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European Screening Centre; Unique Library for Attractive Biology

Periodic Reporting for period 3 - ESCulab (European Screening Centre; Unique Library for Attractive Biology)

Reporting period: 2020-12-01 to 2021-11-30

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. 1. 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 up to 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), put in place new guidance documents for scientist on how to collaborate with ELF, updated communication materials, and implemented new technologies. The first public, EFPIA, and MMV programmes were proposed and selected for screening, and entered the ELF screening pipeline.

In the 2nd reporting year (RP2), we were faced with COVID-19 related challenges. Despite the pandemic, ESCulab remained largely operational and made progress throughout the year, although at a slightly slower pace than anticipated. Other important achievements include the completion of the screening infrastructure for HCS, the agreement on the framework for charity paid screens, and the recruitment of Sars-CoV-2 related proposals.

In total, during RP1, RP2, and RP3 76 EFPIA and 3 MMV programmes were nominated (of which 29 EFPIA programmes and 1 MMV programme in RP3). Of these, 66 (63 EFPIA programmes and 3 MMV programmes) were accepted into the ELF portfolio, and for 36 programmes (34 EFPIA programmes and 2 MMV programmes, of which 25 EFPIA programmes and 2 MMV programmes in RP3) the work was fully completed (QHL delivered).

Up to and including RP3, the ELF Programme Office has been contacted by 98 different researchers who were interested in the opportunities at the ELF. 96 targets or phenotypes were checked for their availability for screening. The European scientific community submitted 60 proposals for screening, (of which 22 in RP3). Of these proposals, 7 were HCS proposals. After review and selection by the Review Committee, 35 were accepted into the portfolio (14 in the past RP). The accepted proposals show a good coverage of different therapeutic areas and diseases (fig. 2), as well as the type of organisation (fig. 3). Notably, during RP3 the geographical spread of received proposals increased significantly (fig. 4). For the crowdsourced programmes, 7 programme owners have received their full QHL reports, and can use the compounds released with the QHL for further exploitation.

Another important milestone for the project was the IMI Mid Term Review meeting, which took place on June 1st, 2021. The feedback provided during the meeting and through the review report greatly assist the consortium in achieving the overall ESCulab goals. The MTR process is now formally closed, and the Project Executive will further ensure ongoing discussions within the consortium towards, implementation of the recommendations.

Significant progress was made in the field of Sustainability of the ELF. A major highlight is that the legal framework of the Charity funded screens was finalised, meaning that the ELF platform is now available to charities and foundations across the globe. In addition, steps were made towards developing an appropriate partnership proposal for Horizon Europe.
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.