European Screening Centre; Unique Library for Attractive Biology

Project Information

ESCulab

Grant agreement ID: 806948

DOI

10.3030/806948

Project closed

EC signature date 18 December 2018

Start date 1 December 2018

End date 30 November 2023

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 36 795 967,50

EU contribution

€ 18 249 992,50

Coordinated by

STICHTING LYGATURE
Netherlands

Periodic Reporting for period 5 - ESCulab (European Screening Centre; Unique Library for Attractive Biology)

Reporting period: 2022-12-01 to 2023-11-30

Summary of the context and overall objectives of the project

The high prevalence of diseases linked to poverty, increased resistance to anti-microbials, and the rise of age-related illnesses and viral threats, 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 increases pharma productivity and positive outcomes for patients and society. Most recent numbers were reported by US FDA showing an average of 49 new drug approvals in the past 5 years (2018-2022). By bridging a gap between basic research and drug development, ESCulab aimed to facilitate the translation of fundamental scientific insights into innovative drug starting points. New biological targets were collected by crowdsourcing, and phenotypes 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 were 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 allows innovators to build a proposition that is likely to attract investors and/or drug developers and stimulate them to further exploit these findings. ESCulab aimed to deliver 3 key results: 1. Screening centre - expanding on the existing ELF screening centre, supporting up to 185 new screens using a larger compound collection for screening. 2. Hit triaging and confirmation - Each screening programme aimed to deliver a list of confirmed hits constituting the Qualified Hit List (QHL), which is based on the results of tailored (u)HT- and HC-screens, hit characterisation, and medicinal chemistry input. 3. Sustainability plan - A business strategy was developed during the project lifetime. The strategy included attracting externally funded screening programmes.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During RP1 the consortium assembled the unique ESCulab Compound Collection (ECC), put in place new guidance documents for scientists, updated communication materials, and implemented new technologies. The first programmes were proposed and selected for screening and entered the screening pipeline. In RP2 we were faced with COVID-19 related challenges. Despite that, ESCulab remained largely operational and made progress throughout the year. Other achievements include completion of the HCS screening infrastructure , agreement on the framework for charity funded screens, and the recruitment of Sars-CoV-2 related proposals.
RP3 and RP4 were marked by a steady influx of programmes, and further detailing of the sustainability strategy of the initiative. RP5 was marked by the finalisation of all the programmes, a final boost towards the recruitment of the charity funded screens (CFS), and decisions on the final sustainability strategy.

In total 112 EFPIA and 5 MMV programmes were nominated. Of these, 109 were accepted into the ELF portfolio, and for 79 programmes the QHL was delivered.

The European scientific community submitted 62 proposals for screening. Of these, 9 were HCS proposals. 38 were accepted into the portfolio. Recruitment was closed in January 2022. The accepted programmes show a good coverage of different therapeutic areas and diseases (fig. 2), as well as the type of organisation (fig. 3). For the crowdsourced programmes, 26 programmes reached QHLs, and the programme owners can use the compounds released with the QHL for further exploitation.

Significant progress was also made on the sustainability of the ELF, and the strategy has been further developed during RP5. For the recruitment of CFS, active discussions with both charities as well as programme owners have taken place. We promoted the CFS opportunity at international meetings, linked to the CFS, a Dutch assay development fund was launched to support scientists in the Netherlands working with a charity or foundation on an early drug discovery project.

In the final period of the project it became clear that there was not enough support from partners nor were other funding sources available to continue sharing the compound collection and keep the infrastructure running for a 3 years post-term period. To ensure a controlled closing of the ELF and adequate delivery on the QHLs of running programmes, we decided to wind down the ELF, and not establish the envisioned ELF foundation. 2 EFPIA partners will continue compound sharing for another 6 months, to allow them to finalise a few pending programmes. The closing of the ELF marks the end of a highly successful partnership, that has made significant contributions to the European drug discovery ecosystem for over a decade.

The results, impact and lessons learned from the ELF were captured in a final report for the general public (https://elfendofprojectreport.europeanleadfactory.eu) Fig. 4 summarizes the key outcomes achieved after 11 years of ELF.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Providing an effective mechanism for academic groups and SMEs to access the capabilities and expertise of pharmaceutical companies, ESCulab offered an opportunity to create value from innovative disease modulation mechanisms and hence to advance human medicine. Providing a unique library and industry-standard screening free of charge to academia and SMEs has generated a significant portfolio of new hits that have the potential to progress in hit-to-lead programmes. In addition, novel insights will emerge from the implementation of phenotypic High Throughput and High Content screens within the ELF framework.

Taking academic and biotech research programmes to the next stage created value, jobs, and when resulting in new therapies, will 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 have been generated serving the needs of patients for effective therapies.

An example of this is how ELF under ESCulab contributed to finding novel treatments against SARS-CoV-2. In response to the pandemic, ELF prioritized programmes addressing COVID-19, implementing a fast-track for review and execution. One of these programmes resulted in high-quality hits. The novel hit series and associated high-quality biological data formed the foundation of a successful proposal to access the medicinal chemistry services available within EU-OPENSCREEN partner sites. This paved the way for the continuation of the programme towards hit-to-lead phase.
The ESCulab library itself had a direct impact on core activities of the participating EFPIA companies to find new drugs in high throughput screening. In addition, the partnership and the newly established networks will continue beyond the end of the project. The successful collaboration helps to change the mindset of pharma companies to work together to find new drugs for patients in a pre-competitive space.

The process from hit identification to testing in the clinic can easily take a decade. As such, we are delighted to see that programmes started under the first tier of ELF funding have recently entered clinical testing. In 3-5 years from now, we expect some of the ESCulab programmes to reach similar milestones.

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Summary of key outcomes achieved after 11 years of ELF