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- Company’s first development candidate in autoimmune and inflammatory disease (AIID) demonstrates potent blockade of IL-4, IL-13, and IL-33 signaling pathways critical in respiratory inflammation
- Novel bispecific design shows promising potential manufacturability and stability to support high dosing concentration and subcutaneous administration
- Regulatory filing to support Phase 1 studies expected in 2H-2026
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VANCOUVER, British Columbia, May 19, 2025 (GLOBE NEWSWIRE) — Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, including cancer, inflammation, and autoimmune disease, today announced the presentation of new preclinical data for ZW1528, a novel IL-4Rα x IL-33 bispecific molecule designed to address respiratory inflammation, at the American Thoracic Society (ATS) International Conference being held May 18-21, 2025 in San Francisco, CA.
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“Our expansion into autoimmune and inflammatory diseases represents a carefully considered R&D strategy to leverage our expertise in multispecific antibodies to deliver meaningful impact for patients with difficult-to-treat respiratory disorders,” said Paul Moore, Ph.D., Chief Scientific Officer of Zymeworks. “The preclinical data presented at ATS demonstrate that ZW1528 binds with high affinity to both IL-4Rα and IL-33, driving potent blockade of two distinct signaling axes implicated in inflammatory disease, including chronic obstructive pulmonary disease (COPD). With its unique dual mechanism of action, ZW1528, which was created using our proprietary AzymetricÔ technology, may translate to better control of COPD in a broader patient population compared to existing therapies.”
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Key findings for ZW1528 include:
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- High-affinity binding to both IL-33 and IL-4Rα and effective blockade of IL-4, IL-13, and IL-33 signaling at levels comparable to clinical benchmark monoclonal antibody controls.
- Suppression of both Type 2 and non-Type 2 responses in primary human immune cells of COPD patients in vitro.
- Efficacy in vivo in acute and chronic murine models of lung inflammation driven by house dust mites.
- Extended pharmacokinetics in rodent and non-human primate models, with incorporation of Fc extending half-life optimization.
- Biophysical stability at high concentration (150 mg/mL), supporting potential for subcutaneous administration.
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Poster Presentation Details:
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Title: ZW1528, a Bispecific Antibody Targeting IL-4Rα and IL-33, Potently Inhibits Key Mediators of Airway Inflammation
Abstract Number: 2982
Session Category: B33 – WHEEZING THROUGH THE MECHANISMS: UNPACKING ASTHMA’S SECRETS
Session Title: Thematic Poster Session
Poster Board: P1567
Date and Time: May 19, 2025 at 11:30 am – 1:15 pm Pacific Time
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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 AIID and hematological cancers, with further Investigational New Drug and equivalent non-U.S. application submissions planned for 2028 and beyond.
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Additional information can be found on the ATS website, and a copy of the poster is available on the Publications page of Zymeworks’ website.
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About ZW1528
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ZW1528 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 IL-4R⍺ 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 demonstrate ZW1528 provides blockade of IL-33 mediated effects beyond that achievable with an anti-IL33 benchmark mAb. With native Immunoglobulin G-like geometry, ZW1528 demonstrates the potential for high manufacturability and incorporates half-life extending Fc modifications.