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

/ 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 482 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 Gastrointestinal Stromal Tumors (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. This study also contains two substudies: 1) a drug-drug interactions (DDI) substudy will investigate the potential for CGT9486 to be a Cytochrome P450 (CYP)3A4 inducer in approximately 16 patients who have received at least one prior line of therapy for GIST and 2) a substudy intended to test the efficacy of bezuclastinib and sunitinib as first-line (1L) treatment of GIST in approximately 40 participants with KIT exon 9 mutations and no prior systemic therapy (with the exception of up to 10 subjects with ongoing imatinib therapy of ≤4 weeks).

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 Apr 2026·JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY

Gastrointestinal Stromal Tumors: Molecular Mechanisms of Drug Resistance and Advances in Therapeutic Strategies

Review

Author: Zhi, Ding ; Fazhi, Zhao ; Huachuan, Zhang ; Yan, Chen ; Jingnuo, Ding ; Da, Zhou

ABSTRACT:

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the digestive tract, are primarily driven by gain‐of‐function mutations in the receptor tyrosine kinases KIT or PDGFRA. The introduction of imatinib, a selective tyrosine kinase inhibitor (TKI), revolutionized the management of advanced GIST. However, the emergence of drug resistance remains a major clinical challenge, limiting long‐term efficacy. Resistance mechanisms are multifactorial, predominantly involving secondary mutations in KIT or PDGFRA that impair TKI binding or stabilize the kinase in an active conformation. Beyond genomic alterations, nonmutational adaptive responses—including dysregulation of noncoding RNAs, metabolic reprogramming, epigenetic modifications, and an immunosuppressive tumor microenvironment—significantly contribute to treatment failure. This review comprehensively analyzes these resistance pathways and discusses the evolution of therapeutic strategies toward precision medicine. Current approaches emphasize molecular subtype‐guided first‐line therapy, ctDNA‐driven sequencing of subsequent lines, and the use of novel TKIs (e.g., avapritinib, ripretinib, bezuclastinib) tailored to specific resistance mutations. Furthermore, we explore emerging modalities such as boron neutron capture therapy (BNCT), which offers a kinase‐independent mechanism to target resistant disease, and combination strategies that integrate immunotherapy, epigenetic modulators, and pathway‐specific inhibitors. Advances in liquid biopsy and molecular profiling are enabling real‐time adaptation of therapy, moving GIST management toward a dynamic, personalized paradigm aimed at overcoming resistance and improving patient outcomes.

03 Jul 2023·Expert opinion on emerging drugs

Systemic mastocytosis: 2023 update on diagnosis and management in adults

Review

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

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.

136

News (Medical) associated with Bezuclastinib

10 Aug 2026

·www.biospace.com

Cogent Biosciences Reports Recent Business Highlights and Second Quarter 2026 Financial Results

