Merck will pay $680 million to acquire Harpoon Therapeutics, a clinical-stage immuno-oncology company developing a new class of off-the-shelf T cell engager therapies for solid tumors. The acquisition gives the big pharma access to Harpoon’s portfolio of T cell engager agents, and to the biotech’s platforms to manufacture trispecific T cell engager therapies. T cell engagers are engineered proteins with two or more binding domains designed to physically redirect T cells to attack and lyse tumor cells. In the case of bispecific T cell engagers, one arm targets an antigen on a cancer cell and another acts as a trigger molecule on T cells, targeting CD3. The approved T cell engagers, such as Blincyto (blinatumomab), Columvi (glofitamab), Lunsumio (mosunetuzumab) and Talvey (talquetamab), are all bispecific. Harpoon’s so-called trispecific T-cell-activating construct (TriTACs) are designed with three binding domains, with the third added to bind human serum albumin to improve half-life. TriTACs, at around 50 kDa, are smaller than monoclonal antibodies, which may boost tumor penetration. Some TriTACs are engineered as prodrugs; they only become activated once they reach the tumor. The company’s lead molecule is HPN328, which targets delta-like ligand 3 (DLL3), an inhibitory Notch ligand highly expressed in cancers such as small cell lung cancer (SCLC). Preliminary clinical data showed that the trispecific molecule shrank tumors in 48% of patients with SCLC and 54% of patients with other tumor types. DLL3 is also the target of Amgen’s bispecific T cell engager tarlatamab, which is in a phase 3 trial for SCLC. Merck also gets clinical-stage HPN217, which targets B cell maturation antigen, and preclinical HPN601, which targets epithelial cell adhesion molecule. The pharma’s deal with Harpoon builds on a 2020 partnership with Janux Therapeutics that gave Merck access to another T cell engager platform, dubbed TRACTr, to identify tumor-activated T cell engagers.
This is a preview of subscription content, access via your institution