Cogent Biosciences, Inc. · NASDAQ:COGT
Cogent Biosciences — Investor Presentation (September 2026)
56 slides from Cogent Biosciences's investor presentation, September 2026
Slide 1: Corporate Presentation September 2026
Corporate Presentation September 2026
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: Three Positive Pivotal Trials Position Bezuclastinib for Three Pending Approvals
Three Positive Pivotal Trials Position Bezuclastinib for Three Pending Approvals Across All KIT-mutant Driven Indications with Potential for Best-in-Class Efficacy Phase 3 trial in 2nd-line Gastrointestinal Stromal Tumors: sunitinib +/- bezuclastinib 600 mg $4 billion+ Global Market Opportunity; Pos
Slide 4: Cogent Biosciences Poised for Transformative 2026
Cogent Biosciences Poised for Transformative 2026 Three Pivotal Trial Wins Position Bezuclastinib as Best-in-Class KIT inhibitor PEAK: First ever positive trial in GIST patients using active comparator SUMMIT: Demonstrated reduction in mast cell burden leads to substantial symptom improvements APEX:
Slide 5: Leadership with Deep Scientific Expertise in Precision Medicine
Leadership with Deep Scientific Expertise in Precision Medicine Andrew Robbins Jessica Sachs, MD Cole Pinnow John Robinson, PhD President & Chief Medical Officer Chief Commercial Officer Chief Scientific Officer Chief Executive Officer Evan Kearns, JD John Green Erin Schellhammer Brad Barnett Chief
Slide 6: Building Robust Pipeline Across Two Franchises
Building Robust Pipeline Across Two Franchises PROGRAM TARGET PATIENT POPULATION PRE-CLINICAL EARLY CLINICAL LATE CLINICAL Bezuclastinib KIT D816V Nonadvanced Systemic Mastocytosis (NonAdvSM) December 30, 2026 PDUFA Bezuclastinib KIT D816V Advanced Systemic Mastocytosis (AdvSM) June 29, 2027 PDUFA H
Slide 7: Bezuclastinib: Compelling Long-Term Exclusivity Expected Through 2046
Bezuclastinib: Compelling Long-Term Exclusivity Expected Through 2046 2026 … 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 2041 2042 2043 2044 2045 2046 PATENT EXCLUSIVITY Orange Book listable patents Patent term extension Compound patent Expected expiration date: Original expiration d
Slide 8: Bezuclastinib in Gastrointestinal Stromal Tumors
BEZUCLASTINIB in Gastrointestinal Stromal Tumors
Slide 9: Significant Unmet Need Remains for Patients with GIST
Significant Unmet Need Remains for Patients with Gastrointestinal Stromal Tumors (GIST) Up to 12,000 GIST cases diagnosed annually in US and EU, 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 Symptoms3 in the
Slide 10: Unmet Medical Need Remains for Patients with Imatinib-Resistant or Intolerant GIST
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
Slide 11: Primary Results of the Phase 3 Peak Study of Bezuclastinib + Sunitinib vs Sunitinib
Primary Results of the Phase 3 Peak Study of Bezuclastinib + Sunitinib vs Sunitinib Monotherapy in Advanced Gastrointestinal Stromal Tumors (GIST) Andrew J. Wagner1, Jonathan C. Trent2, William D. Tap3, Robin L. Jones4, Sebastian Bauer5, Margaret von Mehren6, Michael C. Heinrich7, Min-Hee Ryu8, Bree
Slide 12: Peak Is a Global, Randomized, Open-label, Phase 3 Study
12 Peak Is a Global, Randomized, Open-label, Phase 3 Study Evaluating the efficacy and safety of bezuclastinib + sunitinib vs sunitinib as 2L treatment (NCT05208047) Bezuclastinib 600 mg QD + Sunitinib 37.5 mg QD (n = 204) Patients 1:1 Randomized Sunitinib 37.5 mg QD Crossover allowed following BICR
Slide 13: Peak Part 2 Population Is Representative of Patients With Imatinib-treated GIST
13 Peak Part 2 Population Is Representative of Patients With Imatinib-treated GIST Bezuclastinib Baseline Bezuclastinib Patient Demographics Sunitinib Overall Sunitinib Overall + Sunitinib Characteristics + Sunitinib Patients, n 204 209 413 KIT mutations per molecular pathology report, n (%) Male, n
