CD19 TriTAC-XR

CD19 TriTAC-XR (HPN601) is an investigational, extended-release trispecific T-cell engager (TriTAC) prodrug developed by Harpoon Therapeutics (now part of Merck & Co.) for the treatment of CD19-positive hematologic malignancies. It is engineered using the TriTAC-XR platform, which incorporates a peptide mask and a protease-cleavable linker at the N-terminus of the trispecific construct. The molecule binds to CD19 on B cells, CD3ε on T cells, and human serum albumin for extended half-life. As a prodrug, it remains inactive in systemic circulation until the mask is removed by proteases, allowing for a controlled release of the active T-cell engager. This mechanism is intended to reduce the peak drug concentration (Cmax) and minimize the risk of cytokine release syndrome (CRS) while maintaining therapeutic efficacy.