This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib.

Start Date01 Aug 2024

Sponsor / Collaborator

Sarcoma Alliance for Research through Collaboration

[+3]

NCT05186753

/ Active, not recruitingPhase 2

A Multi-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of The Safety and Efficacy of CGT9486 in Subjects With Nonadvanced Systemic Mastocytosis

This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of bezuclastinib (CGT9486) plus best supportive care (BSC) with placebo plus BSC in patients with nonadvanced systemic mastocytosis (NonAdvSM), including indolent systemic mastocytosis and smoldering systemic mastocytosis, whose symptoms are not adequately controlled by BSC. This study will be conducted in three parts. Patients in Parts 1a, 1b and 2 will receive bezuclastinib or placebo, and may roll over onto Part 3 to receive treatment with bezuclastinib. Additionally, a substudy of subjects will investigate the efficacy, safety, and tolerability of bezuclastinib in patients who are experiencing inadequate symptom control with avapritinib.

Start Date27 Jun 2022

Sponsor / Collaborator

Cogent Biosciences, Inc.

NCT05208047

/ Active, not recruitingPhase 3

A Phase 3 Randomized, Open-Label, Multicenter Clinical Study of CGT9486+Sunitinib vs. Sunitinib in Subjects With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors

This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination with sunitinib. This is a multi-part study that will enroll approximately 442 patients. Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to be used in subsequent parts in approximately 20 patients who have received at least one prior line of therapy for GIST and 2) evaluating the potential for drug-drug interactions between CGT9486 and sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388 patients who are intolerant to, or who failed prior treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being randomized in a 1:1 manner. Additionally, a drug-drug interactions substudy will investigate the potential for CGT9486 to be a CYP3A4 inducer in approximately 16 patients who have received at least one prior line of therapy for GIST.

Start Date14 Apr 2022

Sponsor / Collaborator

Cogent Biosciences, Inc.

100 Clinical Results associated with Bezuclastinib

100 Translational Medicine associated with Bezuclastinib

100 Patents (Medical) associated with Bezuclastinib

Literatures (Medical) associated with Bezuclastinib

01 Aug 2025·Current Opinion in Allergy and Clinical Immunology

New treatments for systemic mastocytosis in 2025

Review

Author: Paoletti, Giovanni ; Heffler, Enrico ; Marzio, Valentina ; Costanzo, Giovanni ; Cavaglià, Edoardo

Purpose of review:

To provide an accessible, comprehensive overview of past, present, imminent, and future therapies for systemic mastocytosis.

Recent findings:

Based on recent trials, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved two drugs for treating advanced systemic mastocytosis: avapritinib and midostaurin. The FDA also approved imatinib for selected cases of aggressive systemic mastocytosis without the D816V c-Kit mutation. Moreover, for the first time, a cytoreductive molecule, avapritinib, has been approved for patients with indolent systemic mastocytosis.

Summary:

Despite the considerable therapeutic progress in recent years, systemic mastocytosis is an incurable disease. In the last 20 years, the management of systemic mastocytosis has transformed from a one-size-fits-all approach, characterized by nonspecific cytoreductive drugs, to a tailored strategy focused on increasingly precise molecular targets, with the most notable example being the KIT inhibitors. Recently, the FDA and EMA have approved two drugs for treating systemic mastocytosis: avapritinib and midostaurin. Moreover, numerous trials are currently assessing the efficacy of new molecules: most are testing new-generation KIT inhibitors (ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib), others focusing on Bruton's kinase (TL-895), interleukin-6 (sarilumab), sialic acid-binding immunoglobulin-like lectin-8 (lirentelimab), mTOR and CD33, among others. Real-life data are needed to confirm preliminary preclinical results.

03 Jul 2023·Expert opinion on emerging drugs

Systemic mastocytosis: 2023 update on diagnosis and management in adults

Review

Author: Costa, Alessandro ; Masucci, Chiara ; Carmosino, Ida ; Ielo, Claudia ; Capriata, Marcello ; Scalzulli, Emilia ; Passucci, Mauro ; Martelli, Maurizio ; Breccia, Massimo

INTRODUCTION:

Systemic mastocytosis (SM) is a complex and heterogeneous disease, characterized by the clonal accumulation of mast cells in one or more organs. In 2022 both the World Health Organization (WHO) and the International Consensus Classification (ICC) modified the diagnostic and classification criteria of SM. Moreover, the identification of new clinical and molecular variables has improved prognostic tools and led to increasingly individualized therapeutic strategies.

