Better Biological Relevancy in Drug Discovery over the Next Five Years – Chapter 3

In the traditional “target-based drug discovery” approach, scientists identify and study individual molecules and their mechanism of action. These have performed poorly at identifying first in class medicines when compared to “phenotypic drug discovery” methods. High content cell-based assays provide rich biological information earlier in the drug discovery process and since most are multi-parameter and analyze single cells they can be considered inherently “phenotypic.” I expect that drug discovery will continue to evolve to a balanced approach that leverages the strengths of both phenotypic and target based strategies.

To unravel complex biology, the generation of rich, multi-parameter phenotypic data, is needed which will drive the continued growth of high content technologies. Imaging based high content systems have been an effective tool for analyzing adherent cells. Cells in suspension and multiplex bead assays, however, are not amenable to imaging and this has left the development of therapeutics in areas like the immune system, underserved. The information contained in the large complex multi-parameter datasets generated by these systems can only be realized with analytical methods and software tools to effectively integrate, analyze, interpret and share them. The ability to provide deep insight into cellular function early in the discovery process will grow and be increasingly important toward lowering costs, reducing attrition rates and improving healthcare outcomes. As a result, technologies such as Intellicyt’s iQue^® Screener platform, which enables high content as well as high throughput, screening of cell and bead-based assays will be more broadly incorporated into the drug discovery process.

Along with the growing use of cell-based assays comes the need for better disease-relevant cell types. The ability to test drug candidates in cells that are representative of the disease and environment they function in will result in better understanding of disease. We expect that technologies such as human induced pluripotent stem cells; cell lines derived from gene-editing technologies; and primary cells obtained from patients with a range of genomic backgrounds will result in more disease relevant cell lines. Many of these cells are scarce (e.g. human primary cells) and/or expensive to develop and are often provided in a suspension format. As a result, the demand for platforms systems which can analyze small sample volumes of suspension cells to study these cell types will continue to expand over the next five years.

R. Terry Dunlay
President and CEO, Intellicyt