Cogent Biosciences, Inc. · NASDAQ:COGT
Cogent Biosciences — ASH 2023 Annual Meeting (Oral Presentation)
17 slides from Cogent Biosciences's conference presentation, December 2023
Slide 1: Initial Results from Summit: Phase 2 Study of Bezuclastinib in NonAdvSM
Initial Results from Summit: An Ongoing, 3-Part, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of Bezuclastinib in Adult Patients with NonAdvanced Systemic Mastocytosis (NonAdvSM) Prithviraj Bose1, MD, Stephen T. Oh2, MD, PhD, Brian Modena3, MD, Anthony M. Hunter4
Slide 2: Systemic Mastocytosis is a Rare Disease Characterized by Neoplastic Mast Cell Infiltration
Systemic Mastocytosis (SM) is a Rare Disease Characterized by Neoplastic Mast Cell Infiltration of Extracutaneous Tissues and Symptoms of Mast Cell Activation • SM is primarily driven by Patients with NonAdvSM experience a variety of disabling, D816V KIT mutation1 potentially serious and severe symp
Slide 3: Bezuclastinib is an Oral, Potent, and Selective Type 1 Tyrosine Kinase Inhibitor
Bezuclastinib is an Oral, Potent, and Selective Type 1 Tyrosine Kinase Inhibitor With Activity Against KIT D816V • Agents targeting KIT D816V in exon 17 have been used to treat AdvSM and NonAdvSM, but unmet need remains.1-3 • High frequency of adverse events, such as cognitive effects and edema, may
Slide 4: Summit: Phase 2 Clinical Study Evaluating Bezuclastinib in NonAdvSM
Summit: Phase 2 Clinical Study Evaluating Bezuclastinib in NonAdvSM PART 1: DOSE OPTIMIZATION (fully enrolled) PART 2: EXPANSION Primary Objective: Determine the recommended dose of Primary Objective: Determine the bezuclastinib efficacy of bezuclastinib Eligibility Double-blind Treatment Period (12
Slide 5: Summit Part 1a Enrolled Highly Symptomatic SM Patients with Moderate to Severe Disease
Summit Part 1a Enrolled Highly Symptomatic SM Patients with Moderate to Severe Disease Patient Demographics All patients (N=20) SM Therapy All patients (N=20) Female, n (%) 15 (75) Prior avapritinib, n (%) 1 (5.0) Median Age in years, n (range) 50.5 (38 – 75) ECOG PS, n (%) Baseline Supportive Care
Slide 6: Encouraging Safety at 100-200 mg QD in Patients from Summit Part 1a
Encouraging Safety at 100-200 mg QD in Patients from Summit Part 1a All cause TEAEs > 1 patient in bezuclastinib cohorts Bezuclastinib Bezuclastinib Placebo • The majority of TEAEs were low grade and reversible 100mg QD 200mg QD n=7 n= 7 n=5 • No related SAEs reported Preferred Term Gr 1 / 2 Gr 3 Gr
Slide 7: Safety and Tolerability Profile in Open-Label Extension Supports Potential for Chronic Dosing
Safety and Tolerability Profile in Open-Label Extension (OLE) Supports Potential for Chronic Dosing All Cause TEAEs > 1 patient • Following completion of Part 1, patients received a Open-Label Extension (n=18) median duration of active treatment in OLE of 16 [assigned doses] weeks (range: 3.3-53.7)
Slide 8: Dose Dependent Increase in Steady State Bezuclastinib Exposure
Dose Dependent Increase in Steady State Bezuclastinib Exposure C2D1 (Steady State) Exposure by Dose 2000 1600 [Bezuclastinib] (ng/mL) 1200 100 mg QD (n=6, excluding 1 outlier) 100 mg QD (n=1, outlier) a 800 200 mg QD (n=5) 400 mg QD (n=1) 400 0 1 3 5 7 9 24 Time (hour) a Patient with outlier PK had
Slide 9: 100% of Bezuclastinib Treated Patients Achieved >50% Reduction in Markers of Mast Cell Burden
Within 12 Weeks, 100% of Bezuclastinib Treated Patients Achieved >50% Reduction in Markers of Mast Cell Burden Serum Tryptase KIT D816V VAF Mast Cell Burden n=20 n=15 a n=16 b 400% 100% 50 50 50 Best Percent Change in S S S S S S Part 1a (12 Weeks) 0 0 0 -50 -50 -50 -100 -100 -100 a Patients with un
Slide 10: Patient Reported Outcome Measures Used to Assess Severity of Symptoms, HRQoL, and Treatment Benefit
Patient Reported Outcome Measures (PROMs) Used to Assess Severity of Symptoms, HRQoL, and Treatment Benefit a Mastocytosis Quality of Life (MC-QoL) b Patient Global Impression of Severity (PGIS) Disease-specific health-related quality of life measure Anchor measure designed to assess patient’s impre
Slide 11: Encouraging Signs of Rapid Improvement in Quality of Life and Symptom Severity
Encouraging Signs of Rapid Improvement in Quality of Life and Symptom Severity Quality-of-life assessed by MC-QoL Part 1A – Double-blind Open-Label Extension Symptom Severity assessed by MAS 70 Treatment Severe 65 64.8 Mastocytosis Activity Score (MAS) 60 % change from baseline at week 12a MC-QoL To
Slide 12: Bezuclastinib Treatment Provided Rapid and Continued Improvement in Overall Symptom Severity
Bezuclastinib Treatment Provided Rapid and Continued Improvement in Overall Symptom Severity Patient Global Impression of Severity (PGIS) Patients with ≥1 point improvement on PGIS 100 Part 1A – Double-blind Treatment Open-label Extension • By the first assessment (4 weeks), 71% (5/7) of patients wh
Slide 13: Bezuclastinib-Treated Patients Reported Overall Symptom Improvement Sustained During OLE
100% Bezuclastinib-Treated Patients Reported Overall Symptom Improvement During Part 1a Which Was Sustained During OLE Overall Symptoms • At week 12, 63% of patients receiving bezuclastinib reported overall symptoms were Bezuclastinib Bezuclastinib Placebo Bezu much better to very much better. After
Slide 14: Patients Reported Symptomatic Improvement Across Domains Which Deepened During OLE
Bezuclastinib-treated Patients Reported Symptomatic Improvement Across Domains During Part 1a Which Deepened During OLE Patient Global Impression of Change (PGIC) • With extended treatment (at 20 weeks), 100% of patients reported pain Very much better symptoms were better and 78% of patients reporte
Slide 15: Normalization of Serum Tryptase and Concurrent Improvement in Symptoms After 4 Weeks
Normalization of Serum Tryptase and Concurrent Improvement in Symptoms After 4 Weeks of Bezuclastinib 100mg QD 46 yo woman diagnosed with ISM -23% change from baseline MAS with -36% change in skin domain • Moderate symptoms despite use of 2 anti-mediator 0 25 Percent Change From Baseline in Serum th
Slide 16: Bezuclastinib treatment demonstrated rapid reduction in mast cell burden and encouraging safety
Bezuclastinib treatment demonstrated rapid reduction in mast cell burden, evidence of clinical activity and an encouraging safety profile • The majority of TEAEs were low grade and reversible with no related SAEs reported • Safety and tolerability profile in OLE supports potential for chronic dosing
Slide 17: The authors would like to acknowledge
The authors would like to acknowledge: • The patients who participated in the trial and those who support them, including family, caregivers, and patient advocates. • Part 1 Enrolling Study sites, investigators, and site staff: Prithviraj Bose, MD Anderson Cancer Center; Brian Modena, Modena Allergy
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