Efficacy and Safety of BST-236 in Newly Diagnosed Acute Myeloid Leukemia Patients, Unfit for Standard Induction Therapy

BST-236 is a cytarabine pro drug designed to release cytarabine inside the target cells with
reduced systemic exposure to free cytarabine. As such, BST-236 may enable delivery of high
doses of cytarabine to medically-unfit or older adults who otherwise cannot be treated with
standard cytarabine therapy. This study aims to validate this hypothesis.

The study is an open-label, single arm, single agent, multi-center study in adults with newly
diagnosed AML who are unfit for standard therapy. The patients will receive up to 4 courses
of six-days treatment with intravenous BST-236; 1 or 2 induction courses followed by 1 to 2
consolidation courses. The study participation will be 52 weeks including treatment and
follow-up periods. An additional 1 year post study follow-up for the evaluation of survival
is optional.

Inclusion Criteria:

1. Adult ≥18 years of age

2. AML according to the 2016 revision to the World Health Organization (WHO)
classification of myeloid neoplasms and acute leukemia: ≥20% blasts in peripheral
blood or marrow

1. de-novo AML or

2. AML secondary to MDS or

3. AML secondary to exposure to potentially leukemogenic therapies or agents (e.g.
radiation therapy, alkylating agents, topoisomerase II inhibitors) with the
primary malignancy in remission for at least 2 years

3. Not eligible for standard induction chemotherapy;

1. Age ≥75 years or

2. Age ≥18 years with at least one of the following comorbidities:

i. Clinically significant heart or lung comorbidities, as reflected by at least one
of:

- Left ventricular ejection fraction (LVEF) ≤50%

- Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected

- Forced expiratory volume in 1 second (FEV1) ≤65% of expected ii. Chronic stable
angina or congestive heart failure controlled with medication iii. Other
contraindication(s) to anthracycline therapy (must be documented) iv. Other
comorbidity that the Investigator judges as incompatible with intensive remission
induction chemotherapy, which must be documented

4. Creatinine clearance (estimated by the Cockroft-Gault (C-G) or measured by 24 hours
urine collection) ≥45 mL/min

5. Liver enzymes (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)
≤2.5 times the upper limits of normal (ULN)

6. Total bilirubin ≤1.5 x ULN unless due to known history of Gilbert's disease

7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening

8. Prepared and able to give written (signed and dated) informed consent, which includes
compliance with study requirements and restrictions prior to admission to the study

9. Women of reproductive potential must have a negative serum pregnancy test within 48
hours of the first day of any BST-236 treatment course

10. Women or men of reproductive potential must use (or have his/her partner use) two
forms of effective birth control methods starting from 1 month prior to screening and
until 3 months following the last BST-236 administration day (acceptable methods of
birth control in this study include: surgical sterilization, intrauterine devices,
oral contraceptives, contraceptive patch, long-acting injectable contraceptives,
partner's vasectomy, or double-barrier method condom or diaphragm with spermicide)

11. Patient must voluntarily sign and date an ICF, approved by an Independent Ethics
Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any
screening or study-specific procedures

12. Patient must be able to adhere to the study visit schedule and other protocol
requirements

Exclusion Criteria:

1. Patient has relapsed or refractory AML

2. Patient has acute promyelocytic leukemia

3. Any previous treatment for AML (except for hydroxyurea or up to one treatment course
with hypomethylating agents (HMA))

4. Patient has history of myeloproliferative neoplasm (MPN) including myelofibrosis,
essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or
without BCR-ABL1 translocation and AML with BCR-ABL1 translocation

5. Previous use (prior to study initiation) of drugs containing cytarabine as an active
ingredient

6. Use of any HMA for the treatment of MDS within 30 days of study Day 1

7. Participation in a previous clinical trial and/or use of an investigational drug
within 90 days or at least 5 half-lives of tested drug (whichever is longer) of
initial screening assessment

8. Peripheral White Blood Cell (WBC) count >30,000 /µL in the 48 hours prior to first
BST-236 dose administration. Hydroxyurea administration or leukapheresis is permitted
to meet this criterion

9. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing
signs/symptoms related to the infection without improvement despite appropriate
antibiotics or other treatment)

10. Any medical or surgical condition, presence of laboratory abnormalities or psychiatric
illness that may preclude safe and complete study participation based on the
Investigator's judgment

11. Diagnosis of malignant disease within the previous 12 months (excluding basal cell
carcinoma of the skin without complications, "in-situ" carcinoma, or other local
malignancy excised or irradiated with a high probability of cure and not treated with
chemotherapy)

12. Active malignant disease other than AML

13. Leptomeningeal/central nervous system involvement of AML

14. Myeloid sarcoma as a sole manifestation of AML

15. Surgical procedure, excluding central venous catheter placement or other minor
procedures (e.g. skin biopsy) in the 14 days prior to BST-236 administration

16. Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA)
class 4 congestive heart failure

17. Shortness of breath requiring continuous oxygen treatment for at least 15 hours per
day in chronically hypoxemic patients

18. History of allergic reactions attributed to compounds of similar chemical composition
as BST-236 and/or cytarabine

19. Life expectancy shorter than 3 months attributed to any known medical condition other
than AML

20. Active/chronic Hepatitis B Virus (HBV) infection (based on positive surface antigen
(HBsAg)), Hepatitis C Virus (HCV) infection (HCV) (based on positive HCV antibody
(Ab)), or Human Immunodeficiency Virus (HIV)-1 or HIV-2 (based on positive HIV
antibody)