RYZ801 targeting GPC3 for hepatocellular carcinoma (HCC)
Liver cancer is the sixth most common cause of cancer death in United States, with an estimated 29,380 deaths per year with a five-year survival rate of approximately 20%. GPC3 is an oncofetal protein that is overexpressed in up to 75% of hepatocellular tumors, with minimal to no expression in normal tissues.
RYZ801 is our novel proprietary peptide which targets GPC3 for delivery of Ac225 for the treatment of HCC.
Preclinical biodistribution studies in the liver cancer cell line HepG2 xenograft mouse models show tumor uptake and retention with low amounts of uptake in normal tissues. Tumor levels are approximately three- to 20- fold higher than the kidney at various timepoints.
In preclinical studies of HCC xenograft models, our GPC3 binding peptide showed specific tumor uptake, and significant tumor growth inhibition including regression with single doses delivering Ac225 or Lu177.
We are also developing RYZ811, which is a paired diagnostic imaging agent with the same peptide binder and chelator as RYZ801 but with Gallium 68, or Ga68, as the imaging radioisotope. Via compassionate use, we have shown uptake of our novel proprietary peptide binder in patients with HCC via early human imaging studies using Ga68.
We have also conducted imaging at later timepoints using low-dose Lu177 and observed tumor retention up to 196 hrs, or 8 days.
We expect to file an IND for RYZ801 and RYZ811 in 1H 2024.