On track for potential approval of bezuclastinib for GIST patients (PDUFA November 30) and NonAdvSM patients (PDUFA December 30) later this year; AdvSM New Drug Application submitted to FDA on June 30 Completed onboarding of expert cross-functional Cogent customer-facing team, including all field-based commercial and medical team members Strong pro forma cash balance of $865.9 million, sufficient to fund operations into late 2028 WALTHAM, Mass. and BOULDER, Colo., Aug. 10, 2026 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today reported financial results for the second quarter ended June 30, 2026. ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); “The first half of 2026 has been marked by transformative milestones toward our vision of creating best-in-class therapies for patients fighting rare, mutationally driven diseases as we submitted three New Drug Applications following positive results from each of the bezuclastinib pivotal trials,” said Andrew Robbins, the Company’s President and Chief Executive Officer. “We are excited to welcome the new Cogent customer facing team to the company, and supported by our strong balance sheet, we are well prepared to launch bezuclastinib and advance the standard of care for patients with GIST and Systemic Mastocytosis while continuing to invest in our broader pipeline of precision therapies for genetically defined diseases.” Recent Business Highlights Cogent Biosciences Integrated Business Team Successfully hired and onboarded all Integrated Business Team members, spanning clinical account managers, patient access navigators and patient educators. Selected for their expertise in commercializing Oncology and Rare Disease products, Cogent now has an exceptional commercial field team in place across the country. Together with our existing medical affairs team, Cogent is well prepared for potential launch with a broad, expert, cross-functional customer-facing organization. Bezuclastinib in GIST Presented detailed clinical data from the Phase 3 PEAK trial evaluating bezuclastinib in combination with sunitinib vs. sunitinib monotherapy in patients with imatinib-resistant or intolerant Gastrointestinal Stromal Tumors (GIST) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. As of the cutoff date, September 30, 2025, the bezuclastinib combination demonstrated a substantial and highly statistically significant clinical benefit on the primary endpoint of PFS, reducing risk of disease progression or death compared to the current standard of care by 50% (hazard ratio of 0.50, 95% CI: 0.39 – 0.65). mPFS, as assessed by blinded independent central review, was 16.5 months for the bezuclastinib combination vs. 9.2 months for sunitinib monotherapy. Additionally, the bezuclastinib combination demonstrated an unprecedented ORR in imatinib-resistant/intolerant patients, with 46% of patients treated with the bezuclastinib combination achieving an objective response compared to 26% of patients treated with sunitinib. Data for overall survival remains immature. Based on the ongoing patients receiving treatment on the bezuclastinib arm as of March 31, 2026, the mean duration of treatment for the bezuclastinib combination is estimated to be 21.4 months. Announced the initiation of a single-arm, 40 patient extension cohort of the PEAK trial investigating the safety and efficacy of the bezuclastinib combination in first-line GIST patients with KIT exon 9 primary mutations who have received limited or no imatinib treatment. This cohort is designed to prospectively measure ORR and PFS in this patient population, building upon the 25.1 month mPFS reported in a subgroup of 32 patients with detectable exon 9 mutations treated with the bezuclastinib combination in the Phase 3 PEAK trial. Announced FDA acceptance of the New Drug Application (NDA) with priority review for bezuclastinib in combination with sunitinib in patients with GIST who have received prior treatment with imatinib. Bezuclastinib in Systemic Mastocytosis Announced submission of the NDA for bezuclastinib in Advanced Systemic Mastocytosis (AdvSM). Presented detailed data from the pivotal APEX trial at the 2026 European Hematology Association (EHA) Congress. As of the March 31, 2026 data cutoff, 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. The primary endpoint of response per mIWG-MRT-ECNM was assessed on 68 evaluable patients and showed 65% ORR (CR+CRh+PR+CI), including 57% of patients who achieved CR, CRh or PR as best response. Announced completion of enrollment in the “avapritinib switch” SUMMIT extension trial with preliminary results expected by end of 2026. Presented preclinical data from the novel JAK2 V617F program at EHA. The poster highlighted CGT1145, a potent inhibitor of the JAK2 V617F mutation with >100x selectivity over JAK2 WT and the JAK1/3 isoforms, along with high oral bioavailability and low clearance across species. CGT1145 has the potential to eradicate JAK2 V617F myeloproliferative neoplasm propagating cells and induce molecular remission with improved hematologic tolerability. Anticipated Upcoming Milestones Potential FDA approval of bezuclastinib in GIST – PDUFA date of November 30, 2026 Potential FDA