Head of Preclinical Development ORIC Pharmaceuticals South San Francisco, California
In vitro and in vivo models to explore the disposition of drug candidates have advanced significantly. Yet, there continues to be many unknowns and pitfalls associated with forecasting human ADME properties. Ideally, in vivo preclinical models would serve as sufficient surrogate to assess the human disposition of drug candidates. Unfortunately however, in reality, preclinical species are not useful in estimating human PK parameters, in part, because there can be striking species differences in the expression and activity of drug metabolizing enzymes and drug transporters, as well as their regulatory pathways. To address this disconnect, genetically modified animal models have been developed with the hope of bridging the gap between the preclinical models to the clinic. There are several varieties of models which have been identified or developed, ranging from genetically-deficient to genetically-engineered knockout and humanization of a particular ADME-related proteins. This presentation will showcase several genetically modified animal models and demonstrate how they have been used to elucidate the mechanism of ADME-related phenomenon, as well as their potential utility in complementing current drug research.
understand the advantages and disadvantages of the genetically modified models.
articulate the utility of genetically modified models in drug research.
use the learnings to explore opportunities to implement genetically modified models in their research.