Full Press Release Details
Stromal Tumors (GIST) Top-Line Results Investor Webcast November 10, 2025
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
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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
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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
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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
Agenda and Speakers Andrew Robbins Neeta Somaiah, M.D. Jessica Sachs,
M.D. President and Chief Executive Officer Professor and Department Chair, Chief Medical Officer Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center Introduction Andrew
Robbins GIST Disease Overview Peak Top-Line Results Dr. Neeta Somaiah Patient Cases Summary Andrew Robbins Q&A All 3
Unmet Medical Need Remains for Patients with Imatinib-Resistant or
Intolerant GIST ORR ~60% ORR ~7% ORR ~5% ORR ~9% PFS ~19 1L PFS ~5.5 2L PFS ~4.8 3L PFS ~6.3 4L months months months months Imatinib Sunitinib Regorafenib Ripretinib Modest historical performance of novel agents in imatinib-resistant setting
emphasizes unmet need Bezuclastinib + Sunitinib PEAK 1 Ripretinib INTRIGUE 8.0 GIST mPFS Sunitinib INTRIGUE 2L 8.3 benchmarks Sunitinib USPI 5.5 Regorafenib USPI 4.8 3L Avapritinib VOYAGER 5.6 0 1 2 3 4 5 6 7 8 9 Months ORR/PFS for all approved
agents was obtained from labeled information from those agents 4
Peak Phase 3 Top-Line Results Full Results Expected to be Presented at
an Upcoming Medical Meeting
Significant Unmet Need Remains for Patients with Gastrointestinal
Stromal Tumors (GIST) Up to 6,000 GIST cases diagnosed annually in US, over 80% 1,2 of which express KIT mutations, typically exons 11 and 9. Tumors can start anywhere in the GI tract, but they occur 3 Symptoms most often in the
stomach (about 60%) or the small Diarrhea, Nausea, Vomiting, 1 intestine (about 35%). Abdominal pain, Bloating, Gastroesophageal reflux While imatinib provides disease control in the majority of disease, GI bleeding, Loss of patients in the
1L setting, ~60% of patients with GIST appetite, Weight loss develop resistance within 2 years, primarily due to 1,2 mutations in exon 13/14 and/or exon 17/18. 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. 1 Key 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 6
Combination of Bezuclastinib + Sunitinib Inhibits the Full Spectrum of
Primary and Secondary Mutations Exon Exon Exon Exon Exon Exon Treatments D816V 9 11 13 14 17 18 1-11 No single TKI inhibits all KIT mutations. Imatinib The combination of bezuclastinib + Regorafenib sunitinib inhibits mutations in
KIT exons 9, Velzatinib 11, 13, 14, 17, and 18, targeting the full (IDRX-42) spectrum of primary and secondary Ripretinib mutations relevant in advanced GIST. Sunitinib Bezuclastinib + Sunitinib Strong Inhibition No Inhibition Moderate Inhibition 1
5 9 Plexxikon. Data on file. Smith P et al. AACR [poster]. 2018. Heinrich MC, et al. Nature Medicine, 2024. 2 6 10 Serrano C et al. Br J Cancer, 2019. Wagner AJ et al. JAMA Oncol. 2021. Blum SM, et al. JMedChem, 2023. 3 7 11 Evans EK et al. Sci
Transl Med, 2017. Serrano C and Fletcher O. Oncotarget, 2019. Wagner AJ et al. CTOS 2022. 4 8 Trent J et al. CTOS [presentation]. 2020. Muhlenberg T et al. J Clin Oncol, 2024. 7
Peak: Randomized Clinical Study Evaluating Bezuclastinib in Combination
with Sunitinib in Patients with GIST Bezuclastinib 600mg QD + Sunitinib 37.5mg QD n=204 Patients 1:1 Randomized C Sunitinib 37.5mg QD n=209 Crossover allowed following BICR confirmed PD Primary Endpoint Progression Free Survival per BICR
Patient Eligibility Key Secondary Objective Response Rate per BICR Age 18 years Endpoints Overall Survival Histologically confirmed GIST with at least 1 measurable lesion per mRECIST v1.1 Progression
Free Survival per Investigator Locally advanced, unresectable or metastatic GIST Secondary Disease Control Rate Documented disease progression on or intolerance to Endpoints Time to Response imatinib Duration
