Canadian biotech Zymeworks have announced that the US Food and Drug Administration (FDA) have granted their novel antibody-drug conjugate (ADC), ZW251, investigational new drug (IND) clearance. The news means that ZW251 can start clinical trials for the treatment of hepatocellular carcinoma (HCC), the most common type of liver cancer.
ZW251 targets the protein glypican-3 (GPC3), which is expressed on over 75% of HCC tumours. The candidate is conjugated to Zymeworks’ proprietary payload, a topoisomerase 1 inhibitor (TOPO1i) named ZD06519.
Zymeworks’ CSO, Paul Moore, commented: “This advancement marks the second ADC from our wholly-owned pipeline, utilising our proprietary TOPO1i payload, to progress into clinical development, reinforcing confidence in our approach.”
The chronic liver disease and cirrhosis that often accompanies HCC means that patients are commonly burdened by impairment of liver function. To navigate this challenge, the candidate has a drug-antibody-ratio (DAR) of four, which means that ZW251 could potentially be used at a broader range of dose levels.
ZW251 builds on Zymeworks’ clinical antibody, ZW191, using the same payload. Moore said: “Our observations with ZW191 in the clinic to date provide a strong foundation as we initiate clinical development of this second ADC.”
“With its novel design, unique mechanism of action, and promising preclinical activity, ZW251 offers the potential to meaningfully improve upon the current standard of care for HCC either as a monotherapy or in combination,” he commented.
The candidate has performed well in preclinical studies, exhibiting strong activity in a range of HCC models including patient derived xenografts. Furthermore, ZW251 demonstrated favourable tolerability in non-human primate toxicology studies at doses up to 120 mg/kg.
The company said in a press statement that they plan to commence phase I clinical studies for the candidate later this year.
