211-LB: Antifibrotic Effect of a Novel Long-Acting GLP-1/GCG/FGF21/Anti-Cytokine Tetra-Specific Liver Microenvironment-Targeting Drug (OGB21502) in CCl4-Induced Liver Fibrosis Mice Model

Liver fibrosis is a feature in the majority of chronic liver disease and oxidative stress. If not treated, it may lead to fibrotic liver disease, liver failure and hepatocellular carcinoma (HCC). Since complex biological pathways are involved, therapeutic strategies simultaneously targeting multiple aspects might be required to effectively treat fibrosis as well as NASH. Therefore, we developed a novel long-acting and multi-target drug (GCGR, GLP-1R, FGFR1/KLB, cytokineR), OGB21502 using UniStac technology, which is our proprietary multi-specific platform. OGB21502 prevents inflammation and fibrosis of liver tissue by controlling players in liver microenvironment (LME) such as apoptosis, macrophage activation, and fibroblast activation. Here we evaluate the effect of OGB21502 in liver fibrosis using CCl₄ induced mice. Ocaliva was used as comparative control. In CCl₄ induced mice (8 weeks induction), OGB21502 treatment led to a significant decrease in blood ALT (-38.1% vs. vehicle); hepatic hydroxyproline (-31.5% vs. vehicle) and total bilirubin in blood. Histopathological analysis indicated that OGB21502 meaningfully reduced fibrosis score (-37.5% vs. vehicle); hepatocyte ballooning score (-50% vs. vehicle) and inflammation score (-16.7% vs. vehicle). While all of the vehicle progressed to cirrhosis, 80% of the population administered OGB21502 at high concentrations had cirrhosis progression inhibition. Also, OGB21502 reduced the level of picosirius red positive area (-32.5% vs. vehicle); collagen I (-23.7% vs. vehicle); TGF-β (-27.2% vs. vehicle) and α-SMA (-32.3% vs. vehicle). Based on these results, OGB21502, a novel long-acting tetra-specific LME-targeting drug offers a therapeutic anti-inflammatory and anti-fibrotic effect.