The European Lead Factory set out to create a shared platform for collaborative drug discovery. Despite significant scientific advances, many medical needs remain unmet. Drug discovery is a long, complex and expensive process that starts with identifying chemical compounds or biological molecules that can modulate a drug target involved in the disease course.
A key tool in these earlier stages of drug discovery is a technique called High Throughput Screening (HTS), in which researchers screen large collections of chemical compounds in the hunt for molecules that could be potential drugs or be used in drug development in other ways. Although pharmaceutical companies have built up large libraries of compounds over the years, access to these collections was tightly restricted to in-house use by the owners. The European Lead Factory changed that by creating the 500 000 strong Joint European Compound Library comprising compounds from pharmaceutical companies’ own collections as well as 200 000 compounds that were newly designed and synthesised by academics and SMEs. The project also set up a European Screening Centre to run high throughput screening programmes on the compound collection.
Researchers from European universities and SMEs could apply to use the screening centre and compound collection for their own medical research and drug development programmes. In addition to a ‘hit list’ with up to 50 compounds identified through HTS, researchers who used the European Lead Factory services also received advice on experimental design, medicinal chemistry, and on setting up partnerships to further explore and develop the results. The pharmaceutical companies in the projects were also able to use the compound collection and screening centre. Underpinning the compound collection and screening centre were three specially-designed IT systems, including an honest data broker.
The system proved successful; by the end of the project, the team had delivered:
- 72 qualified and 37 improved hit lists from crowdsourcing programmes delivered to target owners;
- 30 % follow-up work on pharmaceutical partners screens (29 of 89);
- more than 3 000 bespoke compounds synthesised in the hit validation and hit-to-lead phase of crowdsourced target programmes;
- 280 bespoke assays developed to extract the most interesting hits for crowdsourced programmes.
The creation and successful running of the compound collection and screening centre was an achievement in itself. However, on top of that, the project delivered exciting results in many therapeutic areas, including some of the world’s biggest health challenges like cancer, metabolic disorders, neurodegenerative diseases, antimicrobial resistance and neglected tropical diseases.
ELF results directly lead to further funding for new programmes, two start-ups, along with two major partnering deals with pharmaceutical companies outside the consortium (one between ScandiCure AB and Servier - for metabolic diseases) and more than 70 new scientific publications. Five patents based on ELF compounds for the treatment of multi-resistant bacterial infections, pain and cancer, were registered, and one charity-funded virtual biotech emerged (Keapstone Therapeutics, addressing Parkinson’s disease) with EUR 2.4 million in additional funding.
ELF also led to another success in transferring results to the preclinical development IMI programme, ENABLE, working on novel potential antibiotics against Gram-negative bacteria, such as Escherichia coli.
A collaborative, scientific environment
By combining the experience of big pharmaceutical companies with the agility of SMEs and the innovation in academia, ELF created a highly collaborative scientific environment and unlocked untapped potential of medical innovations, benefiting all the partners involved and the general public by addressing their unmet needs.
The project was in particularly interesting for SMEs, who got the opportunity to translate their innovative design ideas into industry‐standard compound libraries, and access to the industrial screening capabilities without upfront costs. Out of 30 ELF project partners, 10 were SMEs. Furthermore, the ELF consortium’s activities created 150 new jobs and trained more than 190 young scientists and postdocs.
This pioneering project has already delivered excellent results, and the demand for ELF’s services continue to grow. Taking into account that the timeline for drug discovery is from 10 to 15 years from disease hypothesis through to drug approval, even more, tangible results are expected in the future.
Meanwhile the ELF’s assets, processes, tools, network and experience are being further extended and expanded through the IMI2 project ESCulab (European Screening Centre; Unique Library for Attractive Biology). Partners in ESCulab are planning, among others, to develop a fee-for-service payment model, and, most importantly, to move ESCulab operations from hit generation to lead generation.