HPN601

HPN601 is a protease-activated, conditionally active T cell engager targeting the epithelial cell adhesion molecule (EpCAM), which is highly expressed in many solid tumors. It is the first clinical candidate from Harpoon Therapeutics’ ProTriTAC platform. The molecule consists of three binding domains: an anti-albumin domain for half-life extension and masking, an anti-CD3e domain for T cell engagement, and an anti-EpCAM domain for tumor targeting. The drug remains inert in circulation due to a masking moiety linked via a protease-cleavable linker; it becomes activated only within the tumor microenvironment where tumor-associated proteases remove the mask, exposing the active drug. This design aims to minimize on-target/off-tumor toxicity by restricting potent activity to EpCAM-positive tumors while reducing systemic side effects such as cytokine release syndrome. Preclinical studies have shown that HPN601 has improved safety and efficacy compared to constitutively active EpCAM-targeting T cell engagers, with significant attenuation of cytokine production and expanded therapeutic index across multiple solid tumor models[1][5][6][7][9].

Other names

HPN 601HPN601HPN-601EpCAM ProTriTAC