Cogent Biosciences Reports Positive SUMMIT Trial Results for Bezuclastinib

Overview

Cogent Biosciences, Inc. announced positive results from the SUMMIT clinical trial's Part 2, showing that the treatment bezuclastinib significantly improved total symptom scores in patients with non-advanced systemic mastocytosis compared to placebo. Patients receiving bezuclastinib experienced a mean symptom score reduction of 24.3 points at 24 weeks, contrasted with 15.4 points for placebo, leading to a placebo-adjusted difference of 8.91 points (p=0.0002). Additionally, 87.4% of treated patients saw at least a 50% reduction in serum tryptase levels, while no placebo patients did. Bezuclastinib was also found to have a favorable safety profile, enhancing its potential for chronic use. Cogent plans to submit its New Drug Application to the FDA for bezuclastinib by the end of 2025 and will present detailed trial results at an upcoming medical meeting. The company remains financially strong with a cash balance of $237 million and access to additional funds via a debt facility.

Potential Positives

• Patients treated with bezuclastinib showed a superior mean change in total symptom score at 24 weeks, establishing new benchmarks for symptomatic improvement.
• Bezuclastinib demonstrated a significant effect on mast cell burden, with 87.4% of patients achieving at least a 50% reduction in serum tryptase, compared to none in the placebo group.
• The drug exhibited a favorable safety and tolerability profile, supporting its potential for chronic use in patients.
• Cogent Biosciences is on track to submit a New Drug Application (NDA) to the FDA for bezuclastinib by the end of 2025 and reported a strong financial position with a substantial cash balance and access to additional funds.

Potential Negatives

• Cogent is not expected to submit its New Drug Application (NDA) for bezuclastinib to the FDA until the end of 2025, indicating a prolonged timeline before potential market access.
• The press release notes a significant percentage of treatment-emergent adverse events (TEAEs) occurred in the bezuclastinib arm (98.3%), which may raise concerns about the overall safety profile despite being of low grade.
• The company relies on external financing options (access to $350 million via a debt facility), which may pose financial risks and indicate reliance on debt rather than positive cash flow for growth.

FAQ

What are the results of the SUMMIT trial for bezuclastinib?
Bezuclastinib achieved significant symptom improvements compared to placebo, with a mean change in total symptom score of -24.3 points.
What percentage of patients showed a reduction in serum tryptase?
87.4% of patients treated with bezuclastinib achieved at least a 50% reduction in serum tryptase.

When is the NDA for bezuclastinib expected to be submitted?
The NDA submission to the FDA for bezuclastinib is expected by the end of 2025.
Safety profile of bezuclastinib
Bezuclastinib demonstrated a favorable safety and tolerability profile, supporting its chronic use in patients.

When will Cogent present detailed trial results?
--Cogent plans to present detailed results from the SUMMIT trial at an upcoming medical meeting later this year. Bezuclastinib demonstrated a favorable safety and tolerability profile supporting chronic use in this patient population 
-- Bezuclastinib NDA submission to FDA expected by end of 2025; strong financial position with $237 million current cash balance and access up to an additional $350 million via recently announced debt facility with SLR Capital Partners 
-- On track to share pivotal trial results from PEAK in GIST and APEX in AdvSM in 2H 2025 
-- Cogent to host investor conference call and webcast today at 8:00 a.m. ET 

Cogent Reports Positive SUMMIT Trial Results, Plans NDA Submission for Bezuclastinib 

• (NASDAQ: COGT) today announced positive top-line results from the registration-directed Part 2 of the SUMMIT clinical trial of bezuclastinib in patients with non-advanced systemic mastocytosis (NonAdvSM) demonstrating clinically meaningful and highly statistically significant improvements across the primary and all key secondary endpoints, including patient-reported symptoms and objective measures of mast cell burden. 
• Based on these data, Cogent is on track to submit its first new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for bezuclastinib in NonAdvSM by the end of 2025. 
• In addition, Cogent plans to present detailed results from the SUMMIT trial at an upcoming medical meeting later this year.

Words from Andrew Robbins, Cogent’s President & CEO

We have been eagerly awaiting this day and are thrilled to announce bezuclastinib’s performance in the SUMMIT trial, demonstrating clinically meaningful and statistically significant results across all trial endpoints,” said Andrew Robbins, Cogent’s President and CEO. 
“Our team is already at work on our first New Drug Application for bezuclastinib that we expect to file with the FDA later this year. We are committed to providing bezuclastinib access to the thousands of patients with Non-Advanced Systemic Mastocytosis as quickly as possible, including through our recently announced Bezuclastinib Expanded Access Program.”

The SUMMIT trial results

• The SUMMIT trial, which was designed to assess the clinical benefit of bezuclastinib versus placebo, achieved its primary endpoint with a highly statistically significant difference in the mean change in total symptom score (TSS) at 24 weeks (p=0.0002). 
• TSS was assessed by the Mastocytosis Symptom Severity Daily Diary (MS2D2). The bezuclastinib arm had a mean reduction of 24.3 points in TSS at 24 weeks, versus the placebo arm which had a mean reduction of 15.4 points in TSS, resulting in a placebo-adjusted TSS improvement of 8.91 points. 
• In addition, the SUMMIT trial demonstrated highly statistically significant benefit across all key secondary endpoints, including reduction of serum tryptase on which 87.4% of bezuclastinib-treated patients had ≥50% reduction, compared to no patients in the control arm (87.4% vs. 0%; p<0.0001).

