This study is being conducted to assess the Safety, Tolerability, and Pharmacokinetics of INCB160058 in Participants With Myeloproliferative Neoplasms.

Inclusion Criteria:

• Age ≥ 18 years

• MF:

  • Intermediate-1 or higher risk PMF, post-PV MF, or post-ET MF with evidence of minimum burden of disease based on splenomegaly, and for the monotherapy cohort, participants must have been previously treated with at least 1 JAK inhibitor for ≥ 12 weeks and resistant, refractory, intolerant to, or have lost response to JAK inhibitor treatment.
  • For the MF SubOpt R cohort: Therapeutic regimen prior to enrollment as defined in the protocol and unlikely to benefit from further monotherapy in the opinion of the investigator.

• PV: Confirmed diagnosis of PV and previously treated with at least 1 prior standard cytoreductive therapy and are resistant, refractory, intolerant to, or have lost response to treatment.

• ET: Confirmed diagnosis of high-risk ET as defined in the protocol and previously treated with at least 1 prior standard cytoreductive therapy and are resistant, refractory, intolerant to, or have lost response to treatment.

• Life expectancy > 6 months.

• Willingness to undergo a pretreatment and regular on-study bone marrow biopsies and aspirations (as appropriate to disease).

• Existing documentation of JAK2V617F mutation from a qualified local laboratory.

Exclusion Criteria:

• Presence of a hematological malignancy requiring treatment, other than PMF, post-PV MF, post-ET MF, PV, or ET.
• Prior history of major bleeding or thrombosis within the 3 months prior to study enrollment.
• Participants with abnormal hematologic, hepatic, or renal function based on laboratory evaluation.
• Has undergone prior allogenic or autologous stem-cell transplantation or allogenic stem-cell transplantation is planned
• Active invasive malignancy.
• Significant concurrent, uncontrolled medical condition.
• Acute or chronic HBV, active HCV or known HIV.
• Any prior MPN-directed therapy within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
• Participants undergoing treatment with G-CSF or GM-CSF, romiplostim, or eltrombopag at any time within 4 weeks before the first dose of study treatment.

Other protocol-defined Inclusion/Exclusion Criteria may apply.