Dose Escalation of OXi4503 as Single Agent and Combination With Cytarabine w/Subsequent Ph 2 Cohorts for AML and MDS

Phase 1 dose escalation component will assess the safety, PK/PD, and preliminary efficacy of
OXi4503 as a single agent in subjects with relapsed/refractory AML and MDS, and the safety
and PK/PD of the combination of OXi4503 with intermediate-dose cytarabine in subjects with
AML/MDS.

Phase 2 will assess the preliminary efficacy of the OXi4503+cytarabine combination in 2
cohorts.

Inclusion Criteria:

1. Provide informed consent

2. ≥ 18 years of age

3. Phase 1 (dose escalation) subjects must have either:

- AML that has failed to achieve complete remission or morphologic complete
remission or

- MDS - Marrow blasts must be > 5% and disease failed at least 1 prior
hypomethylating agent

4. Phase 2 (expansion) subjects must have either MDS or relapsed/refractory AML

5. Eastern Cooperative Oncology Group performance status 0, 1, or 2

6. Total bilirubin ≤ 2

7. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5
times upper limit of normal (ULN)

8. Serum creatinine < 2.5 times ULN

9. Prothrombin time (PT)/international normalized ratio and (PTT) in normal range ± 25%

10. Women of child-bearing potential

11. Males with female partners of child-bearing potential must agree to use
physician-approved contraceptive methods

Exclusion Criteria:

1. Acute promyelocytic leukemia

2. Absolute peripheral blood myeloblast count greater than 20,000/mm3

3. Uncontrolled hypertension

4. History of congenital long QT syndrome or torsades de pointes

5. Pathologic bradycardia or heart block

6. Prolonged baseline QTc

7. Hiistory of ventricular arrhythmia

8. Myocardial infarction and/or new ST elevation

9. Any history of hemorrhagic stroke

10. Symptomatic congestive heart failure

11. Major hemorrhagic event within 28 days

12. Suggestive central nervous system involvement with leukemia

13. Any open wound

14. Pregnant and nursing subjects are excluded

15. Treatment with any anticancer therapy

16. Treatment with colchicine is excluded.

17. Psychiatric disorders that would interfere with consent