Pharmaceutical sites have been closing down across Europe, but in a rare change of affairs the recently launched European Lead Factory is giving two shuttered Merck sites a second shot at drug discovery. The new initiative will combine a 500,000‑compound library and a high‑throughput screening (HTS) centre.
“If we ended up with ten drug candidates and one or two drugs on the market, that would be a huge success,” says Michel Goldman, Executive Director of the Innovative Medicines Initiative (IMI), which is
backing the €196 million initiative. It could also fuel patents, publications, partnerships and spin‑outs, so long as it can successfully navigate treacherous intellectual property (IP) waters.
The collaboration brings together 30 academic and industry partners including Bayer, Janssen, Merck‑Serono, AstraZeneca, Sanofi, UCB and Lundbeck. The IMI is providing €80 million in backing, and the 7 pharmaceutical founders are providing €91 million in in‑kind contributions.
On the library side, the pharmaceutical partners will
collectively contribute 300,000 compounds from their in‑house libraries to the newly created Joint European Compound Collection (JECC). European academics as well as small and medium‑sized enterprises (SMEs) will work together to top up this shared JECC with a further 200,000 chemicals. Scientists at the new European Screening Centre, based out of the sites in the Netherlands and Scotland, will then develop high‑throughput assays to screen the JECC against novel targets proposed by academic groups. They will return results to the originating academic
European Lead Factory opens for businessSeven pharmaceutical companies and the Innovative Medicines Initiative have launched a €196 million project in a bid to boost academic and industry lead discovery.
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groups, possibly with a pharmaceutical partnership deal on offer.
“For academics who would like novel chemical matter and want to have their projects on industry’s radar for potential early‑stage licensing, this could be the mechanism through which to make it happen,” says Andrew Hopkins, of the University of Dundee in Scotland and one of the European Lead Factory’s largest grant holders. “You get the entire project done for free,” he adds.
Projects will include some medicinal chemistry, such as the synthesis of a few strategic analogues around a hit to show that an emerging structure–activity relationship exists. But a full hit‑to‑lead optimization project can take up to 2 years and cost €2 million, says Bayer’s Jörg Hüser, who is also the European Lead Factory’s coordinator, and the budget is limited. “The initiative’s name is misleading; what we will generate is really qualified hits. Our aim is to identify patentable compounds that justify additional downstream investment.”
The European Screening Centre will run 24 projects for academics each year, and the collaborating drug developers expect to partner on around 1 in every 6 programmes. The consortium’s pharmaceutical backers will also use the JECC library to run 24 campaigns in‑house on targets of their choosing.
“The fact that companies are willing to share compounds from their library shows a huge change over what they would have done even 5 years ago,” says William Janzen, Director of Assay Development and Compound Profiling at the University of North Carolina. Last year, AstraZeneca and Bayer announced they had granted one another access to their screening libraries — showing just how much the dynamic between competitors has shifted (Nature Rev. Drug Discov. 11, 739; 2012). A host of programmes, including repurposing projects in the United States and the United Kingdom, similarly suggest that boundaries between industry and academia are breaking down (Nature Rev. Drug Discov. 11, 505–506; 2012). “This very innovative sharing reflects a big shift in industry,” says Janzen.
Europe’s screening experimentThe European Lead Factory’s ability to deliver on its promise of leads will depend in part on which targets it selects to screen and which chemistries it develops to populate its compound collection. In both instances, it will focus on novelty. “We are not looking to replicate what has been done by industry already,” says Ton Rijnders, Scientific Director of TI Pharma and the European Lead Factory’s head of screening.
The JECC’s scientific advisory panel, for example, will ask contributing academics and SMEs to explore new chemical space. “We don’t want to stick to the rules that have been used over the past few years by the pharmaceutical partners,” says Dimitrios Tzalis, CEO of Taros Chemicals, who will oversee the synthesis of the JECC’s publicly sourced components. The seven drug developer’s contributions to the JECC will be guided more by pragmatic issues, such as freedom from third‑party rights.
