ELF

Since its inception, IMI has supported almost 150 different research projects. That’s 150 teams of problem-solvers working together in the spirit of what we like to think of as ‘radical collaboration’. For 12 years, these projects have been producing toolboxes of new technologies, spreading best practices, training, skill-building and sharing not just their knowledge but also their valuable data.###

Their results have had a real impact on medicines development, helping European medicine developers better understand diseases, identify targets for new drugs, build biobanks, validate biomarkers and models, and much more. They’ve also had a big socio-economic impact, meaning they’ve been shown to have a positive effect on society, business and public policy.

Some of the projects that were launched in the early days of the partnership are still going strong in one form or another, and their lasting impact can be seen through follow-on projects, start-ups that were born from the outcomes of the projects, or innovative tools that have become staples in the medicines development community.

To pay homage to the longevity of those projects, and to celebrate our birthday (IMI turns 12 in April) IMI is featuring some of these projects on Twitter. Read more about them (and view the tweets) in the following news items:

• EUPATI
• GETREAL
• European Lead Factory
• EHR4CR

The European Lead Factory was launched in 2013 and set up a joint collection of half a million compounds and a state-of-the-art high throughput screening centre. By the time the project ended last year, they had delivered results to researchers in universities, small biotechs and large companies across Europe, helping them to identify potential new drug candidates and breathing new life into a range of disease areas. ###In many cases, the seeds sown by the European Lead Factory resulted in new patents, partnering deals, and two start-ups. Now, a new IMI project, ESCulab will build on the work of the European Lead Factory. This means that researchers with drug targets can apply to screen the project’s compound collection for hits and get help developing any compounds further if they like. Jon de Vlieger, coordinator of the ESCulab consortium at Lygature, said: ‘It’s truly exciting to continue the onboarding of new and innovative proposals for screening and provide high quality starting points for drug discovery to academics and SMEs throughout Europe. In an effort to broaden our scope we are not only looking for target-based approaches, but now also enable phenotypic screens.’

The European Lead Factory has hit another milestone with the announcement that the public part of its compound library now contains 200 000 novel compounds. ###When the project launched, the pharmaceutical companies immediately contributed over 300 000 compounds to the project, allowing it to start its activities early on. Meanwhile, the project got to work crowdsourcing library design ideas for the public part of the library from scientists in academia and industry alike. All ideas were screened by experts and the most promising were turned into physical compounds by the project’s team of chemists. ‘It was a huge challenge to collate and translate those innovative library ideas into physical compounds,’ said Dimitrios Tzalis, Head of Chemistry at the European Lead Factory and CEO of Taros Chemicals. ‘We all hope to have served and to further serve the wider European scientific community on their drug discovery research programmes to ultimately benefit the many patients in need worldwide.’ The project’s compound collection and state-of-the-art screening centre have allowed researchers across Europe to successfully start drug discovery projects in a range of disease areas.

Servier, an independent international pharmaceutical company with its headquarters based in France, and Swedish spin-out ScandiCure, have entered into an agreement on the further development of ScandiCure compounds that show promise as treatments for type 2 diabetes and the liver disease non-alcoholic steatohepatitis (NASH). ###The seeds of the collaboration were sown when Margit Mahlapuu of the University of Gothenburg identified a drug target that could be used to reverse some of the metabolic complications of diabetes. Thanks to the European Lead Factory, she was able to identify a number of compounds that interact with the target. She then set up ScandiCure as a spin-out company to develop the compounds further. Under the new agreement, Servier will carry on the research started by ScandiCure, advancing the novel compounds through preclinical development. Servier will also provide ScandiCure with an upfront payment as well as pre-clinical and clinical milestones. ‘We have identified a new attractive target in metabolic diseases, and the European Lead Factory has provided an access to a high-quality compound library and a platform of expertise for high-throughput screening. This unique combination of a well-validated target with the high-quality output of the European Lead Factory has provided ScandiCure with strong starting points for new and transformative treatments in NASH and related diseases,’ said ScandiCure’s Dr Mahlapuu. ‘Our access to ScandiCure’s target-knowledge and novel chemistry allows us to explore an important pathway in metabolic diseases,’ said Claude Bertrand, General Director of Research and Development at Servier. ‘Our goal is to find effective treatments for patients who suffer from NASH, who are underserved by current therapies. This agreement illustrates Servier’s continued commitment to novel approaches to diseases where significant unmet medical needs still exist.’

