Background

The European Lead Factory (ELF) was first established in 2013 when seven large pharmaceutical companies came together to discuss the pre-competitive sharing of their compound collections with each other and the European scientific community. The infrastructure to allow for compound sharing, screening, and the management of such an endeavour was provided by a handful of specialised Contract Research Organizations (CROs), academic partners, and a foundation.

Over time, the industry collection was supplemented with novel compounds, designed and synthesised by medicinal chemists. The ultimate goal of the ELF was to give scientists working on innovative targets and searching for drug discovery starting points access to an industry-standard screening infrastructure and allow them to screen their drug targets and phenotypes of interest against one large compound library composed of unique high-quality compounds with drug-like properties. Funded by the Innovative Medicines Initiative (IMI, now the Innovative Health Initiative), the ELF was born as a shared platform for open innovation in drug discovery – a first of its kind in Europe. 

Running from 2013-2023, through the support of two consecutive grants from the IMI, the publicly co-funded project was the largest collective drug discovery platform in Europe. It has been a true example of successful public-private collaboration, bringing together the best of industry and academia to drive the development of new medical solutions for patients in need.

Objectives

The ELF sought to jump-start early drug discovery by bridging the gap between innovative biology and creative medicinal chemistry, bringing different expertise together. To achieve this goal, the ELF established a shared platform for collaborative drug discovery. The overall objectives included:

• Creating an industry-standard screening collection of high-quality compounds with drug-like properties
• Making this library of compounds accessible to European academics and biotech SMEs via a transparent and diligent review process
• Providing access to state-of-the-art ultra-high throughput screening (uHTS) and high content screening (HCS) facilities and expertise
• Identifying Qualified Hits and Improved Hits for further optimisation into lead structures or research tools
• Generating and sharing knowledge with the broader drug discovery community on successful strategies in library design, assay development, screening, hit triaging, medicinal chemistry, and other early drug discovery techniques

Fast Facts

• Duration: January 2013 – November 2023 
• Aim: To provide quality hit and lead compounds for innovative disease-related targets and phenotypes to accelerate the long, complex, and expensive process of drug discovery that is so critical to developing innovative medicines for global health challenges
• Total budget: €234 Million: 90 M (IMI from two rounds of funding); 134 M (pharma partners in-kind); 10 M (associated partners in-kind) 
• Number of consortium partners: 33 participants: 13 academic + 10 SMEs + 9 pharmaceutical companies (EFPIA members) + 1 EFPIA associated partner (foundation/charity) 
• Size of the ELF compound collection: 535,000 compounds (>350,000 EFPIA compounds, + ~190,000 compounds of the Public Compound Collection, developed by leading chemistry SMEs and academic groups)
• Screening infrastructure access for: Any researcher at any European SME or academic institution, provided that their screening proposal was selected by the ELF Review Committee
• Output of an individual screening campaign: A maximum of 50 qualified hit compounds, a subset of resynthesised hits, optimized hits through focused medicinal chemistry activities, and a data-rich report with information on experiments that were performed
• Geographical spread of the initiative:
  o  Consortium partners were spread over nine countries
  o   Public screening proposals were received from 20 countries: Norway, Sweden, Finland, Denmark, Ireland, UK, Netherlands, Germany, Poland, Belgium, Czech Republic, Switzerland, Austria, Hungary, France, Italy, Slovenia, Spain, Portugal, Israël
  o   Accepted proposals came from 17 countries: Norway, Sweden, Finland, Denmark, Ireland, UK, Netherlands, Germany, Poland, Belgium, Czech Republic, Austria, France, Italy, Spain, Portugal, Israël

Impact

The European Lead Factory has shown it can deliver health and wealth for society, make open innovation work, and boost science. The initiative successfully established a collaborative model for drug discovery that helped improve the efficiency and capacity of developing new medicines for unmet medical needs. It has demonstrated that it can deliver hit compounds that are highly suitable for further development, collective intelligence that capitalizes on previous investment, interesting partnering programmes, scalable (new) SMEs, and sustained corporate R&D in Europe. The ELF is an excellent example of collaborative open innovation with a focus on enhancing knowledge exchange between academia and industry. 

