744-P: Effects of a Novel Long-Acting GIP/GLP-1/Glucagon Trireceptor Agonist, HISHS-3001, on HbA1c, Body Weight, and Lipid Metabolism

Abstract

HISHS-30is a novel long-acting, Gastric inhibitory peptide (GIP) /Glucagon like peptide-1 (GLP-1) /Glucagon tri-receptor agonist. An in-vitro cyclic AMP assay in human receptor- expressing CHO-K1 cells demonstrated that HISHS-30had a half-maximal effective concentration 2.9 and 6.5 fold higher than exendin-4 or GIP, respectively, and 355-fold lower than glucagon. Subcutaneous dosing every third day for 4 weeks in diabetic db/db mice of HISHS-30at 3 and 20 nmol/kg reduced HbA1c, body weight, triglycerides and glucagon levels robustly and markedly more than tirzepatide (Table) .Treatment with HISHS-30also led to an increase in serum and liver Fibroblast Growth Factor-21 (FGF-21) levels vs. tirzepatide. In conclusion, HISHS-30is a potent, long acting GIP/GLP-1/glucagon tri-receptor agonist, with higher effects on glucose homeostasis and metabolic biomarkers in diabetic mice than tirzepatide. Disclosure V.S. Burade: None. A. Garcia-Ocana: Consultant; Sun Pharmaceutical Industries Ltd. R.E. Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. G.A. Rutter: Advisory Panel; Sun Pharmaceutical Industries Ltd. Research Support; Sun Pharmaceutical Industries Ltd. T. Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd. B. Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd., The Healthy Aging Company.