Slide 14: Bezuclastinib + Sunitinib Extended PFS With 50% Reduction in Risk of Progression or Death
14 Bezuclastinib + Sunitinib Extended PFS With 50% Reduction in Risk of Progression or Death 100% Median PFS 90% Bezuclastinib 16.5 months + Sunitinib 95% CI (13.8 to 19.2) Progression-Free Survival (%) 80% 9.2 months 70% Sunitinib 95% CI (7.2 to 11.0) 60% Hazard Ratio = 0.50 50% 95% CI (0.39 to 0.6
Slide 15: PFS Benefit Across Subgroups and Baseline Mutation Profiles
Bezuclastinib + Sunitinib Demonstrated PFS Benefit vs 15 Sunitinib Monotherapy Across Subgroups and Baseline Mutation Profiles Bezuclastinib + Subgroup Sunitinib Hazard Ratio (95% CI) Median, mos Sunitinib Patients with primary outcomes, n/N (%) Bezu + Sun vs Sun Bezu + Sun Sun <65 69/113 (61.1) 82/
Slide 16: Combination Significantly Improved ORR vs Sunitinib Monotherapy
16 Bezuclastinib + Sunitinib Combination Significantly Improved ORR vs Sunitinib Monotherapy Bezuclastinib + Bezuclastinib + Sunitinib Sunitinib Objective Response Sunitinib Additional End Points Sunitinib (n=204) (n=209) (n=209) (n=204) 45.6 (38.6-52.7) 25.8 (20.0-32.3) Disease control rate,%b (95%
Slide 17: PFS2 Results Support the Durability of Response to Combination
17 PFS2 Results Support the Durability of Response to Combination vs Sunitinib Monotherapy Progression-Free Survival 2 (%) Median PFS2 100 Bezuclastinib Not yet reached + Sunitinib Sunitinib 21.0 months Hazard Ratio = 0.57 50 • PFS2 = time from Sunitinib Bezuclastinib + Sunitinib randomization to pr
Slide 18: Bezuclastinib + Sunitinib Is Generally Well-Tolerated With a Favorable Safety Profile
18 Bezuclastinib + Sunitinib Is Generally Well-Tolerated With a Favorable Safety Profile Bezuclastinib + Sunitinib Sunitinib (n=208)a (n=204) • The incidence of TEAEs and TRAEs was TEAEs, n (%) 204 (100) 207 (99.5) similar between treatment arms TRAEs, n (%) 202 (99.0) 204 (98.1) Gr3+ TRAEs, n (%) 1
Slide 19: All Grade TEAEs ≥ 20% Demonstrate Balance Between Arms
All Grade TEAEs ≥ 20% Demonstrate Balance Between 19 Arms All grade TEAEs ≥ 20% in either treatment arm Bezuclastinib + Sunitinib (n=204) Sunitinib (n=208)a • TEAEs reported at a higher frequency Preferred term, n (%) All Grade Grade 3+ All Grade Grade 3+ (>15%) in combination arm: ALT/AST Diarrhea
Slide 20: Incidence of Grade 3+ TEAEs (≥2%) Balanced Across Arms
20 Incidence of Grade 3+ TEAEs (≥2%) Balanced Across Arms Hypertension 29.4 27.4 • Majority of the Gr 3+ TEAEs were reported Neutropenia* 15.2 15.4 at a similar rate between combination and ALT/AST increased* 10.8 1.4 monotherapy arms; ALT/AST increase and anemia reported at higher incidence in the
Slide 21: Conclusions
21 Conclusions The Peak study represents the first time a combination of inhibitors targeting the same kinase in KIT-mutant GIST has delivered a significant efficacy benefit, balanced with a manageable safety profile. Bezuclastinib + sunitinib demonstrated No new safety risks were identified with th
Slide 22: PEAK Results Dramatically Change 2nd-line GIST Commercial Potential
PEAK Results Dramatically Change 2nd-line GIST Commercial Potential Given Estimated Average Duration of Treatment Large Population with Approved KIT PEAK Results Show Unmet Need Inhibitors Monthly Dramatic Improvement Price Benchmark* in Duration of Treatment (DOT) US + EU: 12,000 GIST patients diag
Slide 23: PEAK Results are Transformative and Expected to be Practice Changing
PEAK Results are Transformative and Expected to be Practice Changing Generally well tolerated with no unique risks Bezuclastinib combination establishes first observed when compared to the known new benchmark for 2L GIST in 20 years safety profile of sunitinib 50% reduced risk of progression or deat