As one of IMI’s flagship projects, the European Lead Factory (ELF), continues to attract attention and has recently been featured as a success story on the European Commission website. ###Among other things, the article talks about how the demand for ELF services continues to grow and how the project is already helping Europe’s pharmaceutical sector deliver real progress. After five years of success, the project is now drawing to a close and will soon have its next stakeholder meeting, which will be held in Brussels, Belgium on 17 April 2018. Registration is still open.

Registration is now open for the European Lead Factory’s stakeholder meeting, which will be held in Brussels, Belgium on 17 April 2018. The theme of the meeting is ‘Collaborative innovation - seeding tomorrow’s priority medicines’, and it will feature presentations and posters from both project partners and programme owners who have made use of the European Lead Factory during its five years of operation. ### One of the speakers is Margit Mahlapuu of the University of Gothenburg, whose experiences with ELF resulted in the creation of a successful spin-out. The event will also include a discussion on the future and how stakeholders can further grow this platform to serve drug discovery for priority medicines.

The European Lead Factory’s Joint European Compound Library now contains 500 095 compounds, taking it over the 500 000 goal set at the start of the project.### Of these, 326 350 are ‘in-kind’ contributions to the project by the 7 large pharmaceutical companies in the project. The rest of the compounds were synthesised by the chemistry partners in the project: Edelris, Mercachem, Sygnature, Syncom and Taros. What’s more, these companies expect to deliver a further 20 000 compounds before the end of the project.

Analyses of the collection have highlighted the quality and diversity of the collection, which has been used to run over 150 screens for public and private partners. The results of these screens have delivered promising results in a wide range of areas, including Parkinson’s disease, diabetes, antimicrobial resistance, and cancer.

• Read the European Lead Factory’s news article
• Read testimonials from users of the European Lead Factory’s services.

Pioneering ideas to improve antidepressant therapies are greatly required since existing antidepressants are moderately effective and the response rate in patients suffering from depression is approximately less than 50%.### IMI’s European Lead Factory (ELF) project has identified novel small molecules that might be transformed into a new medical treatment for depression and pain. The exciting innovative target involved in these debilitating conditions was discovered by Dr Patrick McHugh of the University of Huddersfield. ‘We don’t have the facilities to carry out large scale screening campaigns to fully assess the possibilities of our findings’, said McHugh. ‘That’s why we’ve used the connections in ELF and formed a partnership with Taros Chemicals and Pivot Park Screening Centre to counter this problem and enable further investigation of this target and its potential to modulate disease.’

In a collaborative effort, they successfully created a drug discovery programme which could be submitted to the ELF. Subsequently, the entire Joint European Compound Library of approximately 400 000 compounds was screened, which resulted in 50 confirmed hits. These promising compounds will now be further developed by the consortium, which could lead to an alternative medicine to treat depression as well as chronic pain.

Hungarian company ChemPass has received EUR 5 000, the highest monetary award possible from the European Lead Factory, for the design proposals for compounds it submitted to the project. A large proportion of the project’s compound collection is synthesised based on ideas submitted by chemists around Europe. ### Ideas submitted are assessed by the project, and if they meet the standard, project scientists turn the ideas into compounds which are added to the project’s compound collection. To incentivise proposals, the project pays groups that submit ideas. In this case, ChemPass used its state-of-the-art software to devise some library designs. The first design to be accepted has already been turned into a library of over 90 compounds that have been added to the project’s compound collection. ChemPass CEO and founder Greg Makara is enthusiastic about the system. ‘The whole crowdsourcing idea is great,’ he said. ‘With a reasonable amount of effort, you can get great outcomes.’ Meanwhile, Jorg Benningshof of Mercachem, the European Lead Factory partner who oversaw the synthesis of the compounds based on ChemPass’s ideas, added: ‘External library designers inject further novelty and diversity in JECL [the Joint European Compound Library].’

