Novel Oral Molecules: Preclinical to Clinical Translation of Absorption-Disposition

This rapid fire session will delve into the preclinical ADME properties of novel oral molecules and their successful translation into clinical proof of concept. We will explore recent examples from diverse molecular classes, e.g. macrocyclic peptides (MK-0616), PROTACS (ARV-110), selective estrogen receptor degraders (Elacestrant), non-peptide GLP-1 agonists (Orforglipron), a targeted peptide IL-23R antagonist (Icotrokinra), etc. We will summarize key preclinical ADME studies, exploring both commonalities and differentiation in achieving optimized oral bioavailability and a favorable overall disposition. We will also provide an overview of key aspects of clinical PK, including extent of absorption and oral exposures driving pharmacodynamics and efficacy. These translational case studies will highlight strategic drug development considerations and how R&D teams resolved obstacles.