Cogent Biosciences Announces Positive Top-line Results of APEX Trial of Bezuclastinib in Patients with Advanced Systemic Mastocytosis (AdvSM)

-- Bezuclastinib demonstrated rapid and deep clinical benefit in AdvSM patients resulting in an objective response rate (CR+CRh+PR+CI) of 57% per mIWG criteria and 80% per PPR criteria --

-- Bezuclastinib demonstrated a powerful effect on mast cell burden with 89% of patients achieving ≥50% reduction in bone marrow mast cells or clearance of aggregates –

-- Bezuclastinib was very well tolerated with only 14.8% of patients requiring dose reduction and no patients requiring discontinuation due to treatment related adverse events --

-- APEX NDA submission expected in 1H 2026 –

-- Cogent to host investor conference call and webcast today at 8:00 a.m. ET --

WALTHAM, Mass. and BOULDER, Colo., Dec. 08, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (NASDAQ:COGT) today announced positive top-line results from the registration-directed APEX Part 2 clinical trial of bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) demonstrating clinically meaningful results as measured by consensus criteria used to assess patient response. This is the third positive pivotal trial result for bezuclastinib in 2025, following positive announcements from the SUMMIT trial in NonAdvSM patients and the PEAK trial in GIST patients earlier this year. Based on these top-line data, Cogent expects to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for bezuclastinib in AdvSM during the first half of 2026. In addition, Cogent plans to present detailed data from the APEX trial at an upcoming scientific meeting in the first half of 2026.

"We are excited to announce the third positive pivotal trial for bezuclastinib this year. The results from the APEX trial demonstrate the clear benefit that a highly selective, highly potent KIT mutant inhibitor is capable of providing to patients with AdvSM," said Andrew Robbins, Cogent's President and Chief Executive Officer. "Coupling rapid, deep, durable responses with the safety and tolerability profile demonstrated by bezuclastinib provides these patients with a new choice to fight their disease without compromising their quality of life. With positive results from APEX, taken together with data from SUMMIT and PEAK, Cogent is preparing for multiple commercial launches in the second half of 2026."

In Part 2 of the APEX trial, 81 AdvSM patients were treated with 150 mg of bezuclastinib, including 57 patients with SM-AHN, 11 patients with ASM and 13 patients with MCL. 68 of these patients were mIWG-MRT-ECNM evaluable for assessment on the primary endpoint. Clinical activity analyzed from these patients showed:

• Primary endpoint: 57% ORR (CR+CRh+PR+CI) per mIWG-MRT-ECNM (mIWG) criteria
  • 49% ORR (CR+CRh+PR) per mIWG
  • At the time of data cut-off, multiple additional patients had achieved unconfirmed response criteria and remain on study awaiting follow-up assessment
    
    
    
    
• Key secondary endpoint: 80% ORR (CR+CRh+PR) per pure pathological response (PPR) criteria
  
  
  
  
• Median time to achieve response was 2.0 months and median duration of response is not yet mature.
  
  
  
  
• Bezuclastinib achieved clear and clinically significant reductions in objective disease markers for these AdvSM patients:

"Bezuclastinib demonstrated the rapid, deep clinical activity we were expecting given its earlier clinical results," said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. "What is most exciting about these data is the impressive safety and tolerability results with no discontinuations due to treatment-related adverse events (TRAEs) and only infrequent dose modifications. With this profile, bezuclastinib will become an important treatment option for this patient population."

APEX Part 2 Safety and Tolerability

The most frequent TRAEs reported on bezuclastinib treatment were hair color change (30.9%), neutropenia (29.6%), altered taste (28.4%), thrombocytopenia (24.7%) and ALT/AST elevations (20.9%). Only 14.8% of patients required dose reduction, and no patients discontinued due to TRAEs. The majority of transaminase elevations were of low grade, asymptomatic and reversible. Only one patient experienced Gr 3 transaminase elevation which fully resolved with dose reduction and the patient continues on therapy.

Complete analysis of the full APEX Part 2 data are ongoing, and Cogent plans to present detailed results at an upcoming major medical conference in the first half of 2026.

Webcast Details

Cogent will host a live webcast today, Monday, December 8, at 8:00 a.m. ET to discuss the full data from SUMMIT in NonAdvSM shared at the American Society of Hematology (ASH) Annual Meeting as well as today's APEX top-line results. 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.

Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)

Cogent also announced today that, on December 1, 2025 and December 5, 2025, the Compensation Committee of Cogent's Board of Directors, made up entirely of independent directors, approved the grants of "inducement" equity awards to thirteen new employees under the company's 2020 Inducement Plan with grant dates of December 2, 2025 and December 8, 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, (i) nonqualified options to purchase 294,600 shares of Cogent common stock and (ii) 34,000 restricted stock units (RSUs). 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. The RSUs vest annually over 4 years from the grant date, 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 FGFR2/3 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 AdvSM during the first half of 2026; plans to present detailed results from the APEX trial at an upcoming scientific meeting in the first half of 2026; the expectation that bezuclastinib will provide AdvSM patients with a new choice to fight their disease without compromising their quality of life; the expectation that Cogent will have multiple commercial launches in the second half of 2026 and the expectation that bezuclastinib will become an important treatment option for AdvSM patients. 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 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 Quarterly Report on Form 10-Q 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