Merck inks $680M Harpoon buyout, spearing challenger to Amgen T-cell engager

Merck & Co. has speared an acquisition target, agreeing to pay $680 million for Harpoon Therapeutics and its pipeline of T-cell engagers. The deal will give Merck control of drug candidates that will expand its cancer pipeline and offer opportunities to offset the upcoming loss of Keytruda exclusivity.

Harpoon has built a business on the idea that its trispecific T-cell platform can improve on bispecifics and cell therapies. Smaller than bispecific antibodies, the molecules feature human serum albumin—as well as domains to bind cancer and immune cells—to extend their half life. The small size could boost tissue penetration, enhancing efficacy in solid tumors, but Harpoon has endured lows since its IPO in 2019. 

Merck’s move to buy the biotech, at more than a 100% premium to its closing price Friday, comes after a look at early-phase data on its lead candidate HPN328 reinvigorated interest in the stock. Harpoon saw a 35% response rate in recipients of its anti-DLL3 candidate.

DLL3 is overexpressed in small cell lung cancer (SCLC) and neuroendocrine tumors. Better medicines are needed in both indications. Merck won accelerated approval for Keytruda and SCLC but later withdrew the indication. Other checkpoint inhibitors are still available but only add a few months to median overall survival. Chemotherapy is the only option for patients with other neuroendocrine neoplasms.

Harpoon is testing its anti-DLL3 candidate, HPN328, as a monotherapy and in combination with Roche’s Tecentriq, a rival to Merck’s Keytruda. The presentation of updated HPN328 data at the European Society of Medical Oncology Congress last year was somewhat overshadowed by the release of phase 2 results for Amgen’s rival DLL3 candidate, tarlatamab.

Amgen’s study provided validation of DLL3 T-cell engagers but also set the bar for companies that want to challenge it for the market. Merck, which plans to combine HPN328 with other pipeline prospects, is up for the challenge. 

Buying Harpoon will also give Merck control of T-cell engagers aimed at patients who express BCMA and EpCAM. Multiple companies are pursuing the targets, making the programs another test of Harpoon’s belief in its platform. Merck has previously shown an interest in immune engagers in deals with Janux Therapeutics and Dragonfly Therapeutics.