HPG1860 is a next generation liver enrichment FXR agonist with a non-bile acid scaffold. Through regulation of gene expression of bile acids, FXR serves as a key controller of bile acid homeostasis. FXR has been studied for its role in modulating inflammation and the expression of FXR is down-regulated during NASH development. HPG1860 exhibited superb efficacy and safety profile in preclinical, Phase 1 and 2a clinical trial.

HPG7233: A Highly Selective THR-β Agonist
HPG7233 is a novel liver-targeted and highly selective small molecule thyroid hormone receptor beta (THR-beta) agonist aimed at serum and liver lipid metabolism. HPG7233 demonstrated high selectivity and potency, great liver-enrichment and liver/plasma exposure profile in rodent and non-rodent animals, significant reduction of liver index and serological markers level, and significant reduction of NAS score in NASH model. These results provide strong evidence to support continuing efforts in HPG7233 development for NASH and dyslipidemia indications.

IAP antagonist plays a key role in multiple steps of the programmed cell death or apoptosis pathway. The overexpression of IAPs and loss of endogenous inhibitors of IAPs (e.g., SMAC protein) have been reported to contribute to tumor progression and chemoresistance in various cancers. HPG3466, an investigational small molecule IAP antagonist, can induce apoptosis by mimicking the dimeric form of the SMAC protein. Unlike other IAP inhibitors in development, HPG3466 exhibits potent and specific IAP inhibition activities for XIAP, cIAP1 and cIAP2.

The glucagon-like peptide-1 receptor (GLP-1R) is an effective therapeutic target for type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). HPG5119 is a novel small molecule oral glucagon-like peptide 1 (GLP-1) receptor agonist.

GalNAc delivery system utilized a synthetic trivalent N-acetylgalactosamine (GalNAc) ligand that is covalently conjugated to a chemically modified small interfering RNA (siRNA). This strategy enables safe and effective targeted delivery of siRNA to the liver mediated by the asialoglycoprotein receptor (ASGPR) specifically expressed on the surface of hepatocytes, which triggers clathrin-mediated endocytosis to enable intracellular delivery of siRNA to elicit RNAi-mediated RNA silencing.