Surrozen, Inc. presented a poster on the preliminary results of a Phase 1a study of SZN-043, a novel R-Spondin mimetic, in healthy volunteers and subjects with liver cirrhosis on June 8, 2024 at the 2024 European Association for the Study of the Liver (EASL) in Milan. Study Overview: Safe and well-tolerated doses of SZN-043 were established in the randomized, placebo-controlled, first-in-human, Phase 1a trial in 40 healthy volunteers (HVs) and 8 patients with a history of liver cirrhosis; Single or multiple intravenous infusion doses were administered in a range from 0.5 mg/kg to 3 mg/kg; In some treated subjects, there were mild-to-moderate, transient, and dose-related serum transaminase elevations that resolved without intervention. These serum transaminase elevations were not associated with other changes in clinical pathology that are indicative of liver disease or bile duct damage.

Pharmacodynamic Biomarkers: The study provided evidence of Wnt-mediated pharmacodynamic activity in the liver after treatment with SZN-043. Target engagement was confirmed via transient increases in alkaline phosphatase (ALP). Increases in ALP are indicative of SZN-043 binding to, and elimination of, its targeting receptor asialoglycoprotein (ASGPR) from the surface of the hepatocytes and this reduction in its capacity to clear ALP is consistent with observations in other ASGPR binding agents.

Wnt signal activation was demonstrated by the results of the methacetin breath test. This test showed increased methacetin clearance following SZN-043 administration which is indicative of activation of the Wnt target gene, CYP1A2, in hepatocytes. HepQuant measurements demonstrated increases in the portal hepatic filtration rate (HFR).

The HepQuant test is a quantitative liver function test that measures cholate clearance to assess liver function. The increase in portal HFR is thought to be related to Wnt-mediated induction of cholate clearance by SZN-043.