Zymeworks announced on October 23 that Roche will license ZW209, its trispecific T cell engager targeting DLL3, under an exclusive global license and collaboration agreement. Zymeworks receives $55 million upfront and a further $40 million when the Phase 1b dose-optimization study starts, and is eligible for up to $718 million in development, commercial and sales-based milestones, taking the total potential value to $813 million, plus tiered royalties described as high single digit to mid-teen on future net sales. The transaction is subject to the Hart-Scott-Rodino waiting period and other customary conditions.
ZW209 binds DLL3 on tumor cells and both CD3 and CD28 on T cells: CD3 initiates the attack and CD28 supplies a second, costimulatory signal intended to help T cells proliferate and persist, with the CD28 binding engineered to depend on CD3 engagement on the same cell to limit unintended activation. DLL3 is commonly found on small-cell lung cancer cells and rarely on healthy tissue, and the target is clinically validated by Amgen’s tarlatamab. Zymeworks will run the Phase 1a monotherapy trial in collaboration with Roche, which funds that study; Roche then takes over global development and commercialization. The US Food and Drug Administration has cleared the investigational new drug application, and chief executive Kenneth Galbraith told Reuters the first patient is expected to enroll before the end of 2026.
The signal in the deal is timing. Roche agreed to partner before efficacy data were available, Galbraith said, citing the innovation and differentiation of the trispecific platform, and Roche is returning to DLL3 after discontinuing its own earlier trispecific, which used a different costimulatory design, after Phase 1. Of the $813 million headline, $95 million is scheduled cash (upfront plus the Phase 1b payment) and the remaining $718 million is contingent on a drug that has not yet dosed its first patient.