Multi-target engagement by optimized triple agonism “The right incretin for MASH / fibrosis”
Efocipegtrutide is a long-acting glucagon, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) triple full agonist chemically conjugated with constant region of human immunoglobulin via non-peptidyl flexible linker.
The physiological effects mediated by optimal activation of multiple incretin receptors, Glucagon, GIP, and GLP-1 receptors, could provide an improved therapeutic efficacy in subjects with metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and fibrosis compared to any single targeting medications via simultaneously affecting liver fat accumulation, inflammation, and fibrogenesis - the hallmarks of MASH.
In nonclinical studies, a remarkable reduction in liver fat content and robust improvement in liver inflammation and fibrosis were observed in various animal models of MASH and/or liver fibrosis. Based on these results, we prioritized clinical development of efocipegtrutide as a novel therapeutic medication for MASH/fibrosis. Recently, phase 2b clinical study is being investigated in biopsy-confirmed MASH subjects with fibrosis. The FDA granted fast track designation to efocipegtrutide for the treatment of MASH.
In addition, potential benefits in diverse fibrotic diseases of high unmet medical needs is being investigated for efocipegtrutide’s indication expansion. Based on promising nonclinical study results, efocipegtrutide received orphan drug designation from the FDA and EMA for the treatment of idiopathic pulmonary fibrosis (IPF), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).
Description
Glucagon/GIP/GLP-1 triple agonism
Maximal efficacy for liver fat removal by three combined mode of action
(energy intake, β-oxidation, and de novo lipogenesis)
Maximal efficacy for Improvement of liver inflammation by multiple incretin action in cooperation
with favorable liver targeting
Direct down-regulation of hepatic stellate cell activation
A phase 2b study with biopsy-confirmed MASH subjects is currently ongoing in the US and Korea
NCT04505436
Publications
Poster
Improvement of liver fibrosis by a novel long acting glucagon/GIP/GLP-1 triple agonist, efocipegtrutide (HM15211) in carbon tetrachloride-induced mouse model of liver injury and fibrosis
European Association for the Study of the Liver (EASL) Congress, 2023
Anti-inflammatory and anti-fibrotic effects by simultaneous activation of glucagon, GIP, and GLP-1 of efocipegtrutide (HM15211) in thioacetamide-induced mouse model of liver injury and fibrosis
European Association for the Study of the Liver (EASL) Congress, 2023
Anti-fibrotic and mortality reduction potential of a novel long-acting glucagon/GIP/GLP-1 triple agonist (HM15211) in preclinical models of idiopathic pulmonary fibrosis
American Thoracic Society (ATS) International conference, 2023
Anti-inflammatory and anti-fibrotic effects of a novel long-acting Glucagon/GIP/GLP-1 triple agonist, HM15211, in TAA induced mouse model of liver injury and fibrosis
European association for the study of diabetes (EASD) 58th Annual meeting, 2022
Direct Anti-inflammatory and Anti-fibrotic Effects of a Novel Long-acting Glucagon/GIP/GLP-1 Triple Agonist, HM15211, in TAA-induced Mouse Model of Liver Injuary and Fibrosis
American diabetes association (ADA) 82nd Scientific sessions, 2022
HM15211, a novel long-acting GLP-1/GIP/Glucagon triple agonist, exhibits anti-inflammatory and –fibrotic effects in AMLN/TAA induced liver inflammation and fibrosis mice
American diabetes association (ADA) 80th Scientific sessions, 2020
A double-blinded, placebo controlled, single ascending dose study for safety, tolerability, pharmacokinetics, and pharmacodynamics after subcutaneous administration of novel long-acting GLP-1/GIP/Glucagon triple agonist (HM15211) in healthy obese subjects
American diabetes association (ADA) 79th Scientific sessions, 2019
Novel combination of GLP-1/GIP/Glucagon triple agonist (HM15211) and once-weekly basal insulin offers improved glucose lowering and weight loss in a diabetic animal model
European association for the study of diabetes (EASD) 54th Annual meeting, 2018
Novel combination of a long-acting GLP-1/GIP/Glucagon triple agonist (HM15211) and once-weekly basal insulin (HM12460A) offers improved glucose lowering and weight loss in a diabetic animal model
American diabetes association (ADA) 78th Scientific sessions, 2018
