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Peak Trial: Bezuclastinib + Sunitinib in Gastrointestinal Stromal Tumors (GIST) Top - Line Results Investor Webcast November 10, 2025
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Forward-Looking Statements and Risk Factors This presentation and the accompanying oral commentary contain forward-looking statements that involve risks, uncertainties and assumptions. If the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materially from those expressed or implied by such forward looking statements. All statements other than statements of historical fact could be deemed forward-looking, including, but not limited to, any statements of the plans, strategies, and objectives of management for future operations, including our clinical development and commercialization plans; any projections of financial information; any statement about historical results that may suggest trends for our business; any statement of expectation or belief regarding future events; potential markets or market size, technology developments, our clinical product pipeline, clinical and pre-clinical data or the implications thereof, enforceability of our intellectual property rights, competitive strengths or our position within the industry; any statements regarding the anticipated benefits of our collaborations or other strategic transactions; and any statements of assumptions underlying any of the items mentioned. These statements are based on estimates and information available to us at the time of this presentation and are not guarantees of future performance. Actual results could differ materially from our current expectations as a result of many risks and uncertainties, including but not limited to, risks associated with: the potential impacts of raising additional capital, including dilution to our existing stockholders, restrictions on our operations or requirements that we relinquish rights to our technologies or product candidates; business interruptions resulting from the coronavirus disease outbreak or similar public health crises, which could cause a disruption of the development of our product candidates and adversely impact our business; the success, cost, and timing of our product development activities and clinical trials; the timing of our planned regulatory submissions to the FDA for our product candidate bezuclastinib and feedback from the FDA as to our plans; our ability to obtain and maintain regulatory approval for our bezuclastinib product candidate and any other product candidates we may develop, and any related restrictions, limitations, and/or warnings in the label of an approved product candidate; the potential for our identified research priorities to advance our bezuclastinib product candidate; the ability to license additional intellectual property relating to our product candidates from third parties and to comply with our existing license agreements and collaboration agreements; the ability and willingness of our third-party research institution collaborators to continue research and development activities relating to our product candidates; our ability to commercialize our products in light of the intellectual property rights of others; our ability to obtain funding for our operations, including funding necessary to complete further development and commercialization of our product candidates; the scalability and commercial viability of our manufacturing methods and processes; the commercialization of our product candidates, if approved; our plans to research, develop, and commercialize our product candidates; our ability to attract collaborators with development, regulatory, and commercialization expertise; our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidates; and the fact that interim clinical data may not be indicative of future results, among others. