80-LB: Evaluation of the Pharmacokinetics of Glucagon-Like-Peptide-1 (GLP-1) Receptor Agonist Delivered through the BIOJET Oral Biotherapeutic Delivery Platform in Porcine Model

Glucagon-like-peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and suppress glucagon release. Semaglutide is a GLP-1 agonist currently injected subcutaneously or taken orally to treat type 2 diabetes and for weight management. However, oral administration of protein/peptide therapeutics has proven difficult due to the harsh conditions of the upper gastrointestinal tract (GIT) and poor absorption rates in the small intestine. The BIOJET™ oral biotherapeutic delivery platform is an ingestible drug-device combination developed to increase drug bioavailability via needleless jet injection in the proximal small intestine following oral administration. Previous testing of an earlier, autonomously triggered version of the device in animal models was presented at ACG 2022. In this study we evaluated the pharmacokinetics (PK) of semaglutide delivered through the BIOJET device in a porcine model. Due to prolonged and variable gastric residence times in the porcine model, devices filled with semaglutide (~1mg) were administered by intraduodenal (ID) endoscopic placement and activated in the proximal small intestine of Yucatan swine. PK blood sampling was performed from 0 to 240 hours post-dose to evaluate systemic exposure of semaglutide. Seven of eight (7/8) devices were successfully placed and activated in the duodenum. All seven animals showed detectable drug levels up to ten days post-dosing and had an oral bioavailability average of 37% ± 15% (CV: 40%), ranging from 19%-60% compared to IV control. No significant clinical signs were observed in the animals. This study demonstrated that administration of the BIOJET device has the potential to achieve a magnitude greater bioavailability than the currently marketed oral semaglutide (< 1%). The BIOJET device could provide an alternative for the oral administration of large molecules and may improve patient compliance.