A Phase 2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis

Inclusion Criteria

- Adult (aged ≥ 18 years)

- Phase 2 part: Patients with confirmed diagnosis of MF who meet all of the following
criteria:

- Dynamic International Prognostic Scoring System (DIPSS; see Appendix 3) risk
category of intermediate-1 or higher.

- ANC ≥ 1 x 10^9/L without the assistance of granulocyte growth factors

- Peripheral blood blast count <10%

- ECOG performance status ≤ 2.

- Adequate hematological, renal, hepatic, and coagulation laboratory assessments

- Patients must give written informed consent to participate in this study before the
performance of any study-related procedure.

For Arm 1 and 2 the following criteria should be considered:

- Palpable spleen ≥ 5 cm that is below the costal margin on physical examination OR RBC
transfusion dependent (defined as an average of ≥2 units of RBC transfusions per month
over the 12 weeks prior to enrollment)

- At least 2 symptoms measurable (score ≥ 1) using the Myelofibrosis Symptom Assessment
Form Version 4.0 (MFSAF v4.0)

- Platelet count ≥ 75 x 10^9/L without the assistance of thrombopoietic factors or
transfusions for at least 14 days

- Monotherapy Arm (Arm 1): Previously treated with a JAK inhibitor and be intolerant,
resistant, refractory or lost response to the JAK inhibitor

- Combination Arm (Arm 2): Must have received single agent ruxolitinib and be on a
stable dose for a minimum 8 weeks

For Arm 3 (JAK inhibitors naïve) the following criteria should be considered:

- Platelet count ≥ 100 x 10^9/L without the assistance of thrombopoietic factors or
transfusions

- Palpable spleen ≥ 5 cm that is below the costal margin on physical examination

- Anemic, defined as a hemoglobin < 10g/dL

- At least 2 symptoms measurable (score ≥ 3) or a total score of ≥ 10 using the MFSAF
v4.0

- No prior treatment with JAKi allowed

Exclusion Criteria

- Current known active or chronic infection with human immunodeficiency virus (HIV),
Hepatitis B or Hepatitis C.

- Impaired cardiac function or clinically significant cardiac diseases

- Patients with Child-Pugh Class B or C

- Impairment of gastrointestinal (GI) function or GI disease that could significantly
alter the absorption of CPI-0610 and/or ruxolitinib, including any unresolved nausea,
vomiting, or diarrhea that is CTCAE grade >1

- Prior treatment with a BET inhibitor.

- Pregnant or lactating women

- Any other concurrent severe and/or uncontrolled concomitant medical condition that
could compromise participation in the study

- Patients unwilling or unable to comply with this study protocol.