HFG1 is an mRNA based GLP-1R agonist encoding a fusion protein of a GLP-1 analogue and a pH sensitive binder of human FcRn. The mRNA is encapsulated inside lipid nano-structures (LNPs) designed for subcutaneous gene delivery and local transfection, and the proteins expressed would be secreted and distributed into systemic circulation. In order to characterize the HFG1 activities in vivo, five monkeys with naturally occurred diabetes (FPG≥9.69 mg/dl, HbA1c≥5.6%) were selected to receive one subcutaneous injection of LNPs of slightly variable compositions containing about 0.5-1.0mg mRNA. The monkeys were closely monitored for 60 days and no behavior changes were observed except that they all had greatly reduced food uptake on the first few days after injection. By D56 they lost an average of 0.22kg each. Blood samples were collected at various time points and assayed in a GLP-1R/CRE Luciferase Reporter Cell system for GLP-1 equivalent activities. Figure 1 plotted the individual measurements (solid dots) and average value changes (solid line). The HbA1c% levels were assayed by Suzhou Xihua Scientific Co. and shown as open squares. Even though some time points are missing (TBD), the trend of HbA1c% reduction after a single HFG1 injection is significant.
F. Xu: Employee; highfield. K. Wu: Employee; high field. L. Zhang: Employee; HighField Biopharmaceuticals Corporation. Y. Dai: Employee; HighField Biopharmaceuticals Corporation. Y. Xu: Employee; Hangzhou HighField Biopharm. Stock/Shareholder; Hangzhou HighField Biopharm.
