SZN-043

SZN-043 is a novel hepatocyte-targeted R-spondin mimetic bispecific recombinant fusion protein developed by Surrozen for the treatment of severe liver diseases, with an initial focus on severe alcohol-associated hepatitis. It is the first clinical candidate using Surrozen’s proprietary SWEETS technology. Mechanistically, SZN-043 selectively activates the Wnt signaling pathway in hepatocytes by binding to asialoglycoprotein receptor 1 (ASGR1), thereby stimulating Wnt/β-catenin target gene expression and promoting hepatocyte proliferation and regeneration. This targeted approach circumvents the need for LGR co-receptors and leverages ASGR1’s high abundance on hepatocytes to enhance specificity and efficacy while minimizing off-target effects. Preclinical studies demonstrated robust induction of Wnt target genes (such as Cyp1a2, Axin2, Notum, Ccnd1) and increased markers of cell proliferation (Mki67). In Phase 1a clinical trials involving healthy volunteers and patients with cirrhosis, SZN-043 was well tolerated at single or multiple intravenous doses up to 3 mg/kg; it showed evidence of pharmacodynamic activity including dose-dependent activation of hepatic Wnt signaling (measured via methacetin breath test), transient increases in serum alkaline phosphatase due to ASGR1 engagement, and improvements in liver function tests such as cholate clearance (HepQuant). Mild-to-moderate transient transaminase elevations were observed but resolved without intervention or sequelae[5][6][7][3][9].

Other names

SZN 043SZN043SZN-043SWEETS-1SWEETS1SWEETS 1