A Phase 1 Study of PRT12396 in Participants With Select Myeloproliferative Neoplasms

Inclusion Criteria:

• Willing and able to comply with all scheduled visits, treatment plan, laboratorytests, lifestyle considerations (including contraception requirements), and otherstudy procedures.

• Confirmed diagnosis of PV or MF according to WHO 2016 or revised ICC/WHO 2022criteria

• Documented presence of a JAK2 V617 mutation

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Estimate life expectancy of ≥12 weeks per investigator assessment.

• Negative serum or urine pregnancy test and agree to use contraception or maintaintrue abstinence.

• Adequate organ function and bone marrow reserves (hematology, renal, and hepatic)

Exclusion Criteria:

• History of another malignancy within 3 years prior to enrollment, except formalignancy considered cured with low risk of recurrence.

• Clinically significant anemia due to nutritional deficiency or hemolytic disorders.

• Active or uncontrolled infection requiring systemic therapy or hospitalization.

• Any other medical or psychiatric conditions that, in the Investigator's judgment,would increase risk or interfere with study participation or interpretation ofresults.

• Clinically significant or uncontrolled medical conditions, including activeinfection or cardiovascular disease, that would increase risk or interfere withstudy participation.

• Unresolved toxicity > Grade 1 from prior anticancer therapy, except for alopecia orperipheral neuropathy ≤ Grade 2.

• Pregnancy or breastfeeding

• Known sensitivity or contraindication to any component of study, or the excipientsof study treatment.

• Prior systemic therapy for PV or MF, prior or planned allogeneic hematopoieticstem-cell transplantation, recent major surgery, prior splenectomy or prior splenicirradiation, or use of hematopoietic growth factors within protocol-defined washoutperiods.

• Use of strong or moderate cytochrome P450 (CYP) 3A4 inhibitor or inducer, sensitiveCYP3A substrates with narrow therapeutic range, or acid-reducing agents that cannotbe discontinued prior to study treatment.

• Participation in another interventional clinical study.