Cogent Biosciences, Inc. · NASDAQ:COGT
Cogent Biosciences — Investor Presentation (December 2025)
33 slides from Cogent Biosciences's investor presentation, Dec 8, 2025
Slide 1: Investor Webcast
Investor Webcast December 8, 2025
Slide 2: Forward Looking Statements and Risk Factors
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 materiall
Slide 3: Agenda and Speakers
Agenda and Speakers Andrew Robbins President and Lindsay A.M. Rein, MD Jessica Sachs, M.D. Chief Executive Officer Associate Professor of Medicine in the Chief Medical Officer Division of Hematologic Malignancies and Cellular Therapy, Duke University • Introduction and Corporate Overview Andrew Robb
Slide 4: Bezuclastinib Emerging as Potential Best-in-Class KIT Inhibitor Across Indications
Bezuclastinib Emerging as Potential Best-in-Class KIT Inhibitor Across Indications 2025 2026 $3 billion+ Global annual market Registration-directed study in NonAdvSM Positive TLR Announced bezuclastinib vs. placebo opportunity; TLR NDA FDA Best-in-class symptomatic Positive Results Announced July 20
Slide 5: SUMMIT Trial Bezuclastinib in NonAdvSM ASH 2025 Full Results
SUMMIT Trial Bezuclastinib in NonAdvSM ASH 2025 Full Results Full Results Expected to be Presented at an Upcoming Medical Meeting
Slide 6: Efficacy and Safety Results From the Pivotal SUMMIT Trial in Non-Advanced Systemic Mastocytosis
Efficacy and Safety Results From the Pivotal Summit Trial: Bezuclastinib in Adults with Non-Advanced Systemic Mastocytosis Lindsay Rein1, Nathan A. Boggs2, Prithviraj Bose3, Brian D. Modena4, Vito Sabato5, Karin Hartmann6, Cem Akin7, Tracy I. George8, Cecilia Arana Yi9, Hanneke Oude Elberink10, Deep
Slide 7: Bezuclastinib is an oral, potent, selective type 1 TKI with activity against KIT p.D816V
Bezuclastinib (CGT9486) is an oral, potent, and selective type 1 TKI with activity against KIT p.D816V, the activating mutation in most patients with systemic mastocytosis1-5 Symptoms of NonAdvSM • Non-advanced SM (NonAdvSM), including Neurocognitive indolent SM, smoldering SM, and bone Difficulty c
Slide 8: SUMMIT: Pivotal phase 2 randomized, placebo-controlled study in NonAdvSM
Summit (NCT05186753): Pivotal phase 2 multicenter, randomized, double-blind, placebo-controlled study evaluating bezuclastinib in NonAdvSM Eligibility PART 1: PART 2: DOSE OPTIMIZATION EXPANSION ISM, BMM, or SSM Primary Objective: Primary Objective: based on WHO 2022 Determine the recommended Determ
Slide 9: Patient demographics and characteristics representative of broad NonAdvSM population
Patient demographics and characteristics were representative of a broad NonAdvSM population Bezuclastinib Bezuclastinib Placebo Placebo Baseline Characteristics 100 mg QD Disease Severity 100 mg QD (N=60) (N=60) (N=119) (N=119) Female, n (%) 74 (62.2) 44 (73.3) 57.1 52.6 Mean MS2D2 TSS, (range) (18–
Slide 10: Primary endpoint achieved through rapid, durable symptom improvement
Primary endpoint was achieved through rapid, durable, statistically significant, and clinically meaningful symptom improvement 0 P<0.001 Mean Change in TSS at Week 24 [95% CI] Worsening -5 Bezuclastinib Placebo P Value LS Mean (SE) Change From Baseline Symptoms -24.32 -15.41 -10 (-27.56, -21.08) (-1
Slide 11: Bezuclastinib achieves robust symptom reduction
Bezuclastinib achieves robust symptom reduction A significantly greater proportion of patients treated with bezuclastinib achieved ≥30% a and ≥50% reductions in MS2D2 TSS compared with placebo Individual Patients Receiving Bezuclastinib 100 mg Individual Patients Receiving Placebo 50 Patients reachi
Slide 12: Clinically meaningful symptom relief across all symptoms measured
