FLT3 TriTAC-XR

FLT3 TriTAC-XR is a preclinical T-cell engager prodrug developed by Harpoon Therapeutics (now a subsidiary of Merck) using its proprietary TriTAC-XR (extended-release) platform. The molecule is designed to target Fms-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase frequently overexpressed or mutated in hematologic malignancies such as acute myeloid leukemia (AML). As a TriTAC (Tri-specific T-cell Activating Construct), it simultaneously binds to FLT3 on tumor cells, CD3 on T cells, and serum albumin for extended half-life. The XR designation refers to a prodrug modification where the CD3-binding domain is masked by a cleavable linker, allowing for the slow, temporally controlled release of the active T-cell engager within the tumor microenvironment. This approach is intended to mitigate systemic cytokine release syndrome (CRS) by reducing peak cytokine levels while maintaining potent anti-tumor efficacy. Preclinical data in non-human primates demonstrated a 100-fold reduction in cytokine levels compared to conventional TriTAC molecules while achieving similar depletion of FLT3-positive cells.