Photos courtesy of James Clare Photography, BioCity Scotland and Pivot Park Screening Center Oss.
When challenges are big, people look to each other for support. To tackle one of the biggest challenges facing mankind today – developing effective new medicines – large pan-European pharmaceutical companies have joined forces with small and medium-sized enterprises and academia in a wide-ranging drug discovery platform, the European Lead Factory.
On February 7, 2013, an international consortium of 30 partners launched the European Lead Factory to create "unprecedented opportunities for the discovery of new medicines by providing public partners with an industry-like discovery platform to translate cutting-edge academic research into high-quality drug lead molecules on a scale and speed that was not possible previously." The consortium is supported by the Innovative Medicines Initiative (IMI), Europe's largest public-private partnership supporting collaborative pharmaceutical research projects and building creative teams.
"IMI is supporting the European Lead Factory because it fits in with IMI's efforts to promote greater collaboration and knowledge sharing in the drug research and development sector," states Hugh Laverty, IMI senior scientific project manager. "Specifically, it aims to open up the chemical libraries of companies so they are not only available to other companies, but also to public bodies and small and medium-sized enterprises (SMEs) within Europe. It therefore represents a unique experiment to investigate whether drug screening can be done in a different way from the current model. It also offers academics and SMEs the opportunity to screen a chemical library not available elsewhere. Because eligible public projects will be funded by IMI, it also is hoped that this project will accelerate the discovery of novel medicines."
In the end, of course, the desired result of accelerated progress is to put new drugs in the hands of doctors whose patients are in need. Collaboration for this purpose is a theme heard far and wide today. In a previous SLAS Electronic Laboratory Neighborhood e-zine feature, Martyn Banks, Bristol-Myers Squibb, spoke about collaboration as the focus of an SLAS2013 panel presentation.
"What we are trying to achieve at SLAS2013 is to understand how we can work together – both in screening and early drug discovery to benefit everybody," Banks said in the article. "I call this the ecology of drug discovery – where you have a partnership between pharma, biotech, government and academia all working together. We need to work through the challenges and issues of developing this complex network."
"The idea for the European Lead Factory was generated by pharma companies in the EFPIA (European Federation of Pharmaceutical Industries and Associations) working closely with IMI," says Ton Rijnders, scientific director of Top Institute Pharma (TI Pharma). "They see this as a great opportunity to expand their access to novel and innovative chemistry for their markets. They receive enhanced screening capabilities and access to compounds, and early access to novel targets. The chemistry academic groups participating will see their chemistry ideas being realized in libraries that will actually be screened, which is otherwise very difficult for them. The academics that bring in screens will get access to a unique collection of compounds that they would otherwise never have been able to access and will have the opportunity to develop results from that if they wish."
TI Pharma was selected to oversee the European Lead Factory due to its expertise in establishing and managing international public-private partnerships. TI Pharma is a non-profit organization with a mission to enable groundbreaking pharmaceutical research that results in new medicines for better human health. Rijnders, who also serves as the head of screening for the European Lead Factory, is a huge proponent of open innovation and crowdsourcing that allows businesses to benefit from accessing the combined knowledge of others. "For pharmaceutical companies," Rijnders says, "open innovation can improve the efficiency and creativity of bringing drugs to market."
The European Lead Factory began, as all IMI projects do, with an open call. From March to May 2012, interested parties could submit an Expression of Interest to be considered for participation. After review, the finalists were invited to submit a full project proposal by September 2012. Upon final approval of proposals, offers were made and contract negotiations began.
"Of course, the major discussions of the project originally revolved around how we make sure that what comes out of this is supported by an equitable sharing and reward system," Rijnders says. "We came up with a plan that is attractive to everyone and makes sure that project results – a qualified hit list – can be developed by the target owner whether that target owner is a pharma company or academic partner. They are always in the driver's seat with respect to progression of these projects – whether to publish, use the compounds to develop a drug or partner further with companies. There are certain milestones associated once the hit becomes commercial so the consortium also benefits.
"I think in all honestly it was a major achievement of this consortium to come to agreement on this very difficult issue," Rijnders continues. "Difficult it was. It's based on a number of intellectual property rules set out by IMI as public money is being spent. Attorneys from consortium members also helped craft the contract. It was not an easy task, but we did create it and we created it in a reasonable timeframe."
