FDA has granted orphan drug designation to CG’806, a highly potent pan-FLT3/pan-BTK inhibitor, for the treatment of patients with acute myeloid leukemia.
AML cells utilize multiple forms of the FLT3 receptor tyrosine kinase and other pathways to promote rapid proliferation and to escape the inhibitory activities of many therapeutics. CG’806 is a highly potent inhibitor that simultaneously targets all known forms of FLT3 and other key oncogenic pathways that drive the proliferation of AML cancer cells, thereby providing CG’806 with a broad range of activity against AML and a strategy to delay mutational escape.
CG’806, sponsored by Aptose Biosciences Inc., is an oral, first-in-class pan-FLT3/pan-BTK inhibitor. This small molecule demonstrates potent inhibition of all wild type and mutant forms of FLT3 tested (including internal tandem duplication and mutations of the receptor tyrosine kinase domain and gatekeeper region), suppresses multiple oncogenic pathways operative in AML, eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML.
Likewise, CG’806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting CG’806 may also be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.