Parkinson’s UK has allocated GBP 1 million (approx. EUR 1.2 million) for the creation of a virtual joint venture biotech company with the University of Sheffield to further develop compounds that were identified through the European Lead Factory and that could prove useful in the hunt for a treatment for Parkinson’s disease.### The European Lead Factory comprises a collection of over 400 000 compounds from public and private sources as well as a state of the art screening centre. Richard Mead of the University of Sheffield turned to the European Lead Factory for help identifying compounds that could prove effective against a drug target involved in oxidative stress, which plays an important role in Parkinson’s. The European Lead Factory set up and ran the screens, and the results were so interesting that Parkinson’s UK decided to set up a ‘virtual biotech’ company, Keapstone Therapeutics, to support further work on the compounds identified. According to Richard Mead, the results would have been ‘absolutely impossible’ without the European Lead Factory. ‘We made incredible breakthroughs!’ he said. ‘Many, including ourselves, have screened various commercial and academic libraries, but never found anything useful. The diversity and quality of the Joint European Compound Library is not available anywhere else.’ Meanwhile, Arthur Roach, Director of Research at Parkinson’s UK added: ‘We were convinced that these early results are really good starting points in developing new treatments for Parkinson's and formed Keapstone Therapeutics as a new way to further this research.’

 - Read Richard Mead’s testimonial on his experience of working with the European Lead Factory

 - Read the Parkinson’s UK press release

The assay and compounds screened through the European Lead Factory are an important part of the PhD thesis of Freek Janssen of Leiden University in the Netherlands. Freek was studying a protein called diacylglycerol lipase (DAGL) that makes endocannabinoids, molecules that are made by the body and have a similar effect to marijuana. ###He was interested in whether DAGL could be a target for treatments of obesity or neurodegenerative disorders for example. When a screen of a commercial library failed to deliver results, he turned to the European Lead Factory. ‘The access to the expertise and the very high quality drug-like compounds in the Joint European Compound Library is unique,’ he said. Janssen and his colleagues optimised the results obtained from the European Lead Factory to create a ‘drug-like’ compound. Some of the developed compounds have undergone further tests and initial results are promising. A number of Freek’s colleagues are also busy working on results from European Lead Factory screens. ‘The EU Lead Factory doesn’t just boost a single drug discovery project; but it can boost the research of several people,’ he says. ‘My advice to other academics with a high quality assay: apply for the EU Lead Factory as soon as possible!’

After helping 73 drug discovery programmes, academics and SMEs, to identify potential new drug candidates, the European Lead Factory (ELF) recently reported another milestone. One of the academic researchers who benefited from ELF screening activities by identifying a drug candidate series for type 2 diabetes, went on to create a spin-out company based on these findings.### The researcher, Dr Margit Mahlapuu from the University of Gothenburg, first identified a new target which could be used to reverse metabolic complications in type 2 diabetes. With the help of the ELF, she then screened the ELF library of the then 320 000 industry compounds and identified a set of selective and potent small molecules which interfere with this target. She went on to create a spin-out company, ScandiCure, whose aim is to further develop these molecules into a first-in-class anti-diabetic drug. The company already secured an investment from GU Ventures AB, an investment company and an incubator owned by the Swedish state. This is the first spin-out created as a result of ELF, but project representatives hope it won’t be the last. ‘As the European Lead Factory offers access to high-quality compounds to any researcher in the EU, similar spin-outs in various disease domains are expected in the future’, said Ton Rijnders of Lygature, one of the ELF project partners. ‘The value of such spin-outs is not only in the expected commercialization of products developed, but also in the societal impact. ELF contributes to the faster development of new innovative medicines, which will eventually benefit the patient.’

Two IMI flagship projects, the European Lead Factory and ENABLE, have together propelled a promising, new antibiotic programme, which could result in new antibiotics for patients. A researcher from the University of Oxford, Chris Schofield, kick-started the process through his group’s focus on a potential target within gram-negative bacteria that could eliminate resistance### against antibiotics. He applied to the European Lead Factory project, where the target was screened against their library of about 300,000 compounds. Small molecule hits with very promising activity against the target were identified. The Oxford and ELF teams worked further to improve the hits, resulting in highly potent compounds that create a strong base for further development. Schofield then turned to the ENABLE project, which has the mission to develop attractive antibacterial candidates for testing in the clinic. The application was deemed to have high novelty and potential for development and was accepted by the project. Schofield’s group is now collaborating with ENABLE partners in the pharmaceutical industry, SMEs and universities from across Europe to develop these early stage compounds towards clinical trials. ‘Through collaborative efforts across Europe, we have been able to take a potential antibiotic target and identify compounds active against it, improve them and start development towards the holy grail of new antibiotics for patients’, said Schofield. ‘This is transforming an almost impossible task for an individual academic group into a solid scientific and commercially viable pathway.’ And there is more in the pipeline: ELF is currently working on another 5 antibiotic programmes and ENABLE accommodates 8 active programmes.

