Assessing the performance of an oral biotherapeutic delivery system (OBDS) using intra-duodenal endoscopy delivery in Yucatan minipigs

This preclinical study developed a method for administration of semi-autonomous OBDS capsules in the swine model, due to inability to swallow capsules, and provides preliminary pharmacokinetic data on PGN-001 in swine.

Oral delivery of biologics, peptides, and nucleic acids has proven difficult due to the harsh conditions of the upper gastrointestinal tract and poor absorption in the small intestinal mucosa. The current state of-the-art technology for a successful oral protein delivery provides around 1% bioavailability when delivered as an oral tablet (Rybelsus® oral Semaglutide).

We aim to develop an oral biotherapeutic delivery system (OBDS) that avoids drug degradation in the upper gastrointestinal tract and increases bioavailability via liquid jet delivery to the small intestine. The OBDS capsule operates autonomously and provides a needleless injection to deposit the liquid drug payload into the submucosal space of the proximal small intestine.

Biora is developing the PGN-OB1 program, which consists of a variant of adalimumab (PGN-001) delivered via liquid jet administration to the small intestine via the OBDS capsule, for the treatment of inflammatory conditions. An oral variant of adalimumab presents an opportunity for the many patients who would like to avoid painful injections.

In this study, our objectives were to:

  1. Develop a method to endoscopically place the OBDS device into the small intestine of swine, due to their inability to swallow capsules, which then allows natural transit, triggering, and deployment of the device.
  2. Evaluate the pharmacokinetics of PGN-OB1 in swine via endoscopic placement, natural transit, and autonomous deployment in vivo.

What did we find?

All OBDS capsules were successfully advanced through the pyloric sphincter, without early deployment, and were released in the proximal duodenum to transit naturally and autonomously deploy in vivo.

Eight animals showed detectable drug levels of PGN-001 with an oral bioavailability average of 25% (range from 7-55%), excluding one animal with a late deployment at 72 hours post-dose.

In this study, we demonstrated that PGN-OB1 can achieve as high as 55% bioavailability of a variant of adalimumab in swine, which is a magnitude greater than current oral protein or peptide delivery technology in the market, and at levels much closer to the subcutaneous route of administration estimated in human trials.1

Poster presented at Controlled Release Society Annual Meeting, July 13-14, 2022

View the Poster

references

  1. Lee SN, Stork C, Smith J, et al. Assessing the performance of an oral biotherapeutic delivery system (OBDS) using intra-duodenal endoscopy delivery in Yucatan minipigs. Poster presented at: Controlled Release Society Annual Meeting, July 13-14, 2022, Montreal, Canada.