AREAS COVERED:

The aim of this review is to present the updates introduced by the International Consensus Classification in diagnostic criteria of SM. In addition, we report the latest data available from the most important clinical trials in patients both with non-advanced and advanced disease, including elenestinib and bezuclastinib.

EXPERT OPINION:

Diagnosis and classification of SM has evolved over years. The most recent WHO and ICC classification improved SM diagnostic work-up, providing clinicians with a clear and simplified diagnostic scheme. New approved targeted therapies such as midostaurin and avapritinib modified the treatment paradigm in patients in advanced stage, and next-generation inhibitors actually investigated in clinical trials are expected in the next future.

09 Dec 2022·Hematology. American Society of Hematology. Education Program

Available and emerging therapies for bona fide advanced systemic mastocytosis and primary eosinophilic neoplasms

Review

Author: Gotlib, Jason

Abstract:

The historically poor prognosis of patients with advanced systemic mastocytosis (AdvSM) and primary eosinophilic neoplasms has shifted to increasingly favorable outcomes with the discovery of druggable targets. The multikinase/KIT inhibitor midostaurin and the highly selective KIT D816V inhibitor avapritinib can elicit marked improvements in measures of mast cell (MC) burden as well as reversion of MC-mediated organ damage (C-findings) and disease symptoms. With avapritinib, the achievement of molecular remission of KIT D816V and improved survival compared with historical therapy suggests a potential to affect disease natural history. BLU-263 and bezuclastinib are KIT D816V inhibitors currently being tested in trials of AdvSM. In the new World Health Organization and International Consensus Classifications, the category of “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions” is inclusive of rearrangements involving PDGFRA, PDGFRB, FGFR1, JAK2, FLT3, and ETV6::ABL1. While the successful outcomes with imatinib in FIP1L1::PDGFRA-positive cases and PDGFRB-rearranged neoplasms have become the “poster children” of these disorders, the responses of the other TK-driven neoplasms to small-molecule inhibitors are more variable. The selective FGFR inhibitor pemigatinib, approved in August 2022, is a promising therapy in aggressive FGFR1-driven diseases and highlights the role of such agents in bridging patients to allogeneic transplantation. This review summarizes the data for these approved and investigational agents and discusses open questions and future priorities regarding the management of these rare diseases.

117

News (Medical) associated with Bezuclastinib

19 Feb 2026

·www.biospace.com

Biodexa Licenses Phase 1 Ready Drug Candidate from Otsuka for Rare Stomach Cancer

