Efinopegdutide(LAPSGLP/GCG) is a long-acting glucagon-like peptide 1 and glucagon dual agonist chemically conjugated with constant region of human immunoglobulin via non-peptidyl flexible linker (LAPSCOVERY). A dual GLP-1/glucagon agonist activates both GLP-1 and glucagon receptors as oxyntomodulin, which is an endogenous peptide secreted by cells in the gut in response to nutrient ingestion.

The physiological effects mediated by GLP-1 receptor (enhanced glucose-stimulated insulin secretion, suppression of food intake, and regulation of inflammatory cytokines in liver) and glucagon receptor (suppression of food intake, increased energy expenditure, improved lipid metabolism, and regulation of inflammatory cytokines in liver) suggest a therapeutic potential in subjects with obesity and/or non-alcoholic steatohepatitis (NASH).

In clinical studies, we observed a remarkable weight loss effect with improved lipid profile and several metabolic phenotypes such as cardiovascular and renal function. Furthermore, in preclinical studies, glucagon action on liver such as liver fat burning and improvement in inflammation was recently revealed and these may suggest additional benefits for liver health such as non-alcoholic fatty liver disease (NAFLD) and NASH. Based on this, Hanmi and the licensed partner, MSD, are set to expand the clinical development for NASH besides obesity.

1. GLP-1/Glucagon dual agonism
   • Remarkable body weight loss via synergistic effects of GLP-1 and glucagon
   • Counteraction on glycemic control
   • Liver fat removal by three combined mode of action (energy intake, β-oxidation, and de novo lipogenesis) and Improvement of liver inflammation
2. Weekly injection by application of LAPS technology
   • Extended duration of action via vascular endothelium recycling without effector functions (ADCC and CDC)
   • Targeting first-in-class weekly GLP-1/glucagon dual agonist

Clinical experience with HM12525A includes two phase 1 multiple ascending dose (MAD) studies (NCT02862431 and NCT03235219). Additional four phase 1 studies was completed to assess the effect of HM12525A of titration (NCT03586843) and on cardiac repolarization (NCT03606057) and on PK and safety in subjects with varying degrees of renal function (NCT03546205), and on PK and safety in japanese subjects (NCT03618160). Two phase 2 studies was completed to evaluate safety and efficacy of HM12525A in severe obese patients without or with T2DM (NCT03486392 and NCT03586830).

Potent cholesterol lowering effect by HM12525A, A novel long-acting GLP-1/Glucagon dual receptor agonist

Poster, American diabetes association (ADA) 76th Scientific sessions, 2016

The ultra-long acting ^LAPSGLP/GCG dual agonist, HM12525A, demonstrated safety and prolonged pharmacokinetics in healthy volunteers: a phase 1 first-in-human study

Poster, European association for the study of diabetes (EASD) 51st Annual meeting, 2015

Potent weight loss mechanism and improvement of NASH by the long-acting GLP-1/Glucagon receptor dual agonist HM12525A

Poster, European association for the study of diabetes (EASD) 51st Annual meeting, 2015

A novel long-acting GLP-1/Glucagon dual receptor agonist: Potent weight loss mechanism and improvement of NASH by HM12525A

Poster, American diabetes association (ADA) 75th Scientific sessions, 2015

Lipolytic, energy expenditure, and insulinotropic effects of HM12525A: A novel long‐acting GLP‐1/Glucagon dual agonist

Poster, American diabetes association (ADA) 74th Scientific sessions, 2014

Poster, European association for the study of diabetes (EASD) 50th Annual meeting, 2014

The novel long-acting GLP-1/Glucagon dual agonist HM12525A reduces body weight and improves glycemic control in rodent models

Poster, American diabetes association (ADA) 73rd Scientific sessions, 2013

Sep 03, 2020

Hanmi Pharmaceutical and Merck Enter into Licensing Agreement to Develop Efinopegdutide

Jan 16, 2020

[38th J.P. Morgan healthcare conference] Hanmi, ready to lead global pharmaceutical market with innovative R&D pipeline