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European Screening Centre; Unique Library for Attractive Biology

Periodic Reporting for period 2 - ESCulab (European Screening Centre; Unique Library for Attractive Biology)

Reporting period: 2019-12-01 to 2020-11-30

The high prevalence of diseases linked to poverty, increased resistance to anti-microbials, and the rise of age-related illnesses, mean that pharmaceutical innovation is crucial to meet medical needs and to reduce 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, including public-private-partnerships may have positive outcomes on pharma productivity. By bridging a gap between basic research and drug development, ESCulab will facilitate the translation of fundamental scientific insights into innovative drug starting points. New biological targets will be collected by crowdsourcing, and phenotypes and pathways will be translated and de-risked by delivering high-quality chemical starting points for drug development (see fig. 3). Innovators from EU academics and SMEs are offered access to state-of-the-art industry-grade facilities, drug discovery expertise, and a top-quality library with 535.000 unique compounds. The data generated will allow innovators to build a proposition that is likely to attract investors and/or drug developers and stimulate them to further exploit these findings.

ESCulab will expand and enhance the European Lead Factory (ELF) by supporting 185 new screens, of which 50 will be crowdsourced. Important additions include the application of a larger compound collection for screening, the ability to accommodate phenotypic screening assays, and building a sustainable business model.

ESCulab will deliver 3 key results:
1. Screening centre - ESCulab will build on the existing ELF screening centre to deliver the ESCulab screening centre.
2. Hit triaging and confirmation - Each screening programme aims to deliver a list of confirmed hits constituting the Qualified Hit List (QHL), which is based on the results of the tailored (u)HT- and HC screens, hit characterisation 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.
During the 1st year (RP1), the consortium assembled the unique ESCulab Compound Collection (ECC), consisting of 535.000 compounds, originating from 13 different partners. The consortium also put in place new guidance documents for scientist on how to collaborate with ELF and updated communication materials to include new features such as High Content Screening, a phenotypic screening and powerful approach to identify novel chemical starting points for drug discovery. New technologies were implemented to facilitate innovative ideas from the scientific community. During the first year, 18 proposals were received, from scientists all over Europe, from both academia and SMEs. Nine were positively reviewed and screening programmes initiated. Fifteen programmes for EFPIA partners and the Medicines for Malaria Venture were nominated, approved for screening, and added to the ELF portfolio.

In the 2nd reporting year (RP2), we were faced with challenges associated with the COVID-19 pandemic. Despite the pandemic, ESCulab remained largely operational and made progress throughout the year, although at a lower pace than anticipated.

In total, during RP1 and RP2, 49 EFPIA programmes were nominated. Of these, 42 were accepted into the ELF portfolio, and for 9 programmes the work was fully completed.

In RP2, 2 IMI2- associated partner programmes for MMV were progressed and results are expected to be released to MMV early in 2021. The European scientific community submitted 38 proposals for screening, (18 in RP1 and 20 in RP2). After review and selection by the ELF committees, 21 were accepted into the portfolio (9 in RP1 and 12 in RP2). In total, 17 contracts were signed with programme owners (6 in RP1 and 11 in RP2). The accepted proposals show a good coverage of different therapeutic areas and diseases (fig. 1), as well as the type of organisation (fig. 2).

Two programme owners received their results, including an extensive report on activities and outcomes. The resynthesis and retesting of the top-ranked compounds for 1 programme was completed.

To facilitate High Content Screening (HCS) within ESCulab, criteria were established to select 50.000 compounds for HCS. This subset was plated and shipped to the HCS centre at UnivDundee in RP2. A promotional campaign led to submission of interesting proposals for phenotypic screens. https://www.europeanleadfactory.eu/newsroom/phenotypic-screening-now-offered-european-lead-factory

Another key achievement was the finalisation of the paid screen agreement, making ESCulab services and assets now available for interested charities across the world. The consortium has approached the first charities to engage in such activity and is currently preparing to launch a public marketing and communication campaign.

In response to the pandemic and the associated local rules and regulations, ESCulab changed its proposal recruitment strategy, and moved from engaging in meetings and conferences to an increased online presence and activities such as ELF webinars. https://www.europeanleadfactory.eu/newsroom/european-lead-factory-launches-online-seminar-series

As the ELF library could provide leads for the development of novel antivirals or other medicines that can help treat COVID-19, we are currently running screening programmes from a public partner (https://www.europeanleadfactory.eu/newsroom/european-lead-factory-selects-first-covid-19-proposal) and EFPIA partners that aim to find chemical leads against SARS-CoV-2 (https://www.europeanleadfactory.eu/newsroom/european-lead-factory-launches-multiple-approaches-aiming-discover-novel-sars-cov-2). We have also actively reached out to several virologists within the EU to inform them of the opportunities at the ELF and reached out to the CARE consortium for active collaboration.
Providing an effective 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 unique, high-quality library and an industry-standard screening free of charge to academics and SMEs will generate a significant portfolio of new hits that have the potential to progress 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, jobs, and, when resulting in new therapies, improve global health. A validated portfolio of new starting points for drug discovery, addressing unmet medical needs, is an attractive proposition for venture capital and corporate funds. Through this, a multitude of starting points for new drug candidates will be generated serving the needs of patients for effective therapies.
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