SOUTH SAN FRANCISCO, Calif., Oct. 15, 2020 (GLOBE NEWSWIRE) -- Surrozen Inc., a biotechnology company pioneering a new class of targeted regenerative antibodies, has been awarded an NIH grant to support development of SZN-043, a novel liver-targeted regenerative antibody. The NIH grant is titled: "A hepatocyte-specific R-spondin mimetic bispecific fusion protein to stimulate hepatocyte regeneration in patients with acute alcoholic hepatitis." The federal grant amount is $1 million for the first year. An additional potential $2 million in grants may be awarded over the subsequent four years subject to the availability of funds and satisfactory progress of the project.
Alcoholic hepatitis (AH) is characterized by inflammatory liver injury caused by heavy alcohol consumption, with high rates of morbidity and mortality. Importantly, lack of hepatocyte regeneration and maturation is a major issue in AH patients. Increased hepatocyte proliferation has been shown to be associated with better outcomes.
The hepatocyte targeted R-spondin-mimetic, SZN-043, is currently in preclinical development for severe alcoholic hepatitis. In pre-clinical models of liver injury, treatment with SZN-043 can selectively stimulate hepatocyte regeneration and improve hepatic function. “By selectively activating the Wnt signaling pathway in the liver, SZN-043 has the potential to stimulate liver regeneration in patients with liver damage and impaired function.” says Wen-Chen Yeh, MD, PhD, chief scientific officer at Surrozen.
Surrozen plans to file an IND and begin clinical trials in the fourth quarter of 2021. “This grant will help support IND-enabling studies and early clinical development in this severe disease.” says Trudy Vanhove, MD, PhD, chief medical officer at Surrozen. “Severe alcoholic hepatitis is associated with significant short-term mortality and represents a major unmet medical need.”
Research reported in this press release is supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number U01AA028951. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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.
SZN-043 is the first development candidate designed using Surrozen’s SWEETS platform. In preclinical animal models of liver injury and fibrosis, SZN-043 has been shown to selectively activate Wnt signaling in the liver, stimulate hepatocyte proliferation, improve synthetic function, and reduce fibrosis. Surrozen will develop SZN-043 for severe liver diseases including severe alcoholic hepatitis and decompensated liver cirrhosis.
SZN-1326 is the first development candidate designed using Surrozen’s SWAP platform. SZN-1326 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 intestine, stimulate intestinal epithelial regeneration, and reduce disease activity. Surrozen will develop SZN-1326 for moderate to severe inflammatory bowel disease.
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 tissue-specific 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, including severe liver diseases, inflammatory bowel disease, retinopathies, hearing loss, lung and airway diseases, and certain neurological disorders. For more information, please visit surrozen.com.
VP, Corporate Development and Strategy