Zymeworks Licenses DLL3-Targeted Trispecific T-Cell Engager ZW209 to Roche in Deal Worth Up to $813 Million

Zymeworks has granted Roche exclusive global rights to develop and commercialize ZW209, a trispecific T-cell engager targeting DLL3, CD3, and CD28, under a license and collaboration agreement worth up to $813 million in upfront and milestone payments, plus royalties.¹ FDA has cleared the Investigational New Drug application for ZW209, and a phase 1 study in small cell lung cancer (SCLC) and other DLL3-expressing neuroendocrine tumors has been initiated.¹

How is ZW209 designed?

ZW209 binds DLL3 on tumor cells while engaging T cells through both CD3 and CD28.¹ CD3 engagement provides the primary T-cell activation signal used by bispecific T-cell engagers, while CD28 adds a co-stimulatory signal intended to enhance antitumor T-cell responses.¹ According to Zymeworks, the molecule relies on obligate cis T-cell binding and conditional CD28 engagement, which are intended to prevent unintended T-cell activation while enabling tumor-targeted cytotoxicity.¹

The company built ZW209 using its TriTCE Co-Stim platform together with its Azymetric and EFECT antibody engineering platforms.¹ In preclinical studies, ZW209 showed long-term cytotoxicity in vitro along with enhanced T-cell proliferation and survival, which Zymeworks said could increase the durability of responses in DLL3-expressing cancers.¹

Why target DLL3 in SCLC?

SCLC accounts for approximately 13% to 15% of lung cancers diagnosed worldwide, and five-year relative survival in the US is 5% to 10% across all stages.² DLL3 is expressed on the surface of SCLC cells in approximately 85% to 96% of patients and is minimally expressed on healthy cells.²

The target has already been validated with a T-cell engager. Amgen’s DLL3×CD3 bispecific tarlatamab (Imdelltra) received full FDA approval in November 2025 for adults with extensive-stage SCLC that progressed on or after platinum-based chemotherapy.² In the Phase 3 DeLLphi-304 trial, tarlatamab reduced the risk of death by 40% compared with chemotherapy, with median overall survival of 13.6 months vs 8.3 months.^2,3 In September, BioPharm International® reported that tarlatamab plus durvalumab (Imfinzi) also improved overall survival as first-line maintenance therapy in extensive-stage SCLC.

In a BioPharm International interview at BIO 2026, Sabeen Mekan, MD, senior vice president and chief medical officer of Zymeworks, discussed why tolerability matters as cancer therapies are used over longer treatment courses. “The goal is to make cancer a chronic disease,” Mekan said. “Then tolerability becomes very, very important.”

What are the terms of the agreement?

Zymeworks is eligible to receive $55 million upfront, $40 million when the Phase 1b trial begins, and up to $718 million in development, commercial, and sales-based milestones.¹ The company is also eligible for tiered royalties ranging from high single digits to mid-teens on global net sales, with patent protection extending into the 2040s.¹

Zymeworks will conduct the phase 1a monotherapy trial in collaboration with Roche, which will fund the study and be responsible for subsequent global development and commercialization.¹

“This collaboration allows us to continue advancing ZW209 through its initial clinical development while leveraging Roche’s complementary capabilities to accelerate and expand its development across indications and treatment settings,” said Adam Schayowitz, PhD, MBA, executive vice president and head of R&D at Zymeworks.¹

ZW209 adds to Roche’s DLL3 portfolio. In January 2025, the company acquired exclusive global rights to Innovent Biologics’ DLL3-targeted antibody-drug conjugate IBI3009, as BioPharm International reported at the time.

What happens next?

The phase 1 open-label, multicenter, global study will evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of ZW209 in adults with select advanced solid tumors.¹ Zymeworks plans additional regulatory applications to open clinical sites outside the US.¹

The transaction is subject to expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions.¹ Beyond ZW209, Zymeworks has research programs of multispecific T-cell engagers in solid tumors, hematologic cancers, and autoimmune and inflammatory diseases.¹ The company will host an investor call on October 27, 2026.¹

References

1. Zymeworks enters into an exclusive global license and collaboration agreement with Roche for ZW209, a trispecific T cell engager targeting DLL3. News release. Zymeworks Inc. October 23, 2026. Accessed October 23, 2026.
2. FDA grants full approval to Amgen’s Imdelltra in extensive stage small cell lung cancer. News release. Amgen. November 19, 2025. Accessed October 23, 2026.
3. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Engl J Med. 2025;393(4):349-361. doi:10.1056/NEJMoa2502099