Alvocidib Biomarker-driven Phase 2 AML Study

In Stage 1 of the study, all eligible AML patients with demonstrated MCL-1 dependence of ≥
40% by mitochondrial profiling in bone marrow will receive treatment with ACM.

In Stage 2, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 40% by
mitochondrial profiling in bone marrow will be randomized 1:1 to receive either treatment
with ACM or CM.

In the NDHR exploratory arm, all eligible patients with newly diagnosed high-risk (NDHR) AML
with MCL-1 dependence of ≥40% by mitochondrial profiling in bone marrow will receive
treatment with ACM.

In the MCL-1 dependency exploratory arms, all eligible AML patients with demonstrated MCL-1
dependence of ≥ 30 - <40% (Arm A), 15% - <30% (Arm B), or 0 - <15% (Arm C) by mitochondrial
profiling in bone marrow who are either in first relapse (within 24 months of CR) or have
primary refractory AML (ie, no CR or CRi after 2 cycles of intensive anthracycline/cytarabine
± etoposide or cladribine induction) will receive treatment with ACM.

Inclusion Criteria:

1. Be between the ages of ≥18 and ≤65 years

2. Have an established, pathologically confirmed diagnoses of AML by World Health
Organization (WHO) criteria excluding acute promyelocytic leukemia (APL-M3) with a
bone marrow of >5% blasts based on histology or flow cytometry

3. Be in first relapse (within 24 months of CR) or have failed induction therapy* (no CR
or CRi after treatment with an intensive regimen (eg, anthracycline/cytarabine ±
etoposide, gemtuzumab ozogamicin, or cladribine) or have newly diagnosed high-risk AML
as defined in this protocol.

*Induction therapy may involve 1 or 2 cycles of the same regimen. Efficacy assessment
of induction therapy must be >21 days from the start of the previous induction cycle.

4. Demonstrate MCL-1 dependence of ≥40% by mitochondrial profiling in bone marrow, 30 -
<40% for MCL-1 Dependency Exploratory Arm A, 15% - <30% (MCL-1 Dependency Exploratory
Arm B), or 0 - <15% (MCL-1 Dependency Exploratory Arm C)

5. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2

6. Have a serum creatinine level ≤1.8 mg/dL

7. Have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤5 times
upper limit of normal (ULN)

8. Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome,
hemolysis, or leukemia)

9. Have a left ventricular ejection fraction (LVEF) >45% by echocardiogram (ECHO) or
multigated acquisition (MUGA) scan

10. Be nonfertile or agree to use an adequate method of contraception. Sexually active
patients and their partners must use an effective method of contraception associated
with a low failure rate during and for 6 months after completion of study therapy.

11. Be able to comply with the requirements of the entire study.

12. Provide written informed consent prior to any study related procedure.

Exclusion Criteria:

1. Received more than 2 cycles of induction therapy for AML. Investigational agents as
part of front-line therapy for AML may by acceptable following discussion with the
Medical Monitor. Hydroxyurea is permitted (see #5 below).

2. Received any previous treatment with alvocidib or any other CDK inhibitor

3. Received a hematopoietic stem cell transplant within the previous 2 months

4. Have clinically significant graft versus host disease (GVHD), or GVHD requiring
initiation or escalation of treatment within the last 21 days

5. Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is
allowed up to the evening before starting (but not within 12 hours) of starting
treatment on either arm.

6. Received >360 mg/m2 equivalents of daunorubicin

7. Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #5 above)

8. Received antileukemic therapy within the last 3 weeks (with the exception of
hydroxyurea or if the patient has definite refractory disease). Refractory patients
who received therapy within the last 3 weeks may be eligible with prior approval of
the Medical Monitor.

9. Diagnosed with acute promyelocytic leukemia (APL, M3)

10. Have active central nervous system (CNS) leukemia

11. Have evidence of uncontrolled disseminated intravascular coagulation

12. Have an active, uncontrolled infection

13. Have other life-threatening illness

14. Have other active malignancies or diagnosed with other malignancies within the last 6
months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia

15. Have mental deficits and/or psychiatric history that may compromise the ability to
give written informed consent or to comply with the study protocol.

16. Are pregnant and/or nursing

17. Have received any live vaccine within 14 days prior to first study drug
administration.