Inclusion Criteria:

• Age 18 years or older at the time of signing the ICF
• ECOG performance status of 0 to 1 for the dose escalation (Part 1a) and 0 to 2 for the dose expansion (Part 1b)
• Documented CALR exon-9 mutation
• Confirmed diagnosis of MPN according to the 2022 ICC criteria:
  • DIPSS+ intermediate-2/high-risk MF with prior JAKi, <20% blasts, and measurable spleen
  • High-risk ET with platelets >450×10⁹/L
• Resistant, refractory, intolerant, or has lost response to ≥1 prior line of therapy for MF and ≥2 prior lines for ET
• No prior stem cell transplant and none planned within 6 months
• Minimum Laboratory Requirements:
  • Platelet count ≥50 × 10⁹/L
  • Absolute neutrophil count ≥1 × 10⁹/L
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN), unless receiving vitamin K antagonists
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 × ULN
  • Total bilirubin <2 × ULN
  • Estimated creatinine clearance >45 or >30 mL/min (depending on study part)

Exclusion Criteria:

• Major bleeding or thrombosis (e.g., stroke, DVT, PE) within the past 3 months
• Active or high-risk HBV, HCV, or HIV infection, or other chronic active infections requiring systemic treatment
• Active invasive cancer within the past 2 years, except certain early-stage or low-risk cancers (e.g., resected skin, cervical, thyroid, or prostate cancer)
• Pregnant or unwilling to avoid pregnancy or fathering a child during the study and for a defined period after the last dose.

Other protocol-defined Inclusion/Exclusion Criteria may apply.