approval of bezuclastinib in NonAdvSM – PDUFA date of December 30, 2026 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 Complete dose escalation for CGT4255, Cogent’s CNS-penetrant, selective mutant ErbB2 inhibitor Second Quarter 2026 Financial Results Cash Position: As of June 30, 2026, Cogent had cash, cash equivalents and marketable securities of $792.3 million. The company expects its existing cash, cash equivalents and marketable securities, with the $73.6 million gross proceeds from shares sold through the Company’s at-the-market (ATM) facility after the end of the quarter, will be sufficient to fund its operating expenses and capital expenditure requirements into late 2028, including through potential FDA approvals of bezuclastinib for GIST, NonAdvSM and AdvSM and early commercial launch activities. R&D Expenses: Research and development expenses were $70.8 million for the second quarter of 2026 as compared to $62.2 million for the second quarter of 2025. The increase was primarily driven by costs to support the SUMMIT, PEAK and APEX clinical programs, regulatory activities associated with potential approvals of bezuclastinib, continued investment in the company's early-stage research pipeline, and pre-approval manufacturing costs that will be capitalized following anticipated FDA approval. R&D expenses include non-cash stock compensation expense of $8.6 million for the second quarter of 2026 as compared to $5.0 million for the second quarter of 2025. G&A Expenses: General and administrative expenses were $31.8 million for the second quarter of 2026 as compared to $13.4 million for the second quarter of 2025. The increase was primarily driven by continued investments in commercial readiness, including personnel and infrastructure to support the anticipated launch of bezuclastinib, as well as overall organizational growth. G&A expenses include non-cash stock compensation expense of $8.5 million for the second quarter of 2026 as compared to $4.8 million for the second quarter of 2025. Net Loss: Net loss was $96.4 million for the second quarter of 2026 as compared to a net loss of $73.5 million for the same period of 2025. Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that, on August 4, 2026, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of “inducement” equity awards to 59 new employees under the company’s 2020 Inducement Plan with grant dates of August 4, 2026 and August 10, 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 226,700 shares of Cogent common stock and (ii) 189,700 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. 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 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: the company’s expectation to receive regulatory approval of bezuclastinib later this year for both GIST patients and NonAdvSM patients; the company’s anticipated cash runway into late 2028 and the expectation that it will be sufficient to fund operations through anticipated FDA approvals of bezuclastinib for GIST, NonAdvSM and AdvSM and early commercial launch activities; the company’s level of preparation to launch bezuclastinib and advance the standard of care for patients with GIST and Systemic Mastocytosis while also continuing to invest in its broader pipeline of precision therapies for genetically defined diseases; the company’s expectation that it will present preliminary results from its “avapritinib switch” SUMMIT extension trial by the end of 2026; the potential of CGT1145 to eradicate JAK2 V617F myeloproliferative neoplasm propagating cells and induce molecular remission with improved hematologic tolerability; the company’s plans to submit INDs for both CGT1815, its novel, selective pan-KRAS(ON) inhibitor, and CGT1145, its novel, selective JAK2 V617F inhibitor; and the company’s plans to complete dose escalation for CGT4255, its CNS-penetrant, selective mutant ErbB2 inhibitor. 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, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings 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. COGENT BIOSCIENCES, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands) (unaudited) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 Operating expenses: Research and development $ 70,811 $ 62,203 $ 146,176 $ 125,232 General and administrative 31,827 13,379 60,069 25,283 Total operating expenses 102,638 75,582 206,245 150,515 Loss from operations (102,638 ) (75,582 ) (206,245 ) (150,515 ) Other income: Interest income 7,461 2,373 15,069 5,325 Interest expense (1,217 ) (314 ) (2,430 ) (314 ) Other income (expense), net (11 ) (6 ) (151 ) (11 ) Total other income, net 6,233 2,053 12,488 5,000 Net loss $ (96,405 ) $ (73,529 ) $ (193,757 ) $ (145,515 ) COGENT BIOSCIENCES, INC. SELECTED CONDENSED CONSOLIDATED BALANCE SHEET DATA (in thousands) (unaudited) June 30, December 31, 2026 2025 Cash, cash equivalents and marketable securities $ 792,300 $ 900,765 Working capital $ 745,524 $ 846,402 Total assets $ 834,546 $ 937,607 Total liabilities $ 302,158 $ 301,236 Total stockholders’ equity $ 532,388 $ 636,371 CONTACT: Contact: Christi Waarich Sr. Director, Investor Relations christi.waarich@cogentbio.com 617-830-1653

