On September 10, 2015 BioLineRx Ltd. (NASDAQ: BLRX; TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported that it has filed the regulatory submissions required to commence a Phase 2 trial for BL-8040, in combination with standard-of-care immunosuppressive therapy, as a novel treatment for two bone marrow failure conditions: hypoplastic myelodysplastic syndrome (hMDS) and aplastic anemia (AA) (Press release, BioLineRx, SEP 10, 2015, View Source [SID:1234507442]). The trial is expected to commence shortly after receipt of regulatory approval, anticipated in the next few months.
The open-label Phase 2 trial will be conducted in collaboration with MD Anderson Cancer Center in Houston and is expected to enroll up to 25 patients. The study will examine BL-8040’s ability to improve bone marrow cellularity and peripheral blood counts in patients suffering from these bone marrow failure conditions.
Both hMDS and AA are characterized by a T cell-driven autoimmune attack on the bone marrow that results in depletion of hematopoietic precursors, leading to anemia and low white blood cell counts. In this regard, high CXCR4 expression on pathogenic T cells has been suggested to facilitate infiltration of the bone marrow. BL-8040, a CXCR4 antagonist, is expected to inhibit migration of pathogenic T cells to the bone marrow, thereby mitigating the severe depletion of hematopoietic stem and progenitor cells.
In addition, BL-8040 can directly affect the number of hematopoietic precursors. Preclinical studies in mice showed that multiple doses of BL-8040 led to a marked increase in the number of hematopoietic progenitor cells and hematopoietic stem cells in both the bone marrow and peripheral blood. BL-8040 also promoted production of megakaryocytes in the bone marrow, leading to a prolonged increased platelet production. These direct effects of BL-8040, along with the exclusion of the pathogenic T cells from the bone marrow, may improve bone marrow cellularity and peripheral blood counts.
Dr. Kinneret Savitsky, CEO of BioLineRx, stated, “We are very pleased to have filed the necessary regulatory submissions for an additional Phase 2 trial of BL-8040, our unique oncology platform, in these novel and non-malignant indications. We are honored to collaborate yet again with the prestigious MD Anderson Cancer Center, expanding upon our current collaboration on the Phase 2 trial for treating relapsed/refractory acute myeloid leukemia (AML), as well as our planned Phase 2 trial for treating AML patients with the FLT3-ITD mutation. The hMDS/AA trial will assess BL-8040 in combination with standard of care immunosuppressive therapy, with interim results expected by the end of 2016. Both hMDS and AA represent significant unmet medical needs and we are very hopeful that BL-8040, as part of a novel treatment regimen, will significantly improve bone marrow cellularity and peripheral blood counts in patients suffering from these difficult bone marrow failure conditions.”
About BL-8040
BL-8040 is a clinical-stage drug candidate for the treatment of acute myeloid leukemia, as well as other hematological indications. It is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis (growth of new blood vessels in the tumor), metastasis (spread of the disease to other organs or organ parts) and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a Phase 1/2, open-label, dose escalation, safety and efficacy clinical trial in 18 multiple myeloma patients, BL-8040, when combined with G-CSF, demonstrated an excellent safety profile at all doses tested and was highly effective in the mobilization of hematopoietic stem cells and white blood cells from the bone marrow to the peripheral blood. Additionally, in a Phase 1 stem-cell mobilization study in healthy volunteers, BL-8040 as a single agent was safe and well tolerated at all doses tested and resulted in efficient stem-cell mobilization and collection in all study participants. Importantly, the results of this study support the use of BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care.
BL-8040 also mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer effect by inducing apoptosis. Pre-clinical studies show that BL-8040 inhibits the growth of various tumor types including multiple myeloma, non-Hodgkin’s lymphoma, leukemia, non-small cell lung carcinoma, neuroblastoma and melanoma. BL-8040 also significantly and preferentially stimulated apoptotic cell death of malignant cells (multiple myeloma, non-Hodgkin’s lymphoma and leukemia). Significant synergistic and/or additive tumor cell killing activity has been observed in-vitro and in-vivo when tumor cells were treated with BL-8040 together with Rituximab, Bortezomib, Imatinib, Cytarabine and the FLT-3 inhibitor AC-220 (in NHL, MM, CML, AML, and AML-FLT3-ITD models, respectively). In addition, the current Phase 2 clinical trial in AML patients has demonstrated robust mobilization and apoptosis of cancer cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.
About AA and hMDS
Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hMDS) are hematological conditions caused by progressive bone marrow failure, and characterized by ineffective production of all blood cells, leading to severe anemia and cytopenias (low blood counts). AA and hMDS result from disorders of the hematopoietic stem cells in the bone marrow. Hematopoiesis is disrupted and the number and quality of blood-forming cells decline irreversibly, further impairing blood production. Treatment may include immunosuppressive therapy, chemotherapy or hematopoietic stem cell transplant.