Oral Delivery of beyond Rule of 5 molecules

Previously undruggable targets can be addressed by using new modalities (e.g. peptides, protein degradres, biologics), which leads to targeting of new diseases, ultimately giving hope to patients. At the same time, due to their low enzymatic stability and/or low intestinal permeability, these molecules are mainly administered by needles. The approval of oral Semaglutide (Rybelsus) generated a new interest in the field of oral delivery of these so-called Lipinski’s beyond role of 5 molecules. Oral delivery of these “non-oral” compounds increases patient acceptance, compliance and decreasing sense of being sick, eventually leading to better treatments. Several formulation and drug delivery strategies are applied to Bayer’s pipeline molecules to improve oral bioavailability. These strategies are screened with a mix of in vitro (e.g. enzymatic degradation testing and permeability testing using caco-2 cells) and in vivo tools (intra-intestinal rat PK studies and dog and pig PK studies). Formulation strategies have shown to improve oral bioavailability. Further strategies are currently being applied to improve bioavailability to reach a commercially viable product.