Evidence suggests that the CXC–chemokine receptor-4 (CXCR4) pathway plays a major role in cancer cell homing and metastasis and in shaping the tumor microenvironment (TME), and thus represents a potential target for cancer therapy. Under normal conditions the CXCR4 pathway regulates the hematopoietic stem cell niche in the bone marrow (BM)—a property that has led to the approval of the CXCR4 antagonist plerixafor together with G-CSF (AMD3100, Mozobil) for mobilization from the BM and collection of hematopoietic precursors from the blood for transplantation of myeloma and lymphoma patients.

BKT140/BL8040 is in advance Phase II/III studies for multiple indications in cancer and stem cell mobilization

Biokine leading product, BKT140/BL-8040: best-in-class CXCR4 antagonist is a bio-stable 14-residue cyclic peptide with high affinity (1- 2 nM, compare to 84nM of plerixafor) and a slow off-rate of the receptor. We have recently demonstrated in a Phase I study in healthy volunteers that single dose of the CXCR4 antagonist BL-8040 induces a rapid and robust mobilization and mega dose collection of human CD34+ stem and progenitor cells. Mobilization human CD34+ cells for the purpose of donor (allogeneic) transplantation after high-dose chemotherapy is currently performed using a 4-5-day treatment cycle with G-CSF and a 1-2 day apheresis procedure. In a Phase II study single-agent treatment with BL-8040 showed similar efficacy and non-inferiority in recipient engraftment, with all transplanted recipients successfully engrafting with BL-8040-mobilized grafts. A Phase 3, randomized, double-blind, placebo-controlled, multicenter study, evaluating the safety, tolerability and efficacy of BL-8040 in combination with G-CSF, compared to placebo and G-CSF, for the mobilization of CD34 cells for autologous transplantation in multiple myeloma patients have already initiated. The placebo-controlled part is designed to include 177 patients in more than 25 centers. Treatment will include 5 days of G-CSF, with a single dose of BL-8040 or placebo on day 4 with the option to expand treatment to up to 8 days of G-CSF and up to 2 days of BL-8040. Apheresis for collection of CD34 cells will be performed on day 5. An additional 3 apheresis sessions may be conducted if needed in order to reach the goal of ≥ 6×106 mobilized CD34 cells/kg.

On October 30, 2020 BioLineRx Announces Positive Results from Interim Analysis of GENESIS Phase 3 Trial of Motixafortide (BL-8040) in Stem Cell Mobilization.

BL8040 which as the ability to reshape the microenvironment and is tested in pancreatic cancer indication together with immune check point inhibitors such as Pembrolizumab (Keytruda, Merck) and Atezolizumab (Tecentriq, Genentech/Roche).