DTU Chemistry LEADS the way

DTU Chemistry LEADs The Way

Tuesday 15 Jul 14


Mads Hartvig Clausen
DTU Chemistry
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The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115489, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. www.imi.europa.eu
DTU Chemistry is one of 30 partners in The European Lead Factory, a novel pan European consortium and platform for innovative drug discovery based on crowd sourcing. The European Lead Factory was launched in February 2013 with a budget of 196 million Euros.

The 30 partners were carefully chosen in an effort to combine the agility of the small and medium sized enterprises with the experience of the pharmaceutical companies and the innovation of academia. Danish participants include DTU and H. Lundbeck A/S.

“I’m much honored that Professor Mads H. Clausen’s and my team at DTU Chemistry participate in this consortium,” Professor Thomas E. Nielsen admits. “This is a very big and entirely unique initiative from seven major pharmaceutical companies. Our early involvement and participation in the project confirms that our efforts and the resources DTU Chemistry invested in chemical biology were wisely spent.”

Pharmaceutical companies rely on high-throughput screening of large compound collections in the search for new drugs. One problem is that each company traditionally guards its compound library in the ongoing battle for the next blockbuster drug. As each company has well-defined focus areas and tends to design their search for new drug candidates accordingly, many compound libraries have not yet been fully exploited.

The European Lead Factory will change this rather counterproductive stalemate through shared compound libraries. Access to a sufficiently large stock of small molecules is the starting point for researchers in the drug develop- ment businesses. In the world’s first compound-crowdsourcing effort around 300.000 industrial research compounds have been contributed by the seven founding pharmaceutical companies. Over time, the collection will be expanded by an additional 200.000 new compounds designed through the collaborative forces of the universities and SME’s in the consortium, totaling an unprecedented 500.000 compounds library. And all these compounds will be accessible to the members of the Consortium.

Role model for future drug development
According to Thomas E. Nielsen, The European Lead Factory might very well be the role model for future drug development, but it is also a big experiment. ”It’s the first time in Europe, that this way of pooling resources across the board has ever been tried, and we don’t know how crowd sourcing works at this level” he explains.

But the need for innovative thinking is very acute. For decades the pharmaceutical companies have been in a situation, where productivity is declining and the costs of bringing a new drug to the market keep rising. “The industry is challenged and everybody is looking for new ways to identify the drugs of the future – this initiative might give a push forward”, Thomas E. Nielsen hopes.

Building a large compound library is only the first step on the path to boost European drug discovery. Another aspect is the actual screening of the compound collection. The European Lead Factory will develop and fund this screening in state-of-the-art facilities based in Scotland and the Netherlands. The screening centers take responsibility for compound logistics, characterization, data analysis and program management. At the same time the screening centers function as a marketplace to foster new public-private partnership programs between the pharmaceutical companies and public partners.

European academia and SMEs on the search for bioactive compounds in the pursuit of a target receive a qualified hit list with up to 50 chemical structures of compounds per target program from the screening centers. Each of the pharmaceutical companies can use the created compound collection in 4 screening campaigns per year.

DTU Chemistry’s contribution
Professor Thomas E. Nielsen and DTU Chemistry’s contributions to the European Lead Factory comprise the design and validation of innovative strategies to be used by SME’s in the consortium to produce compound libraries. “We are well through the curve on this one” he states. “In 2013 we designed and received approval for 11 proposals. We have validated four of these proposals and our partner SME (Edelris, France) has synthesized more than 1000 compounds. This is an impressive achievement for the hardworking and dedicated chemists working with us.”

2013 was Year One for the European Lead Factory. At DTU Chemistry this meant staffing up with 4 Post Docs and starting out at full speed. “We have some very tough deliverables” Thomas E. Nielsen explains. “This is not trivial, it’s hard work and we have to keep up momentum. Yes, we have validated 4 proposals already and the funding for the next year is in place. But we have to remember that we, the public partners of The European Lead Factory, have to deliver 200.000 compounds in five years. That is no small task, but we are confident that we’ll make it”.

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