Drug Discovery


Traditional manual expansion methods


Figure 3 An illustration of the benefits of automation of the growth of organoids by novel bioprocessing technology.


Complex manual process


Batch-to-batch variation Bioprocessor expansion technology


Limited scalability


Semi-automated process


Reproducible batches


Scalable


For example, organoids derived from metastatic biopsies predict responses to drugs that are subse- quently observed in patients from whom the organoids were derived2. In 100% of cases in this study, if a drug did not work on a patient’s organoids, then it also did not work in that patient. Furthermore, in nearly 90% of cases, if a drug did work on the organoids, then it also worked in the patient. Importantly, organoids can potentially be generated for many major classes of solid human cancers, including carcinomas in colorectal, breast, prostate and lung cancer. Organoids are, therefore, a new and potentially disruptive platform technol- ogy solution that could transform in vitro pre-clin- ical drug-screening and lead to improved, specifi- cally targeted cancer treatments. The simple iterative drug discovery cycle of


‘design, make and test’ drives the optimisation of novel compounds and typically needs at least 10,000 new molecules to be synthesised and screened over a 5- to 10-year period. There is an operational need to reduce the number of cycles required to optimise a development candidate by increasing the predictive power of the biological assays. The alternative ‘quick win, fast fail’ approach, in comparison with the more traditional linear sequence of drug discovery, requires pivotal decision-making to be introduced earlier in the drug discovery process3. Early decisions then set in motion the long-term development processes that


Drug Discovery World Winter 2018/19


are more closely regulated, less flexible and signif- icantly costlier. As tumour-derived organoids can mimic human cancers in the laboratory, they can be used as a new technology platform to enable pivotal decisions to be made by identifying the most promising compounds early on in drug dis- covery, by discarding the less attractive molecules even earlier. To initiate medicinal chemistry, new chemical


starting points are required to begin the process of compound optimisation. These are typically found by screening targeted compound libraries, such as those for kinase inhibitors4, which are thought to represent up to 50% of current cancer targets5. The screening of such compound libraries also requires larger batches of organoids. Consequently, there is now an opportunity to insert tumour- derived organoids much earlier in the drug discov- ery process but this would require them to be pro- duced consistently at scale to support both hit find- ing strategies and long-term medicinal chemistry programmes. Until recently, however, capitalising on this opportunity was constrained by the reliance on the existing manual processes carried out by individual scientists in specialist laboratories.


Growing organoids at scale for cancer drug discovery If grown on an industrial scale, tumour organoids can be used routinely for compound screening but


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