(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis

Key Inclusion Criteria:

All Participants:

-Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.

Part 1 and PK groups:

• Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review

• Participant must have failed to achieve adequate symptom control for 1 or moreBaseline symptoms, as determined by the Investigator, with at least 2 of thefollowing symptom-directed therapies administered: H1 blockers, H2 blockers,proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, oromalizumab.

• Participants must have SDT for ISM symptom management stabilized for at least 14days prior to starting screening procedures.

• For participants receiving corticosteroids, the dose must be ≤ 20 mg/day prednisoneor equivalent, and the dose must be stable for ≥ 14 days.

Part K:

-Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review

Part S:

-Participant has confirmed diagnosis of SSM, confirmed by Central Pathology Review of BM biopsy and central review of B- and C-findings by WHO diagnostic criteria.

Part 2:

-Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review

Key Exclusion Criteria:

• Participant has been diagnosed with any of the following WHO systemic mastocytosis (SM) sub-classifications: cutaneous mastocytosis only, SM with an associatedhematologic neoplasm of non-MC lineage (SM-AHN), aggressive SM, mast cell leukemia,or mast cell sarcoma.

• Participant has been diagnosed with another myeloproliferative disorder.

• Participant has organ damage attributable to SM.

• Participant has clinically significant, uncontrolled, cardiovascular disease

• Participant has a QT interval corrected using Fridericia's formula (QTcF) > > 470milliseconds (msec) (for females) or > 450 msec (for males).

• Participant has a history of a primary malignancy that has been diagnosed orrequired therapy within 3 years. The following prior malignancies are notexclusionary: completely resected basal cell and squamous cell skin cancer,curatively treated localized prostate cancer, and completely resected carcinoma insitu of any site.

• Time since any cytoreductive therapy including masitinib and midostaurin should beat least 5 half-lives or 14 days (whichever is longer), and for cladribine,interferon alpha, pegylated interferon, or antibody therapy < 28 days or 5half-lives of the drug (whichever is longer), before beginning the screening period.

• Participant has received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the screening period.

Other protocol-defined criteria apply.