MTX240's mechanistic novelty may give it a long-awaited edge in treatments for gastrointestinal stromal tumors (GIST) Meg Flippin, Benzinga Staff Writer CARDIFF, UK / ACCESS Newswire / February 19, 2026 / Biodexa Pharmaceuticals PLC (NASDAQ:BDRX), a clinical-stage biopharmaceutical company developing a pipeline of innovative products for the treatment of rare diseases with an increasing focus on products to treat or prevent gastrointestinal cancers, has added a new Phase 1 ready candidate to its portfolio, this time to target gastrointestinal stromal tumors, or GIST. Several drugs are available to treat GIST, but all ultimately fail when the tumor develops resistance. When that occurs, median overall survival drops to less than a year. The value and hope of a better drug is at least partially evidenced by the eye-popping $1 billion GSK paid last year for a Phase 1 candidate, even though it shares the same mechanism of action as the currently approved drugs. MTX240's unique molecular glue mechanism of action separates it from the current standard of care, notes Stephen Stamp, CEO of Biodexa. "It has the potential to benefit a broader spectrum of GIST patients, including those with TKI-resistant disease, and it strategically aligns with our emerging GI/oncology pipeline which includes our ongoing phase 3 development of eRapa in Familial Adenomatous Polyposis." What is GIST? GIST is a hard-to-treat tumor that grows mainly in the stomach wall and is caused by mutations in the so-called Interstitial Cells of Cajal (ICCs) which facilitate gut motility. Mutations in the key tyrosine kinase proteins KIT or PDGFR perturb intra-cellular signaling pathways in ICCs, causing rapid cell proliferation and tumorgenesis. Patients typically undergo resection but, once the GIST becomes unmanageable or the tumors are unresectable, targeted treatments called tyrosine kinase inhibitors (TKIs) are the current standard of care. Current standard of care Currently, there are four approved TKI treatments for GIST, generally prescribed in the following order as GIST mutations occur and patients acquire resistance to each of them - (1) imatinib (Gleevec) from Novartis AG (NVS); (2) sunitinib (Sutent) from Pfizer Inc. (PFE); (3) regorafenib (Stivarga) from Bayer AG . (BAYN); and (4) ripretinib (Qinlock) from Deciphera Pharmaceuticals Inc (DCPH). Once patients have cycled through the available TKIs, having acquired resistance to all of them, median time to tumor progression is 1.2 months and median overall survival is 9.8 months. As a result of these shortcomings, drug developers, including Biodexa, are jockeying for position in what is currently a $1.3 billion market [1] , with projected growth of around 6.6% annually through 2032. It makes sense that drug developers are eyeing this market. In the U.S. alone, between 4,000 and 6,000 people are diagnosed with GIST each year [2] . Globally, the number of new GIST patient annually is estimated at between 80,000 to 120,000. Biodexa's novel drug candidate - MTX240 Enter MTX240, Biodexa's latest developmental treatment, which it recently licensed from Otsuka Pharmaceutical Co., Ltd. MTX240 is a novel molecular glue that works by forcing PDE3A and SLFN12, two proteins expressed in GIST cells to bind together, in turn triggering the tumor cells to self-destruct in a process called apoptosis. Importantly, healthy ICCs do not significantly express either of these proteins and are not therefore affected by MTX240. Unlike the TKIs that frequently fail once the tumor cells mutate, and render the drug ineffective, MTX240's unique mechanism of action is designed to work whether or not the GIST has acquired secondary mutations. Early success and promise In preclinical PDX models, which use human tumor tissues to mirror real-world genetic complexity, MTX240 demonstrated dose-dependent efficacy in shrinking GIST in both non-resistant (left hand chart) and TKI-resistant tumors (middle and right hand chart) as illustrated below [3]: Note: MTX240 was coded OPB-171775 by Otsuka in the charts. If the preclinical results are replicated in clinical trials and MTX240 proves to be lethal to GIST without inducing resistance, it has the potential for co-administration with TKIs and ultimately, to replace the entire class. MTX240 is eligible for FDA and EU Orphan Drug designation, which means the company is eligible for seven and 10 years of market exclusivity upon approval in the US and EU, respectively. In addition, MTX240 has issued Composition of Matter patents extending through 2037. Next steps Next step is to manufacture clinical trial supplies of MTX240 and then initiate a Phase 1b/2a study by year-end. The study is expected to be in two parts: a standard dose escalation part to determine a maximum tolerated dose, followed by an extension part. The extension part is likely to enrol patients