Slow and steady
A clinical AURKB inhibitor makes an encapsulated comeback
AstraZeneca plc (LSE:AZN; NYSE:AZN) and Bind Therapeutics Inc. (NASDAQ:BIND) have joined forces to stretch the therapeutic index of a kinase inhibitor that had stumbled in the clinic. The partners developed a nanoparticle formulation that slowed the release and reduced the toxicity of a potent but poorly tolerated aurora kinase B (AURKB; Aurora-B) inhibitor.
In 2013, a Phase II trial in acute myelogenous leukemia (AML) showed AstraZeneca's AURKB inhibitor AZD1152 improved the complete response rate compared with standard of care, but was associated with major toxicities, including myelosuppression. In a Science Translational Medicine study published last month, the two companies presented preclinical studies highlighting a strategy to improve the compound's therapeutic index using nanoparticle encapsulation of AZD2811, the active metabolite of the prodrug AZD1152. ...