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Activity of TP‐0903 in FLT3 inhibitor resistant AML models

The development of tyrosine kinase inhibitors (TKIs) for the treatment of acute myeloid leukemia (AML) with FLT3 internal tandem duplication mutations (FLT3‐ITD+) has been challenging due to intrinsic and acquired drug resistance. Important resistance mechanisms that have been described include: 1) the emergence of secondary FLT3 tyrosine kinase domain (TKD) mutations; 2) compensatory signaling pathways (intrinsic to the leukemia cell or due to tumor‐microenvironment interactions), such as Gas6/Axl upregulation; and 3) the co‐occurrence of somatic mutations with FLT3‐ITD, such as IDH1/2, NRAS and MLL‐PTD. TP‐0903, is a new TKI in development as an Axl inhibitor. Previously, we demonstrated that TP‐0903 is a potent inhibitor of FLT3‐ITD and drug resistant FLT3 TKD mutations in preclinical in vitro and in vivo models (Jeon JY et al. ASH 2017). Here, we present the activity of TP‐0903 in additional TKI‐resistant models of FLT3‐ITD+ AML in comparison to other FLT3 TKIs.