•  Read the press release

In a bid to contribute to the development of treatments for neglected tropical diseases (NTDs), IMI’s European Lead Factory project is waiving certain fees for drug discovery programmes in the area. The waiver applies specifically to non-profit programmes on diseases on the World Health Organization list of NTDs.### The diseases on the list, which includes sleeping sickness, rabies, leprosy, and dengue fever, are found in 149 (mainly tropical and sub-tropical) countries and affect one billion people worldwide.

‘For drug target programmes relating to the pathogens on the WHO list of neglected tropical diseases, clinical or diagnostic milestone payments will be waived, thereby freeing charities and other organisations from financial obligations in their pursuit of new therapies for patients in the least developed countries,’ said the project in a statement.

The European Lead Factory allows researchers to propose drug targets for screening against the project’s 400 000-strong compound collection. The project also offers assistance with the follow-up of results generated through the project. Achim Schnaufer of University of Edinburgh recently drew on the project for his research. ‘The compounds that were identified by the European Lead Factory have really promising properties and we look forward to building on these discoveries,’ he said. ‘We are very grateful for European Lead Factory's support for our efforts to develop new therapies for African sleeping sickness and other related diseases.’

The European Lead Factory has selected its first drug target programme from Spain, in the form of a cancer drug development programme led by the Center for Applied Medical Research (CIMA) at the University of Navarra. The CIMA has pioneered the development of molecules that show signs (in animal tests) of being effective in the treatment of blood and liver cancers. ###According to Julen Oyarzabal, Director of Translational Science and the Molecular Therapy Program at CIMA, the goal of this project is to ‘identify new molecules that enable more effective treatments with fewer side effects’. He adds: ‘Our study also allows us to assess their impact on other diseases of the central nervous system, cardiac complaints and metabolic illnesses.’ The intellectual property model of the European Lead Factory will allow CIMA to file patents on the identified molecules for future development of a possible new drug.

Read the CIMA press release.

IMI’s European Lead Factory (ELF) project is running a screening programme on dengue fever for British biotech company Effecta Pharma. There are currently no treatments for dengue fever, which causes flu-like symptoms and can turn into the more serious, potentially fatal ‘severe dengue’.### Effecta is using the European Lead Factory in its hunt for molecules that could be transformed into urgently-needed safe, effective dengue treatments. ‘We are excited we can continue our initial collaboration with the ELF and its European Screening Centre researchers in Oss, Oxford and Newhouse, which has yielded a screenable assay for one of the critical dengue virus proteins,’ said Effecta directors Helmuth van Es and Paul Edwards. ‘Having ELF as part of our concerted effort to generate preclinical candidates for dengue is welcome support for Effecta and the patients suffering from this disease.’ Dengue fever is caused by a virus and transmitted by certain mosquitoes. Cases are on the rise worldwide, as the disease-bearing mosquitoes spread through globalisation. Furthermore, one mosquito species capable of transmitting the virus is now spreading into cooler regions, including Europe. Moreover, as dengue is closely related to the Zika virus, the researchers are hopeful that the results of their dengue programme could prove useful in the fight against Zika.

Scientists from the University of Oxford have filed a patent to protect compounds identified with the help of the IMI project the European Lead Factory. The patent addresses multidrug resistance in bacterial infections. This important milestone, reached less than three years into the project, reflects the European Lead Factory’s ability to deliver on its promise, and highlights the potential of this shared innovation approach to drug discovery.###

The drug target programme was submitted to the European Lead Factory for high-throughput screening by Professor Christopher Schofield and co-workers from the University of Oxford. ‘We had identified what we believed was a good target, but we did not have the resources to run high-throughput screening,’ explains Professor Schofield. ‘That’s when we became aware of the EU Lead Factory. Jurgen Brem from our laboratory worked productively with the EU Lead Factory team to optimise a suitable assay.

