Cogent Biosciences, Inc. reported positive Part 1b data from the Company?s ongoing SUMMIT trial evaluating bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM) at the 2024 American Academy of Allergy Asthma & Immunology Annual Meeting (AAAAI) meeting taking place February 23-26, 2024 in Washington, D.C. SUMMIT is a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 clinical trial of bezuclastinib in patients with NonAdvSM. Thirty-four patients in Part 1b were treated with either bezuclastinib or placebo plus best supportive care. The median age of patients at study entry was 52 years (ranging from 27-76 years).

Patients were enrolled with the following sub-types: 33 patients with indolent systemic mastocytosis (ISM) and one patient with smoldering systemic mastocytosis (SSM). One patient had received prior avapritinib. The majority of treatment emergent adverse events were low grade and reversible with no bleeding or cognitive impairment events reported across cohorts.

There were no dose reductions in the 100 mg cohort and two dose reductions in the 150 mg cohort (Grade 1 ALT and Grade 2 abdominal pain). Only one serious adverse event (SAE) was reported in the 150mg cohort in which a patient experienced ALT/AST increase that led to discontinuation. Thirty-four patients enrolled in SUMMIT Part 1b were evaluated for signs of clinical activity over 12 weeks, including well-accepted biomarkers of disease burden.

At the recommended phase 2 dose (RP2D) of 100 mg once daily bezuclastinib, results showed: 51% week 12 mean change in MS2D2 TSS (improvement in overall symptom severity from baseline) versus 18% improvement for placebo, Statistically significant reduction in total symptom severity after 12 weeks when compared to placebo (-23.78 vs. -9.03; p=0.0003), 70% of patients achieved =50% reduction in MS2D2 TSS at Week 12 vs. 8% placebo patients.

49% week 12 mean improvement in quality of life (MC-QoL) versus 24% for placebo, Statistically significant improvement in quality of life after 12 weeks when compared to placebo (?24.86 vs. -12.39, p=0.046). Based on the complete SUMMIT Part 1 data, along with the recommendation from an Independent Data Monitoring Committee, Cogent has initiated SUMMIT Part 2, a registration-directed, global, randomized placebo-controlled trial utilizing the 100 mg once daily dose of bezuclastinib.

SUMMIT Part 2 is expected to include 159 patients and complete enrollment in Second Quarter 2025, with estimated top-line results by the end of 2025. Patient enrollment continues on the registration-directed APEX trial which is expected to include approximately 65 AdvSM patients and remains on-track to complete enrollment by the end of 2024, with top-line results expected in mid-2025. In second-line Gastrointestinal Stromal Tumors (GIST) patients, Cogent continues to actively enroll the global Phase 3 PEAK trial and expects to complete enrollment by the end of 2024, with top-line results expected by the end of 2025.