This study evaluates TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of Myelofibrosis (Cohorts 1-3) or Indolent Systemic Mastocytosis (Cohort 5). Participants must be diagnosed with Myelofibrosis and be relapsed/refractory (e.g., having failed prior therapy), intolerant, or ineligible to receive JAKi treatment, or be diagnosed with Indolent Systemic Mastocytosis.

Cohorts 1-3

Key Inclusion Criteria:

• Adults ≥18 years of age
• Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
• Adequate hematologic, hepatic, and renal functions
• MF symptoms as defined by having at least 2 symptoms with an average baseline (Day -7 to Day -1) score of at least 1 for each of the 2 symptoms per MFSAF v4.0
• Cohort 3 only: Ineligibility for JAKi treatment with a platelet count of ≥ 25 and < 50 x 10^9/L

Key Exclusion Criteria:

• Prior treatment with any BTK or BMX inhibitors
• Prior treatment with JAKi within 28 days prior to study treatment
• Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment

Cohort 5

Key Inclusion Criteria:

• Adults ≥18 years of age
• Confirmed diagnosis of ISM as defined by WHO diagnostic criteria based on review of bone marrow biopsy pathology report results
• Subject must have moderate-to-severe symptoms

Key Exclusion Criteria:

• Prior treatment with any BTK or BMX inhibitors
• Prior treatment with Avapritinib, bezuclastinib, or BLU-263/elenestinib
• Diagnosis with another myeloproliferative disorder