Bezuclastinib delivers clinically meaningful symptom relief across all symptoms measured in patients with NonAdvSM at 24 weeks Symptoms in MS2D2 Total Symptom Score Additional MS2D2 Symptoms Most Skin Fatigue Neurocognitive Other Severe Abdominal Diarrhea Symptom Itching Flushing Skin redness Spots
Slide 13: Significantly reduced serum tryptase
Bezuclastinib significantly reduced serum tryptase, a core indicator of mast cell burden Individual Patients Receiving Bezuclastinib 100 mg Individual Patients Receiving Placebo 95.4% of patientsa Reduction ≥50% 0% of patientsa with 50 with ≥50% reduction 50 ≥50% reduction P<0.0001 Serum Tryptase 25
Slide 14: Significantly reduced bone marrow mast cell burden
Bezuclastinib significantly reduced bone marrow mast cell burden and abnormal mast cell phenotype Individual Patients Receiving Bezuclastinib 100 mg Individual Patients Receiving Placebo MC Burden in Bone Marrow 100 88.2% of patientsa with ≥50% Reduction ≥50% 100 25.5% of patientsa with ≥50% reducti
Slide 15: Significantly reduced KIT p.D816V variant allele frequency
Bezuclastinib significantly reduced KIT p.D816V variant allele frequency, a molecular driver of disease Individual Patients Receiving Bezuclastinib 100 mg Individual Patients Receiving Placebo 242% 180% KIT p.D816V VAF in blood 100 97.5% of patientsa with ≥50% Reduction ≥50% 100 0% of patientsa with
Slide 16: Smoldering SM and prior avapritinib subgroups show meaningful improvements
Smoldering SM and prior avapritinib subgroups demonstrate meaningful improvements in symptoms and objective measures of disease Patients Receiving Bezuclastinib With prior Overall population Smoldering SM avapritinib (N=119) (N=8) exposure (N=11) Symptom severity at 24 weeks, change from baseline LS
Slide 17: Symptom improvement correlates with mast cell burden improvement
The magnitude of symptom improvement correlates with the degree of mast cell burden improvement • Greater reduction in serum tryptase, bone marrow MCs, and KIT p.D816V VAF was significantly correlated with greater reduction in symptom severity, as assessed with the MS2D2 TSS Bezuclastinib Increase 1
Slide 18: Bezuclastinib demonstrated a favorable and manageable safety profile
Bezuclastinib demonstrated a favorable and manageable safety profile Bezuclastinib Placebo – The majority of TEAEs were of low grade (70% grade 1) and 100 mg QD reversible (N=118) (N=60) TEAEs, n (%) 116 (98.3) 53 (88.3) – Variety of AEs occurred more often in the placebo group (vs the bezuclastinib
Slide 19: Bezuclastinib represents a promising new treatment with evidence of disease modification
Bezuclastinib represents a promising new treatment with evidence of disease modification in patients with NonAdvSM • Patients receiving bezuclastinib achieved clinically meaningful symptom improvement, with a mean TSS reduction of -24.32 at Week 24 vs -15.41 for placebo alongside improvements across
Slide 20: SUMMIT Trial Pathobiology and 48 Week Follow-Up
SUMMIT Trial Pathobiology and 48 Week Follow-Up
Slide 21: Treatment Demonstrates Reversal of Key Bone Marrow Pathology in NonAdvSM
Bezuclastinib Treatment Demonstrates Reversal of Key Bone Marrow Pathology in Non Advanced Systemic Mastocytosis Patients Monday, Dec 8th 5:00 pm: ASH Oral Presentation Presenter: Dr. Tracy George, MD, President and Chief Scientific Officer at ARUP Laboratories; Professor, University of Utah Locatio
Slide 22: 55% No Longer Meet WHO Diagnostic Criteria and 91% Achieve Pure Pathologic Response
55% of Patients Receiving Bezuclastinib No Longer Meet WHO Diagnostic Criteria and 91% Achieve Pure Pathologic Response Percent of Patients with Exploratory Pure Pathologic Response1 (PPR) at 24 Weeks of Treatment Percent of Patients Not Meeting WHO Diagnostic Criteria at 24 Weeks of Bezuclastinib P
