FDA Clears ZW191 for Clinical Trials: Novel Drug Targets NSCLC and Ovarian Cancer

The FDA has greenlighted the IND for ZW191, a novel cancer therapy for clinical trials. This approval is crucial as it targets FRα, a receptor prevalent in many difficult cancers such as NSCLC and ovarian cancer. ZW191's novel mechanism could significantly improve treatment efficacy and tolerability, offering new hope for effective therapies.

Zymeworks Inc. announced that the United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for ZW191, an innovative cancer therapy targeting folate receptor-α (FRα). This clearance paves the way for clinical trials of ZW191, which is designed to enhance the efficacy of treatment for FRα-expressing tumors, including non-small cell lung cancer (NSCLC) and ovarian and other gynecological cancers.

ZW191 is a topoisomerase I inhibitor (TOPO1i) antibody-drug conjugate (ADC), a type of targeted cancer therapy that combines an antibody with a cancer-killing drug. This novel therapy utilizes a unique antibody and drug-linker, ensuring stability and potent delivery of the drug to the cancer cells. This approach is intended to improve the treatment's effectiveness while minimizing side effects.

Paul Moore, Chief Scientific Officer at Zymeworks, highlighted the drug's potential, noting its advanced design and strong preclinical results. “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," Moore explained.

FRα is a promising target in cancer treatment, expressed in approximately 75% of ovarian carcinomas and 70% of NSCLC. The decision to move forward with ZW191 follows the recent FDA clearance of another Zymeworks candidate, ZW171, and marks a significant step in the company’s ambitious ‘5 by 5’ strategy—to advance five novel biotherapeutic products in clinical trials by 2025.

The clinical development of ZW191 is set to commence this year, with additional regulatory applications expected to be filed for conducting trials in other international jurisdictions in the second half of 2024. Zymeworks also plans to continue the development of its two other ADC molecules, ZW220 and ZW251, scheduled for clinical trial applications in 2025.