The European Lead Factory, supported by IMI, combines a high-throughput screening centre and a high-quality compound library. The screen against Professor Schofield’s drug target identified an array of promising compounds that were subsequently optimised. The patent that was filed protects these compounds in combination with the biological effect.

‘Overall, we are extremely satisfied with the progress, from assay optimisation to post-hit validation, and the synthesis of follow up compounds/medicinal chemistry expertise,’ said Professor Schofield. ‘The EU Lead Factory really offers a collaborative effort rather than a service, with an exemplary level of commitment and professionalism from the EU Lead Factory scientists on the different sites.’

The quality and diversity of the compounds found in the European Lead Factory’s Joint European Compound Library (JECL) is highlighted in two recent publications. The project’s goal is to compile a 500 000-strong compound collection that researchers can screen (at no upfront cost) to identify compounds that could prove interesting for their own research.### The pharmaceutical companies in the project have already contributed over 300 000 compounds to the library.

A paper published earlier this year in Drug Discovery Today reveals that many of these compounds are likely to be of interest for medical research. Meanwhile, ‘public’ partners (like universities and small biotechs) are adding novel compounds to the collection all the time.

A recent paper, also in Drug Discovery Today, analyses the first 55 000 compounds added to the ‘public’ collection. According to the project, ‘Both analyses reveal the high-quality and diverse nature of the compound collection, that is complementary to already existing libraries and provides access to novel chemical space.’ By January 2016, the project expects the compound collection to hit the 400 000 mark – a significant milestone.

Just a few months after it was included in drug target screening programmes, one of the first compounds synthesised within the European Lead Factory was identified as a ‘drug-like’ hit. The compounds were synthesised by the Public Chemistry Consortium, based on library proposals from academic groups and small- and medium-sized enterprises (SMEs) in Europe. ###The EU Lead Factory carefully selects library proposals for novelty, drug-like properties, diversity and synthetic tractability. The hit compound was among the first compounds to be synthesised within the EU Lead Factory, and was added to the Joint European Compound Library (JECL) along with 28 000 other compounds in January 2015. In addition to the hit compound, another 130 compounds have already been identified as ‘preliminary hits’ over multiple drug-target screening programmes in only 5 months, highlighting the potential of the EU Lead Factory compounds. Together with 326 000 high-quality compounds that were already contributed by 7 large pharmaceutical companies, the JECL now holds over 350 000 compounds. The collection is available for screening against novel drug targets and will continue to grow. Want to learn more about the EU Lead Factory? Visit www.europeanleadfactory.eu or meet them in person at MipTec 2015 in Basel, Switzerland in September 2015 where the team will be at stand D25 in the exhibition.

The European Lead Factory has won a prestigious Bio-IT World Best Practices prize in the knowledge management category for its Honest Data Broker (HDB) implementation of the ScienceCloud platform from BIOVIA.### ScienceCloud HDB is a core technology providing an innovative solution to the particular challenges of this open innovation platform in drug discovery: providing access to ELF’s extensive library with compounds from the pharmaceutical industry and public partners, as well as to details on the screening data, the HDB also provides reassurance to compound and target owners that their intellectual property is protected. The HDB therefore combines fine-grained permissions with efficient access to the vast range of chemistry and biology data it stores, which allows good science to be carried out while safeguarding IP interests. For the Bio-IT judges, the HDB is ‘the only platform in its class’.

This peer recognition coincides with a number of high-impact scientific publications from the ELF chemistry partners in a special issue of Bioorganic & Medicinal Chemistry on ‘Emerging Approaches for the Design and Synthesis of Innovative Small Molecule Libraries’.

This is the second time an IMI project has received a Bio-IT World Best Practice award; in 2014, severe asthma project U-BIOPRED won in the research and drug discovery category.

• Announcement  of the Bio IT Winners
• Read the press release
• Bioorganic & Medicinal Chemistry Journal 

IMI’s European Lead Factory has published four short videos to help SMEs and academics understand how the programme works. The videos explain the programme’s aims and give an overview of how target assays are introduced and handled###, as well as how to test chemical scaffold ideas using the European Lead Factory’s online compound tool. Programme owners' rights & obligations are also covered in this light-hearted series of animations.  

