FDA Clears IND Application of ZW171 in Mesothelin-Expressing Cancers

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ZW171, a bispecific antibody targeting MSLN-expressing cancers, has shown promising preclinical results and plans for further regulatory submissions outside the US in late 2024.

  • The FDA cleared the investigational new drug (IND) application for ZW171 for mesothelin (MSLN)-expressing cancers.

  • ZW171 is a novel 2+1 T-cell-targeting bispecific antibody.

  • Zymeworks Inc plans to submit applications for regulatory approval to start clinical trials for ZW171 in various regions outside the US later this year.

An IND application for ZW171 has been cleared by the FDA for the treatment of MSLN-expressing cancers.1

ZW171 is a bispecific antibody that works to enable T-cell-mediated tumor cell killing. This is achieved by simultaneously binding to the extracellular domain of the MSLN protein on tumor cells and engaging CD3 on T cells.

Moderate to high membranous MSLN expression is common in ovarian cancer, non–small cell lung cancer, and mesothelioma, among others.

“We are excited to reach this [research and development] milestone with ZW171, reflecting our commitment to advancing innovative therapies for cancer treatment,” said Paul Moore, chief scientific officer of Zymeworks, in a press release. “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.”

Cell microscopic- pyloric division stomach: © digital photo - stock.adobe.com

Cell microscopic- pyloric division stomach: © digital photo - stock.adobe.com

According to preliminary evidence, antitumor activity with engineered T-cell therapy supports the utility of T-cell-targeted therapies in treating patients with MSLN-expressing solid tumors.1,2

The unique 2+1 format of ZW171 and the incorporation of a novel low-affinity anti-CD3 binder work to better the therapeutic window in patients. This approach helps limit on-target, off-tumor effects and cytokine release syndrome. At the same time, it maintains potent antitumor activity against cancers that express MSLN.

Additionally, ZW171 is made to target tumors selectively while sparing normal tissues and aims to improve tolerability and antitumor activity against these types of cancers. Through the utilization of Azymetric and EFECT technologies, ZW171 is designed to show better antitumor activity and safety in preclinical models.

It is expected that the company will file applications for regulatory consent to initiate clinical studies for ZW171 in countries other than the US during the second half of 2024.1

“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,” added Moore, in the press release.

REFERENCES
1. Zymeworks announces FDA clearance of investigational new drug application for ZW171, a novel 2+1 T-cell targeting bispecific antibody for mesothelin-expressing cancers. News release. Zymeworks Inc. June 17, 2024. Accessed June 18, 2024. https://tinyurl.com/5ae6rr6c
2. Pipeline. Zymeworks Inc. Accessed June 18, 2024. https://www.zymeworks.com/pipeline/
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