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to our business in general, see our periodic filings filed from time to time with the Securities and Exchange Commission. Unless as required by law, we assume no obligation and do not intend to update these forward-looking statements or to conform these statements to actual results or to changes in our expectations. All of Cogent Biosciences, Inc. (“Cogent”) product candidates are investigational product candidates and their safety and efficacy have not yet been established. Cogent has not obtained marketing approval for any product, and there is no certainty that any marketing approvals will be obtained or as to the timelines on which they will be obtained. 2
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Agenda and Speakers 3 Andrew Robbins President and Chief Executive Officer Neeta Somaiah, M.D. Professor and Department Chair, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center Jessica Sachs, M.D. Chief Medical Officer • Introduction Andrew Robbins • GIST Disease Overview • Peak Top-Line Results • Patient Cases Dr. Neeta Somaiah • Summary Andrew Robbins • Q&A All
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4 Imatinib Sunitinib Regorafenib Ripretinib ORR ~60% PFS ~19 months ORR ~7% PFS ~5.5 months ORR ~5% PFS ~4.8 months 1L 2L 3L 5.6 4.8 5.5 8.3 8.0 1 0 1 2 3 4 5 6 7 8 9 Avapritinib VOYAGER Regorafenib USPI Sunitinib USPI Sunitinib INTRIGUE Ripretinib INTRIGUE Bezuclastinib + Sunitinib PEAK 2L 3L Months GIST mPFS benchmarks ORR/PFS for all approved agents was obtained from labeled information from those agents ORR ~9% PFS ~6.3 months 4L Modest historical performance of novel agents in imatinib-resistant setting emphasizes unmet need Unmet Medical Need Remains for Patients with Imatinib-Resistant or Intolerant GIST
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Peak Phase 3 Top - Line Results Full Results Expected to be Presented at an Upcoming Medical Meeting
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Significant Unmet Need Remains for Patients with Gastrointestinal Stromal Tumors (GIST) 6 Symptoms3 Diarrhea, Nausea, Vomiting, Abdominal pain, Bloating, Gastroesophageal reflux disease, GI bleeding, Loss of appetite, Weight loss 1Key statistics for gastrointestinal stromal tumors. American Cancer Society. 2 Gramza AW, Corless CL, Heinrich MC., 2009. 3 Signs and symptoms of gastrointestinal stromal tumors. American Cancer Society. L: Line of Therapy • Up to 6,000 GIST cases diagnosed annually in US, over 80% of which express KIT mutations, typically exons 11 and 9.1,2 • Tumors can start anywhere in the GI tract, but they occur most often in the stomach (about 60%) or the small intestine (about 35%).1 • While imatinib provides disease control in the majority of patients in the 1L setting, ~60% of patients with GIST develop resistance within 2 years, primarily due to mutations in exon 13/14 and/or exon 17/18.1,2 • Additional FDA-approved sequential lines of therapy include sunitinib, regorafenib, and ripretinib; however, each is only effective against a subset of resistance mutations and disease progression results from clonal heterogeneity.
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Combination of Bezuclastinib + Sunitinib Inhibits the Full Spectrum of Primary and Secondary Mutations • No single TKI inhibits all KIT mutations. 1-11 • The combination of bezuclastinib + sunitinib inhibits mutations in KIT exons 9, 11, 13, 14, 17, and 18, targeting the full spectrum of primary and secondary mutations relevant in advanced GIST. 7 Treatments Exon 9 Exon 11 Exon 13 Exon 14 Exon 17 D816V Exon 18 Imatinib Regorafenib Velzatinib (IDRX-42) Ripretinib Sunitinib Bezuclastinib + Sunitinib Moderate InhibitionNo Inhibition Strong Inhibition 1 Plexxikon. Data on file. 2 Serrano C et al. Br J Cancer, 2019. 3 Evans EK et al. Sci Transl Med, 2017. 4 Trent J et al. CTOS [presentation]. 2020. 5 Smith P et al. AACR [poster]. 2018. 6 Wagner AJ et al. JAMA Oncol. 2021. 7 Serrano C and Fletcher O. Oncotarget, 2019. 8 Muhlenberg T et al. J Clin Oncol, 2024. 9 Heinrich MC, et al. Nature Medicine, 2024. 10 Blum SM, et al. JMedChem, 2023. 11 Wagner AJ et al. CTOS 2022.
