Preclinical Development – Chemical
2019 PharmSci 360
Inflammation is an ill-understood root cause of many drug side effects. Preclinically, cell culture systems often fail to recapitulate the sophisticated interplay between cell subsets, architecture and time. Animal models may poorly translate due to species differences, are inaccessible to mechanistic investigation or ethically concerning. Here we present our efforts to leverage human cell-based in-vitro systems to understand mechanisms and safety liabilities, scaling to a corporate early discovery pipeline. We outline how we combine commercial microfluidic platforms (e.g. Mimetas organoplates) with conventional culture systems to model intestinal barrier leakiness, neutrophil recruitment or stroma remodeling. To understand immune cell triggered vascular leakage, we employ static and microfluidic endothelial cell systems that are scalable, inspectable and sensitive to therapeutic immune modulation. In summary, we strive to adopt available technology to our portfolio specifics, to render in-vitro system and organ-on-a-chip approaches a contributing instance of the drug discovery value chain.