Inclusion Criteria:

• - Be ≥ 18 years of age at time of signing the ICF.

• - Able to voluntarily sign the ICF.

• - Have a pathologically confirmed diagnosis of PMF, post-ET-MF, or post-PV-MF as per the WHO diagnostic criteria with intermediate-2 or higher risk disease by DIPSS.

• - Have an ECOG performance status ≤ 2.

• - Willing to undergo a bone marrow biopsy at screening; however, a bone marrow biopsy obtained within 90 days of screening without intervening treatments and approved by the study chair may suffice.

• - Be refractory/resistant to or intolerant of/inappropriate for JAKi therapy as defined by at least one of the following: - Treatment for ≥ 3 months with inadequate efficacy as demonstrated by persistent palpable splenomegaly ≥ 5cm or symptoms related to splenomegaly.

• - Treatment for ≥ 28 days complicated by either: - Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months) - NCI CTCAE grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of < 20 mg BID.

• - In the Investigator's judgment, are not candidates for available approved JAKi.

• - Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia.

• - At least two weeks must have elapsed between the last dose of any MF-directed drug treatments (including investigational therapies and excluding hydroxyurea) and study enrollment.

• - Have adequate organ function as demonstrated by the following: - ALT (SGPT) and/or AST (SGOT) ≤ 3x ULN, or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to MF-related EMH); - Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to MF-related EMH or documented Gilbert's syndrome); - Creatinine clearance ≥ 40 mL/min ; - Platelet count ≥ 25 x 109/L; - Bone marrow and peripheral blood blast count < 10%; - ANC ≥ 1000 mm3.

• - Life expectancy of at least six months.

• - Women of childbearing potential (WCBP) and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 120 days following completion of therapy.

WCBP must also have a negative serum pregnancy test at screening and Cycle 1 Day 1. Should a woman become pregnant or suspect she is pregnant while participating, she should inform her treating physician immediately.

• - Ability to adhere to the study visit schedule and all protocol requirements.

Exclusion Criteria:

• - Use of an investigational agent or an investigational device within 4 weeks of the first dose of study therapy.

• - History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months.

• - Other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer.

• - Moderate or severe cardiovascular disease meeting one or both of the below criteria: - Presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.

• - Documented major ECG abnormalities (not responding to medical treatments) - Presence of active serious infection.

• - Any serious, unstable medical or psychiatric condition that would prevent (as judged by the Investigator) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

• - Participants who have undergone a hematopoietic cell transplant (HCT) within 100 days of the first dose of study therapy, participants on immunosuppressive therapy post-HCT at screening, use of calcineurin inhibitors within 4 weeks prior to first dose of study therapy, or participants with clinically significant graft-versus-host disease (GVHD) - Note: The use of topical steroids or < 10mg oral prednisone for ongoing skin GVHD is permitted.

• - Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection.

• - Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of reparixin, including any unresolved nausea, vomiting, or diarrhea > CTCAE grade 1.

• - Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject.

• - Organ transplant recipients other than bone marrow transplant.

- Women who are pregnant or lactating

Arms

Experimental: Reparixin

Eligible patients will receive oral reparixin three times daily on a 4-week cycle for a core study period of 6 cycles (24 weeks). After cycle 6, patients may continue receiving reparixin once daily on a 4-week cycle if at least stable disease (SD) is met by IWG-MRT criteria until loss of response, disease progression, unacceptable toxicity, patient/physician withdrawal, or termination of study by sponsor.

Interventions

Drug: - reparixin

reparixin at 1200mg TID three times per day.