with TKI-resistant GIST. By focusing on this high-need population, Biodexa is aiming to rapidly validate MTX240's potential as a way to treat patients who don't respond to the current standards of care. Deal validation Biodexa in-licensed exclusive worldwide rights to MTX240 with the exception of Japan rights, which were retained by Otsuka for an undisclosed upfront fee. The deal includes one modest development milestone, low double digit approval milestones and mid single-digit tiered royalties. Biodexa's entrance into the GIST market with MTX240 puts it in a space that's garnering interest from Big Pharma as well as Wall Street. Take GSK Plc. (GSK) as one example. In January 2025 GSK paid $1 billion cash upfront to buy IDRx, Inc., a single product company developing IDRX-42, another TKI for GIST that was in Phase 1 at the time [4]. Meanwhile, Cogent Biosciences Inc. (COGT), which is developing bezuclastinib (another TKI) for co-administration with sunitinib, saw its market cap surge approximately $2Bn following the release of Phase 3 trial data [5], which demonstrated bezuclastinib plus sunitinib compared with sunitinib alone extended median progression free survival from 9.2 months to 16.5 months in imatinib-resistant patients, underscoring the importance of this sector [6]. With Biodexa showing promising initial results with MTX240, this is a treatment investors may want to pay attention to. To learn more about Biodexa and MTX240, click here . References: DataBridge Market Research. (2023). Gastrointestinal stromal tumor market size, trends and forecasts (2024-2032). Retrieved from Zhu, H., et al. (2023). Update of epidemiology, survival and initial treatment in gastrointestinal stromal tumor: A population-based analysis. BMJ Open, 13(7), e072945. Takaki, E. O., et al. (2024). A PDE3A-SLFN12 molecular glue exhibits significant antitumor activity in TKI-resistant gastrointestinal stromal tumors. Clinical Cancer Research. GSK. (2025, January 13). GSK enters agreement to acquire IDRx, Inc. Talk Bio. (2025, November 11). Cogent Biosciences soars on positive Phase 3 PEAK results in gastrointestinal stromal tumors (GIST). Cogent Biosciences Stock Soars 346% in a Year, but One Fund Just Sold Off $4.5 Million Cogent Biosciences, Inc. (2025, November 10). Cogent Biosciences reports positive results from bezuclastinib PEAK Phase 3 trial in gastrointestinal stromal tumors (GIST). Featured image from Shutterstock . This post contains sponsored content. This content is for informational purposes only and is not intended to be investing advice. Please see 17(b) disclosure here for more information. Click here for more information on Biodexa Pharmaceuticals. Contact: Stephen Stamp, CEO, CFO ir@biodexapharma.com Important notice, please read : Certain statements in this article may constitute "forward-looking statements" within the meaning of legislation in the United Kingdom and/or United States. Such statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and are based on management's belief or interpretation. All statements contained in this article that do not relate to matters of historical fact should be considered forward-looking statements. In certain cases, forward-looking statements can be identified by the use of words such as "plans", "expects" or "does not anticipate", or "believes", or variations of such words and phrases or statements that certain actions, events or results "may", "could", "would", "might" or "will be taken", "occur" or "be achieved." Forward-looking statements and information are subject to various known and unknown risks and uncertainties, many of which are beyond the ability of the Company to control or predict, that may cause their actual results, performance or achievements to be materially different from those expressed or implied thereby, and are developed based on assumptions about such risks, uncertainties and other factors set out herein. Reference should be made to those documents that Biodexa shall time to time or announcements that may be made by Biodexa in accordance with the rules and regulations promulgated by the SEC, which contain and identify other important factors that could cause actual results to differ materially from those contained in any projections or forward-looking statements. These forward-looking statements speak only as of the date of this article. All subsequent written and oral forward-looking statements by or concerning Biodexa are expressly qualified in their entirety by the cautionary statements above. Except as may be required under relevant laws in the United States, Biodexa does not undertake any obligation to publicly update or revise any forward-looking statements because of new information, future events or events otherwise arising. SOURCE: Biodexa Pharmaceuticals PLC View the original press release on ACCESS Newswire

