. Twenty patients in Part 1a were treated with either bezuclastinib or placebo plus best supportive care for all arms. The median age of patients at study entry was 50.5 years (ranging from 38-75 years).

Patients were enrolled with the following sub-types: 18 patients with indolent systemic mastocytosis (ISM) and two patients with smoldering systemic mastocytosis (SSM). One patient had received prior avapritinib. Safety Data: Bezuclastinib demonstrated an encouraging safety and tolerability profile for patients dosed at both 100 mg and 200 mg QD.

The majority of treatment emergent adverse events were low grade and reversible with no related serious adverse events, bleeding or cognitive impairment events reported. There were two dose reductions for fatigue and one patient discontinued treatment due to increased ALT. One patient with SSM enrolled at a 400mg dose and following Grade 4 neutropenia was dose reduced to 200mg.

Following completion of Part 1a patients received a median duration of treatment in the open label extension (OLE) of 16 weeks. A consistent safety and tolerability profile was observed for patients starting bezuclastinib treatment following placebo. Pharmacodynamic Data: Twenty patients enrolled in SUMMIT Part 1a were evaluated for signs of clinical activity within the first 12 weeks, including well-accepted biomarkers of disease burden; 100% of bezuclastinib patients achieved =50% reduction in serum tryptase levels vs.

0% of placebo patients; 90% (9/10) of bezuclastinib patients with elevated baseline serum tryptase (>20 ng/ml) achieved reduction below 20 ng/ml within 12 weeks; 67% (8/12) of patients with abnormal baseline serum tryptase (=11.4ng/mL) achieved a normal tryptase value (<11.4ng/mL) after 12 weeks of bezuclastinib; 100% of bezuclastinib patients with detectable baseline variant allele fraction (VAF) achieved =50% reduction in KIT D816V VAF vs. 0% of placebo patients; 100% of bezuclastinib patients with measurable baseline mast cell aggregates achieved =50% reduction in bone marrow mast cell burden vs. 14% of placebo patients.

Patient Reported Outcomes (PRO) Data: Twenty patients enrolled in SUMMIT Part 1a were evaluated for signs of clinical activity within the first 12 weeks across quality-of-life and/or symptomatic severity scales including Mast Cell Quality-of-Life (MC-QoL), Mastocytosis Activity Scale (MAS), Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC). Additional patient assessments were made during the open-label extension using MC-QoL, PGIS and PGIC. In patients with completed questionnaires: By week 12, bezuclastinib patients showed a median best improvement of 37% on MC-QoL vs.

24% for placebo patients; By week 20, bezuclastinib patients increased median best improvement to 57% on MC-QoL; Patients who crossed over from placebo to bezuclastinib, showed median best improvement on MC-QoL of 75% by week 8 of active treatment; At week 12, bezuclastinib patients showed a 35% change from baseline on MAS vs. a 28% change from baseline for placebo; For bezuclastinib patients treated at 100 mg QD, the MAS improvement from baseline at week 12 was 49%; At week 12, 63% of bezculastinib patients showed a =1 point improvement on PGIS (5 point scale) compared with 0% of placebo patients; At week 20, this increased to 78% of bezuclastinib patients reporting =1 point improvement; 67% of patients who crossed over from placebo to bezuclastinib showed =1 point improvement on PGIS by week 8 of active treatment; At week 12, 63% of bezuclastinib patients reported overall symptoms were ?much better? to ?very much better?

on PGIC vs. 0% of placebo patients; At week 20, this increased to 78% of bezuclastinib patients; 43% of patients who crossed over from placebo to bezuclastinib reported symptoms were ?much better? to ?very much better?

by week 8 of active treatment; By week 20, 100% of patients treated with bezuclastinib reported improved Dermatological and Pain symptoms, 75% of patients reported improvement in Fatigue, and 67% of patients reported improvement in Gastrointestinal symptoms. Bezuclastinib Clinical Development: Cogent completed enrollment in SUMMIT Part 1 and plans to initiate SUMMIT Part 2, a registration-directed, global, randomized placebo-controlled trial in the first half of 2024. In addition, Cogent plans to present data from the completed SUMMIT Part 1 trial (1a and 1b), including all 54 patients enrolled across Part 1a and Part 1b, in the first quarter of 2024. Data from Part 1 of the Phase 2 APEX clinical trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) will be presented in a poster session at ASH on Monday, December 11, 2023 at ASH.

Cogent continues to actively enroll Part 2 of the APEX trial which is expected to include approximately 65 AdvSM patients and is on-track to complete enrollment by the end of 2024. In Gastrointestinal Stromal Tumors (GIST), Cogent continues to actively enroll patients in Part 2 of the Phase 3 registration-enabling PEAK trial and remains on track to complete enrollment by the end of 2024, with over 100 active sites globally.