FP02-3 The Long-Acting Dual GLP-1/Glucagon Agonist, Mod-6030 Improves Glycemic Control and Induces a Prolonged Weight Loss in Diet Induced Obesity Mice Following a Once Weekly Administration

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP02-Obesity and Diabetes: Drugs & Interventions
Basic/Translational
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:10 AM
Room 303 (Moscone Center)

Poster Board SAT-787
Oren Hershkovitz*1, Ahuva Bar-Ilan1, Gili Hart2 and Eyal Fima2
1Prolor-Biotech, Nes-Ziona, Israel, 2Prolor Biotech, Nes Ziona, Israel
Background: 

Prolor Biotech Inc. is a clinical stage public company developing long acting therapeutic proteins and peptides, utilizing licensed platform technologies. Reversible PEGylaton technology was applied for the development of a long acting oxyntomodulin (OXM, a dual GLP-1/Glucagon agonist) for treatment of type 2 diabetes and obesity. The technology is based on a synthetic bi-functional spacer that indirectly links between the PEG moiety and the peptide. Once injected, the intact OXM is slowly released, enabling a prolonged peptide exposure while maintaining its biological activity and the ability to pass throw the blood brain barrier (BBB).

Objectives:

To determine the efficacy and prolonged anti-diabetic and anti-obesity activity of reversibly PEGylated GLP-1/Glucagon agonist (MOD-6030) in Diet Induced Obesity (DIO) mice.

Methods:

DIO C57BL/6J mice (n = 8/group) were treated (s.c.) twice daily with vehicle (PBS) and OXM (6000nmol/kg) or once a week with vehicle (PEG-SH), non-reversible PEGylated OXM (6000nmol/kg) and MOD-6030 (reversible PEGylated OXM) (6000nmol/kg)  for 30 days. Body weight and food intake were monitored daily and OGTT was performed on Day 2 and Day 23. At the end of the study, plasma samples were analyzed for glucose, insulin and cholesterol levels followed by body composition analysis.

Results:

Twice daily injections of non-modified OXM inhibited food intake by 12% and induced weight loss by 16%. Remarkably, administration of MOD-6030 having the same OXM peptide content per dose but injected only once a week, manifested a substantial inhibition of food intake of 29% and marked weight loss of 28%. Body composition analysis confirmed that observed weight loss results from a specific fat reduction. Administration of non-reversible OXM had no effect on cumulative food intake and body weight, emphasizing the importance of the release of the intact OXM from the PEG moiety which enables it to penetrate throw the BBB. MOD-6030 profoundly improved glucose tolerance, non-fasting glucose levels, and insulin blood levels. Finally, MOD-6030 significantly reduced terminal plasma cholesterol levels by 56% as compared to vehicle group.

 

Conclusion:

Reversibly PEGylated OXM markedly induces weight loss while improving the glycemic control and the lipidic profile in DIO mice following a once weekly injection, suggesting that MOD-6030 is a potent long acting dual GLP-1/Glucagon for the treatment of obese and type 2 diabetic human subjects.

Nothing to Disclose: OH, AB, GH, EF

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm