Traditionally, in First in Human clinical trials the primary/secondary endpoints are concerned with safety. By expanding these studies to include exploratory biomarkers it is possible to gain added value, as such biomarkers can indicate efficacy and confirm mode of action of the therapeutic. Incorporating this information from an early stage can assist in go/no-go decisions and can greatly increase the likelihood of success. We show here how we currently use this strategy to monitor biomarkers in a translation manner using LPS induced immune responses as an example. In vitro assays using human whole blood and PBMCs are routinely used to screen test compounds and determine their influence at the gene and protein level, using luminex (cytokines) and nanostring platforms. This can be followed by in vivo pharmacology PD models (small rodent LPS challenge) to further refine the compound selection and develop suitable readouts such as Multiplex cytokine analysis. When a candidate compound then progresses to First In Human clinical trials, we can support the inclusion of exploratory biomarkers using ‘uplifted’ Good Clinical Laboratory Practice (GCLP) level assay validation, to ensure reliable clinical data. At this stage, a more focussed panel of cytokines can be selected and measured either directly in plasma or secondary to ex vivo stimulation. In addition, the use of flow cytometry and ELISPOT support investigations of T cell modulating therapies. Such a strategy provides early indications on whether a therapeutic is hitting it’s expected target in man.