Phase 1, Two-arm, Open-label Study of Once Daily, Oral BMN 673 in Patients With Advanced Hematological Malignancies

Inclusion Criteria:

1. 18 years of age or older.

2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

3. Arm 1 AML/MDS: Must have available tissue

4. Arm 2 CLL/MCL: Must have available tissue

5. Have adequate organ function as defined below:

1. Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 X
upper limit of normal (ULN);

2. Total serum bilirubin ≤ 1.5 X ULN;

6. Able to take oral medications

7. Recovered from acute toxicity of prior treatment

8. Willing and able to provide written, signed informed consent after the nature of the
study has been explained, and prior to any research-related procedures.

9. If sexually active, must be willing to use an acceptable method of contraception
during therapy and for 30 days after the last dose of BMN 673.

10. If female of childbearing potential, must have a negative serum pregnancy test at
screening and be willing to have additional pregnancy tests during the study.

11. Willing and able to comply with all study procedures.

Exclusion Criteria:

1. Acute promyelocytic leukemia, APL [AML with t(15;17)(q22;q12), PML-RARA and
variants].

2. Disease-specific exclusion criteria:

a. AML: i. Marrow cellularity < 25% ii. Circulating blasts > 50,000/mm3 b. MCL and
CLL: i. Platelet count < 50,000/mm3 ii. Neutrophil count < 1000/mm3

3. Autologous bone marrow transplant < 6 months before Cycle 1 Day 1

4. Prior allogeneic bone marrow transplant < 6 months before Cycle 1 Day 1 and/or with
the presence of graft versus host disease (GVHD)

5. Prior treatment:

1. AML: anti-leukemia treatment within 14 days before Cycle 1 Day 1; hydroxyurea
treatment within 7 days before Cycle 1 Day 1.

2. CLL, MCL or MDS: anti-lymphoma/leukemia treatment within 28 days before Cycle 1
Day 1;

6. CLL/MCL patients who have received transfusion, hematopoietic growth factors within 7
days before Cycle 1 Day 1.

7. Symptomatic central nervous system (CNS) involvement.

8. Known to have human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or
hepatitis B virus (HBV).

9. Major surgery within 28 days before Cycle 1, Day 1.

10. Active peptic ulcer disease.

11. Active gastrointestinal tract disease with malabsorption syndrome.

12. Requirement for IV alimentation.

13. Prior surgical procedures affecting absorption.

14. Uncontrolled inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

15. Myocardial infarction within 6 months before Cycle 1 Day 1, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or unstable
cardiac arrhythmia requiring medication.

16. Breastfeeding at screening or planning to become pregnant (self or partner) at any
time during study participation.

17. Use of any investigational product or investigational medical device within 28 days
before Cycle 1, Day 1.

18. Concurrent disease or condition that would interfere with study participation or
safety, such as:

1. CLL/MCL patients with active, clinically significant infection requiring the use
of parenteral anti-microbial agents, or grade > 2 infection by NCI CTCAE (v4.03)
within 14 days before Cycle 1, Day 1(AML/MDS patients with controlled infection
are eligible for the study with no specific time requirement prior to Cycle 1,
Day 1);

2. Clinically significant bleeding diathesis or coagulopathy, including known
platelet function disorders;

3. Non-healing wound, ulcer, or bone fracture.

19. Patients who have received prior treatment with a PARP inhibitor are not eligible for
Part 2 of the study (expansion), but are eligible for Part 1 (dose escalation) of the
study.