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8 Data cut-off as of 30Sep2025 QD: Once daily; BICR: blinded independent central review; PD: Progressive Disease Patient Eligibility • Age ≥ 18 years • Histologically confirmed GIST with at least 1 measurable lesion per mRECIST v1.1 • Locally advanced, unresectable or metastatic GIST • Documented disease progression on or intolerance to imatinib Bezuclastinib 600mg QD + Sunitinib 37.5mg QD n=204 Sunitinib 37.5mg QD n=209 Patients 1:1 Randomized C Primary Endpoint • Progression Free Survival per BICR Key Secondary Endpoints • Objective Response Rate per BICR • Overall Survival Secondary Endpoints • Progression Free Survival per Investigator • Disease Control Rate • Time to Response • Duration of Response Crossover allowed following BICR confirmed PD Peak: Randomized Clinical Study Evaluating Bezuclastinib in Combination with Sunitinib in Patients with GIST
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Peak Part 2 Population is Representative of Second-Line Patients with GIST 9 Patient Demographics Bezuclastinib + Sunitinib Sunitinib Overall # Patients 204 209 413 Male, n (%) 131 (64.2) 133 (63.6) 264 (63.9) Median Age in years, (range) 63 (32 - 83) 64 (30 – 88) 63 (30 – 88) ECOG PS at baseline, n (%) 0 140 (68.6) 132 (63.2) 272 (65.9) 1 61 (29.9) 74 (35.4) 135 (32.7) 2 3 (1.5) 3 (1.4) 6 (1.5) Region Bezuclastinib + Sunitinib Sunitinib Overall North America, n (%) 76 (37.3) 85 (40.7) 161 (39.0) Europe, n (%) 94 (46.1) 94 (45.0) 188 (45.5) Latin America, n (%) 20 (9.8) 11 (5.3) 31 (7.5) Asia-Pacific, n (%) 14 (6.9) 19 (9.1) 33 (8.0) Data cut-off as of 30Sep2025 Baseline Characteristics Bezuclastinib + Sunitinib Sunitinib Overall KIT Mutations per molecular pathology report, n (%) Mutation Detected Any Exon 9 31 (15.2) 34 (16.3) 65 (15.7) Exon 11 only 120 (58.8) 126 (60.3) 246 (59.6) Neither Exon 9 nor 11 10 (4.9) 11 (5.3) 21 (5.1) Other 30 (14.7) 34 (16.3) 64 (15.5) No KIT Mutation Detected 13 (6.4) 4 (1.9) 17 (4.1) Treatment History Imatinib intolerance 6 (2.9) 8 (3.8) 14 (3.4) Prior Radiotherapy 14 (6.9) 8 (3.8) 22 (5.3) Prior Anti-Cancer Surgery 156 (76.5) 167 (79.9) 323 (78.2)
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0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 Time Sunitinib Sunitinib + Bezuclastinib Bezuclastinib Combination Extends PFS with 50% Reduction in Risk of Progression or Death 10 PFS: Progression-Free Survival; mRECIST v1.1: modified Response Evaluation Criteria in Solid Tumors version 1.1; BICR: Blinded Independent Central Review Progression-Free Survival (%) Data cut-off as of 30Sep2025 MonthsPatients at Risk Bezuclastinib + Sunitinib 204 180 166 146 130 119 102 76 72 51 24 23 8 6 2 2 2 0 Sunitinib 209 161 137 113 97 85 64 39 35 19 9 9 4 4 2 2 2 0 Median PFS Bezuclastinib + Sunitinib 16.5 months 95% CI, 13.8 to 19.2 Sunitinib 9.2 months 95% CI, 7.2 to 11.0 Hazard Ratio = 0.50 95% CI, 0.39 to 0.65; p<0.0001
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Bezuclastinib + Sunitinib Demonstrates Unprecedented 46% Objective Response Rate 11Data cut-off as of 30Sep2025 ; BICR: blinded independent central review; ORR: Objective Response Rate; BOR: Best Overall Response BOR per BICR, n (%) Bezuclastinib + Sunitinib Sunitinib Complete Response (CR) 13 (6.4) 4 (1.9) Partial Response (PR) 80 (39.2) 50 (23.9) Stable Disease (SD) 91 (44.6) 108 (51.7) Progressive Disease (PD) 15 (7.4) 41 (19.6) Not Evaluable (NE) 5 (2.5) 6 (2.9) ORR per BICR , %, n [95% CI] Bezuclastinib + Sunitinib (n=204) 45.6% 93 [38.6, 52.7] Sunitinib (n=209) 25.8% 54 [20.0, 32.3] Difference in ORR, % [95% CI]; P Value 19.8 [10.6, 28.6]; P Value <0.0001
