Clinical Trial of BP1001 (L-Grb-2 Antisense Oligonucleotide) in CML, AML, ALL & MDS

The Philadelphia Chromosome is an unusual genetic trait found in 90-95% of patients with CML
and approximately 20-25% of patients with ALL. The protein created by this unusual trait
causes normal cells within the body to become cancer cells, and then causes these cells to
grow and divide at a rapid rate. Researchers think that the protein "Growth Factor Receptor
Bound Protein-2 (Grb-2)" plays an important role in the rapid growth of leukemic cells. The
study drug (BP1001) may be able to inhibit the cells from making Grb-2. Researchers hope that
without this protein, the leukemia cells will die.

Up to 60 patients are expected to be enrolled on this study.

Part A: Dose escalation: Each cohort will receive BP1001 at a dose higher than the previous
group.

Part B: Dose-expansion Cohorts: Subjects with relapsed or refractory AML will receive
escalating doses of BP1001 concurrently with fixed low-dose ara-C (LDAC)

The study drug is an antisense molecule complementary to the messenger RNA (mRNA) code for
the cell's expression of the protein Grb-2. The study drug is incorporated into lipid (fat)
particles known as liposomes. This incorporation process is part of the manufacturing process
and is done before the study drug is administered. The liposomes (which carry the study drug)
will be administered intravenously twice a week for 28 days. Subjects enrolled in Part B of
the study will receive study drug twice a week for 28 days concurrently with low dose ara-C,
self administered twice daily for 10 consecutive days.

Inclusion Criteria

1. Male or female patients 18 years of age or older

2. A diagnosis of refractory or relapsed AML, or Ph+ CML (in chronic, accelerated or
blast phase, or acute lymphoblastic leukemia, or myelodysplastic syndrome.

One of the following parameters is required to meet criteria for accelerated phase
CML:

- Blasts in Peripheral Blood or Bone Marrow ≥15%

- Promyelocytes and Blasts in Peripheral Blood or Bone Marrow ≥30%

- PB or BM basophils ≥20%

- Thrombocytopenia <100 x 103/ml, not resulting from therapy

Blast phase is defined as ≥30% blasts in peripheral blood or bone marrow, or presence
of extramedullary disease, except for liver or spleen.

3. Patients with CML must have demonstrated resistance and/or intolerance to therapy with
at least 2 tyrosine kinase inhibitors (TKI)

4. Patients with AML and ALL should have received at least 1 prior treatment regimen and
either failed to achieve response or relapsed on treatment

5. Patients with MDS should have failed prior therapy with a hypomethylating agent or, if
associated with a 5q- chromosomal abnormality, lenalidomide. NOTE: Patients with 5q-
unable to receive or intolerant to lenalidomide are also eligible.

6. Have clinically adequate hepatic and renal functions as defined by:

- ALT<2x ULN

- Serum creatinine concentration <2x ULN

- Serum bilirubin <2x ULN

7. Patients must sign an informed consent

8. Women of childbearing age must have a negative serum or urine pregnancy test prior to
the initiation of study drug.

9. Barrier contraceptive precautions are to be used throughout the trial by all study
participants of child bearing potential.

10. Have not received anti-cancer therapy for at least 2 weeks prior to study entry, with
the exception of low dose ara-C (LDAC) given as subcutaneous injections (no less than
15 days prior), hydroxyurea or anagrelide (no less than 24 hours prior), TKI (no less
than 5 days prior), and interferon (no less than 2 weeks prior)

11. Have an ECOG Performance of 0-2

12. Have a life-expectancy ≥3 months

Exclusion Criteria

1. Serious intercurrent medical illnesses which would interfere with the ability of the
patient to carry out the treatment program

2. Pregnant or breastfeeding women

3. Patients who have uncontrolled active infection

4. Patients who have received another investigational product within the longer of 14
days or 5 half-lives of the previous product

5. Any history of adverse reaction or hypersensitivity to LDAC

Part B: BP1001 with Concurrent LDAC Dose-Expansion Cohorts

Enrollment in the dose-expansion cohorts (DEC) will be limited to only those patients with
a diagnosis of refractory or relapsed AML(except acute promyelocytic leukemia) or those who
are refractory to at least 1 prior therapy regimen and no more than 1 prior salvage
regimen.