Zymeworks Receives FDA Clearance for Investigational Drug ZW251 to Treat Liver Cancer
Tuesday, July 29, 2025
Zymeworks Inc., a clinical-stage biotechnology company, has announced that the US Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for ZW251. This experimental therapy is being developed for the treatment of hepatocellular carcinoma (HCC), the most common type of primary liver cancer.
ZW251 is a glypican-3 (GPC3)-targeted antibody-drug conjugate (ADC). GPC3 is a protein found in over 75% of HCC cases. The treatment combines a humanised antibody with a novel topoisomerase 1 inhibitor (TOPO1i) payload, ZD06519, developed by Zymeworks. The payload is linked to the antibody using a validated cleavable peptide linker. A drug-to-antibody ratio (DAR) of four was chosen to allow for greater flexibility in dosing, which may benefit patients with impaired liver function, a common issue in those with chronic liver disease or cirrhosis.
ZW251 has shown strong anti-tumour activity in preclinical studies across various HCC models, including patient-derived xenografts with different levels of GPC3 expression. In addition, non-human primate studies demonstrated good tolerability at doses of up to 120 mg/kg.
ZW251 is the second ADC in Zymeworks’ pipeline using its proprietary TOPO1i technology, following ZW191, which is already in clinical trials. Both therapies use the same payload but are paired with different antibodies tailored to their respective targets.
The company plans to begin Phase 1 clinical trials for ZW251 in 2025, with the aim of evaluating its safety and potential as a monotherapy or in combination with other treatments for liver cancer.
Source: globenewswire.com
