Bl-8040, A Peptidic Cxcr4 Antagonist, Induces Leukemia Cell Death And Specific Leukemia Cell Mobilization In Relapsed/Refractory Acute Myeloid Leukemia Patients In An Ongoing Phase Iia Clinical Trial

Background: The bone marrow (BM) niche protects Acute Myeloid Leukemia (AML) cells from chemotherapy. BM homing of AML cells is dependent on CXCR4 and its ligand CXCL12, and high levels of CXCR4 expression correlate with poor survival in AML patients. It is postulated that blocking the CXCL12/CXCR4 axis with a potent CXCR4 antagonist will disrupt the interaction of the malignant blasts with the BM and augment the anti-leukemic effect of chemotherapy. BL-8040 (BKT140) is a 14-residue, cyclic, synthetic peptide capped with an aromatic ring that acts as a selective inhibitor of the CXCR4 chemokine receptor. BL-8040 has strong affinity for the CXCR4 receptor and long receptor occupancy, resulting in a prolonged pharmacodynamic effect. BL-8040 has superior mobilization capacity, inverse agonism activity and direct pro-apoptotic activity against leukemia cells. Preclinical studies have shown that in addition to its activity as a mobilizer of hematopoietic cells, BL-8040 exhibits a CXCR4-dependent selective anti-tumor effect against malignant cells. A clinical trial for the treatment of adult relapsed/refractory AML patients using a combination of BL-8040 and cytarabine (Ara-C) is currently ongoing (NCT01838395).