SLAS2019 International Conference and Exhibition

Saturday, February 2, 8 AM – 4:30 PM; Location: 151A
3D Cell-Based assays for Drug De-risking
Cell-based in vitro assays are used throughout the drug discovery and development chain, allowing for high throughput efficacy but also mechanistic-based toxicity testing. A big challenge however is the translation of in vitro assays towards the in vivo outcome. Physiological relevance is a key parameter to improve the predictive power of cell-based assays. The better we can reflect tissue architecture, composition and function the more predictive an in vitro assay will become. The 3D course covers advances in 3D cell culature technologies, assays and their use in drug discovery and development. Course instructors include InSphero Chief Scientific Officer Dr. Patrick Guye, and InSphero Head of Technology and Platforms, Dr. Olivier Frey.

Tuesday, February 5, 9:30 – 10:15 AM; Location: Room 144a
3D Tissue Models for Drug Discovery and Development – from Screening to MPS/BOC Applications
The future of drug discovery and development lies in 3D human tissue models. The latest generation of 3D in vitro models are highly predictive, stable over long periods of time (thus appropriate for assessing complex treatment regimens), and permit the cultivation of organotypic tissues, composed of all the relevant cell types required to recapitulate human in vivo physiology. Enabling 3D cell-based technologies, such as microtissue plates and organ-on-a-chip systems as well as accessible endpoints have evolved rapidly and are ready for large-scale implementation in drug discovery and development workflows. In this tutorial, we will present our scalable 3D microtissues models composed of human primary cells for applications in metabolic disease discovery (liver disease/NAFLD/NASH, islet research/T1D/T2D), oncology (PDX and I-O), and safety assessment (liver toxicology). We also discuss specifically engineered, SBSS-compatible plates such as 96-well, 384-well and organ-on-a-chip formats, all highly compatible with state-of-the-art imaging and automation equipment as well as most assay endpoints. Our unique technology platform enables researchers to complement and reduce reliance on animal experiments, saving significant time and resources in the drug development process and ensuring higher confidence in decision making for later clinical stages. Tutorial led by InSphero Chief Scientific Officer Dr. Patrick Guye and Head of Technology and Platforms Dr. Olivier Frey.

Wednesday, February 6, 10:30 – 11 AM; Location: 146B
The next decade of preclinical drug discovery: Integrating disease-tunable 3D human microtissues into higher order systems
The success of drug development programs depends significantly on having in vitro models that reflect the human patient as closely as possible, while being highly practical in their implementation. This practicability should encompass reproducibility and availability of the model in time and space, on-demand production, scalability for screening, amenability to meaningful treatment windows, ease of access to as many relevant endpoints as possible, and compatibility with standard lab processes. We engineered a scalable and SBSS-compatible platform family based on human 3D microtissues models of various organ systems which can be induced to become diseased: Fibrosis, Steatosis/NAFLD, NASH for liver; T1D and T2D for pancreatic islets; and various tumor models. These 3D microtissues are not only immune-competent, but also highly dynamic, as demonstrated by their capability to relax and remodel following injury (e.g., liver fibrosis). In addition, 3D microtissues are organotypic in their cell composition and accessible to all current endpoints ranging from biochemical assays, to single cell extractions, to high content imaging. We leveraged the power of these 3D organotypic microtissues and combined them in a highly robust microphysiological device for establishing meaningful organ-organ interactions. We will discuss the challenges of combining 3D microtissues representing various organ systems in screening-friendly devices, as well as the unique advantages of such multi-tissue systems, including higher functionality, ad-hoc medium conditioning, in-situ compound metabolization and the ability to combine efficacy assessment with toxicity detection in the same system. Highly modular and scalable, such human in vitro modeling platforms for efficacy and safety fit the needs and requirements of many stakeholders/departments in today’s pharmaceutical and biotech enterprises and will greatly simplify and accelerate drug discovery. Presentation by InSphero Chief Scientific Officer Dr. Patrick Guye

Monday, February 5, 9:30 – 10:15 AM; Location: Exhibition Hall, Poster 1011-B
A Screening-compatible 3D Human Liver NASH Model for Drug Discovery
Non-alcoholic steatohepatitis (NASH), an advanced form of non-alcoholic fatty liver disease (NAFLD), is defined as the presence of hepatic steatosis with inflammation and hepatocyte injury. NASH can eventually lead to advanced fibrosis, liver cirrhosis and liver failure. At present, there are no approved and safe therapies for NASH. The most frequently used in vitro model to study the effect of anti-NASH drugs are simple mono-layer cultures of hepatic stellate cells (HSCs) and hepatocytes, which are not relevant enough to account for the complex mechanism of the disease. Here, we describe how we developed a physiological relevant 3D Human Liver NASH model, amenable for drug safety screening by engineering 3D Human Liver Microtissues to incorporate all the relevant primary human liver cell types responsible for the development of the disease: hepatocytes, HSCs, Kupffer cells (KCs) and liver endothelial cells (LECs). We demonstrate that FFA and LPS treatment induced liver inflammation, steatosis and fibrosis in vitro, making this model an ideal tool for anti-NASH drug discovery. Presented by Dr. Jan Lichtenberg, InSphero CEO and Co-founder.