This forum features two presentations: Preclinical Pharmacokinetics, ADME, Formulation | Markus Kohlman, Sanofi-Aventis Preclinical Pharmacology, Selecting animal disease models, Toxicology | Peter Florian, Sanofi Aventis The research and development (R&D) process of a novel medical entity (NME) follows a structured process. After defining a new target opportunity that can be developed into a new drug substantial effort is invested into understanding the biology and profiling NMEs in vitro. Based on potency and a favorable ancillary profile (e.g. eADME, pharmacokinetics, preclinical safety) single NMEs are nominated to proof efficacy in vivo. The typical in vivo screening cascade encompasses acute / mechanistic models before moving into complex animal disease models. Usually, two species (rodent and non-rodent) are utilized to increase the preclinical level of confidence that the NME is biologically effective. Compound plasma exposure is determined to allow for PD/PK modeling and subsequent human dose prediction. In addition information on distribution and metabolism of the candidate and potential drug-drug intercations are acquired in-vitro and in-vivo in preclinical studies. In parallel to exploring the NME pharmacokinetics and efficacy in vivo toxicology profiling takes place to fulfill regulatory requirements prior to first in human studies. In a translational research approach biomarker development is pursued to confirm target occupancy and target engagement prior to clinical proof of concept in Ph2 studies.
During the two presentations the different stages of the R&D process will be outlined and examples describing the challenges to develop a novel NME are shared.