Slide 24: Bezuclastinib in Systemic Mastocytosis
BEZUCLASTINIB in Systemic Mastocytosis
Slide 25: Bezuclastinib is an oral, potent, and selective type 1 TKI with activity against KIT
Bezuclastinib 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 • Nonadvanced SM (NonAdvSM), including Neurocognitive indolent SM, smoldering SM, and bone Difficulty concentratin
Slide 26: Minimal Late-Stage Competitive Activity with Clear Path to Best-in-Class Position
KIT MUTANT COMPETITIVE LANDSCAPE Minimal Late-Stage Competitive Activity with Clear Path to Best-in-Class Position Systemic Mastocytosis avapritinib elenestinib bezuclastinib D816V potent CNS selective PDGFR sparing FLT3/CSF1R sparing Active trials ASM Approved Phase 1/2 NDA Submitted June 2026 NonA
Slide 27: Expanded Results From the Phase 2 Summit Trial in Non-Advanced Systemic Mastocytosis
Expanded Results From the Phase 2 Summit Trial: Bezuclastinib in Adults With Non-Advanced Systemic Mastocytosis Nathan A Boggs1, Lindsay Rein2, Prithviraj Bose3, Brian D Modena4, Vito Sabato5, Karin Hartmann6, Cem Akin7, Tracy I George8, Cecilia Arana Yi9, Hanneke Oude Elberink10, Deepti H Radia11,
Slide 28: Summit: Pivotal Phase 2 Study Evaluating Bezuclastinib in NonAdvSM
Summit (NCT05186753): Pivotal phase 2 multicenter, randomized, double-blind, placebo-controlled study evaluating bezuclastinib in NonAdvSM Eligibility Part 3 OLE Objectives • Characterize long-term safety and 24 weeks 2-5 years tolerability of bezuclastinib ISM, BMM, or SSM • Durability of effect at
Slide 29: Patient demographics and characteristics were representative of a 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 30: Rapid, durable, clinically meaningful symptom improvement deepening to 48 weeks
Rapid, durable, and clinically meaningful symptom improvement that continues to deepen to 48 weeks of treatment Patients crossing over to receive active treatment experience clinically meaningful symptom improvement 0 4 8 12 16 20 24 28 32 36 40 44 48 Double-blind treatment period Open-label extensi
Slide 31: 86% of Patients Achieve Clinically Meaningful Symptom Improvement
Bezuclastinib achieves robust symptom reduction at 48 weeks 86% of Patients Achieve Clinically Meaningful Symptom Improvement Individual Patients Receiving Bezuclastinib 100 mg for 48 Weeks 50 40 86.2% 56.4% 30 81/94 53/94 20 10 Percent Reduction (%) 0 MS2D2 TSS -10 -20 -30 -40 -50 -60 -70 -80 -90 -
Slide 32: Sustained and deepening symptom improvement through 48 weeks in NonAdvSM
Bezuclastinib achieves sustained and deepening symptom improvement through 48 weeks in NonAdvSM Symptoms in MS2D2 Total Symptom Score Additional MS2D2 Symptoms Most Skin Fatigue Neurocognitive Other Severe Abdominal Diarrhea Symptom Itching Flushing Skin redness Spots Tiredness Concentration Remembe
Slide 33: 99% of patients reached ≥50% reduction in serum tryptase at 48 weeks
99% of patients reached ≥50% reduction in serum tryptase at 48 weeks Serum tryptase normalization persisted to 48 weeks of bezuclastinib treatment Individual Patients Receiving Bezuclastinib 100 mg for 48 weeks 0 -10 -20 Serum Tryptase -30 Change (%) -40 -50% -50 -60 -70 -80 -90 Reduction ≥50% -100
Slide 34: Bezuclastinib significantly reduced KIT p.D816V variant allele frequency at 48 weeks
Bezuclastinib significantly reduced KIT p.D816V variant allele frequency, a molecular driver of disease, at 48 weeks Individual Patients Receiving Bezuclastinib 100 mg for 48 weeks 0 KIT p.D816V VAF in Blood -10 -20 Reduction (%) -30 -40 -50% -50 -60 -70 -80 -90 Reduction ≥50% -100 Week 48 Bezuclast
Slide 35: Well tolerated with no new safety concerns with longer-term treatment
