BioLineRx Ltd. has announced the presentation of positive safety and efficacy results for its lead oncology candidate, BL-8040, as a novel approach for the collection of stem cells from the peripheral blood circulation. Treatment with BL-8040 as a single agent was found safe and well tolerated at all doses, and resulted in efficient stem-cell mobilization and collection in all study participants.
Furthermore, the results support BL-8040 as a one-day, single-dose collection regimen, which is a significant improvement compared to the current standard of care. The full Phase 1 data set was presented in an oral presentation at the 20th Annual Congress of the European Hematology Association (EHA) in Vienna, Austria.
Robust stem-cell mobilization was evident in all treated participants across the different doses tested, leading to a median 9.5-fold increase of stem cells in the peripheral blood following a single BL-8040 treatment. Two to four hours after a single administration, BL-8040 enabled collection of a stem-cell yield exceeding the number of cells required to support a transplant in all treated participants, following only one collection procedure.
These results support a novel approach to stem-cell collection for transplantation purposes in patients with hematological malignancies or other indications. Importantly, the collection of CD34+ cells was accompanied by mobilization and collection of colony-forming cells, as well as T, B and NK cells.
The collected human graft was further assessed for its viability and quality in vitro and in vivo. The cells collected from the subjects treated with BL-8040 showed excellent engraftment in irradiated mice, followed by a rapid reconstitution of normal hematopoiesis.
The Phase 1 clinical trial was performed on healthy volunteers and consisted of two parts. The first part of the study was a randomized, double-blind, placebo-controlled, dose-escalation study in three cohorts of eight participants each, with each participant receiving two consecutive injections of BL-8040.
Results show that BL-8040 is safe and well tolerated up to a dose of 1 mg/kg, and that dramatic mobilization of hematopoietic stem and progenitor cells (HSPCs) was observed across all doses tested. The robust mobilization supports the further use of a single injection of BL-8040 for HSPC collection.
In the second part of the Phase 1 study, eight healthy participants received a single injection of BL-8040 at the highest dose of 1 mg/kg, and four hours later underwent a single, standard leukapheresis procedure. Robust and rapid stem-cell mobilization was evident in all treated participants, supporting a novel approach to stem-cell collection.
The median level of collected stem cells was higher than 11 x 106 cells per kg, and the level of HPSCs in the peripheral blood circulation 24 hours after injection of BL-8040 enabled an additional apheresis on Day 2, if needed. These data support the use of BL-8040 as a single-agent, single-injection, one-day regimen for the collection of stem cells.
“We are very happy to report these outstanding results supporting BL-8040 as an effective one-day monotherapy for collection of sufficient stem cells for hematopoietic cell transplantation. This is a major improvement over currently available procedures, which are lengthier and sometimes require the combination of several agents and multiple time-consuming apheresis sessions. Moreover, we see an improvement in composition of the collected cells, suggesting the potential of a better quality graft that may improve stem cell transplantation outcomes,” said Dr. Kinneret Savitsky, CEO of BioLineRx. “We intend to meet with the U.S. Food and Drug Administration (FDA) in order to discuss our next steps in the clinical development program for this indication, including the design of the planned follow-up Phase 2 study. In addition, we are looking forward to reporting top-line results from the on-going Phase 2 study of BL-8040 for treating relapsed and refractory acute myeloid leukemia patients, which we expect in the fourth quarter of 2015. We also look forward to initiating clinical studies for BL-8040 in three additional indications over the next few months, thus expanding and enhancing the potential of our oncology platform.”
At the same conference, the Company also presented positive preclinical results for the treatment of acute myeloid leukemia (AML) at a poster session. The results show that BL-8040 rapidly and efficiently induces cell death of AML cells, and demonstrates for the first time that CXCR4 inhibition is associated with induction of terminal differentiation of AML cells.