Phase 3Clinical ResultPhase 1License out/inOrphan Drug

17 Feb 2026

·www.biospace.com

Cogent Biosciences Reports Recent Business Highlights and Fourth Quarter and Full Year 2025 Financial Results

SUMMIT NDA for bezuclastinib in patients with NonAdvSM submitted in December 2025; APEX NDA submission for bezuclastinib in patients with AdvSM on track for 1H 2026 PEAK NDA initiated for bezuclastinib in patients with 2L GIST under Real-Time Oncology Review (RTOR) and Breakthrough Therapy Designation (BTD); completion of NDA on track for April 2026 Six abstracts from SUMMIT trial of bezuclastinib in patients with NonAdvSM accepted for presentation at 2026 AAAAI annual meeting Strong financial position with $901 million sufficient to fund operations into 2028 WALTHAM, Mass. and BOULDER, Colo., Feb. 17, 2026 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today provided a business update and reported financial results for the fourth quarter and full year of 2025. “Following three positive pivotal trials in 2025, we have entered 2026 with tremendous momentum and multiple value-creating regulatory catalysts underway,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “We have submitted our SUMMIT NDA for bezuclastinib in patients with NonAdvSM, initiated our PEAK NDA under the FDA’s RTOR program for bezuclastinib in patients with second-line GIST, and remain on track to submit our APEX NDA for bezuclastinib in patients with AdvSM in the first half of this year. These recent and upcoming milestones underscore the breadth of bezuclastinib’s best-in-class potential across KIT-mutant driven diseases. With a very strong balance sheet entering 2026, we will soon finish building our commercial organization and will be ready to launch bezuclastinib in the second half of 2026.” Recent Company Highlights In February 2026, announced that six abstracts from the SUMMIT trial of bezuclastinib in patients with NonAdvanced Systemic Mastocytosis (NonAdvSM) have been accepted for presentation at the 2026 AAAAI annual meeting. In January 2026, announced that the U. S. Food and Drug Administration (FDA) agreed to accept the PEAK NDA for bezuclastinib in patients with Gastrointestinal Stromal Tumors (GIST) who have received prior treatment with imatinib under the Real-Time Oncology Review (RTOR) program. Shortly thereafter Cogent initiated the NDA submission to the FDA under this program. Based on the results from the PEAK trial, in January 2026 bezuclastinib was also granted Breakthrough Therapy Designation for this patient population. In December 2025, presented full data from the SUMMIT trial evaluating bezuclastinib in patients with NonAdvSM, at the American Society of Hematology (ASH) annual meeting, and submitted an NDA for bezuclastinib in NonAdvSM, supported by the SUMMIT dataset. Key findings from SUMMIT included: Clear clinical benefit across all symptom domains, including significant improvements across 11 individual symptoms and the most severe symptom at baseline Reduction in objective measures of disease, including serum tryptase, correlating with improvements in symptom severity, representing the first demonstration of this relationship in NonAdvSM patients Forty-eight-week data showing continued deepening of symptomatic improvement over time In December 2025, announced topline results from the APEX trial evaluating bezuclastinib in patients with Advanced Systemic Mastocytosis (AdvSM), APEX is a registration-directed, global, open-label trial evaluating bezuclastinib in patients with AdvSM. Key findings included: Rapid and deep clinical benefit, with an objective response rate (CR+CRh+PR+CI) of 57% per mIWG criteria and 80% per PPR criteria A powerful effect on mast cell burden, with 89% of patients achieving a ≥50% reduction in bone marrow mast cells or clearance of aggregates In December 2025, announced initial preclinical results from the company’s novel, potent, selective JAK2 V617F inhibitor CGT1145 at the ASH annual meeting. These results showcased greater than 100-fold selectivity for JAK2 V617F mutations over JAK2 WT inhibition, positioning CGT1145 with a potential best-in-class profile. In November 2025, successfully completed concurrent public offerings of common stock and convertible senior notes for net proceeds of approximately $546.8 million. In November 2025, announced topline results from the Phase 3 PEAK trial of bezuclastinib in combination with sunitinib for patients with GIST who have received prior treatment with imatinib, becoming the first positive Phase 3 trial in second-line GIST patients in over 20 years. Highlights include: 16.5 months median progression free survival (mPFS) for bezuclastinib plus sunitinib compared to 9.2 months mPFS for sunitinib monotherapy (HR=0.50, CI: 0.39-0.65; p<0.0001) 46% Objective Response Rate (ORR) reported for bezuclastinib combination compared to 26% ORR for sunitinib monotherapy (p<0.0001) The safety pro the bezuclastinib combination was well tolerated with no unique risks observed with the combination when compared to the known safety pro sunitinib In October 2025, shared progress on Cogent’s internally developed KRAS(ON/OFF) inhibitor CGT1263 in a poster at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Updated results demonstrated clear selectivity over HRAS and NRAS, with picomolar (pM) activity across a broad panel of KRAS mutant cell lines. In addition, the poster also characterized CGT1815 (the prodrug of CGT1263), which is designed to optimize human pharmacokinetic performance, supported by pharmacokinetics data from both CGT1815 and CGT1263 across multiple species. Finally, the poster highlighted outcompete data in KRAS G12D and KRAS G12V tumor growth inhibition studies when compared to other KRAS exemplars including RMC-6236. Projected Near-Term Milestones Bezuclastinib Acceptance of the NDA for bezuclastinib in NonAdvSM in February 2026 Complete submission of PEAK NDA in April 2026 for bezuclastinib in patients with GIST who have received prior treatment with imatinib Submit APEX NDA in 1H 2026 for bezuclastinib in patients with AdvSM Present detailed clinical data from the PEAK and APEX pivotal trials at major medical meetings during 1H 2026 Present updated SUMMIT data across six poster