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Bezuclastinib + Sunitinib is Generally Well Tolerated with a Favorable Safety Profile • The incidence of TEAEs and TRAEs was similar between treatment arms • No TRAEs leading to death in patients on bezuclastinib + sunitinib combination • Only TRAEs leading to discontinuation of either drug in >1 patient on the combination arm were neutropenia (2.9%), ALT/AST increased (1.5%), and diarrhea (1%) Data cut-off as of 30Sep2025; SAE: serious adverse event; TEAE: treatment-emergent adverse event; TRAE: treatment-related adverse event; SAR: serious adverse reaction; DC: discontinuation Study Treatment Bezuclastinib + Sunitinib (n=204) Sunitinib (n=208)1 TEAEs, n (%) 204 (100) 207 (99.5) TRAEs, n (%) 202 (99.0) 204 (98.1) Gr3+ TRAEs, n (%) 146 (71.6) 109 (52.4) Bezuclastinib related Gr3+ 126 (61.8) N/A Sunitinib related Gr3+ 141 (69.1) 109 (52.4) SARs, n (%) 34 (16.7) 24 (11.5) Bezuclastinib related SAEs 25 (12.3) N/A Sunitinib related SAEs 31 (15.2) 24 (11.5) TRAEs leading to death, n (%) 0 1 (0.5) Reductions of either drug due to TRAEs, n (%) 114 (55.9) 92 (44.2) DC of study treatment due to TRAEs, n (%) 15 (7.4) 8 (3.8) 12 Randomized Period Data; 1: One patient randomized to sunitinib but never dosed
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All Grade TEAEs ≥ 20% Demonstrate Balance Between Arms • TEAEs reported at a higher frequency (>15%) in combination arm: ALT/AST increased, taste disorder, and hair color changes • TEAEs reported less frequently in combination arm: PPE, stomatitis and thrombocytopenia • The safety profile of bezuclastinib combination is generally consistent with the known safety profile of sunitinib alone and no new risks were identified with the combination 13 Bezuclastinib + Sunitinib (n=204) Sunitinib (n=208)1 Preferred term, n (%) All Grade Grade 3+ All Grade Grade 3+ Diarrhea 159 (77.9) 16 (7.8) 138 (66.3) 15 (7.2) ALT/AST increased* 115 (56.4) 22 (10.8) 35 (16.8) 3 (1.4) Hypertension 106 (52.0) 60 (29.4) 108 (51.9) 57 (27.4) Taste disorder* 97 (47.5) 0 52 (25.0) 0 Nausea 81 (39.7) 1 (0.5) 56 (26.9) 2 (1.0) Hair color changes 79 (38.7) 0 37 (17.8) 0 Fatigue 72 (35.3) 9 (4.4) 70 (33.7) 5 (2.4) Neutropenia* 71 (34.8) 31 (15.2) 70 (33.7) 32 (15.4) PPE 59 (28.9) 6 (2.9) 95 (45.7) 5 (2.4) Vomiting 56 (27.5) 2 (1.0) 45 (21.6) 4 (1.9) Decreased appetite 55 (27.0) 6 (2.9) 46 (22.1) 0 Anemia 54 (26.5) 19 (9.3) 42 (20.2) 10 (4.8) Abdominal pain 51 (25.0) 6 (2.9) 52 (25.0) 4 (1.9) Stomatitis 46 (22.5) 6 (2.9) 68 (32.7) 10 (4.8) GERD 45 (22.1) 0 30 (14.4) 0 Dyspepsia 43 (21.1) 5 (2.5) 29 (13.9) 0 Thrombocytopenia* 39 (19.1) 2 (1.0) 55 (26.4) 9 (4.3) Randomized Period Data; 1: One patient randomized to sunitinib but never dosed Data cut-off as of 30Sep2025; *Pooled terms; TEAE, treatment-emergent adverse event; PPE, Palmar-Plantar Erythrodysesthesia; GERD Gastroesophageal Reflux Disease
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Incidence of Grade 3+ TEAEs (≥2%) Balanced Across Arms • Majority of the Gr 3+ TEAEs were reported at a similar rate between combination and monotherapy arms; ALT/AST increase and anemia reported at higher incidence in the combination arm • No increase in frequency of severe events observed in combination arm for some key risks seen with sunitinib (hypertension, neutropenia and diarrhea) • ALT/AST elevations led to bezuclastinib dose reductions in 12.7% of patients and only 1.5% of patients discontinued. All Grade 3 ALT/AST events resolved, and no Grade 4 elevations were reported across the study 14 Data cut-off as of 30Sep2025; *Pooled Terms; PPE: Palmar-Plantar Erythrodysesthesia 29.4 15.2 10.8 9.3 7.8 4.4 2.9 2.9 2.9 2.5 1.0 27.4 15.4 1.4 4.8 7.2 2.4 4.8 2.4 1.9 1.9 4.3 Hypertension Neutropenia* ALT/AST increased* Anemia Diarrhea Fatigue Stomatitis PPE Abdominal pain White blood cell count decreased Thrombocytopenia* Percentage of Subjects Bezu + Suni Suni