Health and Wealth for Society

Using collective intelligence and capitalizing on previous public and private investments, the ELF combined the experience of big pharmaceutical companies with the agility of SMEs and the innovation of academia to unlock new medical innovations. Without the efforts of the consortium, many targets identified by academic researchers or SMEs would have gone unscreened and the high-quality chemical compounds in corporate libraries would have been underused (let alone expanded upon with novel compounds in a library open to all). Having tapped into this potential, the ELF increased the chance of finding relevant hits and leveraged earlier investments made through public funding of fundamental research and private investments in high-quality chemical matter. Ultimately, the ELF was able to unlock opportunities that no partner working alone would have been able to seize.

In addition to leveraging earlier investments in chemistry and biology, the activities of the ELF have had a positive economic benefit on the European research landscape. The collaboration produced investable programmes that led to hits or leads that could be progressed into clinical candidates. Through the partnership, academic groups, SMEs, corporations, and charities/foundations (e.g. the Medicines for Malaria Venture) were provided with the necessary tools and capabilities to develop their programmes outside of the ELF framework. This opened doors for new business ventures that could in turn attract funding and be scaled up into viable, growing European SMEs. The ELF has, without a doubt, helped strengthen the European research infrastructure and increase the competitiveness of its academic, SME, and industry partners.

Impact on Different Therapeutic Areas

Through its balanced portfolio, the ELF has delivered results in many different therapeutic areas, including those that pose some of the world’s biggest health challenges. Achievements within the different therapeutic areas range from the identification of tool compounds in diabetes and cardiovascular research to the announcement of collaborations between partners in metabolic diseases, and the launch of clinical studies in oncology (see below). As it typically takes about 7-10 years for targets and compounds to progress from identification to clinical testing, we expect more ELF programmes to progress to the clinic over the coming years. In addition to these successes, the partnership has contributed to other European projects, including IMI’s ENABLE and the Horizon Europe Project EXSCALATE4CoV. The following examples illustrate the impacts of the ELF drug discovery platform within various disease areas:

ONCOLOGY

Cancer is the second leading cause of death globally with rates continuing to rise. In 2022, new cancer cases in Europe rose by 2.3%, reaching 2.74 million. Providing new hope for the development of cancer drugs, the ELF partnership helped identify two drug candidates for cancer treatment that have progressed to phase 1 clinical trial testing.

ANTIMICROBIAL RESISTANCE

Referred to as the silent pandemic, antimicrobial resistance (AMR) is one of the greatest health threats that humanity faces today. The overuse and misuse of antibiotics are driving drug-resistant pathogens, leading to an increasingly urgent global health crisis. Research, based on the results and improved hit compounds delivered by the ELF, led to the discovery of a much-needed new class of drug that has the potential to reverse antibiotic resistance for conditions such as pneumonia and sepsis.

PANDEMIC PREPAREDNESS

During the first year of the COVID-19 pandemic, the ELF decided to prioritise COVID-19-related screening proposals through a fast-track procedure. One of the programmes selected for screening in 2020 progressed to hit-to-lead phase, leading to the discovery and development of novel antivirals against SARS-CoV2. Another programme on COVID-19 managed to successfully secure follow-up funding.

NEGLECTED TROPICAL DISEASES

Neglected tropical diseases (NTDs) threaten millions of people living in the poorest countries and communities around the world. As a project aimed at catalysing the discovery of new medicines for some of the world’s most complex health challenges, the ELF partnership made a concerted effort to attract more programmes addressing NTDs, achieving results in NTD drug discovery programmes. One example is the disease leishmaniasis, for which the ELF embarked on a screening programme. Another example is malaria through the ELF’s partnership with the Medicines for Malaria Venture (MMV), a partner of the ELF since 2018, which ran high-throughput screens for novel antimalarials.

THE CENTRAL NERVOUS SYSTEM (CNS) & NEUROLOGY

Within the field of CNS & Neurology, unmet medical need continues to be high. The ELF helped boost drug discovery in this area with successful developments for both chronic pain and anxiety disorders.  

Portfolio

From the start, the ELF set out to recruit the most innovative, high-quality programmes from across Europe in all disease areas. The partnership combined complementary industry and crowdsourced portfolios to address critical unmet medical needs. For the crowdsourced portfolio, an application and review process was established to ensure scientific quality, novelty, and (technical) compatibility with the available screening infrastructure. The ELF took a strategic approach to its portfolio management aiming for a balanced portfolio of projects that were selected based first and foremost on patient benefit, but also on scientific impact, risk diversity, and economic potential of the full portfolio.