The contract negotiations took roughly four months, October 2012 to January 2013, Rijnders notes.
"Everybody in this group really wants this to work and showed that by coming to agreement," he says. "Without commitment of all the partners, especially from pharma, it would have been impossible to come to this point."
The European Lead Factory, currently funded for five years to the tune of €200 million, calls for developing a library of 500,000 compounds and conducting some 48 high-throughput screens (HTS) per year. Half will come from pharmaceutical company partners running their own screens and the other 24 HTS projects will be selected from the public sector following competitive calls for proposals.
"The initiative is split into two parts – the Joint European Compound Collection and the European Screening Centre," Rijnders states. "Key to the initiative's process is the building of an exceptional collection of compounds. As part of the European Lead Factory agreement, the seven participating EFPIA companies will contribute at least 300,000 compounds from their personal chemical libraries. An estimated additional 200,000 novel compounds will be developed by participating academic institutions and SMEs."
His colleague running the chemistry side is Dimitrios Tzalis of Taros Chemicals. Rijnders describes gathering the compounds as step one. At the end of May, the number collected mounted to that initial goal of 300,000 compounds.
"What we need to do first is bring together the library," he says. "All companies have to submit their compound sets. Then, we have to check them for redundancies and make sure they are unique compounds and that nothing in there is available through commercial sources. We reckon that to collect and replate will take us through the summer of this year."
Rijnders said simultaneously, they also started recruiting assays from within the partnership to begin the assay development process. In the second part of 2013, they plan to start running screens.
Another key element in position to support success is outstanding facilities, Rijnders says. The project boasts former Organon BioSciences (then Schering-Plough, then Merck) sites in Newhouse, Scotland and Oss, The Netherlands, which have been updated with state-of-the-art equipment for compounds and screening, respectively.
"Of most interest to SLAS members is the screening facility in The Netherlands," Rijnders says. "Formerly known as Life Sciences Park Oss, it is now called Pivot Park." Rijnders explains Pivot Park has been revamped and retooled to handle the ultra-high-throughput screening (uHTS) needs of the European Lead Factory.
"The state-of-the art equipment needed to run 120 public screens over five years includes read-out equipment for most major assay technologies plus acoustic dispensing that will allow for high precision low volume dispensing," Rijnders notes. "The short-term goals are to get the whole thing up and running and have something like 10 to 15 screens done by the end of 2013."
Key to the contract negotiation completed earlier this year is who owns what and how targets can be moved along the drug discovery pipeline.
"What is shared is the target only," Rijnders explains. "We have agreed that the end point for the program is a qualified hit list – a set of compounds that meet certain requirements and offer meaningful results that can progress. Program owners are expected to get a set of compounds, with a limit of 50 to each. This ensures the compound library will not be depleted."
A February 7, 2013, Nature article says the difference between the European Lead Factory and the United States National Institutes of Health Molecular Libraries Program is that in the European Lead Factory, "both the chemicals in the screening library and results from the assays will be proprietary. [European Lead] Factory partners will get first right of refusal in licensing deals."
Both Rijnders and Laverty state that the European Lead Factory is an experiment – albeit well orchestrated to position members for success – but an experiment just the same.
"At the very least the project needs to have met its milestones and objectives in providing a unique platform that is accessible to all project partners and public third parties," Laverty summarizes. "It is hoped that the results of the screens will lead to the generation of intellectual property that can be exploited by target owners. It would be good to see further alliances and collaborations based on the European Lead Factory's output. Finally, in the longer term it would be exciting to see chemistries derived from the results of screens entering into pre-clinical development programs, particularly those of public third parties."
"The project aims to make better use of existing libraries within companies to create novel chemistry on relevant targets and to open up those libraries to competitors," Rijnders adds. "It is also a large-scale experiment to the academic world to see whether they can increase the innovative potential both on the chemistry and the biology side – to match creative and innovative target ideas that live out there in the academic world with chemistry that would otherwise not be available to them to create starting points for new projects. These new models based on knowledge sharing and open innovation are quite different from what we've been doing to date.
"The ultimate goal, of course, is to get something to patients," he concludes. "It's not going to happen overnight but it is really focused on that end goal."
European Lead Factory Members
Universities, Research Organizations, Public Bodies, Non-profit Groups
May 28, 2013