Cogent Biosciences Announces Positive Initial Data from Phase 2 SUMMIT Trial Evaluating Bezuclastinib in Patients with Nonadvanced Systemic Mastocytosis (NonAdvSM)

Rapid and ongoing improvement in patient symptoms, with 57% median best improvement on MC-QoL and 78% of patients reporting ≥1 point improvement on PGIS by week 20

100% of bezuclastinib treated patients achieved at least 50% improvement across all relevant biomarker measures, including serum tryptase, KIT D816V VAF, and mast cell burden;

Placebo patients, after cross-over to bezuclastinib, also demonstrated rapid symptomatic improvement, with 75% median best improvement on MC-QoL, and 67% of patients reporting ≥1 point improvement on PGIS

Bezuclastinib safety and tolerability profile supports potential for chronic dosing with no related serious adverse events and no bleeding or cognitive events

Cogent to host investor webcast on Monday, December 11 at 8:00 a.m. ET

WALTHAM, Mass. and BOULDER, Colo., Dec. 09, 2023 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today 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.

“Nonadvanced systemic mastocytosis is a chronic hematologic disorder that significantly impacts patients’ quality of life,” said principal investigator, Prithviraj Bose, M.D., professor, Department of Leukemia at The University of Texas MD Anderson Cancer Center. “Significant unmet need remains for these patients and the availability of a well-tolerated, efficacious therapy with rapid symptom improvement could represent an important advancement in treatment.”

“The initial data presented today from the SUMMIT trial represent an important step forward in the development of a novel treatment for NonAdvSM patients,” said PD Dr. Frank Siebenhaar, M.D., Head University Outpatient Clinic, Institute of Allergology, Charité - Universitätsmedizin Berlin. “Effectively targeting the underlying driver mutation of this disease is critical, and the impressive outcomes generated with bezuclastinib treatment in these patients is very encouraging.”

“We are very pleased with the emerging profile bezuclastinib is demonstrating in the NonAdvSM patient population,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “Matching the benefit of a selective KIT inhibitor that can potently target overactive and proliferative mast cells, with a safety profile that may support chronic treatment has been elusive up until this point. We are excited to rapidly advance into Part 2 of SUMMIT, a registration-directed, global, randomized placebo-controlled trial, and look forward to presenting additional data from SUMMIT in the first quarter of 2024.”

Patient DemographicsSUMMIT 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 DataBezuclastinib 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 was 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 DataTwenty 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 (