Cogent Biosciences Presents Full SUMMIT Results of Bezuclastinib in Patients with NonAdvanced Systemic Mastocytosis (NonAdvSM) at the 67th Annual Meeting of the American Society of Hematology (ASH)
-- Bezuclastinib achieves clear clinical benefit across all symptom domains including significant improvements on 11 individual symptoms plus the most severe symptom at baseline --
-- Bezuclastinib demonstrates that reducing objective measures of disease, including serum tryptase, correlates with improvement in symptom severity; the first time this has been shown in NonAdvSM patients --
-- New 48-week data demonstrate a clear, continued deepening of symptomatic improvement over time --
-- Bezuclastinib demonstrated a favorable safety and tolerability profile supporting chronic use --
-- Granted Breakthrough Therapy Designation for bezuclastinib in October 2025; New Drug Application (NDA) on track for submission in December 2025 --
-- Cogent to host investor conference call and webcast on Monday, December 8, at 8:00 a.m. ET --
WALTHAM, Mass. and BOULDER, Colo., Dec. 06, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (NASDAQ:COGT) today announced complete results from the registration-directed Part 2 of the SUMMIT clinical trial of bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM). As previously reported, bezuclastinib demonstrated clinically meaningful and highly statistically significant improvements across the primary and all key secondary endpoints. New results further highlight the benefit of bezuclastinib on patient-reported symptoms and objective measures of mast cell burden and demonstrate significant correlation between improvement in disease pathology and patient-reported symptom severity.
"We are excited to present additional data from the SUMMIT trial that support our conviction that bezuclastinib will be the best-in-class treatment option for patients with nonadvanced systemic mastocytosis," said Andrew Robbins, Cogent's President and Chief Executive Officer. "We remain on track to submit our first New Drug Application for bezuclastinib in NonAdvSM with the FDA this month and are encouraged by the increased interest in our Expanded Access Program."
"Nonadvanced systemic mastocytosis patients currently have very limited treatment options, and the benefit bezuclastinib demonstrated in the SUMMIT trial across measures of disease pathology and symptomatic improvement is very exciting for this patient population," said Lindsay Rein, MD, Associate Professor of Medicine in the Division of Hematologic Malignancies and Cellular Therapy, Duke University. "The SUMMIT trial results match my clinical experience using bezuclastinib with NonAdvSM patients, delivering rapid and deep improvement in symptom control and objective measures of disease without tolerability challenges."
SUMMIT Trial Data
In the registration-directed Part 2 of the SUMMIT clinical trial, 118 patients received bezuclastinib once daily plus best supportive care (BSC) and 60 patients received placebo plus BSC. The study included adults with a NonAdvSM diagnosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized regimen of BSC.
Following completion of the 24-week treatment period, patients had the option to receive bezuclastinib in an open-label extension study. Baseline patient demographics were balanced between treatment arms and reflected significant disease burden. Disease symptoms were assessed using the Mastocytosis Symptom Severity Daily Diary (MS2D2).
Bezuclastinib delivered clinically meaningful and statistically significant symptomatic improvement
| Outcome measure | Bezuclastinib | Placebo | p-value |
| At 24 weeks of treatment (primary endpoint and key secondary endpoints) | |||
| Mean change TSS (%) | -24.3 (-43%) | -15.4 (-29%) | p<0.001 |
| Proportion of patients with ≥50% reduction in TSS | 34.3% | 18.1% | p=0.01 |
| Proportion of patients with ≥30% reduction in TSS | 65.4% | 38.6% | p<0.001 |
| For patients treated through 48 weeks (follow-up data cut off Nov 2025) | |||
| Mean change TSS (%) | -32.0 (-54%) | n/a | n/a |
| Proportion of patients with ≥50% reduction in TSS | 56.4% | n/a | n/a |
| Proportion of patients with ≥30% reduction in TSS | 86.2% | n/a | n/a |
Across several additional key secondary endpoints, bezuclastinib demonstrated rapid, deep and sustained improvement on objective disease markers of mast cell burden. At week 24, 87.4% of patients achieved ≥50% reduction in serum tryptase levels, 75.6% of patients demonstrated ≥50% reduction in bone marrow mast cells or clearance of aggregates and 85.7% of patients achieved ≥50% reduction in KIT D816V variant allele frequency or undetectable, each of which was statistically significant when compared to placebo. Additional pathobiology data from SUMMIT patients will be shared in an oral presentation on Monday, December 8th at ASH.
SUMMIT Subgroups
As part of the SUMMIT study, patients with Smoldering Systemic Mastocytosis (n=8 bezuclastinib arm, n=4 placebo arm) and patients who had previously been treated with avapritinib (n=11 bezuclastinib arm, n=3 placebo arm) were enrolled. Patients treated with bezuclastinib in these subgroups showed a mean change in TSS of -35.6 and -21.6, respectively. The response in objective measures of disease burden in these patients was consistent with results from the broader SUMMIT population, as were their related adverse events and overall tolerability.
Safety Data
As previously reported on July 7, 2025, 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.
SUMMIT Long Term Follow-up
Data from longer term follow-up in patients participating in the SUMMIT trial are expected to be presented at an upcoming scientific meeting in Q1 2026. Preliminary 48-week data will be shared during the investor call scheduled for Monday, December 8th.
Webcast Information
Cogent will host a live webcast on Monday, December 8, at 8:00 a.m. ET to discuss these additional data from SUMMIT in NonAdvSM. The live event will be available on the Investors & Media page of Cogent's website at investors.cogentbio.com. A replay of the webcast will be available approximately two hours after the completion of the event and will be archived for up to 30 days.
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 FGFR2/3 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, KRAS and JAK2. 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: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: plans to submit an NDA to the FDA for bezuclastinib in patients with NonAdvSM in December 2025; the company's belief that bezuclastinib will be the best-in-class treatment option for NonAdvSM patients and plans to present data from longer term follow-up in patients participating in the SUMMIT trial at an upcoming scientific meeting in Q1 2026. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words or expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Annual Report on Form 10-K filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof.
Contact:
Christi Waarich
Senior Director, Investor Relations
[email protected]
617-830-1653
