Current drug discovery workflows are inefficient. 90% of therapeutic agents reaching clinical trials fail, predominantly because traditional laboratory experiments fail to adequately predict a drug’s safety or efficacy in human.
Building more predictive, human-relevant models is key to reducing drug attrition rates and the financial burden to pharmaceutical companies, however, this is not an insignificant task. Microphysiological systems (MPS), also known as organ-on-a-chip (OOC), have been designed to meet this need, filling the gap between preclinical testing and the clinic. MPS enable us to grow 3D organs and tissues from human cells with flow circulating through them to simulate blood and deliver nutrients. These lab-cultured mimics function and respond to drugs in the same way as in humans.
Currently, single-organ models that recapitulate either individual organ functions (such as the liver), or routes of entry into the body (such as gut and lung), are most common. While traditional in vitro approaches fail to recapitulate a human organs’ phenotype, architecture and function for more than seven days, MPSs extend culture longevity up to a month, enabling studies that were not previously possible, such as the ability to profile phase I and II drug metabolism, characterise slowly metabolised compounds, identify potential metabolite-driven toxicity, or detect chronic toxicity. In this presentation, we will discuss the use of liver and lung MPSs for drug safety, disease modelling and efficacy and provide insights into what is coming next to further improve preclinical drug development workflows.
1. Identify preclinical drug development challenges.
2. Introduce MPSs and how/where they fit into the preclinical workflow.
3. Demonstrate how MPSs provide translatable insights into drug safety and efficacy.