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 (unless only a single standard-of-care option is approved in the participating country)
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
* Estimated creatinine clearance \>45 or \>30 mL/min (depending on study part)
You may not be if
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.
