2008-P: BioChaperone Glucagon Exenatide (BC Glu Exe), a Stable Combination of Glucagon (Glu) and Exenatide (Exe) Achieved Larger Body Weight (BW) Loss than Exe Alone in DIO Mice

Abstract

Figure 4 Cumulated food consumption (n=10)o The coformulation BC Glu Exe induced a significant BW loss compared to vehicle (25%) and to exenatide alone (15%) (Figure 3). In this group the total food intake was intermediate between vehicle and exenatide without statistical significance ( Figure 4) although the BW loss was superior to both groups. This confirms the glucagon effect on weight loss in the combination. This effect can be attributed to an increase in energy expenditure. 50 60 70 80 90 100 110 120 -7 -5 -3 -1 1 3 5 7 9 11 13 15 BW (%) Study day Human formulation: BC Glu Exe in vials → Visual inspection of the formulation at 4°C and 37°C.o BC Glu Exe coformulation is a clear and colorless solution, essentially free of particle, after storage in vials at 4°C for at least 13 months and at 37°C for at least 12 weeks. → Chemical stability after 4 weeks storage at 37°C in vials. o Both glucagon and exenatide recoveries are around 90 % o Glucagon and exenatide impurity contents are of 5.4 and 7.6 % respectively (Figure 2) Mice formulation: BC Glu Exe in cartridges → Visual inspection of the formulation at 4°C and 37°C.o BC Glu Exe coformulation is a clear and colorless solution, essentially free of particle, after storage in cartridges at 4°C for at least 13 months and at 37°C for at least 12 weeks → Chemical stability after 2 weeks storage at 37°C in cartridges o Glucagon and exenatide impurity contents are of 3.6 and 5.8 % respectively (Figure 2) Figure 2. Glucagon and exenatide impurity content in BC Glu Exe coformulations designed for mice in vivo studies or human clinical trials. Animal StudyThe treatments were well tolerated in all groups without any clinical finding reported during the study.Exenatide alone, used as a refence and infused for 14 days led to a significant 10% decrease in BW compared to vehicle (Saline) (Figure 3). The total food intake in this group was significantly decreased when compared to the vehicle (Figure 4). AbstractOver the last decades, obesity and its associated consequences have become a major health issue worldwide. GLP-1 Receptor Agonists (GLP-1 RA) are one of the few treatment options currently available, but achieve limited weight loss.A combination of human glucagon (Glu) and GLP-1 RA is expected to provide a superior body weight (BW) reduction than GLP-1 RA alone. GLP-1 RA acts in the brain to induce satiety while Glu has a lipolytic and thermogenic effect in liver and adipose tissues. BioChaperone (BC) proprietary technology allows the solubilization and stabilization of poorly soluble and/or unstable peptides, such as Glu, at neutral pH and thus the combination of Glu and GLP-1 RA.A combination formulation of glucagon and exenatide (BC Glu Exe) was developed. Such combination is physically and chemically stable for at least 4 weeks at 37°C in cartridges. It was tested in vivo against reference exenatide and vehicle in diet induced obese (DIO) male mice. Mice were dosed with a subcutaneous continuous infusion of vehicle, Exe or BC Glu Exe via osmotic minipumps.After 14 ...