Clinical ResultPhase 3Financial StatementDrug ApprovalASCO

06 Jul 2026

·www.biospace.com

Cogent Biosciences Announces Submission of New Drug Application (NDA) for Bezuclastinib in Advanced Systemic Mastocytosis (AdvSM)

Submission based on results of APEX pivotal trial which demonstrated bezuclastinib objective response rate (CR+CRh+PR+CI) of 65% per mIWG criteria and 81% ORR per PPR criteria with a well-tolerated safety pro AdvSM patients APEX NDA is third submission for bezuclastinib in six months; PEAK and SUMMIT reviews ongoing and on track for anticipated Q4 2026 approval WALTHAM, Mass. and BOULDER, Colo., June 30, 2026 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced it has submitted its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for bezuclastinib in Advanced Systemic Mastocytosis (AdvSM). The submission is based on positive clinical data from the APEX pivotal trial. “We are pleased to announce the submission of our NDA for patients with Advanced Systemic Mastocytosis based on the impressive results from the APEX trial which demonstrated that a highly selective KIT mutant inhibitor like bezuclastinib can deliver clear clinical benefit without the severe tolerability challenges associated with currently available treatments,” said Andrew Robbins, President and Chief Executive Officer. “We are working closely with the FDA on all three of our submissions and remain confident that bezuclastinib will achieve its first approvals later this year. I’d also like to congratulate our small, but exceptionally talented, Cogent development team, whose amazing work analyzing, presenting and submitting data from three pivotal trials in less than twelve months has rapidly positioned the company to achieve our vision of creating best-in-class therapies for patients fighting rare, mutational driven diseases.” The NDA submission is supported by data from the pivotal APEX trial, which were most recently presented at the 2026 European Hematology Association (EHA) Congress. As of the March 31, 2026 data cutoff, 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. The primary endpoint of response per mIWG-MRT-ECNM was assessed on 68 evaluable patients and showed 65% ORR (CR+CRh+PR+CI), including 57% of patients who achieved CR, CRh or PR as best response. Additional highlights included: Key secondary endpoint of response per pure pathological response (PPR) criteria was assessed on 81 patients which showed an 81% ORR (CR+CRh+PR). Bezuclastinib demonstrated reversal of bone marrow pathobiology including rapid and deep reductions in aberrant CD25 and CD30 expression, normalization of mast cell morphology, normalization of bone marrow cellularity, and improvement in myelofibrosis. Bezuclastinib demonstrated durable clinical activity and prolonged PFS with a 12-month PFS rate of 79% and a 12-month OS rate of 87%. Median duration of PFS and OS were immature at the time of the data cutoff. Bezuclastinib achieved clear and clinically significant reductions in objective disease markers for these AdvSM patients: Outcome measure Bezuclastinib Proportion with ≥50% reduction in serum tryptase (n=80) 89 % Proportion with ≥50% reduction in bone marrow mast cells or clearance of aggregates (n=80) 89 % Proportion with ≥50% reduction in KIT D816V variant allele frequency (n=43) 91 % In the APEX study, bezuclastinib also demonstrated robust improvement in disease pathology, with effects observed as early as eight weeks, including high PPR rates, improvement (including normalization) in bone marrow mast cell distribution, improvement in broader bone marrow characteristics and a majority of patients achieving normalization of serum tryptase. In addition, approximately one-third of patients treated with bezuclastinib achieved undetectable levels of KIT D816V VAF, suggesting modification of the underlying AdvSM disease with bezuclastinib treatment. As of the data cutoff, bezuclastinib was well-tolerated, with infrequent need for dose reduction or discontinuation for treatment-related adverse events (TRAEs). The most frequent TRAEs reported on bezuclastinib treatment were hair color change (31%), neutropenia (31%), altered taste (28%), thrombocytopenia (25%), and ALT/AST elevations (21%). The majority of transaminase elevations were of low grade, asymptomatic and reversible. Of the two patients who experienced Grade 3 transaminase elevation, one discontinued treatment and one remains on therapy following dose reduction. Bezuclastinib - Expanded Access Program Working with the FDA, Cogent has established active Expanded Access Programs (EAPs) for U.S. patients SM or GIST who meet disease-specific criteria and could benefit from treatment with bezuclastinib or the combination of bezuclastinib and sunitinib. For more information please visit: . Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that, on June 26, 2026, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of “inducement” equity awards to two new employees under the company’s 2020 Inducement Plan with a grant date of June 29, 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 7,600 shares of Cogent common stock and (ii) 7,000 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. 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: the expectation that both of the company’s NDAs for bezuclastinib in GIST and NonAdvSM will be approved by the FDA in the fourth quarter of 2026 and the expectation that the company will achieve its vision of creating best-in-class therapies for patients fighting rare, mutational driven diseases. 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 Annual Report on Form 10-K, as supplemented by Quarterly Reports on Form 10-Q and other filings Cogent makes with the SEC from time to time . 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 a 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 617-830-1653 CONTACT: christi.waarich@cogentbio.com

Clinical ResultNDAClinical Study

12 Jun 2026

·www.biospace.com

Cogent Biosciences Announces Detailed Data from APEX Pivotal Trial of Bezuclastinib in Patients with Advanced Systemic Mastocytosis at the 2026 European Hematology Association (EHA) Congress

