Fully automated, high-throughput screening for drug discovery

24 July, 2018

A major obstacle to efficient drug discovery and development is the lack of physiologically relevant and predictive cell-based assays. Pharmaceutical companies understandably demand assays that are robust, reliable, and compatible with automated high-throughput screening (HTS) platforms. We are excited toplay a role in this endeavor by developing and commercializing highly predictive cellular assay systems derived from human stem cells. These assays allow our clients to accurately assess drug safety and efficacy.

A successful drug efficacy screening and/or validation study requires not only a physiologically relevant cell model, but also validated HTS protocols to test the effect of drug candidates. To achieve this, scientists at Ncardia have developed a controlled approach for large-scale manufacturing of iPSC-derived (disease) cells and automated platforms for cell culturing in a 384-well microplate format, assay readout, and data handling. Assay performance is continuously evaluated using putative quality-controlled criteria such as S/B ratio, Z-prime and %CV to ensure robustness of high throughput compound screenings.

High throughput screening automation robot

Figure 1: High throughput screening automation robot.

Dedicated assay development is at the core of Ncardia's approach. We design and validate phenotypic assays with a clear link to human disease in combination with functional readouts closely related to the desired clinical readout in patients.

Dr Stefan Braam, co-founder and CEO of Ncardia, explains: “Our aim is to put ‘human’ testing at the forefront of drug discovery, by developing the best possible human cellular models. This is very attractive from an industry perspective, as it ensures only viable candidate drugs are progressed through the pipeline, while minimizing risks and ethical considerations associated with animal testing.”

New capabilities and developments are continuously required to pave the way for pharmaceutical companies to expand effective screening or validatation to tens of thousands of molecules in relevant disease model systems. Ncardia’s human induced stem cell-based cellular models in combination with automated phenotypic screening enables reliable efficacy testing of drugs at a high throughput to advance the drug discovery and development process. Our goal is to employ out state-of-the art technologies in our client's research efforts to help deliver better drugs to patients faster.

Further reading

Gintant G, Fermini B, Stockbridge N, Strauss D. The Evolving Role of Human iPSC-Derived Cardiomyocytes in Drug Safety and Discovery. Cell Stem Cell Forum, Vol. 21, 1, P14 – 17 (2017)

Hutchinson L, Kirk R. High drug attrition rates—where are we going wrong? Nature Reviews Clinical Oncology – Editorial. Vol. 8, P 189-190 (2011)

Mordwinkin NM, Burridge PW, Wu JC. A review of human pluripotent stem cell-derived cardiomyocytes for high-throughput drug discovery, cardiotoxicity screening, and publication standards. J Cardiovasc Transl Res. Vol. 6, 1, P 22 – 30 (2013)