SOUTH SAN FRANCISCO, Calif., May 4, 2020 — Surrozen Inc., a biotechnology company pioneering a new class of targeted regenerative antibodies, announced today that two abstracts were published on the 2020 Digestive Disease Week (DDW) site. These abstracts were originally accepted for presentation during the 2020 DDW Conference which was to be held May 2-5 in Chicago, IL.
Both abstracts describe pre-clinical results with a liver-targeted proprietary molecule that enhances Wnt signaling and stimulates tissue regeneration. SWEETS (Surrozen Wnt signal Enhancers Engineered for Tissue Specificity) are antibody-based molecules that enhance Wnt signaling. SWEETS-1, a hepatocyte-targeted SWEETS, is the first proprietary SWEETS molecule to show preclinical proof of concept. The abstracts highlight that SWEETS-1 demonstrated hepatocyte-specific activation of Wnt target genes such as Axin2, stimulated hepatocyte regeneration, and restored liver function as measured by clotting time in a thioacetamide-induced mouse liver injury model.
The first abstract, titled “HEPATOCYTE-TARGETED R-SPONDIN MIMETIC FOR LIVER REGENERATION (Abstract #3346398)” showed that SWEETS-1 enhanced Wnt signaling in a hepatic cell line to a level similar to that induced by R-spondin. SWEETS-1 induced the expression of the Wnt target gene Axin2 in liver only, while R-spondin also induced Wnt signaling in kidney, salivary gland, intestine, heart, and pancreas. Immunofluorescence analysis revealed that SWEETS-1 induced Ki67 positive nuclei specifically in matures hepatocytes.
The second abstract, titled “HEPATOCYTE-TARGETED R-SPONDIN MIMETIC STIMULATES REGENERATION AND RESTORES COAGULATION IN A THIOACETAMIDE-INDUCED LIVER INJURY MODEL (Abstract #3346773)” demonstrated that Wnt family members were elevated in TAA-injured livers, suggesting that SWEETS-1 could be efficacious in liver injury. Indeed, SWEETS-1 induced liver expression of Axin2 to a level similar to that induced by R-spondin in a thioacetamide-induced mouse liver injury model. In addition, SWEETS-1 induced Ki67 positive nuclei in mature hepatocytes. Furthermore, SWEETS-1 treatment restored TAA-impaired clotting time to baseline levels.
“These results suggest that a cell-specific R-spondin-mimetic can selectively stimulate hepatocyte regeneration, differentiation, and function.” said Wen-Chen Yeh, MD, PhD, Chief Scientific Officer at Surrozen. “We are excited to be able to confirm the relevance of our proprietary SWEETS platform technology and to advance this novel approach to treating liver disease.”
Wnt signaling plays key roles in the control of development, homeostasis, and regeneration of many essential organs and tissues, including liver, intestine, lung, kidney, central nervous system, cochlea, bone, and others. Modulation of Wnt signaling pathways has potential for treatment of degenerative diseases and tissue injuries. There are 19 Wnt ligands (Wnts) in mammals, and they signal through Frizzled receptors 1-10 and co-receptors LRP5 or 6, two families of receptors. Endogenous Wnts bind to multiple Frizzled receptors and are heavily modified post-translationally, making them difficult to manufacture consistently. R-spondin stabilizes Frizzled receptors, enhancing the body’s response to endogenous Wnts.
Since its founding in 2016, Surrozen has developed two proprietary platforms to selectively modulate the Wnt pathway for the potential treatment of injury and disease. Surrozen Wnt-mimetics, also referred to as SWAP (Surrozen Wnt signal Activating Proteins), are bi-specific full-length human (IgG) antibodies that directly activate the canonical Wnt signaling pathway in target tissue. Surrozen R-spondin-mimetics, also referred to as SWEETS (Surrozen Wnt signal Enhancers Engineered for Tissue Specificity), are antibody-based molecules that enhance Wnt signaling by stabilizing Frizzled receptors on targeted cells.
Surrozen is a biotechnology company pioneering a new class of targeted regenerative antibodies to repair a broad range of tissues and organs damaged by serious disease. Surrozen is designing tissuespecific antibodies that engage the body’s own biological repair mechanisms resulting in a broad pipeline of disease-specific therapies to help patients across multiple disease areas. For more information, please visit surrozen.com.
VP, Corporate Development and Strategy