SAT236 Pharmacokinetics (PK) And Pharmacodynamics (PD) Of The Parathyroid Hormone Analog PTH (1-34) (Teriparatide) Delivered Via An Orally Administered Robotic Pill (RT-102)

Disclosure: K. Horlen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. K. Kaminskaya: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Yamaguchi: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. L.C. Fung: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. H. Kennedy: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. S. Nguyen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Dasari: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Toledo Vo: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. B. Archana: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. N. Patel: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. D. Mohan: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. B. Syed: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A.K. Dhalla: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M. Imran: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M.A. Hashim: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. Background: An orally administered robotic pill (RP) protects the drug from digestion during transit through the gastrointestinal tract before painlessly injecting the drug trans-enterically into the peritoneal space. Although parenteral, this unique delivery route can result in altered PK/PD profiles as drug absorption is primarily via mesenteric vasculature which drains into the portal vein. Here we report on two nonclinical studies which, 1) in awake canines, compared the PK profiles of orally delivered teriparatide via the RP (RT-102) versus subcutaneous (SC) injections; and 2) in an ovariectomized (OVX) rat model of osteoporosis, compared the PD (osteoanabolic) effect of intraperitoneal (IP) vs SC administered teriparatide on bone mineral density (BMD).Methods:PK Study: Beagle dogs (n = 43) received a single RT-102 capsule orally containing 20, 40, 80, or 160µg of teriparatide or a SC or intravenous (IV) injection of 20µg of the FDA-approved PTH(1-34) commercial product (Forteo®). Teriparatide concentrations in serial blood samples (collected for up to 300 minutes) were quantitated via a validated ELISA.PD Study: OVX Sprague-Dawley rats (n=50) underwent an 8-week bone depletion period followed