Clinical Trial of BP1001 in Combination With With Venetoclax Plus Decitabine in AML

Summary

Objectives

Improvement of clinical benefit in fragile AML patients while maintaining tolerability is
an important area of further clinical development. Modern aggressive combination
chemotherapy can induce CR in a significant proportion of patients with previously
untreated AML, but relapse occurs in most unless patients undergo intensive allogeneic
hematopoietic stem cell transplantation. Novel therapies are needed for these patients

The Grb2 gene has been mapped to the human chromosome region 17q22-qter, a region that is
duplicated in leukemias and solid tumors, which may result in an increased copy number of
the Grb2 gene product. As Grb2 is important for the transformation of murine
hematopoietic cells, and the proliferation of human leukemia cells that express high
levels of oncogenic tyrosine kinases, inhibition of Grb2 may have a significant impact on
the natural history of leukemias. 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.

This represents an area in which targeted therapies might be of benefit to these
patients. One such potential treatment is BP1001, liposomal anti-sense treatment directed
against Growth Factor Receptor-Bound Protein 2 (Grb2). Decitabine is approved in Europe
for the treatment of adult patients with newly diagnosed de novo or secondary acute
myeloid leukemia (AML). In vitro studies in AML cells co-incubated with BP1001 and
decitabine suggests that treatment of AML patients with decitabine followed by BP1001 may
be a combination that could benefit patients with AML.

This Phase IIa, multicenter, study of BP1001 in combination with Ventoclax plus
decitabine will enroll participants with AML who are not otherwise eligible for for
intensive induction therapy.

This trial will utilize an open label design to assess the safety profile, PK, PD, and
efficacy of of BP1001 in combination with Ventoclax plus decitabine to assess whether the
combination of either provides greater efficacy than intensive chemotherapy alone.

There are 3 cohorts exploring three-drug combinations of BP1001, venetoclax and
decitabine.

- Untreated AML patients will be treated with BP1001 plus venetoclax plus decitabine.

- Refractory/relapsed AML patients will also be treated with BP1001 plus venetoclax
plus decitabine.

- A third cohort of BP1001 + decitabine is offered to refractory/relapsed AML patients
who are venetoclax resistant or intolerant, or not considered by the investigator as
optimal candidates for venetoclax-based therapy.

Each cohort will continue until approximately 19 evaluable participants have been
investigated. At that point, enrollment will be placed on hold so that the Sponsor can
perform an administrative review of the data to determine which treatment cohorts should
continue with enrollment.

Should one or more cohorts continue with enrollment, the sample size will be increased up
to 54 in the refractory/relapsed AML cohorts and 98 in the untreated AML cohort. These
sample sizes for the study are based on the primary endpoint.