Assay Development and Screening
Podium
Jason Ekert, PhD
Head, Complex In Vitro Models
GlaxoSmithKline
The pharmaceutical industry is continuing to face high R&D costs and low overall success rates of clinical compounds during drug development. There is a surge in demand for development and validation of disease relevant and physiological human cellular models that can be implemented in early stage discovery, thereby shifting attrition of future failures to a point in discovery where the costs are significantly lower. The current drug discovery paradigm involves lengthy and costly lead discovery and optimization campaigns, often using simple cellular models with weak translational relevance to human disease or safety. This exemplifies an inability to effectively and efficiently reproduce human disease relevant states at an early stage to steer target and compound selection. Therefore, a fundamental question is how do we recapitulate human biological complexity of a disease state in robust translational in vitro assays for interrogation to increase our success rate in late stage drug discovery programs. The majority of new complex in vitro technologies that promise to be influential and more predictive in the next few years need to be qualified and repurposed for drug discovery efforts. I will provide examples of where we have utilized time-dependent, multiplexed and multi-dimensional 3D cell culture approaches in both safety and efficacy to better characterize targets and progress molecules earlier in discovery. Furthermore, I will discuss how we have automated and miniaturized 3D Oncology models but still mimic certain characteristics of the tumor microenvironment. I will also elaborate on the importance and methodology to qualify these 3D human in vitro models and the translatability of these models to the clinic.