-- Bezuclastinib demonstrated rapid and deep clinical benefit in AdvSM patients resulting in an updated objective response rate (CR+CRh+PR+CI) of 65% per mIWG criteria and 81% ORR per PPR criteria – -- Bezuclastinib demonstrated a powerful effect on mast cell burden with 91% of patients achieving ≥50% reduction in variant allele frequency and 89% of patients achieving ≥50% reduction in bone marrow mast cells or clearance of aggregates – -- Bezuclastinib continues to demonstrate a favorable safety and tolerability profile – -- APEX NDA to be submitted in June 2026 – WALTHAM, Mass. and BOULDER, Colo., June 12, 2026 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced detailed and updated clinical results from the registration-directed APEX 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. The company also shared a more detailed review of the pathobiology data in AdvSM patients from the APEX trial, reinforcing the rapid and deep clinical benefit bezuclastinib has demonstrated in these patients. The data will be presented at the 2026 European Hematology Association (EHA) Congress taking place in Stockholm, Sweden, June 11-14, 2026. “We are excited to share updated and detailed results from the APEX trial in AdvSM patients, building upon previously announced results from bezuclastinib in the SUMMIT trial in NonAdvSM patients,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “The results shown across these two trials demonstrate that a selective, potent KIT D816V inhibitor like bezuclastinib will have tremendous opportunity to become the new standard of care and change the lives of patients living with systemic mastocytosis. We are on track to complete the APEX NDA submission in the very near future and plan to launch bezuclastinib later this year in both systemic mastocytosis and GIST following FDA approval.” As of the updated data cutoff of March 31, 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. The primary endpoint of response per mIWG-MRT-ECNM was assessed on 68 evaluable patients and showed 65% ORR (CR+CRh+PR+CI), including 57% of patients who achieved CR, CRh or PR as best response. Additional highlights include: Key secondary endpoint of response per pure pathological response (PPR) criteria was assessed on 81 patients which showed an 81% ORR (CR+CRh+PR). Bezuclastinib demonstrated reversal of bone marrow pathobiology including rapid and deep reductions in aberrant CD25 and CD30 expression, normalization of mast cell morphology, normalization of bone marrow cellularity, and improvement in myelofibrosis. Bezuclastinib demonstrated durable clinical activity and prolonged PFS with a 12-month PFS rate of 79% and a 12-month OS rate of 87%. Median duration of PFS and OS were immature at the time of the data cutoff. Bezuclastinib achieved clear and clinically significant reductions in objective disease markers for these AdvSM patients: Outcome measure Bezuclastinib Proportion with ≥50% reduction in serum tryptase (n=80) 89 % Proportion with ≥50% reduction in bone marrow mast cells or clearance of aggregates (n=80) 89 % Proportion with ≥50% reduction in KIT D816V variant allele frequency (n=43) 91 % “The results from the APEX trial demonstrate clear evidence of bezuclastinib’s rapid and deep clinical activity in patients with advanced systemic mastocytosis,” 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. "Coupled with an impressive safety and tolerability pro off-target toxicities that allows for long-term therapeutic dosing, bezuclastinib will become an important treatment option for patients with advanced SM.” Pathobiology Data Cogent will also present new data highlighting the impact bezuclastinib has at a cellular level in patients with AdvSM. In the APEX study, bezuclastinib demonstrated robust improvement in disease pathology, with effects observed as early as eight weeks, including high PPR rates, improvement (including normalization) in bone marrow mast cell distribution, improvement in broader bone marrow characteristics and a majority of patients achieving normalization of serum tryptase. In addition, approximately one-third of patients treated with bezuclastinib achieved undetectable levels of KIT D816V VAF, signifying modification of the underlying AdvSM disease with bezuclastinib treatment. APEX Safety and Tolerability As of the data cutoff, bezuclastinib continued to be well-tolerated, with infrequent need for dose reduction or discontinuation for treatment-related adverse events (TRAEs). The most frequent TRAEs reported on bezuclastinib treatment were hair color change (31%), neutropenia (31%), altered taste (28%), thrombocytopenia (25%), and ALT/AST elevations (21%). The majority of transaminase elevations were of low grade, asymptomatic and reversible. Of the two patients who experienced Grade 3 transaminase elevation, one discontinued treatment and one remains on therapy following dose reduction. The EHA posters and presentation will be available on the Cogent website at: Bezuclastinib - Expanded Access Program Working with the FDA, Cogent has established active Expanded Access Programs (EAPs) for U.S. patients SM or GIST who meet disease-specific criteria and could benefit from treatment with bezuclastinib or the combination of bezuclastinib and sunitinib. For more information please visit: 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. 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 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: the company’s plans to submit an IND for bezuclastinib in AdvSM in June 2026; the expectation that bezuclastinib will become the new standard of care and change the lives of patients living with systemic mastocytosis; the company’s plans to launch bezuclastinib commercially later this year in both systemic mastocytosis and GIST following FDA approval; and the expectation that bezuclastinib will become an important treatment option for patients with AdvSM. 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 Annual Report on Form 10-K, as supplemented by Quarterly Reports on Form 10-Q and other filings Cogent makes with the SEC from time to time . 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 a 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: Contact: Christi Waarich Senior Director, Investor Relations christi.waarich@cogentbio.com 617-830-1653

