212-LB: Therapeutic Effect of a Novel Long-Acting GLP-1/GCG/FGF21/Anticytokine Tetra-Specific Liver Microenvironment-Targeting Drug (OGB21502) in MCD-Induced NASH Mice Model

Abstract

Nonalcoholic steatohepatitis (NASH) is liver inflammation and damage caused by a buildup of fat in the liver. It is characterized by varying degrees of hepatic steatosis, cytoskeletal damage, and lobular inflammation which further leads to fibrosis, cirrhosis and even liver failure. Due to the complexity of the occurrence of NASH and fibrosis, a multi-targeting strategy attracts much attention to effectively address the vicious cycle formed in liver microenvironment. In this respect, we developed a novel long-acting and multi-target drug (GCGR, GLP-1R, FGFR1/KLB, cytokineR), OGB21502, using UniStac technology, which is our proprietary multispecific platform. Here we evaluate the effect of OGB21502 in NASH and fibrosis using MCD diet induced mice model. Liraglutide (Saxenda, Eli lilly) and dulaglutide (Trulicity, Eli lilly) was used as comparative control. In MCD diet-fed mice (8 weeks induction), OGB21502 treatment led to a significant decrease in blood ALT (-45.2% vs. vehicle). Histopathological analysis indicated that OGB21502 meaningfully reduced NAS score (NAFLD activity score, -56.5% vs. vehicle); steatosis score (-57.1% vs. vehicle) and inflammation score (-84.6% vs. vehicle). Compared to vehicle, 100% of OGB21502 dramatically showed “Not NASH” histopathological results. Also, the level of TGF-β (-39.9% vs. vehicle) and α-SMA in liver were significantly decreased in the OGB21502 treatment group. Based on these results, OGB21502, a novel long-acting tetra-specific drug, elicited anti-inflammatory and anti-fibrotic effects in MCD-induced mice model. Disclosure M. Kim: None.