Slide 1: Efficacy and Safety Results From the Pivotal Summit Trial: Bezuclastinib in Adults with 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 2: Bezuclastinib is an oral, potent, selective type 1 TKI active 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 3: Summit: Pivotal phase 2 randomized, double-blind, 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 4: MS2D2: A patient-reported outcome measure of symptom severity across NonAdvSM
MS2D2: A comprehensive patient-reported outcome measure of symptom severity in patients across the spectrum of NonAdvSM MS2D2 Total Symptom Score (TSS) • The MS2D2a is a 17-item measure addressing signs Domain Symptom and symptoms of NonAdvSM • Difficulty concentrating • Eleven symptoms within 4 dom
Slide 5: 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 6: Primary endpoint achieved with significant, clinically meaningful 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 7: 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 reachin
Slide 8: Clinically meaningful symptom relief across all symptoms measured at 24 weeks
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 9: Significantly reduced serum tryptase, a core indicator of mast cell burden
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 25 P<0.0001 Serum Tryptase
Slide 10: Significantly reduced bone marrow mast cell burden and abnormal mast cell phenotype
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 11: 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 12: 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 13: 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 p < 0.001,
Slide 14: 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) • Variety of AEs occurred more often in the placebo group (vs the TEAEs, n (%) 116 (98.3) 53 (88.3) bezuclastinib
Slide 15: 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 16: Acknowledgements, additional Summit data, and expanded access
Acknowledgements, additional Summit data, and expanded access • The authors would like to thank the For additional information on bezuclastinib in systemic mastocytosis: patients participating in this study, as well • The Effect of Bezuclastinib on the Pathobiology of Mastocytosis: as their families