Words from Nathan Boggs: Walter Reed National Military Medical Center

People living with NonAdvSM experience debilitating symptoms with enormous impact on their physical and psychological quality of life,” said Nathan Boggs, MD, PhD, Allergy Division Director, Uniformed Services University, Walter Reed National Military Medical Center. 
“It is extremely encouraging to see the results of the SUMMIT trial, which match my own experience treating patients with bezuclastinib, as these results suggest there will soon be a new standard of care available for this patient population with significant unmet medical need.”

SUMMIT Endpoints

All primary and secondary endpoints demonstrated statistically significant comparisons in favor of bezuclastinib over placebo:
SUMMIT Endpoints P-Value
(two-sided)
Primary Endpoint Mean Change TSS at 24 weeks 0.0002
Secondary Endpoints

≥ 50% Reduction in Serum Tryptase <0.0001
 ≥ 50% Reduction in KIT D816V VAF <0.0001
 ≥ 50% Reduction in TSS 0.0142
 ≥ 50% Reduction in Bone Marrow MC Aggregates < 0.0001
 ≥ 30% Reduction in TSS 0.0004
 Mean Change in Most Severe Symptom at Baseline 0.0001

Treatment emergent adverse events (TEAEs) 

• The majority of treatment emergent adverse events (TEAEs) (98.3% in bezuclastinib arm vs. 88.3% in placebo arm) were of low grade. The most frequent TEAEs reported on bezuclastinib treatment were hair color change (69.5% bezuclastinib vs. 5.0% placebo), altered taste (23.7% bezuclastinib vs. 0% placebo), nausea (22.0% bezuclastinib vs. 13.3% placebo) and ALT/AST elevations (22.0% bezuclastinib vs. 6.6% placebo; ≥Gr 3, 5.9% vs. 0%). 
• Serious AEs occurred in 4.2% of patients treated with bezuclastinib, compared to 5.0% of patients treated with placebo. 
• Discontinuations due to treatment-related AEs occurred in 5.9% of patients treated with bezuclastinib, all due to ALT/AST elevations and all patients fully resolved. There were no hepatic AEs reported in any patient other than transient and manageable lab abnormalities.

Words from Lindsay Rein, MD, Duke University 

In addition to its impressive effects on improving patient symptoms, the safety and tolerability profile of bezuclastinib is very attractive for a patient population anticipating taking this disease-modifying agent on a chronic basis,” said Lindsay Rein, MD, Associate Professor of Medicine in the Division of Hematologic Malignancies and Cellular Therapy, Duke University. 
“I am excited to see these top-line results from the SUMMIT trial as bezuclastinib represents a new, powerful treatment option for patients with Non-Advanced Systemic Mastocytosis.”

Complete analysis of the full SUMMIT Part 2 data are ongoing, and Cogent plans to present detailed results at an upcoming major medical conference later this year.

Cogent Prepares for Key Trial Results and Grants Inducement Awards

• Cogent remains on track to provide top-line results from both PEAK, a Phase 3 trial of bezuclastinib in combination with sunitinib in patients with gastrointestinal stromal tumors (GIST), and APEX, a registration-directed trial of bezuclastinib in advanced systemic mastocytosis (AdvSM) patients, during the second half of 2025.
• Cogent also announced today that, on June 30, 2025, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grant of “inducement” equity awards to three new employees under the company’s 2020 Inducement Plan with grant dates of July 3, 2025 and July 7, 2025. 
• The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, nonqualified options to purchase 92,500 shares of Cogent common stock. 
• Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date.

About Cogent Biosciences, Inc.

• Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. 
• The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. 
• KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. 
• Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. 
• The company also has an ongoing Phase 1 study of its novel internally discovered FGFR2 inhibitor. In addition, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases targeting mutations in ErbB2, PI3Kα and KRAS. 
• Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media:

Optimize Your trial insights with Clival Database.

Are you exhausted from the uncertainty of trial insights pricing? Clival Database ensures the clarity in the midst of the global scenario for clinical trials to you.

Clival Database is one of the best databases that offers an outstanding number of clinical trial data in terms of 50,000+ molecules and from primary regulatory markets as well as new entrants like Indian and Chinese markets.

With Clival, you get accurate positioning of historical sales data, patent database, company profiling, safety & efficacy, and prediction of launch of new innovative molecules helping you to align your research and driving down the cost.

To add value, we further break down our analytics for you so that improving your operational effectiveness; optimizing your clinical trials; and offering you accurate and high-quality data at lowest possible prices becomes possible.

Elevate your trial success rate with the cutting-edge insights from Clival database.

Check it out today and make more informed sourcing decisions! Learn More!