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66 yo Man with Metastatic GIST who Experienced an Early (PR at C3, CR at C9) and Durable Response to bezuclastinib + sunitinib (ongoing at C26) 15 Data cut-off as of 30Sep2025; C: Cycle; 1 cycle = 28 days; aExcision of abdominal tumors, intestinal resection; AE: adverse event; ALT: alanine transaminase; Gr: grade; GERD: gastroesophageal reflux disease; TRAE: treatment-related AE Relevant Medical History Site of tumor diagnosis: Jejunum/Ileum Sites of disease: • Target lesions: Peritoneum, mesentery, small intestine • Baseline Sum of Diameters: 84 mm Relevant comorbidities: Obesity; hypertension; anemia; elevated ALT and creatinine; abdominal distention; leg swelling; back pain; GERD Peak Treatment and Dose Modifications Bezuclastinib 600 mg QD + sunitinib 37.5 mg QD • Sunitinib reduced to 25 mg for diarrhea TRAEs (maximum Gr reported) Gr 1 • Acneiform dermatitis • Hair color changes • Nausea Gr 2 • Localized edema Gr 3 • Diarrhea (resolved) • Neutropenia (resolved) Response in Target Lesions over Time -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 Cycle 3 Cycle 5 Cycle 7 Cycle 9 Cycle 11 Cycle 13 Cycle 16 Cycle 19 Cycle 22 Cycle 26 % Change from Baseline Treatment History 2020 2021 2022 2023 2024 2025 Diagnosis Debulking surgerya Treatment ongoing CR C9: CR achieved 0mm each C26 0mm each Baseline 19mm each PR Disease progression, Peak enrollment, Bezuclastinib + sunitinib initiated Neoadjuvant Imatinib Imatinib reinitiated -30% (PR)
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69 yo Man with Metastatic GIST Responded to bezuclastinib + sunitinib Treatment at Cycle 5 (PR) and is Continuing to Benefit at Cycle 38 aMultiple bowel/colon excisions and resections (Jan/Mar/Sep 2021), partial omentectomy (Sep2021). AE, adverse event; C, cycle; Gr, grade; PR, partial response; QD, once daily; TRAE, treatment-related AE. Relevant Medical History Site of tumor diagnosis: Small intestine/bowel Sites of disease: • Target lesions: Peritoneum • Baseline Sum of Diameters: 65 mm Relevant comorbidities: Hemorrhoids; Gr 1 hypertension, Gr 1 anemia, anxiety, sleep apnea, hyperlipidemia, irregular heartbeat Peak Treatment and Dose Modifications Bezuclastinib 600 mg QD + sunitinib 37.5 mg • Following Gr 3 anemia/neutropenia: • Bezuclastinib interrupted→resumed at 600mg • Sunitinib interrupted→reduced to 25 mg TRAEs (maximum Gr reported) Gr 1 • Diarrhea • Hair color changes Gr 2 • Hypertension • Hypothyroidism Gr 3 • Neutropenia (resolved) • Anemia (related to Sunitinib only, resolved) Treatment History 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 Disease progression, Peak enrollment, Bezuclastinib + sunitinib initiated Diagnosis Imatinib initiated Surgerya Treatment ongoing PR Baseline C5: PR achieved C36 Imatinib dose increased 16 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 Cycle 3 Cycle 5 Cycle 7 Cycle 9 Cycle 11 Cycle 13 Cycle 16 Cycle 19 Cycle 22 Cycle 26 Cycle 30 Cycle 36 % Change from Baseline Response in Target Lesions over Time -30% (PR) Data cut-off as of 30Sep2025 Data cut-off as of 30Sep2025; 1 cycle = 28 days
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We Believe Peak Results are Transformative and Practice Changing 17 • Bezuclastinib combination establishes first new benchmark for 2L GIST in 20 years • 50% reduced risk of progression or death compared to current standard of care • 16.5 months mPFS compared to 9.2 months for sunitinib alone (p<0.0001) • 46% ORR compared to 26% for sunitinib alone (p<0.0001) • OS immature with event rate of less than 20% at time of PFS analysis • Generally well tolerated with no unique risks observed when compared to the known safety profile of sunitinib • Estimated 19 months+ mean treatment duration for bezuclastinib combination patients based on projection for patients remaining on combination therapy • Active Expanded Access Program allowing immediate availability of the bezuclastinib combination for 2L patients with GIST • NDA submission for bezuclastinib in imatinib-resistant or intolerant GIST planned 1H 2026 based on results of the Peak trial
