Roche bets up to $813M on Zymeworks lung cancer candidate
Swiss big pharma Roche has agreed to license ZW209, an experimental cancer immunotherapy from Vancouver-based Zymeworks, for $55 million upfront and up to $758 million more in conditional payments, plus royalties on future sales. The agreement returns Roche to DLL3, a lung cancer target it previously pursued with a different antibody.
Why it matters: Roche is returning to a clinically validated cancer target with an unproven design. Amgen’s DLL3-targeted tarlatamab extended median survival to 13.6 months versus 8.3 months with chemotherapy in previously treated small-cell lung cancer patients. Roche discontinued its own DLL3-targeted trispecific after Phase 1, but is now betting that ZW209’s different approach to stimulating T cells could deliver better results, despite the absence of human efficacy data.
- “ZW209 represents an innovative approach that complements our ongoing efforts to develop new treatment options for people living with lung cancer,” said Boris L. Zaïtra, Roche’s Head of Corporate Business Development, in the press release.
Zoom in: ZW209 binds DLL3 on tumour cells and CD3 and CD28 on T cells. CD3 initiates the immune attack, while CD28 provides a second signal intended to help T cells proliferate and survive. Its engineered CD28 binding depends on CD3 engagement on the same T cell, a design intended to limit unintended activation.
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In preclinical experiments, ZW209 sustained cancer-cell killing through repeated laboratory challenges 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.
- A Phase 1a study has been initiated, with the first patient expected to enroll before year-end, Zymeworks CEO Kenneth Galbraith told Reuters.
A previous attempt: Roche’s own trispecific, RO7616789, targeted DLL3 but used 4-1BB rather than CD28 for costimulation.
- In the 41-patient Phase 1 TRIDENIS study, five of 23 evaluable small-cell lung cancer patients had tumour responses, while seven of 41 participants experienced serious cytokine-release syndrome.
- Roche stopped the study in March 2025, before determining the highest safely tolerated dose, saying it was prioritising other medicines.
Follow the money: Zymeworks is eligible for another $40 million when Phase 1b begins and up to $718 million in additional development, commercial and sales milestones, plus tiered royalties ranging from “high-single-digit to mid-teen” percentages of future global net sales. Roche will fund the initial Phase 1a trial, conducted by Zymeworks in collaboration with Roche, before assuming subsequent development. The agreement remains subject to regulatory closing conditions.
Reality check: ZW209 has received FDA clearance to enter human testing, but has yet to demonstrate safety or efficacy in patients. Amgen’s approved DLL3-targeted competitor, tarlatamab, has demonstrated a survival benefit but carries boxed warnings for potentially fatal immune and neurological reactions.
Bottom line: Amgen has already shown that targeting DLL3 can extend survival. Roche now needs to demonstrate that ZW209’s additional CD28 signal delivers a meaningful advantage without unacceptable toxicity.
