Non-alcoholic steatohepatitis (NASH) is an advanced stage of non-alcoholic fatty liver disease (NAFLD), characterized by inflammation and hepatocyte injury due to the continuous accumulation of fat in liver tissue and secretion of inflammatory cytokines. The underlying mechanism for the progression of NASH is multifactorial and incorporates an interplay of metabolic, inflammatory, and fibrogenic processes. Currently, there are multiple therapeutic programs for NASH showing promising outcomes; however, treating severely advanced NASH and cirrhosis is still challenging.

FGF21 has emerged as a best-in-class mechanism for resolving both NASH and fibrosis. Its efficacy stems from its ability to regulate glucose and lipid metabolism, as well as its direct anti-fibrotic actions. FGF21's strong antifibrotic effects is attributed to its ability to not only directly suppress HSC activation but also reduce the expression and secretion of pro-fibrotic factors derived from Kupffer cells and injured hepatocytes. 

There is growing evidence to suggest tha  the NLRP3 inflammasome/IL-1β pathway with liver damage and fibrosis, and underscores the potential for IL-1 pathway interference to treat liver fibrosis. The use of recombinant IL-1 receptor antagonist anakinra is one such therapy that has been extensively studied for reducing NLRP3 activation.  In various studies, anakinra treatment led to a reduction in HSC activation and serum levels of fibrosis markers.

OGB21502 is a tetraspecific molecule that targets GLP-1/GCG/FGF21/IL-1RA, to improve the effectiveness of FGF21. OGB21502 is anticipated to become a holistic treatment option for individuals with advanced NASH and cirrhosis.