Dr Paul Newbold
Humanising Drug Discovery to Make Earlier & Better Stop/Go Decisions in Pharma R & D
Drug Discovery and Safety Assessment has traditionally relied on use of various data ranging from in-vitro (human and animal) to in-vivo (animal and human) experimental data to progress novel targets. Although many of these paradigms will not change in the immediate future, there is increasing understanding that there are significant differences between species (e.g Tegenero) and that certain experimental data need confirmation in a number of experimental systems (including human) to try and predict efficacy and safety risk in humans. These data are absolutely critical for identification of novel and better therapies for unmet medical need.
Newer technologies are emerging that allow us to see molecular events that translate to cellular events and which might better predict behaviour of novel targets (small molecules and biologicals) in the in-vivo setting in humans. Some of these methods now supersede the need for some in-vitro and in-vivo experiments in animals, although it is very unlikely that we will be able to get away from some work in animals, particularly when looking for off-target effects induced by certain chemical classes. This remains an essential requirement for small molecule drug discovery and safety assessment for secondary pharmacology, safety pharmacology and chemical toxicity will always be required as part of the regulatory process..
Irrespective of the size of the compound or molecule, primary pharmacology will always need validation in the appropriate species and receptor homology, expression, function, biological redundancy will all need addressing as we progress through the drug discovery and safety assessment process to eventual testing in the correct patient population in humans.
Newer technologies such as in-vivo cellular imaging, Taxiscan, Cellomics, Microdosing, Microdialysis, Multiplex biomarkers methodologies, Microfluidics, Omics and Imaging technologies (e.g PET) can all be applied to human tissues and cells and in the intact in-vivo human setting to provide a rich array of data which can better inform us about our targets and compounds. Some of this experimental data will be described from human studies to help understand the translation of our targets from preclinical to the clinical setting. Some of these methodologies are particularly suited to novel complex targets and examples will be provided how this has allowed better decision making.