XL092, a multi-targeted inhibitor of MET, VEGFR2, AXL and MER with an optimized pharmacokinetic profile

Background: Receptor tyrosine kinases (RTKs) MET, VEGFR2, AXL and MER are believed to play important roles in tumor growth, vascularization, resistance to therapy and in modulating the tumor immune microenvironment. Consistent with this the multi-targeted RTK inhibitor cabozantinib, a potent inhibitor of these RTKs as well as others, has shown significant clinical activity in a variety of solid tumors, and shows promising activity in combination with checkpoint inhibitors. Cabozantinib has an extended plasma half-life which results in drug accumulation during initial dosing. We sought to develop a novel RTK inhibitor that retains the target profile of cabozantinib but with a significantly shorter clinical half-life. The profile of XL092, a compound meeting these criteria, will be presented.