presentations at the AAAAI Annual meeting in February 2026 Pending FDA approval, launch bezuclastinib in the second half of 2026 Pipeline Submit Investigational New Drug (IND) applications for CGT1815, Cogent’s novel, selective pan-KRAS(ON) inhibitor and CGT1145, Cogent’s novel, selective JAK2 V617F inhibitor Share clinical data on CGT4859, Cogent’s selective and potent FGFR 2/3 inhibitor, from its Phase 1/2 study in patients with alterations in FGFR2 or FGFR3 Complete dose escalation for both CGT4255, Cogent’s CNS-penetrant, selective mutant ErbB2 inhibitor, and CGT6297, Cogent’s novel, selective PI3Kα inhibitor Bezuclastinib - Expanded Access Program Working with the FDA, Cogent has established active Expanded Access Programs (EAPs) for U.S. patients with GIST or SM who meet disease-specific criteria and could benefit from treatment with bezuclastinib or the combination of bezuclastinib and sunitinib. A growing number of sites now offer access to the bezuclastinib EAPs. For more information please visit: Upcoming Investor Conference Leerink Healthcare Conference on Wednesday, March 11 at 10:40 a.m. ET. A live webcast can be accessed on the Investors & Media page of Cogent’s website at investors.cogentbio.com/events. A replay will be available approximately two hours after completion of the event and will be archived for up to 30 days. Fourth Quarter and Full Year 2025 Financial Results Cash and Cash Equivalents: As of December 31, 2025, Cogent had cash, cash equivalents and marketable securities of $900.8 million. Fourth quarter cash usage was driven largely by non-recurring items, including the repayment of $54.8 million of long-term debt and approximately $38.5 million of one-time, performance-based equity compensation. R&D Expenses: Research and development expenses were $75.6 million for the fourth quarter of 2025 and $269.8 million for the year ended December 31, 2025, as compared to $62.0 million for the fourth quarter of 2024 and $232.7 million for the year ended December 31, 2024. The change was driven by the continued development of bezuclastinib across three pivotal trials, including costs associated with the completed and planned NDA filings, as well as the continued progression of our early stage, preclinical and discovery programs. R&D expenses include non-cash stock compensation expense of $7.5 million for the fourth quarter of 2025 and $23.1 million for the year ended December 31, 2025, as compared to $5.0 million for the fourth quarter of 2024 and $19.0 million for the year ended December 31, 2024. G&A Expenses : General and administrative expenses were $23.9 million for the fourth quarter of 2025 and $63.6 million for the year ended December 31, 2025, as compared to $11.7 million for the fourth quarter of 2024 and $43.3 million for the year ended December 31, 2024. The increase was primarily due to the growth of the organization and activities related to the anticipated commercial launch of bezuclastinib. G&A expenses include non-cash stock compensation expense of $8.3 million for the fourth quarter of 2025 and $23.0 million for the year ended December 31, 2025, as compared to $5.0 million for the fourth quarter of 2024 and $20.8 million for the year ended December 31, 2024. Net Loss: Net loss was $102.5 million for the fourth quarter of 2025 and $328.9 million for the year ended December 31, 2025, as compared to a net loss of $67.9 million for the fourth quarter of 2024 and $255.9 million for the year ended December 31, 2024. Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that, on February 11, 2026, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of “inducement” equity awards to twelve new employees under the company’s 2020 Inducement Plan with grant dates of February 11, 2026 and February 16, 2026. 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 59,300 shares of Cogent common stock and (ii) 47,000 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 in equal installments 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 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 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 for bezuclastinib in patients with AdvSM in the first half of 2026; plans to complete the submission of an NDA for bezuclastinib in combination with sunitinib in patients with GIST in April 2026; the anticipated cash runway into 2028; bezuclastinib’s best-in-class potential across KIT-mutant driven diseases; plans to finish building a commercial organization and to launch bezuclastinib in the second half of 2026; the potential best-in-class pro the company’s JAK2 V617F inhibitor; the expectation for FDA to accept the company’s NDA for bezuclastinib in NonAdvSM in February 2026; plans to present additional clinical data from the PEAK and APEX trials at major medical meetings during the first half of 2026; and plans to submit INDs and present data on the company’s pre-clinical and early clinical stage candidates. 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 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 the date hereof. COGENT BIOSCIENCES, INC. CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands) (unaudited) Three Months Ended December 31, Year Ended December 31, 2025 2024 2025 2024 Operating expenses: Research and development $ 75,559 $ 62,045 $ 269,780 $ 232,658 General and administrative 23,934 11,689 63,583 43,281 Total operating expenses 99,493 73,734 333,363 275,939 Loss from operations (99,493 ) (73,734 ) (333,363 ) (275,939 ) Other income: Interest income 5,477 3,859 14,689 18,088 Interest expense (1,289 ) — (3,062 ) — Loss on debt extinguishment (7,181 ) — (7,181 ) — Other income (expense), net (6 ) 1,948 (20 ) 1,992 Total other income, net (2,999 ) 5,807 4,426 20,080 Net loss $ (102,492 ) $ (67,927 ) $ (328,937 ) $ (255,859 ) COGENT BIOSCIENCES, INC. SELECTED CONSOLIDATED BALANCE SHEET DATA (in thousands) (unaudited) December 31, December 31, 2025 2024 Cash, cash equivalents and marketable securities $ 900,765 $ 287,077 Working capital $ 846,402 $ 240,762 Total assets $ 937,607 $ 327,898 Total liabilities $ 301,236 $ 71,612 Total stockholders’ equity $ 636,371 $ 256,286 Contact: Christi Waarich Senior Director, Investor Relations christi.waarich@cogentbio.com 617-830-1653

