Screening Study for KIT D816V Mutated Mast Cell Disease in Select Populations

Key Inclusion Criteria:

• Cohort 1 participants must meet inclusion criteria for either SMAC-A or SMAC-B:

• SMAC-A
• Documented anaphylaxis due to Hymenoptera venom with cardiovascular symptoms or
• Documented anaphylaxis without known trigger(s) or allergen(s) warranting hospitalization, emergency room visit, and/or epinephrine with cardiovascular symptoms 2. SMAC-B
• Episodic or recurrent signs and symptoms consistent with mast cell activation without known triggers or allergens in at least 2 of the following organ systems: skin, respiratory/naso-ocular, gastrointestinal tract, or cardiovascular.
• Any clinical response on one or more optimally dosed therapies intended to mitigate mast cell mediators, as determined by the Investigator.
• Cohort 2 participants must have confirmed, known diagnosis of 1 of the following criteria:

• Either hypermobile Ehlers-Danlos syndrome or documented history of hypermobility spectrum disorder.
• Postural orthostatic tachycardia syndrome with one or more systemic symptoms.
• Early onset (≤50 years old) osteoporosis or osteopenia.
• Cohort 3 participants must have documented diagnosis of 1 of the following, according to World Health Organization 5th edition criteria: chronic myelomonocytic leukemia or myelodysplastic syndrome/myeloproliferative neoplasm not otherwise specified.

Key Exclusion Criteria:

• Participants previously diagnosed with any of the following:

• Monoclonal mast cell activation syndrome with a known KIT mutation
• Cutaneous mastocytosis only (that is, no documentation of systemic mast cell disease via bone marrow biopsy)
• Any subtype of systemic mastocytosis
• Mast cell sarcoma
• Cohort 2 only: Osteopenia or osteoporosis attributed to known genetic, endocrine, nutritional, or other medical conditions.

Note: Additional protocol-defined criteria apply.