We are pleased to present preclinical data for ZW1528, a novel IL-4Rα x IL-33 bispecific molecule designed to address respiratory inflammation, at the at European Respiratory Society (ERS) Congress 2025, taking place September 27 – October 1, 2025, in Amsterdam, Netherlands and virtually.

The poster presentation titled “ZW1528, a Bispecific Antibody Targeting IL-4Rα and IL-33, Potently Inhibits Key Mediators of Airway Inflammation” (Abstract #: 4587) demonstrates how ZW1528, which was constructed using Zymeworks’ proprietary Azymetric™ technology with IgG-like geometry and Fc optimization, has the ability to inhibit key cytokines involved in the pathology of chronic obstructive pulmonary disease (COPD). This concomitant inhibition may translate into broader suppression of airway inflammation, opening avenues for efficient treatment of patients with COPD.

Key findings for ZW1528 include:

• High affinity for IL-4Rα and IL-33 with potent blockade of IL-4/13 and IL-33 signalling comparable to clinical benchmark monoclonal antibody controls.
• Exhibits in vitro inhibition of T2 and non-T2 responses in primary immune cells (PBMCs) of COPD patients, illustrated by downregulation of IgE receptors and blockade of inflammatory cytokine responses.
• Elicits biomarkers of IL-33 and IL-4Rα engagement in vivo and reduces lung inflammation in murine models. The bispecific has antibody-like PK in rodents and non-human primates and extended serum half-life via Fc optimization.
• Notably, in primary human cell models, ZW1528 shows dual IL-4Rα/IL-33 blockade above that observed with clinical benchmark antibody combinations.

Beyond ZW1528, Zymeworks is also developing ZW1572, a bispecific inhibitor of IL-4Rα and IL-31 for atopic dermatitis, as part of its growing IL-4Rα program portfolio. The Company continues to advance additional product candidates in multiple formats across selected therapeutic indications in solid tumors, with further Investigational New Drug and equivalent non-U.S. application submissions planned for 2028 and beyond.

Additional information can be found on the ERS Congress website, and a copy of the poster is available on the Publications page of Zymeworks’ website.

About 1528

Zymeworks’ first program in autoimmune and inflammatory disorders (AIID), is a novel IL-4R⍺ x IL-33 bispecific molecule designed to address respiratory inflammation such as mixed-type chronic obstructive pulmonary disease (COPD) by inhibiting multiple pathways. By blocking three cytokines (IL-4, IL-13 and IL-33) in a single biologic, ZW1528 offers a unique approach to inhibit clinically validated pathways. The bispecific antibody is designed to provide complete, prolonged IL4R⍺ blockade with simultaneous blockade of IL-33. Based on non-clinical in vitro studies, the bispecific can independently suppress IL-13, IL-4 and IL-33 driven cell signaling equivalent to that achieved with anti-IL-4R⍺ monoclonal antibody (mAb) or anti-IL-33 clinical benchmarks mAbs. Furthermore, in preclinical studies, ZW1528-mediated blockade of cytokine-driven activation of human epithelial cells was superior to that achieved with mAbs targeting either IL-4R⍺ or IL-33, indicating potential benefits of dual blockade. Additionally, preclinical studies with human peripheral blood mononuclear cells (PBMCs) demonstrate ZW1528 provides blockade of IL-33 mediated effects beyond that achievable with an anti-IL33 benchmark mAb. With native Immunoglobulin G (IgG)-like geometry, ZW1528 demonstrates the potential for high manufacturability and incorporates half-life extending Fc modifications. We expect to submit an IND to commence Phase 1 clinical studies for ZW1528 in 2H-2026, with equivalent non-U.S. applications to be submitted thereafter.