Bezuclastinib was well tolerated and no new safety concerns observed with longer-term treatment TEAEs during OLE Placebo → Bezuclastinib Bezuclastinib (n=58) (n=103) Median (range) duration of bezuclastinib 8.8 (2.8 – 14.4) 8.6 (0.46 – 15.0) treatment (months) in the OLE o The majority of TEAEs were
Slide 36: Bezuclastinib represents a promising new treatment for patients with NonAdvSM
Bezuclastinib represents a promising new treatment for patients with NonAdvSM Disease modification and symptom improvement continue out to 48 weeks of treatment Rapid, statistically significant, and clinically Safety and tolerability profile in OLE, with > 24 meaningful symptom improvement is durabl
Slide 37: Lorem Ipsum Advanced Systemic Mastocytosis
Lorem Ipsum Advancedetsilon Dolorum Systemic Mastocytosis Lorem 123
Slide 38: Efficacy and Safety of Bezuclastinib in Advanced Systemic Mastocytosis: Apex Study
Efficacy and Safety of Bezuclastinib in Patients With Advanced Systemic Mastocytosis: Results From the Apex Study Daniel J. DeAngelo1, Deepti H. Radia2, Tracy I. George3, Isaac Goncalves4, Khalid Shoumariyeh5, Cristina Papayannidis6, Pankit Vachhani7, Tsewang Tashi8, Anthony M. Hunter9, Vinod Pullar
Slide 39: Unmet Need Remains for Patients with Advanced Systemic Mastocytosis (AdvSM)
Unmet Need Remains for Patients with Advanced Systemic Mastocytosis (AdvSM) • AdvSM, a rare myeloid neoplasm, is an aggressive and life- threatening form of SM driven by the KIT p.D816V mutation in most patients1-4 — Leads to increased production and accumulation of neoplastic mast cells (MC), organ
Slide 40: Bezuclastinib is a Highly Selective Tyrosine Kinase Inhibitor with Potent Activity Against KIT D816V
Bezuclastinib is an Investigational, Oral, Highly Selective Tyrosine Kinase Inhibitor with Potent Activity Against KIT D816V • From nonclinical studies, bezuclastinib1,2 — Has high activity with specificity for mutations in KIT exons 11, 17, and 18 — Spares closely related kinases, which may minimiz
Slide 41: Apex: Phase 2 Multipart Open-Label Study of Bezuclastinib in AdvSM
Apex (NCT04996875): Phase 2, Multipart, Multicenter, Open-Label Study of Bezuclastinib in Patients with AdvSM PART 2: PIVOTAL TRIAL (N=81) Key Eligibilitya Stage 1 Stage 2 Part 2 Endpoints bezuclastinib Confirmed ASM and SM-AHN patients with • ASM, SM-AHN, or MCL per Primary: 150 mg QD Dose: mIWG-MR
Slide 42: Baseline Characteristics
Baseline Characteristics Characteristic Bezuclastinib 150 mg QD (N=81) Female, n (%) 23 (28) Median age, years (range) 70 (43–87) 0 22 (27) ECOG Performance Status, n (%) 1 40 (49) ≥2 19 (23) ASM 11 (14) AdvSM subtype per central eligibility review, n (%) SM-AHNa 57 (70) MCLb 13 (16) Median bone mar
Slide 43: High Response Rates Across AdvSM Subtypes, per mIWG-MRT-ECNM Criteria
Bezuclastinib Demonstrated High Response Rates Across AdvSM Subtypes, per mIWG-MRT-ECNM Criteria All Evaluable ASM SM-AHN MCL Best Overall Response, n (%) Patients (n=8) (n=47) (n=13) (N=68) Overall Response Rate (CR+CRh+PR+CI) 44 (65) 5 (63) 34 (72) 5 (38) CR+CRh+PR 39 (57) 3 (38) 31 (66) 5 (38) CR
Slide 44: High Response Rates Across AdvSM Subtypes, per PPR Criteria
Bezuclastinib Demonstrated High Response Rates Across AdvSM Subtypes, per Pure Pathologic Response (PPR) Criteria All Evaluable ASM SM-AHN MCL Best Overall Response, n (%) Patients (n=11) (n=57) (n=13) (N=81) Overall Response Rate (CR+CRh+PR) 66 (81) 9 (82) 51 (89) 6 (46) CR+CRh 50 (62) 6 (55) 39 (6
Slide 45: Marked Reductions in Objective Measures of Disease in Patients with AdvSM
Bezuclastinib Demonstrated Marked Reductions in Objective Measures of Disease in Patients with AdvSM Individual Patients Receiving Bezuclastinib 150 mg QD Bone Marrow MC Burden (n=80) Serum Tryptase (n=80) 332% KIT p.D816V VAF in PBa (n=43) 40 40 40 Best % Change from Baseline 20 20 20 0 0 0 -20 -20