• Watch the videos
• Find out more about the European Lead Factory
• Read the latest European Lead Factory newsletter

IMI’s European Lead Factory project will demonstrate how its services can help to boost the drug discovery programmes of diverse organisations at a free workshop on 25 March at the SLAS Conference on Compound Management in Dortmund, Germany.### The event will spotlight the extensive drug target screening and compound synthesis resources now available through the European Lead Factory. As such, it offers attendees an excellent opportunity to think about their target assay development and compound library design plans. Meanwhile the panel will be able to answer questions on the wider role of crowdsourced innovation and on working within extended public-private partnerships.

The European Lead Factory currently comprises a 350 000-compound screening collection originating from private partners or synthesised by public partners, as well as a screening centre that is accepting proposals for screening programmes. The first screens have already been completed and feedback from users is highly positive.

• Register to attend the workshop
• Find out how to submit a proposal for a target or scaffold
• Learn more about the European Lead Factory’s successes in its latest newsletter

IMI’s European Lead Factory project has proven its potential for drug discovery with the delivery of its first results in the form of four ‘qualified hit lists’ – lists of up to 50 compounds identified as showing activity against a drug target submitted to the European Lead Factory’s screening programme.### One of the beneficiaries of these results is the Netherlands Cancer Institute, which stated that access to the European Lead Factory had fast-forwarded its oncology drug discovery work ‘by several years’. Another list went to pharmaceutical company UCB, which noted that access to the 300 000-strong Joint European Compound Collection had provided it with a list of ‘highly interesting’ compounds that would allow it to take a fresh look at a particularly challenging drug target.

Organisations wishing to take advantage of the project’s extensive compound collection can submit target proposals via the project website. The project is also accepting proposals for external compound libraries via its website. If proposals result in the addition of over 50 compounds to the library, the proposer receives a payment.

• Read the project’s press release on the results
• Find out how to submit compounds to the library
• Find out how to submit target programmes to the project

The European Lead Factory project is now accepting proposals for both compounds and target programmes from project partners as well as external academics and small and medium-sized enterprises (SMEs).### Compound ideas will be assessed by a selection committee made up of respected chemists from the pharmaceutical industry, SMEs, and academia. The committee, which is bound by a confidentiality agreement, will assess proposals on the basis of their molecular properties, structural features, novelty, and innovation, among other things. Compounds that make the grade will be added to the Joint European Compound Collection; the selection committee will decide the financial reward due to the proposers.
Meanwhile, the project’s biology target programme is open to submissions for all disease areas, including oncology, cardiovascular, central nervous system (CNS), respiratory, and neglected diseases. Target screening programmes should be novel, of high quality, and ready for high throughput screening (HTS).

• Details of how to apply, plus information on the project's intellectual property policy, can be found on the project website.

This summer, IMI’s European Lead Factory project successfully completed its first miniaturised screening programme, highlighting the capabilities of the project’s Screening Centre at Pivot Park in Oss, the Netherlands.### Where a traditional lab would test tens to hundreds of compounds per day, the robot in Oss completed testing of 300 000 compounds in under 3 days. The European Lead Factory has two main components – the Screening Centre in the Netherlands, and the Compound Collection, which is based in Scotland and currently comprises the 300 000 compounds contributed to the project by the pharmaceutical companies. A further 200 000 compounds will be added to the Compound Collection throughout the project by the public partners. Looking to the future, the project hopes to open Calls for further public screens in the near future.

Registration open for European Lead Factory Stakeholder Meeting 2017
IMI’s European Lead Factory project will hold its Stakeholder Meeting 2017 on 25-26 April in Heathrow/Windsor, UK. The theme of this year’s event is ‘hitting the targets’, ###and there will be a focus on sharing the experiences of the project with a broad group of stakeholders from policy, science, business and health. As detailed in the agenda, partners will present the results of their collaboration, and the unique assets of the Lead Factory will be highlighted in a dedicated poster session. Additionally, attendees will have the opportunity to discuss the future of drug discovery with programme owners and other experts. Registration is free but obligatory.  
(March 2017)

European Lead Factory featured on Euronews
Taros Chemicals, one of the partners in IMI’s European Lead Factory project, was recently featured on Business Planet, the Euronews programme dedicated to SME success stories. ### The episode aimed to show how SMEs can benefit from being involved in IMI projects. Missed it? You can still watch it online. 
(November 2016)