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Designed to provide bezuclastinib coadministered with sunitinib outside of a clinical trial to real-world patients with GIST who meet specific criteria including, but not limited to, having no comparable or satisfactory alternative therapy to treat the disease. Bezuclastinib GIST Expanded Access Program is Currently Open to Requests for Access from Treating Physicians in the United States (NCT069489551) 18 1. ClinicalTrials.gov. Expanded Access to Bezuclastinib to be Coadministered With Sunitinib for Patients With Gastrointestinal Stromal Tumors Identifier: NCT06948955. Retrieved July 16, 2025 from: https://clinicaltrials.gov/study/NCT06948955. ; *Other protocol-defined criteria apply Key Inclusion Criteria* Key Exclusion Criteria* Age ≥ 18 years Eligibility for and/or enrolled in an ongoing bezuclastinib clinical trial Diagnosis of histologically confirmed locally advanced metastatic and/or unresectable GIST, disease progression on imatinib or intolerance to imatinib Discontinuation of investigational bezuclastinib due to toxicity or withdrawal of consent Lack of adequate disease control on current therapies Pregnant or currently breastfeeding MethodsAim Patients will receive oral bezuclastinib 600 mg QD plus sunitinib 37.5 mg QD. Treating physician to assess patients, report any SAEs, and determine treatment duration.
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Top-line Results: Expected Dec 2025 19 • Centrally Confirmed ASM, SM-AHN, or MCL • Measurable disease per mIWG-MRT-ECNM • ECOG PS 0 to 3 Key Entry Criteria Bezuclastinib 150 mg QD Primary endpoint: ORR using mIWG-MRT-ECNM • Apex enrollment complete Q1 2025; TLR on track for Dec 2025 • Positive Summit results provide expected read-through to Apex • Current standard of care associated with significant safety concerns; no other investigational products in clinical development Single- arm • ASH 2025 Presentations • Two oral presentations from Summit in NonAdvanced Systemic Mastocytosis (NonAdvSM) • Novel selective JAK2 V617F inhibitor showcasing best-in-class potential • Submit first NDA for bezuclastinib in NonAdvSM expected by the end of 2025 • Submit NDA for bezuclastinib in imatinib-resistant or intolerant GIST patients expected in the first half of 2026 Several Additional Near Term Cogent Biosciences Catalysts
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Phase 3 study in 2nd-line GIST sunitinib +/- bezuclastinib Positive Results Announced November 2025 Registration-directed study in NonAdvSM bezuclastinib vs. placebo Positive Results Announced July 2025 Registration-directed study in AdvSM bezuclastinib monotherapy Results on Track for December 2025 NDATLR TLR LPFV TLR 2025 2026 $3 billion+ Global annual market opportunity; Best-in-class symptomatic improvement and biomarker data support potential market leadership $4 billion+ Global annual market opportunity; first positive 2nd-line GIST trial in over 20 years, 50% reduction in risk of progression or death $500 million Global annual market opportunity; differentiated safety/tolerability results would provide clear path to market leadership Estimated aggregate global annual sales opportunity >$7.5 billion with limited competition; IP protection anticipated through 2043 based on strength of COM, PTE and pending formulation patent application Bezuclastinib Emerging as Potential Best-in-Class KIT Inhibitor Across Indications 20TLR: Top-line results including primary endpoint, COM: Composition of Matter; PTE: Patent term extension Submission Today Dec Positive TLR Announced Positive TLR Announced TLR on track December 2025 FDA Potential FDA Approval Submission in 1H 2026 NDA
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Q&A