Phase IIa Study Evaluating Safety and Efficacy of BL-8040 in Relapsed/Refractory AML Patients

Open-label, multicenter, phase IIa, dose escalating study in subjects with
relapsed/refractory AML, defined according to WHO criteria (1), including subjects who failed
chemotherapy only and those who failed previous Autologous Stem Cell Transplantation (ASCT) /
Allogeneic Stem Cell Transplantation (AlloSCT), provided at least 6 months have passed from
transplant.

Eligible subjects will receive subcutaneous (SC) injections of BL-8040 ("monotherapy period")
over two days (one injection per day) followed by concurrent administration of BL-8040 with
standard salvage chemotherapy ("combined period") over 5 days. During the "combined period,"
BL-8040 will be administered 4 hours prior to chemotherapy. The chemotherapy will consist of
cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age), administered intravenously (IV)
over 3 hours, for 5 days and will not be escalated.

The first part of the study (Part 1) will include escalating dose groups and be considered
the 'escalation phase'. Six potential dose levels (see Table 1) will be investigated starting
at dose level 1. Patients will be accrued in a conventional 3+3 design. Applying this study
design, the first cohort of 3 patients will be treated at dose level 1 and evaluated for dose
escalation.

Inclusion Criteria:

1. Adult men and women subjects aged 18 to 75, inclusive.

2. Confirmed diagnosis of relapsed/refractory AML (WHO criteria) Refractory subjects, up
to second consecutive salvage . Relapsed subjects including first and second relapse.

3. AML relapse > 6 months since autologous or allogeneic stem cell transplantation,
provided they are in first or second relapse and:

No active graft-versus-host disease (GVHD > grade 1). No treatment with high dose
steroids for GVHD (up to 20 mg Prednisolone or equivalent, Appendix G). No treatment
with immunosuppressive drugs with the exception of low dose cyclosporine and
tacrolimus (blood levels of 0.5-0.6 µg/mL).

4. Clinical laboratory values should be as follows:

WBC < 30,000/mL Blasts in PB ≤ 20,000. Treatment with Hydroxyurea is permitted up to
24 hrs prior to BL-8040 administration to achieve blast counts < 20,000 prior to
enrollment. Creatinine < 1.3 mg/dL; if Creatinine is > 1 mg/dL the Creatinine
clearance should be > 40 mL/min as calculated using the Cockcroft-Gault formula.

5. Women of childbearing potential and all men must agree to use an approved form of
contraception (e.g. oral, transdermal patch, implanted contraceptives, intrauterine
device, diaphragm, condom, abstinence or surgical sterility) prior to study entry and
for the duration of study participation through 30 days after the last dose of
BL-8040. Confirmation that female subjects are not pregnant must be established by a
negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained
during screening. Pregnancy testing is not required for post-menopausal or surgically
sterilized women.

6. Subject is able and willing to comply with the requirements of the protocol.

7. Subject is able to voluntarily provide written informed consent.

Exclusion Criteria:

1. Administration of conventional chemotherapy within 2 weeks of enrollment date. In the
event that subjects have received chemotherapy > 2 weeks from the date of enrollment,
they may be included provided they have recovered from the associated
non-hematological toxicities to ≤ grade 1.

2. Life expectancy of ≤ 2 months.

3. Known allergy or hypersensitivity to any of the test compounds, materials or
contraindication to test product.

4. Use of investigational device or agents within 2 weeks of enrollment date.

5. Low Performance Status (ECOG > 2; Appendix E).

6. O2 saturation < 92% (on room air), evidence of TLS > grade 2 (according to the
Cairo-Bishop criteria (3)) or leukostasis (2).

7. Abnormal liver function tests:

Serum aspartate transaminase (AST/SGOT) or alanine transaminase ( ALT/SGPT) 2 x upper
limit of normal (ULN). Serum bilirubin. Total bilirubin > 2.0 mg/dL (34 µmol/L),
conjugated bilirubin > 0.8 mg/dL.

8. Left ventricular ejection fraction < 40 %.

9. History of myocardial infarction or cerebrovascular accident within 6 months of
enrollment date.

10. Presence of active, uncontrolled infection.

11. Known central nervous system disease (e.g., Alzheimer's disease).

12. Acute promyelocytic leukemia.

13. Exposure to high dose Ara-C within 6 months of enrollment.

14. Subject has concurrent, uncontrolled medical condition, laboratory abnormality, or
psychiatric illness which could place him/her at unacceptable risk, including, but not
limited to:

Subject has been diagnosed or treated for another malignancy within 3 years of
enrolment, except in situ malignancy, or low-risk prostate, skin or cervix cancer
after curative therapy A co-morbid condition which, in the view of the Investigators,
renders the subject at high risk from treatment complications.

15. Female subjects who are pregnant or breastfeeding.

16. Prior clinically significant grade 3-4 non-hematological toxicity to high dose Ara-C
or grade ≥ 2 of neurological toxicity.

17. Seropositive for HIV antibodies (HIV1 and HIV2), Hepatitis C antibody (Hep C Ab) or a
Hepatitis B carrier (positive for Hepatitis B surface antigen [HBsAg]).

18. Unable to comply with study requirements in the opinion of the Investigator.