BC Combo is a co-formulation of prandial insulin lispro (25%) and basal insulin glargine (75%) with a rapid “prandial“ insulin component and prolonged flat “basal“ component compared to LMx. In this study the effects of BC Combo on PPG vs. LMx and G+L were investigated. Thirty-nine T2DM subjects (mean±SD age 60.8±7.5 years and HbA1c 7.97±0.6%) were randomized to receive the three insulin combinations immediately before a standardized solid meal test (MMT, 20% protein 30% fat 50% carbohydrates) in a double-blind, double-dummy, cross-over design. The individual insulin dose was the same for each visit day (mean 0.62 U/kg). BC Combo demonstrated improved PPG compared to LMx (Figure, reduction ∆AUCBG,0-2h of 18%, p=0.0009) and G+L (reduction ∆AUCBG,0-2h of 10%, p=0.0450). The proportion of subjects experiencing documented symptomatic hypoglycemic events (plasma glucose <70 mg/mL) over 24h was numerically lower with BC Combo (15.8%) vs. LMx (32.4%) and G+L (21.6%). The total insulin PK profile of BC Combo showed a faster time to insulin peak and a lower exposure in the late prandial phase (2-6 h) than LMx and G+L. In conclusion, BC Combo demonstrated superior PPG control in T2DM subjects with numerically fewer subjects experiencing symptomatic hypoglycemia compared to both LMx and separate G+L. Disclosure T. Heise: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Janssen Research & Development, MedImmune, Merck Sharp & Dohme Corp., Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi, Senseonics, Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk A/S, Mylan. Speaker's Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi. L. Plum-Moerschel: None. C. Mégret: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. T. Herbrand: None. V. Vacher: Employee; Self; ADOCIA. E. Anastassiadis: None. O. Klein: None. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. S. Glezer: Stock/Shareholder; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Sanofi. Employee; Self; ADOCIA, Novo Nordisk Inc.. Employee; Spouse/Partner; Pfizer Inc., Teva Pharmaceutical Industries Ltd.. Stock/Shareholder; Spouse/Partner; Teva Pharmaceutical Industries Ltd.. B. Alluis: None. G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA.

Pramlintide (Symlin®) is currently used on top of mealtime insulin therapy by T1D or T2D patients to achieve a better control of post-prandial glucose excursion. Indeed, pramlintide affects the rate of postprandial glucose appearance by slowing down gastric emptying, reducing postprandial glucagon secretion and modulating satiety, which affects caloric intake. Nevertheless, the use of pramlintide is currently limited as it cannot be combined with prandial insulin due to formulation pH incompatibility and results in a high burden of the number of injections. BioChaperone (BC) technology stabilizes pramlintide in aqueous solution at neutral pH and enables a pramlintide - prandial insulin co-formulation. BC pramlintide-human insulin (BC Pram Ins) formulation is physically and chemically stable for at least 6 weeks at 30°C and 9 weeks at 25°C. Physical stability was evidenced by visual inspection and MFI analysis. Chemical stability (recovery measured by RP-HPLC and high molecular weight species measured by SE-HPLC) was similar to that of commercial Humulin® and Symlin®. Under simulated in-use pump conditions at 37°C, BC Pram Ins formulation shows excellent physical and chemical stability for at least 1 week, with insulin and pramlintide recoveries higher than 95% and a formulation essentially free of particles. The pharmacokinetics of pramlintide was evaluated following single subcutaneous administration (0.1875 U/kg insulin, 1.125 µg/kg pramlintide) of BC Pram Ins formulation and pramlintide co-injected with human insulin (separate injections) to fasted healthy pigs. BC Pram Ins shows a slower absorption of pramlintide (LSM ratio [95% CI] ΔAUC Pram0-30min : 0.45 [0.20; 1.05]) while the late exposure to pramlintide is higher (ΔAUC Pram60-180min : 2.65 [1.44; 4.90]) compared to the separate injections. In conclusion, the in-vitro and preclinical PD properties of BC Pram Ins support its clinical development to afford a better mealtime treatment for T1D and T2D patients. Disclosure G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. A. Geissler: None. Y. Meyer: None. A. Ranson: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. C. Fortier: None. O. Soula: Board Member; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. R. Soula: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Board Member; Self; Cellnovo. B. Alluis: None. R. Charvet: None.

BioChaperone Lispro (BCLIS) is an ultra-rapid insulin lispro (LIS) formulation designed to better mimic the physiological timing of prandial insulin action. The primary objective of this study was to compare the PPBG after administration of BCLIS and LIS in subjects with type 1 diabetes.