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European Screening Centre; Unique Library for Attractive Biology

Periodic Reporting for period 1 - ESCulab (European Screening Centre; Unique Library for Attractive Biology)

Reporting period: 2018-12-01 to 2019-11-30

The high prevalence of diseases linked to poverty, increased resistance to anti-microbials, and the rising complexity of age-related illnesses, mean that pharmaceutical innovation is crucial to meeting contemporary medical needs and reducing personal and societal burdens. However, despite technological advancements and large R&D investments, only 20–25 new drugs have reached the market per year in 2005-2010. Encouragingly, some post-2010 figures suggest that taking new approaches (e.g. merging complimentary R&D capacity; engaging in more collaborations, i.a. large public-private partnerships (PPPs)) may have positive outcomes on pharma productivity.
By bridging an important gap between basic research and drug development, ESCulab will facilitate the translation of fundamental scientific insights into innovative drug starting points. New biological ideas will be collected by crowdsourcing novel targets, phenotypes and pathways translated and de-risked by delivering high-quality chemical starting points for drug development. Innovators from EU academics and SMEs are offered access to state-of-the-art industry-grade facilities, drug discovery expertise, and a top-quality, curated library with approximately 535,000 unique compounds suitable for screening potential drug targets. The ESCulab drug discovery data generated will allow the innovators to build a proposition that is likely to attract investors and/or drug developers and stimulate them to further exploit these findings.
Starting off the shoulders of the European Lead Factory (ELF), where this principle has been successfully implemented, ESCulab will expand and enhance ELF by supporting 185 new screens, of which at least 50 will be crowdsourced and provided by public programme owners. Important additions include the application of a larger compound collection for screening, the ability to accommodate more complex phenotypic screening assays, and building a sustainable business model to ensure access to Collaborative Drug Discovery activities beyond the funding period.

ESCulab will deliver 3 key results:

1. Screening Centre - ESCulab will build on the existing ELF screening centre to deliver the ESCulab screening centre. Several new features will be added to increase the level and abilities of the services offered.
2. Hit Triaging and confirmation - Each screening programme will aim to deliver a list of confirmed hits constituting the QHL, which is based on the results of the tailored (u)HT- and HC screens, hit characterization using broad range of technologies and medicinal chemistry input.
3. Sustainability plan - A business strategy will be delivered during the project lifetime. The strategy will include attracting screening programmes that are externally funded by charities and/or patient foundations. Offering support for the further development of hits to leads for (clinical) drug development is an additional value-added offering that will create an additional income stream to continue activities in the public interest but will happen outside the project.

Finally, ESCulab’s overall mission is to be the long-term operational partner-of-choice for EU-scientists wanting to translate new disease-relevant biological targets and phenotypic assays by delivering, high-quality, most relevant chemical assets, with a view to discovering investable starting points for new therapies. Ultimately, this will result in novel medicines, alleviating unmet medical needs.
The ESCulab Consortium kickstarted its activities in December 2018. One of the priority tasks was to assemble the ESCulab Compound Collection (ECC). This was done following a strict protocol for inclusion of compounds from partners. After the selection phase, physical samples were shipped from each compound owner to the ESCulab Compound Logistics Facilities at partner BioAscent in Scotland. There, compound plates were reformatted and prepared to be included in the first screening set. All screening centres were supplied with a set of approx. 535.000 compounds, allowing them to start screening the new ECC within the first 10 months of the project.
Another important achievement was the implementation of the new terms and conditions into existing operating systems (e.g.Honest Data Broker), and the development of application forms for phenotypic screens. These are also important steps towards achieving sustainability of the initiative.
As part of the initial ramp-up strategy, the first public programmes which were earlier assessed within the ELF framework, but not executed, underwent reassessment based on the ESCulab selection criteria. The ones that passed review were transferred to screening at the European Screening Centre. Dissemination activities (i.a. a first stakeholder meeting) and the reactivation of the ELF network stimulated the submission of further innovative screening proposals by public programme owners, in total 18 programmes in the first year.
After selection, 9 programmes entered the ESCulab portfolio. Within the first year, 8 assays have been developed at Pivot Park Screening Center and first Qualified Hit Lists are expected in Q1 2020. The first EFPIA and MMV programmes have also been nominated and approved, of which most have been registered in HDB already (15 programmes).
In summary, ESCulab is fully operational, started its first screening initiatives, and is confident to reach its ambitious objectives within the project timelines.
Academic and SME research groups are best positioned to explore new biology and broadening basic scientific understanding of disease mechanisms. However they lack the capacity, infrastructure and resources required to translate their insights into chemical matter that might serve as tool or starting point for drug discovery. Pharmaceutical companies, on the other hand, are well poised to drive drug discovery efforts with their strong technological base but are committed to a very focussed research remit and spend less resources on basic biology. Providing a mechanism for academic groups and SME’s to access the capabilities and expertise of pharmaceutical companies, ESCulab offers the chance to create value from innovative disease modulation mechanisms and hence to advance human medicine.
Providing a high-quality library and an industry-standard screening free of charge to top notch scientists will generate a significant portfolio of new innovative and relevant hits that have the potential to progres in hit-to-lead programmes. In addition, it is expected that novel insights will emerge from the implementation of phenotypic screens.
Taking academic and biotech research programmes to the next stage creates value, more jobs, and in the end when resulting in new therapies, improve global health directly. A validated portfolio of new starting points for drug discovery, that takes into account unmet medical needs, is an attractive proposition for venture capital and corporate funds. Such investments allow for a scaling-up of research and development efforts, attracting highly talented people and building an improved research infrastructure. Through this, a multitude of starting points for new drug candidates will be generated serving the needs of patients for effective therapies. ESCulab is committed to make a lasting impact on public health worldwide.
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