Oral delivery of therapeutic peptides reduces patient burden and increases adherence. Nevertheless, existing technologies have limited performance and versatility. AdOral® is an oral delivery platform based on non-specific MoA (Mechanism of Action) via intestine paracellular passage leading to improved absorption.The MoA of AdOral® and its permeation effect on several peptides were evaluated in vitro, using gold-standard Caco-2 monolayers. Then, AdOral® platform was evaluated in vivo, in rat and dog. In vitro, apparent permeability coefficient of insulin lispro and semaglutide were improved by 16 and 25 vs. control, mostly due to the concentration-dependent and reversible tight junctions opening, leading to paracellular passage of peptides. AdOral® has a distinct MoA and higher permeation enhancing properties compared to SNAC (effective concentration of 10 mM vs. 100 mM for SNAC). In rats, AdOral® had a good safety profile after daily oral administration for 2 weeks.In dogs, AdOral® capsules allowed oral absorption of semaglutide and insulin lispro, demonstrating the versatility of the platform. AdOral® semaglutide showed 2.5-fold improvement in median semaglutide AUC0-5h and bioavailability vs. Rybelsus®. Thus, AdOral® is a versatile and performant platform that could lead to cost-effective oral formulations for a wide range of therapeutic peptides.
U. Naessens: Employee; ADOCIA. Stock/Shareholder; ADOCIA. A. Gutjahr: Employee; ADOCIA. Stock/Shareholder; ADOCIA. G. Blache: Other Relationship; ADOCIA. S. Hakim: Employee; ADOCIA. Stock/Shareholder; ADOCIA. A. Marechal: Employee; ADOCIA. Stock/Shareholder; ADOCIA. R. Noel: Employee; ADOCIA. Stock/Shareholder; ADOCIA. M. Gaudier: Employee; ADOCIA. Stock/Shareholder; ADOCIA. O. Soula: Board Member; ADOCIA. Stock/Shareholder; ADOCIA.
