Current landscape and future opportunities in implementing human microphysiological models in pre-clinical drug development

Recorded On: 02/07/2018

The pharmaceutical industry is facing great challenges still owing to high R&D costs and low overall success rates of clinical compounds during drug development. In phase I clinical trials the majority of failures are due to safety related issues. While more than 50% of failures in phase II and III clinical trial are due to a lack of efficacy and a quarter due to safety issues, where safety includes those failures that were due to an insufficient therapeutic index.  Drug failures in clinical trials are mainly due to the poor translational relevance and clinical predictive power of existing preclinical models which include human cell based in vitro and animal models. The drug discovery community has recognized the critical need for new testing approaches to generate more translatable and reliable predictions of drug efficacy and safety in humans. This has driven the recent advancements in cell biology, tissue engineering, biomaterials, and emerging platforms such as microfabrication, microfluidics and bioprinting in the development of innovative in vitro technologies that more closely recapitulate human tissues and organs. These three dimensional (3D) human in vitro models such as 3D spheroids/organoids, organs-on-chips, and bioprinted tissues could provide the basis for preclinical assays with greater translatability and predictive power. They could be applied for greater insight into mechanisms of human disease, mechanisms of toxicity or for early confirmation of new therapy efficacy. I will provide a perspective on the breadth of new opportunities available for the integration of these 3D human in vitro models within drug discovery and the related challenges in adoption. I will introduce key technological background and advantages/limitations of each novel 3D human in vitro models with examples from recent studies or cases. Furthermore, I will discuss the essential validation process for these 3D human in vitro technology and the importance of integration of various models and the translatability to the clinic. I will conclude by examining how 3D in vitro technology will begin to tackle major technical challenges at the critical steps of conventional and the evolving drug discovery process.

Jason Ekert

R&D Platform Technology & Science, GlaxoSmithKline

Dr Ekert leads an integrated enterprise strategy for sustained, portfolio driven growth in R&D application of complex human-relevant and translatable complex in vitro models. Dr Ekert’s group drives the coordination and prioritization of development and integrated use of complex in vitro technologies for efficacy, safety and biometabolism studies. Dr Ekert received his PhD in Medical Science from Adelaide University in Australia. He performed post-doctoral training at the University of California, Davis and Coriell Institute for Medical Research. Before coming to GSK Dr Ekert worked for 11 years at Janssen BioThereapeutics in early biotherapeutic drug discovery in target discovery, drug validation and mechanism of action studies applying 3D cell cultures, iPSCs and primary cells in complex cell-based assays across multiple therapeutic areas. His current focus at GSK is to improve predictive validity of early preclinical models leading to better characterized molecules, decreased R&D cycle time and a reduction in attrition.

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