• Age 18 years and older at the time of signing the informed consent.

• Part 1 Monotherapy: Participants with confirmed diagnosis of relapsed or refractory MF (primary, or post-PV and post-ET), MDS, MDS/MPN, or ET who have received at least 1 prior line of therapy; are either refractory, relapsed, or intolerant to the last therapy; and there is no available therapy that would provide clinical benefit in the opinion of the investigator.

‣ a. MF with measurable disease (palpable spleen and symptoms) as defined in the protocol and risk category of intermediate 2 or high according to DIPSS. MF participants must have received a JAK inhibitor(s), such as ruxolitinib.

⁃ b. ET participants should have disease refractory to hydroxyurea as defined by the protocol.

• Part 2 Combination with ruxolitinib.

‣ a. Primary MF or secondary MFs (post-PV MF and post-ET MF), histologically or cytologically confirmed, with measurable disease (palpable spleen and symptoms) as defined in the protocol, either currently receiving ruxolitinib with suboptimal response or JAKi-naive.

⁃ b. Suboptimal response is defined as currently being treated with ruxolitinib monotherapy at a stable dose for ≥ 8 weeks immediately preceding the first dose of study treatment. One dose reduction due to toxicities within 8 weeks prior to Study Day 1 is permitted.

⁃ c. JAKi-naive is defined as those participants that have no prior use of any JAK inhibitor, including ruxolitinib, and;

⁃ d. Part 2 dose escalation: Risk category of intermediate-2 or high according to DIPSS.

⁃ e. Part 2 dose expansion: Risk category of intermediate-1, intermediate-2, or high according to DIPSS.

⁃ f. Part 2 dose expansion participants with chronic MF are defined as participants with bone marrow myeloblast percentage \< 5% (not applicable if dry tap or blast count deemed not reliable by the investigator) and blast count in peripheral blood \< 1% at screening and who are currently receiving ruxolitinib and having a suboptimal response.

∙ Note: Study treatment should be delayed if peripheral blood blast count at baseline is \> 3%; treatment should only be started with medical monitor approval.

• g. Part 2 dose expansion participants with accelerated-phase MF are defined as having either a bone marrow myeloblast percentage ≥ 5% to \< 20% or a myeloblast percentage ≥ 10% in peripheral blood on 2 occasions at least 2 weeks apart, AND are currently receiving ruxolitinib and have a suboptimal response.

• h. Part 2 dose expansion participants with JAKi-naive MF are eligible to receive ruxolitinib, with peripheral blood blast count of \< 10% at the screening hematology assessment.

‣ Must not be a candidate for potentially curative therapy, including hematopoietic stem cell transplantation.

⁃ ECOG performance status 0 to 2.

⁃ Life expectancy ≥ 24 weeks.

⁃ Willingness to avoid pregnancy or fathering children based on criteria.

• a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of study treatment and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.

• b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.

• c. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea without any other medical reasons such as treatment with anticancer agents) are eligible.