Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF

This is a Phase 1/2 study that is currently enrolling JAK2 failures into the Phase 2 portion
of the study.

Inclusion Criteria:

- Primary myelofibrosis, post-PV MF, or post-ET MF that requires therapy

- MF patients must have received prior JAK2 inhibitor therapy, and been found to be
intolerant, or refractory/relapsed from prior JAK2 inhibitor therapy, based on
investigator assessment

- ≥18 years old

- ECOG Performance Status of ≤ 3

- Estimated life expectancy of ≥12 weeks

- Male or non-pregnant, non-lactating female patients

- Serum creatinine of ≤1.5 × the upper limit of normal (ULN)OR estimated creatinine
clearance (CrCl) ≥ 40 ml/min/1.73 m2

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × the upper
limit of normal (ULN) and total bilirubin ≤1.5 × ULN. If the total bilirubin is
elevated between 1.5 x and 3 x ULN, patients with a direct bilirubin ≤ 1.5 X ULN are
eligible during the Phase II portion.

- Absolute neutrophil count (ANC) >1000/μL and Platelet count > 25,000/μL

- QTcB ≤ 480 msec

- No MF-directed treatment for at least 2 weeks prior to initiation of NS-018, including
any use of corticosteroids for Myelofibrosis symptom or blood count management. Low
dose corticosteroids ≤ 10 mg/day prednisone or equivalent is allowed for
non-myelofibrosis purposes.

Exclusion Criteria:

- Active, uncontrolled systemic infection

- Patients with any unresolved toxicity greater than Grade 1 from previous anticancer
therapy

- Potentially curative therapy is available

- Currently taking medication that is substantially metabolized by cytochrome P450 (CYP)
1A2 or CYP3A4 or taking medication known to be strong inhibitors or inducers of CYP3A4

- Patients with a serious cardiac condition within the past 6 months

- Pregnant or lactating

- Radiation therapy for splenomegaly within 6 months prior to study entry

- Splenectomy (Phase 2 portion of the study only)

- Known HIV positive status

- Known active hepatitis, a history of viral hepatitis B or hepatitis C