Cogent Biosciences' Bezuclastinib Shows Promise in Systemic Mastocytosis Trials
Key Insights
Cogent Biosciences reports that bezuclastinib shows a 56% average improvement in Total Symptom Score (TSS) at 24 weeks in non-advanced systemic mastocytosis (search) (NonAdvSM) patients.
In advanced systemic mastocytosis (search) (AdvSM) patients, bezuclastinib shows a 52% ORR per mIWG criteria, including 83% ORR for patients receiving 100 mg BID.
The APEX trial of bezuclastinib in AdvSM demonstrates rapid and deep clinical responses with a favorable safety profile, avoiding concerning side effects.
Cogent Biosciences, Inc. (NASDAQ:COGT) has announced positive updated data from its Phase 2 APEX trial and the SUMMIT trial, evaluating bezuclastinib in patients with advanced systemic mastocytosis (search) (AdvSM) and non-advanced systemic mastocytosis (NonAdvSM), respectively. The data, presented at the American Society of Hematology (ASH) Annual Meeting, highlight the potential of bezuclastinib as a precision therapy for these genetically defined diseases.
APEX Trial: AdvSM Results
The APEX trial is a global, open-label, multi-center, two-part Phase 2 clinical trial evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib in patients with AdvSM. Updated data from Part 1 of the APEX trial, with a data cutoff date of October 11, 2024, included 32 patients across four dose levels. The study showed a 52% Overall Response Rate (ORR) per mIWG-MRT-ECNM criteria, with an 83% ORR in patients receiving 100 mg BID. The median time to response was 2.2 months, and the median duration of response and median Progression-Free Survival (PFS) have not yet been reached. The PFS rate at 24 months was 82%.
Daniel J. DeAngelo, M.D., Ph.D., from Dana-Farber Cancer Institute, noted, "Bezuclastinib has the potential to transform the treatment landscape for people living with advanced systemic mastocytosis (search)," emphasizing the rapid and deep clinical responses and a safety profile that avoids several concerning side effects.
SUMMIT Trial: NonAdvSM Results
Preliminary data from the Open Label Extension (OLE) part of the SUMMIT trial showed a 56% average improvement in Total Symptom Score (TSS) at 24 weeks, with 76% of patients experiencing at least a 50% reduction in TSS. Additionally, 89% of patients showed more than a 50% reduction in serum tryptase levels within four weeks of treatment, and 95% of participants with elevated baseline tryptase achieved levels below 20 ng/ml by the 24-week mark.
Safety and Tolerability
Bezuclastinib continues to demonstrate a favorable safety and tolerability profile across doses. The majority of hematological adverse events were low grade and reversible. No new treatment-related serious adverse events or discontinuations have been reported since ASH 2023. The most common side effects reported were hair discoloration and transaminase elevations, with no severe treatment-related bleeding or cognitive impairment events.
Ongoing and Future Studies
Cogent is actively enrolling patients in APEX Part 2, which is anticipated to complete enrollment in Q1 2025, with top-line results expected in mid-2025. Enrollment for SUMMIT Part 2 has been completed ahead of schedule, with 179 patients now part of the study. Top-line results are expected in July 2025.
Analyst Perspective
Analysts have shown considerable interest in Cogent's developments, with price targets ranging from $10 to $23. Piper Sandler and Citi have maintained Overweight and Buy ratings, respectively, reflecting confidence in the upcoming data from the bezuclastinib trials. Needham revised its stock price target for Cogent from $16.00 to $15.00, maintaining a Buy rating.