TRANSLATIONAL RESEARCH CORE – ABSTRACT The Translational Research Core will support Project Teams to select and advance promising clinical candidates by conducting essential in vitro and in vivo ADMET (absorption, distribution, metabolism, excretion and toxicology) studies. This will be achieved primarily by specialist teams in Pharmacokinetic Sciences (PKS) and Preclinical Safety (PCS) housed at Novartis. PKS teams will provide in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) data. To achieve this, they will contribute in depth knowledge of preclinical pharmacokinetics, drug metabolism, and clinical pharmacology to inform compound design, formulation development, and optimal human dosing regimens. Specifically, the Translational Research Core will bring to bear a cross-disciplinary team (including expertise in biotransformation, transporters, drug-drug interactions, plasma protein binding, in vivo models, and more) to help select and optimize potential candidates for drug delivery. The PKS function will also conduct toxicokinetics studies to calculate therapeutic margins and determine safe starting doses for first-in-human studies. Further, it will deploy cutting edge machine learning, translational, biophysical and other modelling techniques to predict human efficacious exposures based upon available in vitro and in vivo pharmacokinetics, pharmacology and toxicology data. PCS teams will provide in vitro and in vivo preclinical safety data from early discovery to registration trials and assure patient safety is fully compliant with requirements by stringent regulatory agencies. PCS specialists will conduct a wide range of in vitro and in vivo exploratory/mechanistic and regulatory toxicology studies tailored to the specific needs of each project, eventually assembling a complete regulatory toxicology package to identify hazards and establish safety margins. This group will conduct non-GLP screening assays and GLP studies to determine genotoxicity, phototoxicity, and safety pharmacology liabilities at the Development Candidate (DC) selection stage and as part of IND applications. In summary, the Translational Research Core will play a pivotal role in bridging drug discovery and translation to the clinic by helping evaluate, differentiate, and ultimately select the best molecules.