Surrozen, Inc. announced the presentation of data supporting the continued development of its lead therapeutic programs at Digestive Disease Week (DDW) 2022 in San Diego. In an oral presentation entitled, “SZN-1326 promotes colonic mucosal healing in an acute injury model of IBD by first accelerating epithelial regeneration and secondarily reducing inflammation,” Surrozen presented data elucidating the mechanism of action of its proprietary Wnt mimetic, SZN-1326, a FZD5 and LRP6-specific, full-length, effectorless, bi-specific tetravalent IgG1 molecule. The data demonstrate that in an acute dextran sodium sulfate (DSS) epithelial damage model, SZN-1326 promoted mucosal healing by transiently inducing epithelial progenitor cell expansion and accelerating epithelial repair.

The data further show that SZN-1326 also reduced stromal and immune cytokine signaling and immune cell infiltration. In a poster entitled, “Modulation of Wnt signaling via a Wnt mimetic improved epithelial healing without causing hyperplasia in a mouse colitis model,” Surrozen presented data from an acute DSS mouse model for ulcerative colitis (UC). UC is characterized by epithelial lesions, and there is a need for therapies that promote mucosal healing.

Wnt signaling plays critical roles in regulating intestinal stem cell maintenance and differentiation, and modulation of Wnt signaling could allow for epithelial restoration and histological remission. In this study, Surrozen's Wnt mimetic repaired the damaged epithelium without causing hyperproliferation of epithelial cells in the intestine and improved body weight loss, demonstrating its therapeutic potential in IBD. In a poster entitled, “SZN-043 induced quick and robust hepatocyte proliferation in a 14-day daily dosing Edu-labeling study in SCID mice,” Surrozen evaluated the kinetics and the overall effects of daily dosing of SZN-043 on hepatocyte proliferation in mice.

Wnt/ß-catenin signaling plays a key role in hepatocyte regeneration in homeostasis and after liver injury, and SZN-043, a hepatocyte specific R-spondin-mimetic, amplifies the signal of Wnt ligands by stabilizing and increasing the amount of Wnt receptors on the hepatocyte cell surface. Results showed hepatocytes responded quickly to SZN-043 treatment and underwent a limited number of proliferation cycles, despite the continued exposure to SZN-043 and ß-catenin signaling induction for up to 14 days. SZN-1326 is the first development candidate designed using Surrozen's SWAP™ technology and targets the Wnt-signaling pathway in the intestinal epithelium.

In preclinical animal models of acute and chronic colitis, SZN-1326 has been shown to activate Wnt signaling in the diseased intestine, stimulate intestinal epithelial regeneration, reduce inflammation and reduce disease activity with no treatment related adverse effects observed in 13-week toxicology evaluations in rats and non-human primates (NHPs). Surrozen is initially developing SZN-1326 for moderate to severe ulcerative colitis. The Phase 1 clinical study is posted to the Australian New Zealand Clinical Trial Registry.

SZN-043 is the first development candidate designed using Surrozen's SWEETS™ technology. In multiple preclinical animal models of liver injury and fibrosis, SZN-043 has been shown to selectively activate Wnt signaling in the liver, stimulate transient hepatocyte proliferation, improve liver function and reduce fibrosis with no treatment-related adverse effects observed in 4-week GLP toxicology evaluations in mice and NHPs. Surrozen is developing SZN-043 for severe liver diseases, initially focusing on severe alcoholic hepatitis.

Surrozen expects to initiate a Phase 1 clinical trial of SZN-043 in the third quarter if 2022. The Phase 1 clinical study is posted to the Australian New Zealand Clinical Trial Registry.