of Response Data cut-off as of 30Sep2025 QD: Once daily; BICR: blinded independent central review; PD: Progressive Disease 8
Peak Part 2 Population is Representative of Second-Line Patients with
GIST Patient Demographics Bezuclastinib Sunitinib Overall Baseline Characteristics Bezuclastinib Sunitinib Overall + Sunitinib + Sunitinib # Patients 204 209 413 KIT Mutations per molecular pathology report, n (%) Male, n (%) 131 (64.2) 133 (63.6)
264 (63.9) Mutation Detected Median Age in years, (range) 63 (32 - 83) 64 (30 - 88) 63 (30 - 88) Any Exon 9 31 (15.2) 34 (16.3) 65 (15.7) ECOG PS at baseline, n (%) Exon 11 only 120 (58.8) 126 (60.3) 246 (59.6) 0 140 (68.6) 132 (63.2)
272 (65.9) Neither Exon 9 nor 11 10 (4.9) 11 (5.3) 21 (5.1) 1 61 (29.9) 74 (35.4) 135 (32.7) Other 30 (14.7) 34 (16.3) 64 (15.5) 2 3 (1.5) 3 (1.4) 6 (1.5) No KIT Mutation Detected 13 (6.4) 4 (1.9) 17 (4.1) Treatment History Region Bezuclastinib
Sunitinib Overall Imatinib intolerance 6 (2.9) 8 (3.8) 14 (3.4) + Sunitinib Prior Radiotherapy 14 (6.9) 8 (3.8) 22 (5.3) North America, n (%) 76 (37.3) 85 (40.7) 161 (39.0) Prior Anti-Cancer Surgery 156 (76.5) 167 (79.9) 323 (78.2) 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 9
Bezuclastinib Combination Extends PFS with 50% Reduction in Risk of
Progression or Death Median PFS 100% Bezuclastinib 16.5 months 90% + Sunitinib 95% CI, 13.8 to 19.2 80% 9.2 months Sunitinib 95% CI, 7.2 to 11.0 70% Hazard Ratio = 0.50 60% 95% CI, 0.39 to 0.65; p<0.0001 50% 40% 30% 20% 10% 0% 0 2 4 6 8 10 12 14
16 18 20 22 24 26 28 30 32 34 Time Months Patients at Risk Sunitinib Sunitinib + Bezuclastinib 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 PFS:
Progression-Free Survival; mRECIST v1.1: modified Response Evaluation Criteria in Solid Tumors version 1.1; BICR: Blinded Independent Central Review Data cut-off as of 30Sep2025 10 Progression-Free Survival (%)
Bezuclastinib + Sunitinib Demonstrates Unprecedented 46% Objective
Response Rate ORR per BICR , %, n [95% CI] Bezuclastinib + Sunitinib 45.6% (n=204) 93 [38.6, 52.7] Sunitinib 25.8% (n=209) 54 [20.0, 32.3] Difference in ORR, % [95% CI]; P Value 19.8 [10.6, 28.6]; P Value <0.0001 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) 11 Data cut-off as of
30Sep2025 ; BICR: blinded independent central review; ORR: Objective Response Rate; BOR: Best Overall Response
Bezuclastinib + Sunitinib is Generally Well Tolerated with a Favorable
Safety Profile Study Treatment Bezuclastinib + Sunitinib Sunitinib 1 (n=204) (n=208) The incidence of TEAEs and TRAEs was similar TEAEs, n (%) 204 (100) 207 (99.5) between treatment arms TRAEs, n (%) 202 (99.0) 204 (98.1) Gr3+ TRAEs, n (%)
146 (71.6) 109 (52.4) No TRAEs leading to death in patients on Bezuclastinib related Gr3+ 126 (61.8) N/A bezuclastinib + sunitinib combination 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 Only TRAEs leading to discontinuation of either Sunitinib related SAEs 31 (15.2) 24 (11.5) drug in >1 patient on the combination arm were neutropenia (2.9%), ALT/AST increased (1.5%), TRAEs leading to death, n (%) 0 1
(0.5) and diarrhea (1%) 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) Randomized Period Data; 1: One patient randomized to sunitinib but never dosed 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 12
All Grade TEAEs 20% Demonstrate Balance Between Arms
Bezuclastinib + Sunitinib Sunitinib 1 (n=204) (n=208) Preferred term, n (%) All Grade Grade 3+ All Grade Grade 3+ TEAEs reported at a higher frequency (>15%) in 16 (7.8) 15 (7.2) Diarrhea 159 (77.9) 138 (66.3) combination arm: ALT/AST
increased, taste ALT/AST increased* 115 (56.4) 22 (10.8) 35 (16.8) 3 (1.4) disorder, and hair color changes Hypertension 106 (52.0) 60 (29.4) 108 (51.9) 57 (27.4) Taste disorder* 97 (47.5) 0 52 (25.0) 0 1 (0.5) 2 (1.0) Nausea 81 (39.7) 56 (26.9)
