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BioLineRx Reports Encouraging Results of Investigational Combo in FLT3 Mutated Mice

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NEW YORK (GenomeWeb) -- At the Society of Hematologic Oncology's annual meeting in Houston, Tex., BioLineRx presented clinical data showing that the combination of two investigational drugs, BL-8040, and AC220, staved off minimal levels of residual disease in the bone marrow of mice with FLT3-ITD mutations.

BL-8040 selectively inhibits CXCR4 chemokine receptors. These receptors and its activating ligand CXCL12 spur the growth of AML cells in bone marrow. In AML patients, CXCR4 expression is associated with poor prognosis.

Meanwhile, FLT3 mutations are present in 30 percent of AML patients and have been found to activate CXCR4 signaling. AML patients with these mutations also have poor prognosis and are at risk for relapse.

As such, BioLineRx is hoping that the combination AC220, a FLT3 inhibitor, and BL-8020, will inhibit CXCR4 to a degree that AML cells will succumb to chemotherapy and targeted agents. The data presented at the conference showed that BL-8040 caused AML cells to die in in vitro and in vivo models. The BL-8040/AC220 combination, however, seemed to bolster the effect of AC220 (also known as quizartinib) in vitro from a 60 percent drop in AML cell viability to a 97 percent reduction.

BL-8040 also added to the impact of AC220 by reducing the level of residual AML cancer cells in bone marrow in mice from 0.05 percent to 0.006 percent. The combination "eliminated the disease altogether in some mice from this treatment group," BioLineRx said in a statement. "Importantly, reduction of the disease burden in the BL-8040 and AC220 combination therapy group resulted in prolonged survival."

BioLineRx CEO Kinneret Savitsky said in a statement that the 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."

BL-8040 is in Phase II studies, being investigated in AML patients with relapsed or refractory disease. Results are slated for the first part of 2015. The drug is also being studied in an ongoing Phase I stem cell mobilization trial and a Phase I/II chronic myeloid leukemia trial scheduled to begin later this year.

AC220 or quizartinib is the lead drug candidate in Ambit Biosciences' pipeline. The drug entered Phase III studies in April and is being investigated in a trial where more than 300 relapsed or refractory acute myeloid leukemia patients with FLT3 mutations will receive AC220 monotherapy or salvage chemotherapy.

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