Cheryl Stork, PhD1, Shaoying N. Lee, PhD1, Jeffrey A. Smith, PhD2, Bryan Smith, MS1, Nelson Quintana, BA1, Chris Wahl, MD, PhD1, Sharat Singh, PhD1 1Biora Therapeutics, San Diego, CA; 2Biora Therapeutics, Irving, TX
Introduction: Biologics/peptides/nucleic acids are highly effective drugs; however, oral delivery of these therapeutics has proved to be difficult due to the harsh conditions of the upper gastrointestinal tract (GIT) and the poor absorption rate in the small intestinal mucosa. We aim to develop an oral biotherapeutic delivery system (OBDS) that prevents drug degradation in the upper GI and increases bioavailability via submucosal injection. The OBDS capsule operates autonomously and triggers a needleless injection to deposit the liquid drug payload into the submucosal space of the proximal small intestine for absorption. The objective of this study was to assess the autonomous trigger function and performance in the beagle dog model.
Methods: Two versions of autonomous OBDS capsules (Type 1 and 2) were filled with contrast reagent, iohexol (OMNIPAQUE™ 350), and orally dosed to beagle dogs. Fluoroscopy images were taken every 5-15 mins post-dose to visualize capsule deployment of iohexol to assess the deployment time and approximate location post gastric emptying in the intestine. In parallel, OBDS capsules with black India ink were inserted into intact sections of the small intestine in a wet chamber and manually triggered to compare ink deposition on ex-vivo small intestine tissues of dog vs. swine vs. human.
Results: We observed 10 out of 12 capsules dosed orally deployed approximately at the small intestine (Figure 1), one deployed in the colon, and one did not deploy due to manufacturing defects. The overall triggering time was consistent in each group, with trigger type 1 capsules having an average deployment of 1h and 8 min ± 5 min post gastric emptying (N=7), approximately 14 minutes faster than trigger type 2 capsules (N=4). Lower and less consistent ink deposition on the beagle dog GI tissue was observed compared with swine or human tissue (Figure 2). This suggests a lower capacity of canine tissue to accept a liquid bolus as expected due to differences in canine intestinal anatomy compared to humans and swine.
Discussion: We have successfully shown ≥ 83% deployment accuracy of autonomous OBDS capsules in the small intestine without early deployment in the stomach. These results suggest the beagle dog model can be utilized to assess the consistency and reproducibility of the OBDS capsule. However, an assessment of submucosal injection will need to be performed in the swine model for human translation of the oral bioavailability.
Figure: Figure 1. In-Vivo and Ex-vivo performance of OBDS device. A. Representative image of capsule deployment in the small intestine. The drug module is noted with the red arrow. The layer of tungsten on the piston is noted by the white arrow. B. Ex-vivo tissue deposition of India ink in intact bowel tissue in dog vs swine vs human tissue.
Disclosures:
Cheryl Stork: Biora Therapeutics – Employee.
Shaoying Lee: Biora Therapeutics – Employee. crohn's and colitis foundation – Grant/Research Support.
Jeffrey Smith: Biora Therapeutics – Employee.
Bryan Smith: Biora Therapeutics – Employee.
Nelson Quintana: Biora Therapeutics – Employee.
Chris Wahl: Biora Therapeutics – Employee.
Sharat Singh: Bioratherapeutics – Employee.
Cheryl Stork, PhD1, Shaoying N. Lee, PhD1, Jeffrey A. Smith, PhD2, Bryan Smith, MS1, Nelson Quintana, BA1, Chris Wahl, MD, PhD1, Sharat Singh, PhD1. D0637 - Development of Ex Vivo and In Vivo Models to Assess the Performance of an Oral Biotherapeutic Delivery System Capsule, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.
