Cogent Biosciences Releases More Data on Bezuclastinib SUMMIT Trial for NonAdvSM

Patients treated with 100 mg bezuclastinib demonstrated significant reductions in their most severe symptoms and mast cell reactions. Improvements were seen across all MS2D2 symptoms and a notable reduction in skin lesions was correlated with symptomatic relief.

Cogent Biosciences, Inc., a biotechnology firm specializing in precision therapies for genetically defined diseases, released additional data from Part 1 of its SUMMIT clinical trial. This trial assesses the selective KIT D816V inhibitor, bezuclastinib, in patients with nonadvanced systemic mastocytosis (NonAdvSM). The findings were presented at the 2024 European Hematology Association Congress in Madrid.

"We're thrilled to share more analyses from SUMMIT Part 1, which reveal considerable symptomatic reductions and improvements in objective disease measures," stated Andrew Robbins, CEO of Cogent Biosciences. Robbins confirmed the company plans to complete enrollment in the registration-directed SUMMIT Part 2 study by mid-2025 and release top-line results by the end of the same year.

Dr. Lindsay Rein, MD, from Duke University, highlighted the promising aspects of bezuclastinib in treating NonAdvSM, a challenging hematologic disorder. Dr. Rein noted the rapid patient response and symptom reductions seen within 12 weeks, emphasizing the safety and tolerability of the treatment.

The SUMMIT trial is a randomized, double-blind, placebo-controlled, global Phase 2 study examining bezuclastinib in NonAdvSM patients. Part 1 aimed to determine the recommended dose and assess the drug's effects on NonAdvSM symptoms using the Mastocytosis Symptom Severity Daily Diary (MS2D2). As of December 18, 2023, patients treated with 100 mg bezuclastinib showed over 90% reductions in mast cell burden markers. The data also revealed meaningful reductions in symptom severity and objective disease measures, such as:

- Significant reductions in mast cell reactions (over 50%) and severe symptoms as measured by MS2D2
- Clinically meaningful reductions in all individual MS2D2 TSS symptoms and additional symptoms like dizziness, diarrhea severity, and brain fog
- Notable improvements in skin symptoms and reductions in skin lesions

The safety data from SUMMIT Part 1 showed that the 100 mg dose of bezuclastinib had a favorable safety and tolerability profile, with no reports of bleeding, cognitive impairments, or serious adverse events.

Cogent Biosciences is also progressing with other clinical trials. They plan to complete enrollment in the APEX study for advanced systemic mastocytosis (AdvSM) by the end of 2024 and report top-line results by mid-2025. Additionally, the company is conducting the PEAK study, which involves approximately 388 second-line, post-imatinib patients with Gastrointestinal Stromal Tumors (GIST). The PEAK study is expected to complete enrollment by the third quarter of 2024, with top-line results anticipated by the end of 2025.

Cogent Biosciences, headquartered in Waltham, MA, and Boulder, CO, focuses on developing targeted therapies for genetically defined diseases. Bezuclastinib, a selective tyrosine kinase inhibitor, is designed to inhibit the KIT D816V mutation, which is responsible for systemic mastocytosis and certain gastrointestinal stromal tumors (GIST). The company's research team is also developing a portfolio of therapies targeting mutations in FGFR2, ErbB2, and PI3Kα to treat serious genetically driven diseases.

Cogent Biosciences remains committed to advancing its clinical programs and providing new treatment options for patients battling these challenging conditions.