Roche licenses lung cancer drug ZW209 from Zymeworks

Swiss pharma Roche has signed a global licence and collaboration agreement with Vancouver-based Zymeworks for ZW209, a DLL3-targeting T-cell engager. Roche will pay $55 million upfront and up to $758 million in conditional payments, plus royalties on future sales. Those payments include $40 million when a later Phase 1b trial begins and up to $718 million in development, commercial and sales milestones.

ZW209 works by binding the DLL3 protein on cancer cells and the CD3 and CD28 receptors on T cells. CD3 starts the immune attack, while CD28 provides a second signal that encourages the T cells to grow and survive. The CD28 binding is engineered to depend on CD3 engagement, which is intended to limit unwanted activation of T cells.

In preclinical studies, ZW209 repeatedly killed cancer cells and outperformed an in-house version of Amgen's tarlatamab in one mouse model. In another model, both treatments achieved complete tumour regression in six of seven mice.

Next steps for the therapy

A Phase 1a trial of ZW209 is expected to start before the end of the year, with Roche funding the study that Zymeworks will conduct. When the later Phase 1b trial begins, Zymeworks is eligible for another $40 million.

Roche aims to prove that the additional CD28 signal can give a meaningful advantage over existing therapies without causing excessive toxicity. Amgen's tarlatamab has shown a survival benefit but carries boxed warnings for potentially fatal immune and neurological reactions.