But Tudor Oprea, who runs HTS at the University of New Mexico and participated in initial discussions about how to put together the compound collection, voices some reservations. “There are not enough checks and balances to verify that what is assembled into the library is completely unique,” he says. The selection process plays down the role of chemoinformatics analyses in favour of peer review, he says, which could undermine the value of the library. The fact that pharmaceutical partners won’t disclose many details on what they will contribute further complicates matters.
Oprea also raises a broader concern. “How do we know that industry isn’t actually looking at a way to take IP from unsuspecting academics and turn it into blockbusters?”
The scheme’s organizers say that they took IP issues to heart during their discussion, coming up with mutually beneficial arrangements. “At one of the first meetings, there were more lawyers than scientists,” says Goldman.
In terms of biological project proposals, the academics who put forward novel target ideas will own the validated hits that come
out of the screening campaigns. Academics will then be free to partner with the founding pharmaceutical members, take the work forward on their own or engage a third party. Any projects that move towards the clinic will pay milestones back to the lead‑finding initiative. When drug developers use the JECC on in‑house projects, they will similarly own validated hits and pay out relevant milestones.
On the JECC chemistry side, the academics who propose projects and the SMEs that implement chemistries will co‑own resulting chemical matter and will receive a slice of milestone payouts earned on compounds that become validated hits.
“We have measures in place to treat confidential information with all the integrity we need to build up trustful relationships between partners,” adds Hüser. “If we as industry start [taking ideas], that would destroy any potential partnering possibilities in the future.”
Given the focus on commercialization and partnering, the European Lead Factory’s engineers have established rules to temporarily delay the publication of potentially profit‑generating results. “The project has quite strict controls over the amount of information that can be released,” says Hugh Laverty, a scientific project manager with the IMI.
Although the initiative’s closed nature will no doubt raise hackles in some quarters, it is just part of a broader European screening ecosystem, says Ronald Frank, coordinator of ChemBioNet and the EU‑Openscreen, two academically oriented screening initiatives. “There is no single way to solve screening problems.”
The nascent EU‑Openscreen could bring together a network of academic screening centres from across Europe to run 50–200 probe‑finding projects per year on an annual €40 million budget. Like the US National Institutes of Health (NIH)’s Molecular Libraries Program (MLP), the EU‑Openscreen will take an open‑access approach to HTS; its primary emphasis will be on generating probes and publications, rather than drugs and deals.
“There could be some competition between the centres,” says Frank. “But the way they are now conceived, the European Lead Factory and EU‑Openscreen should be seen as complementary activities to bridge academic expertise and pharmaceutical drug development.”
Sustainability mattersThe IMI and the seven founding pharmaceutical members are originally funding the lead factory for 5 years, but
If we ended up with ten drug candidates and one or two drugs on the market, that would be a huge success
I find it ironic, and distressing, that at the time when the Europeans are realizing that this is a great approach, the Americans are retreating
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its engineers hope the venture will last longer. The MLP, however, offers a cautionary tale.
The NIH launched its HTS initiative in 2004 to find chemical probes for academics, with 10 years’ worth of funding. The MLP has since built up a 377,000‑compound library, seeded over 650 publications, identified nearly 300 probes and produced one drug candidate that has made it into clinical trials (RPC1063, a sphingosine‑1‑phosphate receptor 1 agonist, is being tested in multiple sclerosis). It runs around 104 HTS campaigns a year, and had a budget of US$91 million in 2012 alone. Yet it has failed to find an NIH centre to adopt it, and funding will cease next year.
“I find it ironic, and distressing, that at the time when the Europeans are realizing that this is a great approach, the Americans are retreating,” says Chris Austin. “I think
this will turn out to be short‑sighted.” Austin helped launch the MLP, and is now director of the NIH’s National Center for Advancing Translational Sciences (NCATS).
But can the European Lead Factory do better, with a fraction of the budget?
Once details from the experiment’s early ventures are available, discussions around its sustainability will pick up, says Laverty. Early hopes include the possibility that more pharmaceutical companies may want to join the consortium, that it could offer fee‑for‑service screening and chemical tool generation capabilities, and that joint public–private funding could persist.
“We do not claim as yet to know exactly what the long‑term business model will look like,” concedes Rijnders. “But we have agreed to work for its sustainability.”
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