Periodic Reporting for period 4 - ESCulab (European Screening Centre; Unique Library for Attractive Biology)
Okres sprawozdawczy: 2021-12-01 do 2022-11-30
ESCulab’s aim is to expand and enhance the European Lead Factory (ELF) by supporting up to 185 new screens, of which up to 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 and expand on the existing ELF 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.
In the 2nd reporting year (RP2), we were faced with COVID-19 related challenges. Despite that, ESCulab remained largely operational and made progress throughout the year, although at a slightly slower pace than anticipated. Other achievements include completion of the screening infrastructure for HCS, agreement on the framework for charity paid screens, and the recruitment of Sars-CoV-2 related proposals.
In total, during RP1-4 104 EFPIA and 4 MMV programmes were nominated (of which 28 EFPIA and 2 MMV programmes in RP4). Of these, 100 (96 EFPIA and 4 MMV programmes) were accepted into the ELF portfolio, and for 62 programmes (59 EFPIA programmes and 3 MMV programmes, of which 26 EFPIA programmes and 2 MMV programme in RP4) the work was fully completed (QHL delivered).
Up- to and including RP4, the ELF Programme Office has been contacted by >100 different researchers interested in the opportunities at the ELF. A similar number of targets or phenotypes were checked for their availability for screening. The European scientific community submitted 62 proposals for screening, (of which 2 in RP4). Of these, 9 were HCS proposals. After review and selection by the Review Committee, 37 were accepted into the portfolio (2 in RP4). The accepted proposals 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, 12 programme owners have received their full QHL reports, and can use the compounds released with the QHL for further exploitation. To be able to finish all the accepted programmes within the project budget and timeline, it was decided to close recruitment in January 2022.
In addition, the team has made considerable progress in addressing and implementing the feedback received from the Mid Term Review meeting, which took place on June 1st, 2021. Significant progress was also made on the sustainability of the ELF, and the strategy has been further developed during RP4. During the RP4 period, the strategy has been further developed with the previously identified scenarios being outlined in more detail. Terms, conditions and costs for post-ESCulab compound sharing were further discussed and explored. For the recruitment of Charity Funded Screens, several charities have been approached and are looking into the opportunity. In parallel, several investigators have been briefed on the CFS option as an opportunity to pursue their research. Pleasingly, we are currently in the process of contract signing with one of these charities.
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 start points for new drug candidates will be generated serving the needs of patients for effective therapies.
An example of this is how ELF aimed to contribute 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 (https://www.europeanleadfactory.eu/newsroom/cross-consortium-cooperation-strengthens-european-efforts-discover-and-develop-novel).