A Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 and/or Ras Mutations

Phase 1 (Safety Run-In): Following Screening, a total of up to 30 subjects in up to 5 dose
cohorts to establish the RP2D. The safety run-in phase will be a standard 3+3 cohort design.

Phase 2a (Expansion): Once the Phase 1 Safety Run-In portion of the study is complete and an
RP2D is established, additional subjects will be enrolled into the Phase 2 Expansion portion
in three cohorts. Cohort 1 will enroll up to 26 patients with relapsed or refractory AML and
confirmed FLT3 mutation (with or without a Ras mutation) without prior exposure to a FLT3
inhibitor. Cohort 2 will enroll up to 26 patients with relapsed or refractory AML and
confirmed FLT3 mutation (with or without a Ras mutation) with prior exposure to a FLT3
inhibitor. Cohort 3 will enroll up to 10 patients with relapsed or refractory AML with a
confirmed Ras mutation and no FLT3 mutation. Cohort 1 and 2 of the Expansion Phase will
incorporate a Simon 2-stage optimal design. Subjects with AML enrolled in the Phase 1 portion
of the study at the RP2D will count towards the Phase 2a accrual for the appropriate cohort.

Subjects will receive E6201 weekly or bi-weekly on a 28-day schedule, with the schedule and
dose level established in the Safety Run-In portion of the study. Disease assessments,
including analysis of blood and bone marrow samples, will be performed at the end of Cycles 1
and 3 and every 2 cycles thereafter. Disease assessments may be made at other time points at
the discretion of the Investigator.

Subjects who demonstrate clinical benefit (objective response or stable disease) will be
allowed to continue therapy with E6201 until progression of disease, observation of
unacceptable adverse events, intercurrent illness or changes in the patient's condition that
prevents further study participation.

During the study, ECGs will be performed, blood will be collected for hematology, serum
chemistry, pharmacokinetics and pharmacodynamics assessments, and bone marrow will be
collected for the assessment of disease response and mutational status.

Inclusion Criteria:

- Males and females ≥ 18 years of age

- Phase 1: Confirmed relapsed or refractory AML with a documented FLT3 and/or Ras
mutation, or ≥ 60 years with newly diagnosed FLT3+ and/or Ras+ AML and not eligible
for standard induction chemotherapy or FLT3+ and/or Ras+ higher-risk MDS/CMML (defined
as ≥ 10% marrow blasts or ≥ 5% peripheral blood blasts or Revised International
Prognostic Scoring System [IPSS-R] score ≥ 3.5) and relapsed or refractory to prior
therapy

- Phase 2: Confirmed relapsed or refractory AML with a documented FLT3 and/or Ras
mutation, or age ≥ 60 years with newly diagnosed FLT3+ and/or Ras+ AML and not
eligible for standard induction chemotherapy

- At least 3 weeks beyond the last cancer treatment for the disease under study, major
surgery and recovered from all acute toxicities (≤ Grade 1) by first dose of study
drug (C1D1). Hydroxyurea used to control peripheral blast counts is permitted during
the first 2 cycles.

- Adequate performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2

- Adequate renal and hepatic function:

- creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance ≥ 45 mL/minute

- total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's
disease or thought to be due to underlying AML

- ALT and AST ≤ 5 times ULN

- Negative serum pregnancy test within 14 days prior to the first dose of study therapy
for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects
must agree to use adequate methods to avoid pregnancy throughout the study and for 28
days after completion of study treatment.

- Ability to provide written informed consent

Exclusion Criteria:

- History of clinically significant cardiac impairment, congestive heart failure (CHF)
New York Heart Association (NYHA) Class III or IV, unstable angina, or myocardial
infarction during the previous 6 months, or serious cardiac arrhythmia

- QT interval corrected for rate (QTc) ≥ 450 msec for males and ≥ 460 msec for females
on the ECG obtained at Screening using Fridericia method for QTc calculation (average
of 3 readings)

- Concomitant medication(s) that may cause QTc prolongation or induce Torsades de
Pointes with the exception of anti-microbials used as standard of care to prevent or
treat infections and other such drugs that are considered by the investigator to be
essential for the care of the patient. However, if such medications are deemed to be
necessary during the study, more extensive ECG monitoring will be added during the
period of concomitant drug administration.

- Presence of active central nervous system (CNS) leukemia. Subjects adequately treated
for CNS leukemia documented by 2 consecutive cerebrospinal fluid samples negative for
leukemia cells are eligible. Subjects with no history of CNS leukemia will not be
required to undergo cerebrospinal fluid sampling for eligibility.

- Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface
antigen (HBsAg), or hepatitis C virus HCV)

- Active, uncontrolled infection

- Known hypersensitivity to any study drug component

- History of another malignancy; Exception: Patients disease-free for 2 years or treated
in situ carcinoma

- Any other medical intervention or other condition which, in the opinion of the
Principal Investigator, could compromise adherence to study requirements or confound
the interpretation of study results

- Pregnancy or lactation