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Bezuclastinib

Phase 2

SSM | Small molecule | Musculoskeletal |Cogent Biosciences, Inc.|Last Updated: May 22, 2026

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment237
FDA Designations
BREAKTHROUGH_THERAPY
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT05186753(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic MastocytosisPHASE2 ACTIVE NOT_RECRUITING 237Jun 27, 2022Apr 1, 2030May 22, 202657 United States, Australia +13
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Study Endpoints
Primary Endpoints
Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM
3 months

Selection of the recommended dose to be used in subsequent parts of the study.

Part 2: Efficacy of bezuclastinib at the selected dose versus placebo
24 Weeks

Mean absolute change on the Mastocytosis Symptom Severity Daily Diary (MS2D2)

Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events
Up to 5 years

CTCAE v5

Secondary Endpoints
Part 2: Proportion of subjects who had at least 50% reduction in serum tryptase
24 weeks
Part 2: Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction
24 weeks
Part 2: Determine responder rates of subjects treated with bezuclastinib at the selected dose versus placebo
24 weeks
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
(Part 1a) Bezuclastinib Dose 1 + BSCEXPERIMENTAL -
(Part 1a) Bezuclastinib Dose 2 + BSCEXPERIMENTAL -
(Part 1a) Placebo + BSCPLACEBO_COMPARATOR -
(Part 1b) Bezuclastinib Dose 1 + BSCEXPERIMENTAL -
(Part 1b) Bezuclastinib Dose 2 + BSCEXPERIMENTAL -
(Part 1b) Placebo + BSCPLACEBO_COMPARATOR -
(Part 2) Bezuclastinib Selected Dose + BSCEXPERIMENTAL -
(Part 2) Placebo + BSCPLACEBO_COMPARATOR -
(Part 3) Bezuclastinib + BSCEXPERIMENTAL -
(Prior Therapy Sub-study) BezuclastinibEXPERIMENTAL -
Interventions
NameTypeDescription
Bezuclastinib Tablets (Formulation A)DRUGBezuclastinib will be administered orally, once daily continuously for 28-day cycles
Bezuclastinib Tablets (Formulation B)DRUGBezuclastinib will be administered orally, once daily continuously for 28-day cycles
Placebo TabletsDRUGPlacebo will be administered orally, once daily continuously for 28-day cycles
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites57

Key Inclusion Criteria: 1. Diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM): * Indolent systemic mastocytosis (ISM), * Bone marrow mastocytosis (BMM) * Smoldering systemic mastocytosis (SSM) 2. ...

Countries:United StatesAustraliaBelgiumCanadaCzechiaFranceGermanyIrelandItalyNetherlandsNorwayPolandSpainSwitzerlandUnited Kingdom
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Recent Changes (Last 90 Days)
LOWMay 26, 2026NCT05186753primaryCompletionDate: changed
LOWMay 24, 2026NCT05186753studyFirstPostDate: changed