TEAEs reported less frequently in combination 0 0 Hair color changes 79 (38.7) 37 (17.8) arm: PPE, stomatitis and thrombocytopenia 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) The safety profile of bezuclastinib combination is 2 (1.0) 4 (1.9) Vomiting 56 (27.5) 45 (21.6) generally consistent with the known safety 6 (2.9) 0 Decreased appetite 55 (27.0) 46 (22.1) profile of sunitinib alone
and no new risks were Anemia 54 (26.5) 19 (9.3) 42 (20.2) 10 (4.8) identified with the combination 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) 0 0 GERD 45 (22.1) 30 (14.4) 5 (2.5) 0 Dyspepsia 43
(21.1) 29 (13.9) 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 13
Incidence of Grade 3+ TEAEs ( 2%) Balanced Across Arms
Hypertension 29.4 27.4 Majority of the Gr 3+ TEAEs were reported at a Neutropenia* 15.2 15.4 similar rate between combination and monotherapy arms; ALT/AST increase and anemia reported at ALT/AST increased* 10.8 1.4 higher incidence in the
combination arm Anemia 9.3 4.8 No increase in frequency of severe events observed Diarrhea 7.8 7.2 in combination arm for some key risks seen with Fatigue 4.4 2.4 sunitinib (hypertension, neutropenia and diarrhea) Stomatitis 2.9 4.8
ALT/AST elevations led to bezuclastinib dose PPE 2.9 2.4 reductions in 12.7% of patients and only 1.5% of patients discontinued. All Grade 3 ALT/AST events Abdominal pain 2.9 1.9 resolved, and no Grade 4 elevations were reported White blood cell
count decreased 2.5 1.9 across the study Thrombocytopenia* 1.0 4.3 Percentage of Subjects Bezu + Suni Suni Data cut-off as of 30Sep2025; *Pooled Terms; PPE: Palmar-Plantar Erythrodysesthesia 14
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) Relevant Medical History Treatment History 2020 2021 2022 2023 2024 2025 Site of tumor diagnosis: Jejunum/Ileum a Debulking surgery Diagnosis Neoadjuvant Imatinib reinitiated
Treatment PR CR Sites of disease: Imatinib ongoing Target lesions: Peritoneum, mesentery, small Disease progression, Peak enrollment, Bezuclastinib + sunitinib initiated intestine Baseline Sum of Diameters: 84 mm Baseline C9: CR
achieved C26 19mm each 0mm each 0mm each 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 Response in Target Lesions over Time TRAEs (maximum Gr reported) 0 Acneiform dermatitis -10 Hair color changes Gr 1 -20 -30 -30% (PR) Nausea -40 -50
Localized edema Gr 2 -60 -70 -80 Diarrhea (resolved) -90 Gr 3 Neutropenia (resolved) -100 0 Cycle 3 Cycle 5 Cycle 7 Cycle 9 Cycle 11 Cycle 13 Cycle 16 Cycle 19 Cycle 22 Cycle 26 a Data cut-off as of 30Sep2025; C: Cycle; 1 cycle = 28
days; Excision of abdominal tumors, intestinal resection; AE: adverse event; ALT: alanine transaminase; Gr: grade; GERD: 15 gastroesophageal reflux disease; TRAE: treatment-related AE % Change from Baseline
69 yo Man with Metastatic GIST Responded to bezuclastinib + sunitinib
Treatment at Cycle 5 (PR) and is Continuing to Benefit at Cycle 38 Relevant Medical History Treatment History 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 Site of tumor diagnosis: Small intestine/bowel a Diagnosis Surgery PR Treatment
Sites of disease: Imatinib initiated ongoing Imatinib dose Disease progression, Peak enrollment, Target lesions: Peritoneum increased Bezuclastinib + sunitinib initiated Baseline Sum of Diameters: 65 mm Baseline C5: PR achieved C36
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 Response in Target Lesions over Time Sunitinib interrupted reduced to 25 mg 0 TRAEs (maximum Gr reported) -10 -20 Diarrhea -30 -30% (PR) Gr 1
Hair color changes -40 -50 Hypertension -60 Gr 2 -70 Hypothyroidism -80 -90 Neutropenia (resolved) -100 Gr 3 Anemia (related to Sunitinib only, 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 resolved) Data cut-off as of 30Sep2025; 1 cycle = 28 days a Multiple bowel/colon excisions and resections (Jan/Mar/Sep 2021), partial omentectomy (Sep2021). 16 AE, adverse event; C, cycle; Gr, grade; PR, partial
response; QD, once daily; TRAE, treatment-related AE. Data cut-off as of 30Sep2025 % Change from Baseline
We Believe Peak Results are Transformative and Practice Changing
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 17
Bezuclastinib GIST Expanded Access Program is Currently Open to