• Be ≥18 years of age at time of signing the informed consent form (ICF)

• Must voluntarily sign ICF and be willing and able to adhere to the study visit schedule and all protocol requirements

• Have a pathologically confirmed diagnosis of PV, ET, PMF, post-ET-MF, or post-PV-MF as per WHO diagnostic criteria

• Participants with MF may have low, intermediate 1, intermediate 2, or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS). Participants with PV and ET with both low- and high-risk disease may be included.

• Must have received at least 12 weeks of current MPN therapy at stable doses and have persistent clinical burden and/or cytologic abnormalities as defined by the following:

‣ Clinical burden is defined as MPN-SAF TSS \>12 points and/or palpable spleen of ≥5cm

⁃ Cytologic abnormalities include the following for each disease state:

• MF:

‣ Persistent leukocytosis as defined by WBC \>12 x 109/L

∙ PV:

‣ Persistent therapeutic phlebotomy dependence (\>2 phlebotomies within 24 weeks of screening, and \>1 phlebotomy within 16 weeks of screening, as defined in the PROUD-PV studies) for a goal HCT \<45% and/or

⁃ Leukocytosis as defined by WBC \>12 x 109/L and/or

⁃ Thrombocytosis defined as platelet count \>500 x 109/L

∙ ET:

‣ Persistent leukocytosis as defined by WBC \>12 x 109/L and/or

⁃ Thrombocytosis defined as platelet count \>500 x 109/L

⁃ Permitted concurrent MPN therapies include: aspirin, hydroxyurea, anagrelide, ropeginterferon alfa-2b, peginterferon alfa-2a, erythropoiesis-stimulating agents, phlebotomy, and/or ruxolitinib.

• A stable dose is defined as 12 weeks of treatment without a change in dosing

∙ Patients with myelofibrosis must be on stable dose of ruxolitinib

• Must have adequate organ function as demonstrated by the following:

‣ AST, ALT \<3x upper limit of normal (ULN) and no known history of cirrhosis

⁃ Total bilirubin \<3mg/dL

⁃ Creatinine clearance (CrCl) \>40 mL/min as estimated with the Cockcroft-Gault equation

⁃ Baseline platelet count \>50 x 109/L for MF and \>150 x 109/L for ET/PV

⁃ Baseline absolute neutrophil count (ANC) \>1000

⁃ Peripheral blood blast count \<10%

• ECOG performance status ≤2

• Life expectancy of at least six months

• Female participants of childbearing potential must have a negative serum pregnancy test at screening and Cycle 1 Day 1 and must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

‣ Recommended methods of birth control are:

• The consistent use of an approved hormonal contraception (birth control pill/patches, rings), an intrauterine device (IUD), contraceptive injection (Depo-Provera), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), sexual abstinence (no sexual intercourse), or sterilization

⁃ A woman of childbearing potential is any woman (regardless of sexual orientation, having undergone a tubal litigation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

∙ Has not been naturally postmenopausal for at least 12 consecutive months

• Male participants must agree to use an adequate method of contraception and must not father a child or donate sperm starting with the first dose of study therapy through 120 days after the last dose of study therapy