BioLineRx Presents Positive Preclinical Results in Treatment for AML Patients
News Sep 20, 2014
BioLineRx Ltd. has announced the presentation of positive preclinical results of its BL-8040 cancer therapy platform, as a novel treatment for a sub-population of acute myeloid leukemia (AML patients with FLT3 mutations), at the Society of Hematologic Oncology (SOHO) 2014 Annual Meeting in Houston, Texas.
The data show that BL-8040 synergizes with another AML drug in development, the FLT3 inhibitor AC220, to reduce minimal levels of residual disease in the bone marrow of an AML mice model with the FLT3-ITD-mutation.
BL-8040 is a novel, potent and selective inhibitor of the CXCR4 chemokine receptor, which is normally activated by the chemokine ligand CXCL12.
Both CXCL12 and its receptor, CXCR4, are key players in enabling AML cancer cells to hide and thrive in the bone marrow, with CXCR4 expression in AML patients being associated with a poor prognosis.
FLT3 mutations are detected in approximately 30% of AML cases and are associated with a poor prognosis and high incidence of relapse in AML patients. FLT3 mutations have also been shown to activate CXCR4 signaling and are associated with increased CXCR4 expression. Accordingly, it is believed that inhibition of CXCR4 may sensitize AML cells to chemotherapy and FLT-3 targeted therapies.
The data presented during the conference show that BL-8040 rapidly and efficiently induces cell death of AML cells both in-vitro and in-vivo. Additionally, the combination of BL-8040 with the FLT3 inhibitor AC220 (Quizartinib) in-vitro increased the apoptotic effect of AC220, from a 60% reduction to a 97% reduction in AML cell viability.
In-vivo, BL-8040 also augmented the effect of AC220, reducing the level of residual AML cancer cells in the bone marrow from 0.05% to as low as 0.006%, eliminating the disease altogether in some mice from this treatment group. Importantly, reduction of the disease burden in the BL-8040 and AC220 combination therapy group resulted in prolonged survival. Furthermore, the addition of BL-8040 in the combination therapy group also mitigated the reduction in normal white blood cells observed when administering the AC220 treatment on a stand-alone basis.
Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx, stated, “BL-8040, our clinical-stage cancer therapy platform, supports the personalized medicine revolution that aims to deliver precise, efficient therapy specifically tailored to individual cancer patients. The results reported today show that the combination of BL-8040 and AC220 reduces the minimal residual disease of AML cells in treated mice and also increases their survival. These results support potential therapeutic advantages of BL-8040 in AML patients with the FLT3-ITD-mutation, and provide a rational basis for administering BL-8040 therapy in combination with FLT3 inhibitors in this patient population. These promising results further support the data we have accumulated to date - all indicating that BL-8040 has the potential to significantly improve treatment for AML patients.”
BL-8040 is currently undergoing a Phase 2 clinical trial in adult AML patients with relapsed or refractory AML, the results of which are expected in early 2015. Concurrently, a Phase 1 stem cell mobilization study for BL-8040 is ongoing, with results expected by the end of 2014 or the beginning of 2015; and an investigator-led Phase 1/2 study for BL-8040 in Chronic Myeloid Leukemia (CML) is expected to commence in 2014.
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