FDA Clears IND of ZW191, Novel Folate Receptor Alpha-Targeting ADC

• The FDA has cleared the investigational new drug (IND) application for ZW191, a novel antibody-drug conjugate (ADC).
• ZW191 is a topoisomerase I inhibitor (TOPO1i) ADC and targets folate receptor alpha (FR⍺), which is expressed in cancers like gynecologic and non–small cell lung cancer (NSCLC).
• Zymeworks, the manufacturer, will seek regulatory approval to begin clinical studies in the second half of 2024.

The IND application of ZW191, a TOPO1i FR⍺-targeted ADC, has been cleared by the FDA.¹

“ZW191 is a differentiated product candidate in our pipeline that reflects the strength of our approach in developing best-in-class antibody-drug conjugates,” said Paul Moore, chief scientific officer of Zymeworks, in a press release. “Developed to target FR⍺, which is expressed in several types of difficult-to-treat cancers, ZW191 incorporates a novel antibody and drug-linker that provide a unique combination of antibody-linker stability and payload potency, together with strong bystander activity, which could result in improved efficacy and enable targeting lower levels of FR⍺ compared to previously developed drug candidates.”

Zymeworks seeks to begin clinical development of ZW191 later this year.

FR⍺ is expressed in several tumors, including in 75% of ovarian adenocarcinomas and 70% of NSCLC tumors. ZW191 uses a novel TOPO1i-based payload, ZD06519, to target FR⍺. The monoclonal antibody used is also able to target all levels of FR⍺ expression. According to preclinical models, ZW191 has demonstrated robust antitumor activity and tolerable safety.

In June 2024, the FDA cleared the IND application of ZW171, another Zymeworks agent. ZW171 is a bispecfic antibody targeting mesothelin-expressing cancers.² Zymeworks’ preclinical pipeline also includes ZW251, a glypican-3 targeted TOPO1i ADC, and ZW220, a NaPi2b-targeted TOPO1i ADC.³

REFERENCES:

1. Zymeworks announces fda clearance of investigational new drug application for ZW191, a novel folate receptor-⍺ targeted topoisomerase I inhibitor antibody-drug conjugate. News release. Zymeworks. July 22, 2024. Accessed July 22, 2024. https://tinyurl.com/35ywnbfm

2. 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 July 22, 2024. https://tinyurl.com/5ae6rr6c

3. Pipeline. Zymeworks. Accessed July 22, 2024. https://www.zymeworks.com/pipeline/