Slide 46: Early Evidence of Durable Responses and Prolonged PFS in AdvSM
Bezuclastinib Demonstrated Early Evidence of Durable Responses and Prolonged PFS in Patients with AdvSM PFSa per mIWG-MRT-ECNM criteria (n=68) PFS and OS • 12-month PFS rate: 79% 100 (95% CI: 65.5, 87.6) Progression-free Survival (%) Bezuclastinib Bezuclastinib150 150mg mgQDQD • 12-month OS rate: 87
Slide 47: Bezuclastinib Demonstrated a Favorable Safety Profile in AdvSM
Bezuclastinib Demonstrated a Favorable Safety Profile in AdvSM Bezuclastinib 150 mg QD (N=81) Treatment-related AEs (TRAEs), n (%) 75 (93) Treatment-related SAEs, n (%) 6 (7) • Median (range) duration of exposure: 63.0 (1.0–135.3) weeks Dose reductions due to TRAEs, n (%) 13 (16) Discontinuations du
Slide 48: Bezuclastinib Represents a Promising New Treatment Option for ASM Patients
Bezuclastinib Represents a Promising New Treatment Option for ASM Patients Patients receiving bezuclastinib achieved Bezuclastinib was well-tolerated, with high rates of response: infrequent need for dose reduction and no • 65% ORR per mIWG-MRT-ECNM patients requiring discontinuation for • 81% ORR (
Slide 49: Significant Market Opportunity in Systemic Mastocytosis With Bezuclastinib's Clinical Profile
Significant Market Opportunity in Systemic Mastocytosis With Bezuclastinib’s Clinical Profile Promising Growth Limited Competition Large Market Trends in SM Creates Unmet Opportunity Across Management Market Needs Major Markets ~40% $3.5B - NonAdvSM: AYVAKIT has $4 Billion+ suboptimal therapeutic do
Slide 50: Best-in-Class Research Pipeline
Best-in-Class Research Pipeline
Slide 51: Cogent Pipeline Highlight: Pan-KRAS Inhibitor
Cogent Pipeline Highlight: Pan-KRAS Inhibitor Potency Selectivity Drugability No inhibition of H/NRAS for potential Pro drug provides QD / low dose option for Best-in-class across prevalent KRAS mutations improvement in tolerability vs. multi-RAS inhibitors patients with excellent ability to combine
Slide 52: Cogent Pipeline Highlight: JAK2 V617F Inhibitor
Cogent Pipeline Highlight: JAK2 V617F Inhibitor Selectivity Drugability 100+ fold selectivity in both binding and ↑ molecular response vs SOC agents QD dose option for patients with excellent cellular assays for JAK2 V617F over JAK2 WT ↓ thrombosis risk, ↓fibrotic risk, and ↓inflammation ability to
Slide 53: Creating a Best-in-Class CNS-penetrant, pan-mutant ErbB2 Inhibitor
Creating a Best-in-Class CNS-penetrant, pan-mutant ErbB2 Inhibitor CGT4255 is a highly potent and selective ErbB2 inhibitor targeting resistance (YVMA), kinase, and extracellular domain mutations, with best-in-class potential performance in multiple underserved patient populations Prevalence of Onco
Slide 54: Selective pan-mutant PI3Kα Inhibition Avoids PI3Kα Wild Type Toxicity
Selective pan-mutant PI3Kα Inhibition Avoids PI3Kα Wild Type Toxicity for Improved Efficacy and Tolerability 2 • On-target inhibition of wild type PI3Kα by approved inhibitors leads to • A mutant selective inhibitor will avoid these toxicities resulting in better tolerability issues including hyperg
Slide 55: Cogent Biosciences: Major Catalysts Expected in 2026
Cogent Biosciences: Major Catalysts Expected in 2026 Bezuclastinib Pipeline Corporate • Gain approval and successfully • Submit IND for CGT1815; novel, ✓ Build highly capable US launch in GIST & NonAdvSM selective pan-KRAS inhibitor commercial team to support ✓ Complete GIST NDA • Submit IND for CGT
Slide 56: Real Challenges. Real Solutions.
Real Challenges. Real Solutions. Cogentbio.com
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