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20-F
BIOLINERX LTD. filed this Form 20-F on 03/10/2016
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We plan to commence a Phase 2a trial for BL-8040 for the treatment of a third population of AML patients, those with the FLT3-ITD mutation, in the second half of 2016. AML patients with the FLT3-ITD mutation exhibit poor response and high relapse rates when treated with chemotherapy, and exhibit only transient response rates to FLT3 inhibitors. Preclinical data (presented at several conferences during 2014) show that by inhibiting the CXCR4 receptor, BL-8040 enhances the effect of FLT3 inhibition in killing FLT3-mutated leukemic cells. The Phase 1/2 trial, which will be conducted in collaboration with the MD Anderson Cancer Center, is aimed at improving the response of FLT3-ITD mutated AML patients to treatment with a FLT3 inhibitor. We plan to enroll approximately 30-40 patients at two or three sites. Patients testing positive for the FLT3-ITD mutation will receive several treatment cycles of BL-8040 in combination with a FLT3 inhibitor. The safety of the combination treatment, as well as the response rates to the treatment and the duration of the responses will be evaluated.
 
In March 2015, we announced successful top-line results from a Phase 1 trial for a fourth indication of BL-8040 as a novel treatment for the mobilization of stem cells from the bone marrow to the peripheral blood circulation, where they can be harvested for transplant supporting the treatment of hematological indications. The study was conducted at the Hadassah Medical Center in Jerusalem.  It 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, or 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, which is more than two-fold higher than the target concentration, and five-fold higher than the minimum concentration, necessary for transplantation. In addition, 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.
 
In December 2015, we announced the filing of regulatory submissions required to commence a Phase 2 trial for use of BL-8040 in stem cell mobilization. The submission was made following a meeting with the FDA in October 2015 to discuss the BL-8040 stem cell mobilization development program. The open-label trial will be conducted as an investigator-initiated study in collaboration with the Division of Oncology and Hematology of Washington University School of Medicine, and will enroll up to 24 donor/recipient pairs. On the donor side, the primary endpoint of the study is the ability of a single injection of BL-8040 to mobilize sufficient amounts of cells for transplantation following up to two leukapheresis collections. On the recipient side, the study aims to evaluate the functionality and engraftment following transplantation of the BL-8040 collected graft. The trial is expected to commence shortly after receipt of regulatory approval, anticipated in the first quarter of 2016.
 
A fifth clinical development program for BL-8040 is the assessment of the drug for the treatment of hypoplastic myelodysplastic syndrome, or hMDS, and aplastic anemia, or AA. One type of treatment for these bone-marrow failure conditions consists of immunosuppressive therapy with hATG and cyclosporine; however, a sizable fraction of patients do not respond to this therapy. Preclinical data suggest that BL-8040 promotes stem cell proliferation and differentiation thereby allowing recovery of hematopoiesis (formation and development of blood cells). The data show that treatment of mice with BL-8040 contributes to bone marrow regeneration, and increases the number of progenitor cells and the mature components of the blood and immune systems.
 
In November 2015, we announced the commencement of a Phase 1/2 trial, in collaboration with the MD Anderson Cancer Center, for BL-8040, in combination with standard of care immunosuppressive therapy, as a treatment for hMDS and AA. The open-label trial will examine BL-8040’s ability to improve bone marrow cellularity and peripheral blood counts in up to 25 patients suffering from these bone marrow failure conditions. The study’s primary endpoint is to evaluate the safety and tolerability of treatment with BL-8040 on top of the standard immunosuppressive regimen of Anti-Thymocyte Globulin (hATG), Cyclosporine and Methylprednisolone (steroids) in hMDS and AA patients. Secondary endpoints include assessment of the clinical efficacy (response rate), time and duration of response to the treatment, and overall survival following treatment. Safety and efficacy will be assessed at defined time points throughout the study. Duration of response and overall survival will also be assessed as part of the study’s long term follow up protocol.