Slide 23: 48 Week Preview: Deep and Sustained Symptom Improvement
48 Week Preview: Bezuclastinib Effect on Symptoms Shows Deep and Sustained Improvement • Patient benefit appears differentiated from available ISM treatment options o 96-week avapritinib mean TSS change: -17.5* o 156-week avapritinib Avapritinib (ISM-SAF) mean TSS change: -19.4* Bezuclastinib (ISM-S
Slide 24: 48 Week Preview: 86% Achieve Clinically Meaningful Symptom Improvement
48 Week Preview: 86% of Patients Achieve Clinically Meaningful Symptom Improvement Individual Patients Receiving Placebo Then Bezuclastinib Individual Patients Receiving Bezuclastinib 100 mg for 48 Weeks for 24 Weeks 50 50 40 86.2% 56.4% 40 81.1% 54.7% 81/94 53/94 45/53 29/53 30 30 20 20 10 10 Perce
Slide 25: APEX Trial Bezuclastinib in AdvSM Top-Line Results
APEX Trial Bezuclastinib in AdvSM Top-Line Results
Slide 26: APEX Part 2: Registration-Directed, Open-Label Study in Advanced Systemic Mastocytosis
APEX Part 2: Phase 2 Registration-Directed, Open-Label Clinical Study of Bezuclastinib in Patients with Advanced Systemic Mastocytosis PART 1: DOSE OPTIMIZATION PART 2: PIVOTAL TRIAL ORIGINAL FORMULATION Stage 1 Stage 2 50 mg BID Confirmation Expansion Selected ASM, SM-AHN and MCL patients with mIWG
Slide 27: APEX Part 2: Patient Demographics and Baseline Characteristics
APEX Part 2: Patients Demographics and Baseline Characteristics Primary Endpoint: ORR (CR/CRh + PR + CI) per modified IWG-MRT-ECNM response criteria as assessed by CRRC Key Secondary Endpoint: ORR (CR/CRh + PR) per PPR Part 2 Part 2 Patient Demographics SM Therapy 150mg QD 150mg QD # Patients 81 Pri
Slide 28: APEX Part 2: Positive Results on Primary and Key Secondary Endpoints
APEX Part 2: Patients Receiving 150mg Bezuclastinib Achieved Positive Results on Primary (mIWG) and Key Secondary (PPR) Endpoints Best ORR per mIWG, n (%) Best PPR, n (%) N=68 N=81 Overall Response Rate CR+CRh+PR+CI 39 (57.4) - CR+CRh+PR 33 (48.5) 65 (80.2) Best Overall Response Complete Response (C
Slide 29: APEX Part 2: Significantly Reduced Objective Measures of Disease Burden
APEX Part 2: Bezuclastinib Significantly Reduced Objective Measures of Disease Burden Including Mast Cells, Serum Tryptase, and KIT D816V VAF 60 SM-AHN ASM Best Percent Change from Baseline (%) MCL/MCL-AHN 40 ◊ KIT undetected at baseline ◊ 20 ◊ ◊ ◊ Mast Cell Burden ◊ 0 -20 -40 -50% -60 -80 ◊ ◊ -100
Slide 30: APEX Part 2: Well Tolerated with a Favorable Safety Profile
APEX Part 2: Bezuclastinib was Well Tolerated with a Favorable Safety Profile 150mg QD Bezuclastinib N=81 TRAEs, n (%) 75 (92.6) Drug-related SAEs, n (%) 5 (6.2) • Hematological events were reversible and manageable Reductions due to TRAEs, n (%) 12 (14.8) DCs due to TRAEs, n (%) 0 TRAEs in ≥ 10% of
Slide 31: Bezuclastinib Represents a Promising New Treatment Option for ASM Patients
Bezuclastinib Represents a Promising New Treatment Option for ASM Patients • Patients receiving bezuclastinib achieved high rates of response: – 57% ORR (CR+CRh+PR+CI) per mIWG-MRT-ECNM – 80% ORR (CR+CRh+PR) per PPR • Significant reductions in objective disease markers underscore potent target engag
Slide 32: Bezuclastinib Emerging as Potential Best-in-Class KIT Inhibitor Across Indications
Bezuclastinib Emerging as Potential Best-in-Class KIT Inhibitor Across Indications 2025 2026 $3 billion+ Global annual market Registration-directed study in NonAdvSM Positive TLR Announced bezuclastinib vs. placebo opportunity; TLR NDA FDA Best-in-class symptomatic Positive Results Announced July 20
Slide 33: Cogent Biosciences: Real Challenges. Real Solutions.
BIOSCIENCES Real Challenges. Real Solutions. Precision therapies for genetically defined diseases
Cogent Biosciences — Investor Presentation (December 2025) on 6ix