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Aggressive Systemic Mastocytosis	NDA/BLA	United States	Cogent Biosciences, Inc.	30 Jun 2026
Gastrointestinal Stromal Tumors	NDA/BLA	United States	Cogent Biosciences, Inc.	01 Apr 2026
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

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05208047 (Peak, ASCO2026)	Phase 3	Gastrointestinal Stromal Tumors Second line	413	Bezuclastinib 600 mg QD + Sunitinib 37.5 mg QD	emuwccnbbf(iyfmdcuutw) = wlumtnrang cxxbdgkzyq (gulacyllie, 13.8 - 19.2) View more	Positive	29 May 2026
				Sunitinib 37.5 mg QD	emuwccnbbf(iyfmdcuutw) = wssiummjjy cxxbdgkzyq (gulacyllie, 7.2 - 11.0) View more
NCT04996875 (Apex, EHA2026)	Phase 2	Aggressive Systemic Mastocytosis KIT D816V	81	Bezuclastinib 150 mg once daily	ormidjytjz(lmfkygesso) = buladgixpp eouvtsgfuo (rdgffdlcbu ) View more	Positive	12 May 2026
NCT05186753 (Summit, AAAAI2026)	Phase 2	Systemic Mastocytosis KIT c.2447 C>T (p.D816V) mutations	179	Bezuclastinib	wymupggeor(sjoadweeko) = nmhdqiqgmu qmgdjzqyzr (ztzvfthwgw ) View more	Positive	27 Feb 2026
				Placebo	wymupggeor(sjoadweeko) = sigdjksrjx qmgdjzqyzr (ztzvfthwgw ) View more
NCT05186753 (Summit, AAAAI2026)	Phase 2	Systemic Mastocytosis KIT c.2447 C>T (p.D816V) mutation	12	Bezuclastinib	gloxhmguuz(dhzhvwhijh) = jdmkxelwja hdkqdxqchs (kfutlcynqj ) View more	Positive	27 Feb 2026
NCT05186753 (Summit, AAAAI2026)	Phase 2	Systemic Mastocytosis KIT c.2447 C>T (p.D816V)	179	Bezuclastinib	auyzybhfoi(kzmsvonihh) = uwqcnemxuf ysjogbespa (zcrvrobxpn )	Positive	27 Feb 2026
				Placebo	auyzybhfoi(kzmsvonihh) = rwhraxzmts ysjogbespa (zcrvrobxpn )
NCT05186753 (Summit, ASH2025) Manual	Phase 2	Systemic Mastocytosis KIT c.2447 C>T (p.D816V) mutation	179	Bezuclastinib + BSC	aaiyspnzcy(btmcimheah) = zfjicfwibn oripqvwmnq (aqzcdpeqrh, -27.6 to -21.1) View more	Positive	06 Dec 2025
				Placebo + BSC	aaiyspnzcy(btmcimheah) = wijhxmxtwk oripqvwmnq (aqzcdpeqrh, -19.6 to -11.2) View more
NCT05208047 (PEAK, Company_Website) Manual	Phase 3	Gastrointestinal Stromal Tumors Second line	-	bezuclastinib + sunitinib	yyvemshefl(rughwbrgmq) = lxiisszxuo alsstwtday (bfsswtjtxo ) View more	Positive	10 Nov 2025
				sunitinib	yyvemshefl(rughwbrgmq) = fyyvvjtfgm alsstwtday (bfsswtjtxo ) View more
NCT05186753 (SUMMIT, Corporate Publications 1 \| Corporate Publications 2 \| Company_Website) Manual	Phase 2	Systemic Mastocytosis \| Mastocytosis	179	Bezuclastinib	uvonjogypf(hhwlnovxei) = uvitubtqql fqgadcunqj (ksynyczxhb ) Met View more	Positive	07 Jul 2025
				placebo	uvonjogypf(hhwlnovxei) = avrdsbfxfi fqgadcunqj (ksynyczxhb ) Met View more
NCT06208748 (SARC044, ASCO2025)	Phase 2	Gastrointestinal Stromal Tumors KIT exon 9	40	Bezuclastinib 600 mg daily + Sunitinib 37.5 mg daily	bhvegteaif(efytxjoshl) = kkqyrymvhn jmdgqcrpwu (txusgwejbo )	Positive	30 May 2025
NCT05186753 (SUMMIT, Company_Website) Manual	Phase 2	Systemic Mastocytosis	-	Bezuclastinib 100 mg	wuecwmwcic(lqdedzhsml) = fmfxyzvotk tpnykxphep (zuihriuaxi ) View more	Positive	27 Feb 2025
				Placebo	-

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