A Study of Anagrelide Controlled Release (GALE-401) in Patients With High Platelet Counts Due to Bone Marrow Disorders

This is an open-label, single-arm, multicenter, Phase 2 study of anagrelide CR in subjects
with an MPN-related thrombocytosis. Eligible subjects will include those who have not been
previously treated for thrombocytosis or have not received platelet-lowering therapy for at
least 2 weeks prior to study treatment. Each subject will receive anagrelide CR at a
starting dose of 0.5 mg b.i.d. (1.0 mg/day), and is anticipated to continue study treatment
for at least 24 weeks. Subjects who have achieved clinical benefit in the opinion of the
Investigator and who are tolerating the study drug may continue study treatment until they
develop unacceptable toxicity or other discontinuation criteria have been met.

The primary efficacy endpoint will be the proportion of subjects who achieve a platelet
response (CR or PR). The safety and tolerability of study treatment will be assessed by the
frequency and severity of adverse events as determined by NCI Common Terminology Criteria
for Adverse Events (CTCAE) v 4.03. The PK profile of anagrelide CR will be assessed at the
initial (0.5mg b.i.d.) and final titrated dose levels.

Inclusion Criteria:

1. Provide written informed consent prior to any study specific procedure

2. Male or female patients aged ≥ 18 years

3. Diagnosis of a myeloproliferative neoplasm (i.e., chronic myelogenous leukemia (CML),
polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET))
as determined by the treating physician, such as based on the 2008 World Health
Organization (WHO) classification of myeloid malignancies

4. Baseline platelet count ≥600 x 10e9/L as determined on two occasions at least 14 days
apart prior to the first dose of study drug

5. Requirement for platelet reduction therapy as assessed by the Investigator

6. Currently not receiving therapy specifically intended to reduce platelet counts

7. For patients with ET, prior platelet lowering therapy (e.g., hydroxyurea, anagrelide
or interferon) may not be administered within 2 weeks prior to the first dose of
study drug.

For patients with MPN diagnoses other than ET, concurrent anti-MPN treatment is
permitted provided that the treatment has been administered at stable doses for at
least 4 weeks prior to the first dose of study drug. Examples of permitted
medications include but are not limited to hydroxyurea for PV, ruxolitinib for MF,
and imatinib for CML. All patients must have discontinued anagrelide at least 2
weeks prior to the first dose of study drug.

EXCEPTION: busulfan, melphalan and phosphate P-32 must have been discontinued at
least 4 weeks prior to the first dose of study drug.

8. Adequate hepatic function defined as bilirubin ≤1.5 x ULN, INR ≤1.5 x ULN, albumin
>3.5 g/dL, ALT < 3.0 x ULN, AST < 3.0 x ULN

9. If female, must be of non-childbearing potential, i.e. post- menopausal (defined as >
12 months since last menstrual period) or surgically sterilized (i.e. tubal ligation
or hysterectomy at least 6 months prior to screening) or, if of childbearing
potential, must not be pregnant or nursing

10. Males and females of child bearing must agree to use an acceptable form of birth
control until 28 days following the last dose of study drug

Exclusion Criteria:

1. Other MPN diagnoses not specifically included above: Chronic neutrophilic leukemia,
chronic eosinophilic leukemia, mastocytosis, and unclassifiable MPNs

2. Previously found to be refractory to anagrelide therapy (i.e., failure to achieve a
platelet count <600 x 10e9/L for reasons other than anagrelide-related toxicity)

3. History of coronary artery disease requiring a revascularization procedure within 3
months prior to screening

4. Left bundle branch block or sustained ventricular tachycardia (>30 seconds) evident
on 12-lead ECG at screening

5. Tachycardia defined as resting heart rate >100 bpm at screening

6. Unstable angina (characterized by increasingly frequent episodes with modest exertion
or at rest, worsening severity, or prolonged duration) within 3 months prior to
screening

7. Transient ischemic attack (TIA) or stroke within 3 months prior to screening

8. Unstable or clinically significant concurrent medical condition that would, in the
opinion of the Investigator, jeopardize the safety of a subject and/or their
compliance with the protocol.

9. Current alcohol or drug abuse, or a significant medical condition that, in the
opinion of the Investigator, may impair compliance with the requirements of the
protocol

10. History of allergic hypersensitivity to anagrelide or any component of its
formulations

11. Administration of Type 3 phosphodiesterase (PDE3) inhibitors (e.g., inamrinone,
cilostazol, milrinone) within 2 weeks prior to initiating study treatment

12. Administration of any investigational product within 4 weeks prior to initiating
study treatment

13. History of intolerance of other PDE3 inhibitors