Clinical ResultPhase 1Phase 3Breakthrough TherapyFinancial Statement

10 Feb 2026

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Cogent Biosciences Announces Multiple SUMMIT Posters at the 2026 AAAAI Annual Meeting

WALTHAM, Mass. and BOULDER, Colo., Feb. 10, 2026 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced multiple upcoming posters highlighting bezuclastinib results from the SUMMIT trial in NonAdvanced Systemic Mastocytosis (NonAdvSM) patients at the 2026 American Academy of Allergy Asthma & Immunology Annual Meeting (AAAAI) being held in Philadelphia, PA, February 27-March 2, 2026. In December 2025, Cogent announced that the company submitted its New Drug Application for bezuclastinib in NonAdvSM to the U.S. Food and Drug Administration. The submission is based on positive clinical data from the SUMMIT pivotal trial and follows the Breakthrough Therapy Designation for bezuclastinib in patients with SSM and patients with NonAdvSM who have received prior avapritinib. AAAAI Poster Details: Poster Presentation Title: Expanded Results from the Phase 2 Summit Trial: Bezuclastinib in Adults with Nonadvanced Systemic Mastocytosis Session Date and Time: February 28, 2026 – 9:45am – 10:45am ET Poster Number: 519 Location: Convention Center, Ground Level, Hall A Poster Presentation Title: Evaluation of Bone Formation Marker Changes in Summit, a Trial Assessing Bezuclastinib in Adults with Nonadvanced Systemic Mastocytosis: An Exploratory Analysis Session Date and Time: February 28, 2026 – 9:45am – 10:45am ET Poster Number: 520 Location: Convention Center, Ground Level, Hall A Poster Presentation Title: Results From the Phase 2 Summit Trial of Bezuclastinib in Adults with Nonadvanced Systemic Mastocytosis: Patient Experience of Living with NonAdvSM Session Date and Time: February 28, 2026 – 9:45am – 10:45am ET Poster Number: 510 Location: Convention Center, Ground Level, Hall A Poster Presentation Title: Improvement of Symptom Burden in Summit: Bezuclastinib in Adults with Nonadvanced Systemic Mastocytosis Session Date and Time: February 28, 2026 – 9:45am – 10:45am ET Poster Number: 523 Location: Convention Center, Ground Level, Hall A Poster Presentation Title: Results from the Summit Pivotal Trial: Symptom improvement correlates with reductions in objective measures of disease in adults with nonadvanced systemic mastocytosis Session Date and Time: February 28, 2026 – 9:45am – 10:45am ET Poster Number: 532 Location: Convention Center, Ground Level, Hall A Poster Presentation Title: Results in Subgroups with Unmet Need in the Summit Trial: Bezuclastinib in Adults with Nonadvanced Systemic Mastocytosis Session Date and Time: February 28, 2026 – 9:45am – 10:45am ET Poster Number: 521 Location: Convention Center, Ground Level, Hall A 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 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 . Contact: Christi Waarich Senior Director, Investor Relations christi.waarich@cogentbio.com 617-830-1653