Overall, more than 300 drug discovery programmes were progressed through the ELF over the course of 11 years. Of these, 209 were industry programmes, five were programmes for the Medicines for Malaria Venture, and 108 were crowdsourced programmes. The crowdsourced programmes were selected from 215 submitted proposals. Screening proposals for crowdsourced programmes were received from 20 countries across Europe, indicating the richness and diversity of the ELF network. Approximately 30% of the crowdsourced proposals were submitted by SMEs.

A balanced portfolio of innovative targets and phenotypes in various disease areas was established. The ELF contributed to developments for cardiovascular diseases & haematology, CNS & neurology, infectious diseases (including neglected tropical diseases and COVID-19), inflammation and immunology, metabolic diseases, and oncology.

Target classes include enzymes, receptors, ion channels, protein-protein interactions, and various other targets and phenotypes.

In total, over 10,000 hit compounds were provided to programme owners for further hit optimization and drug development.

Efforts to Continue the Success Story

The decade-long success story of the ELF would not have been possible without the support of the Innovative Medicines Initiative (IMI). The IMI funded the ELF with €196.5 million for the initial five years. Based on the success achieved under this first project term, it awarded the consortium a further €36.7 million.

The second round of IMI funding ran from 2018-2023, under the banner ‘ESCulab’ (European Screening Centre: unique library for attractive biology). Whilst the first phase of the ELF focused on defined biochemical targets, the second phase broadened this scope to target-agnostic phenotypic screens and introduced high-content screening to further increase the range of therapeutic applications.

During the second project term, the charity Medicines for Malaria Venture (MMV) joined the consortium to guarantee access to the ELF’s screening capabilities for multiple programmes. As the ELF’s first product development partnership, it was hoped that this collaboration would serve as an example of the benefit of combining the considerable scientific expertise of researchers in the charity sector with the ELF’s resources to expedite drug development for neglected diseases and other non-commercial indications. In particular, the ELF provided charities such as MMV with access to a high-quality, novel, drug-like screening library that they would otherwise not have had access to.

Establishing a long-lasting drug discovery platform was an important aim of the initiative from the beginning. Throughout, the partnership focused its efforts on the continuation of the ELF, actively exploring several avenues to maintain the ELF compound library beyond the lifetime of the project. One of the most notable examples of this was the establishment of a well-defined framework to engage, outside the scope of the IMI project, with charities and non-profits around the world. In early 2022, the consortium launched a new partnering initiative for charities and foundations. The aim here was to provide these organisations, within and outside of Europe, with access to the ELF’s well-established assets, services, and network of experts to support them in their mission of delivering new therapies to patients. With this step, the ELF sought to make a worldwide impact in various areas of unmet medical need, and across all disease areas and geographies. Linked to this work, 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.

The partnering programme for charities and foundations was an ambitious and complex initiative to implement. After thorough investigation and the exploration of multiple avenues, it became apparent that the charity/non-profit scenario would require another tier of co-funding to allow the ELF to continue and take on its semi-public role. Co-funding was not found amongst the stakeholders and it therefore became clear that the ELF’s activities would have to wind down at the end of the second project term.

Over the years, the consortium has worked hard with relevant stakeholders to consolidate the ELF’s position in the pre-competitive drug discovery landscape. A significant effect of these sustainability efforts is the impact of one of the main deliverables of the initiative: the Qualified Hit Lists. These continue to become visible as the first clinical candidates from early programmes are now being tested in clinical studies.

Throughout its decade-long journey, the consortium made it a priority to meet the needs of its stakeholders and worked hard to execute a sustainability strategy that would keep it sufficiently funded. The motivation always remained to serve the drug discovery community at large and take on a semi-public role in finding starting points for new medicines in therapeutic areas of high public need.

A key success factor of the ELF has, and will always be, the fact that the individual partners, whose commercially successful and sometimes competing businesses, were able to work together under the joint ELF mission of delivering innovative drug discovery starting points that would make a tangible contribution to enriching the European research landscape.

The ELF’s legacy and the impacts of its success will continue to be driven by the progression of individual drug discovery campaigns towards the clinic.