“We are excited to reach this R&D milestone with ZW171, reflecting our commitment to advancing innovative therapies for cancer treatment,” said Paul Moore, Chief Scientific Officer of Zymeworks. “ZW171’s unique design is intended to address the limitations of current bispecific T-cell engagers by enhancing tumor selectivity and improving safety. With promising preclinical results, ZW171 has the potential to provide a more effective and tolerable treatment option for patients with MSLN-expressing cancers, including ovarian cancer, non-small cell lung cancer, mesothelioma, and other cancers. We look forward to initiating clinical development of ZW171 during 2024 and continuing to advance additional product candidates in our ‘5 by 5’ strategy over the next 24 months.”

The company expects to file applications seeking regulatory permission to commence clinical studies for ZW171 in other non-US jurisdictions in the second half of 2024.

ZW171 is a bispecific antibody designed to enable T cell-mediated tumor cell killing through simultaneous binding to the extracellular domain of MSLN protein on tumor cells and the engagement of CD3 on T cells. Moderate to high membranous MSLN expression is frequent in ovarian cancer, non-small cell lung cancer, mesothelioma, and other cancers. Preliminary evidence of anti-tumor activity with engineered T-cell therapy supports the utility of T-cell targeted therapies in the treatment of MSLN-expressing solid tumors. ZW171’s unique 2+1 format and incorporation of a novel low-affinity anti-CD3 binder aim to improve the therapeutic window in patients by limiting on-target, off-tumor effects and cytokine release syndrome (CRS) while maintaining potent anti-tumor activity against MSLN-expressing cancers. By selectively binding to tumors and sparing normal tissues, ZW171 is designed to improve both tolerability and anti-tumor activity against MSLN-expressing cancers.

Engineered and optimized using our Azymetric™ and EFECT™ technologies, ZW171 demonstrates enhanced anti-tumor activity and safety in preclinical models, inducing potent, preferential killing of MSLN-overexpressing cells while mitigating the risk of on-target, off-tumor activity, peripheral T cell activation, and CRS.