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Indication	Highest Phase	Country/Location	Organization	Date
Systemic Mastocytosis	NDA/BLA	United States	Cogent Biosciences, Inc.	30 Dec 2025
Metastatic Gastrointestinal Stromal Tumor	Phase 3	United States	Cogent Biosciences, Inc.	14 Apr 2022
Metastatic Gastrointestinal Stromal Tumor	Phase 3	Argentina	Cogent Biosciences, Inc.	14 Apr 2022
Metastatic Gastrointestinal Stromal Tumor	Phase 3	Australia	Cogent Biosciences, Inc.	14 Apr 2022
Metastatic Gastrointestinal Stromal Tumor	Phase 3	Brazil	Cogent Biosciences, Inc.	14 Apr 2022
Metastatic Gastrointestinal Stromal Tumor	Phase 3	Canada	Cogent Biosciences, Inc.	14 Apr 2022
Metastatic Gastrointestinal Stromal Tumor	Phase 3	Chile	Cogent Biosciences, Inc.	14 Apr 2022
Metastatic Gastrointestinal Stromal Tumor	Phase 3	Czechia	Cogent Biosciences, Inc.	14 Apr 2022
Metastatic Gastrointestinal Stromal Tumor	Phase 3	Denmark	Cogent Biosciences, Inc.	14 Apr 2022
Metastatic Gastrointestinal Stromal Tumor	Phase 3	France	Cogent Biosciences, Inc.	14 Apr 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05186753 (Summit, ASH2025) Manual	Phase 2	Systemic Mastocytosis KIT c.2447 C>T (p.D816V) mutation	179	Bezuclastinib + BSC	vrixcpftuz(hjwmnyffuk) = nritlgmmla rrqdndzxvj (rqmvvamvqy, -27.6 to -21.1) View more	Positive	06 Dec 2025
				Placebo + BSC	vrixcpftuz(hjwmnyffuk) = dxvdjabtgo rrqdndzxvj (rqmvvamvqy, -19.6 to -11.2) View more
NCT05208047 (PEAK, Company_Website) Manual	Phase 3	Gastrointestinal Stromal Tumors Second line	-	bezuclastinib + sunitinib	dzieyxsfav(iwiejjbbby) = kpmafkoefp xwoxqveohs (hnorabvywd ) View more	Positive	10 Nov 2025
				sunitinib	dzieyxsfav(iwiejjbbby) = nojyitrtgs xwoxqveohs (hnorabvywd ) View more
NCT05186753 (SUMMIT, Corporate Publications 1 \| Corporate Publications 2 \| Company_Website) Manual	Phase 2	Systemic Mastocytosis \| Mastocytosis	179	Bezuclastinib	ttlxygoxkh(yfkgqhazgn) = mlcitygcnf joezgpzxyy (skruwyvnel ) Met View more	Positive	07 Jul 2025
				placebo	ttlxygoxkh(yfkgqhazgn) = vgafwdmjox joezgpzxyy (skruwyvnel ) Met View more
NCT06208748 (SARC044, ASCO2025)	Phase 2	Gastrointestinal Stromal Tumors KIT exon 9	40	Bezuclastinib 600 mg daily + Sunitinib 37.5 mg daily	qmsgmbypwg(sdjdsqlhzc) = puxoerumeg virgqjdypk (geusujpocn )	Positive	30 May 2025
NCT05186753 (SUMMIT, Company_Website) Manual	Phase 2	Systemic Mastocytosis	-	Bezuclastinib 100 mg	gteexxnblo(alhzwstzrl) = scaptahxfp rxdefpacuy (medczxezpr ) View more	Positive	27 Feb 2025
				Placebo	-
NCT05186753 (SUMMIT, GlobeNewswire) Manual	Not Applicable	Systemic Mastocytosis	27	Bezuclastinib 100 mg	bfquqajvmy(xynculflsv) = uwjewkjpfu asreqvzije (eatkckqmeq ) View more	Positive	09 Dec 2024
NCT04996875 (Apex, ASH2024) Manual	Phase 2	Systemic Mastocytosis	32	Bezuclastinib	lsiweqasjv(tydpabrbrm) = kdfgfrlxbq jeswblnczb (ulbnfxrood ) View more	Positive	08 Dec 2024
NCT05186753 (Summit, SOHO2024)	Phase 2	Aggressive Systemic Mastocytosis Serum tryptase \| KIT D816V positive	-	Bezuclastinib low dose	caktackgqu(ysipfrhzwq) = ydkcwemtls uyiyoswpwg (fyigkrrxyv ) View more	Positive	04 Sep 2024
				Bezuclastinib high dose	caktackgqu(ysipfrhzwq) = kooeaglalk uyiyoswpwg (fyigkrrxyv ) View more
NCT05208047 (Peak, ASCO2024) Manual	Phase 3	Gastrointestinal Stromal Tumors KIT Mutation	42	Bezuclastinib	gxysghkowo(vyebwpzmdi) = The majority of TEAEs were low grade and reversible with low rate (38%) of Grade 3+ events eajpuvedrg (xiqhseqead )	Positive	24 May 2024
NCT05186753 (Summit, AAAAI2024) Manual	Phase 2	Systemic Mastocytosis KIT D816V positive	50	Bezuclastinib low dose	hrgfulugvf(tdvdkxgesz) = jitqsqrmhd nnhpgnswio (lryogdugpr ) View more	Positive	23 Feb 2024
				Bezuclastinib high dose	hrgfulugvf(tdvdkxgesz) = zpnmmbjdjc nnhpgnswio (lryogdugpr ) View more

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