BUSI NESS
TECH TEST-DRIVE
GSK
Early success with a screening technique highlights GSK’s external PARTNERING STRATEGY DRUG COMPANIES are under pres-
sure to improve the performance of their innovation engines at a time when they are also trying to cut their R&D spending. Therein lies a paradox: The most innovative areas of science are often also the financially riskiest. So how can a company access cutting-edge technology without breaking R&D budgets? GlaxoSmithKline thinks it has a solution. In 2005, the company created the Centre of Excellence for External Drug Discovery (CEEDD) as a way to tap into edgy, early-stage science that GSK wouldn’t be willing to explore on its own. CEEDD takes an options-based approach, whereby GSK pays a modest amount up front to a partner company for the option to later license or acquire a technology or product. The model “allows GSK to test-drive technologies in a risk-sharing way rather than being fully exposed to the risk of failure,” Rob Aboud, CEEDD’s vice president of strategy development, recently told reporters at a briefing in Cambridge, Mass. Five years into the “externalization” strategy, GSK is seeing the initial fruits of its labors. The first drug discovered through a novel screening technology developed by Praecis Pharmaceuticals—a Waltham, Mass.-based firm that was one of CEEDD’s early partners—is about to enter clinical trials. And the technology is now being deployed across a variety of drug targets, where it is proving complementary to more traditional screening methods. The externalization strategy is both a cost-saving exercise and an acknowledgement that not all good ideas come from inside big pharma. Biotechs are often deeply specialized in areas where big pharma companies are not, said Patrick Vallance, GSK’s senior vice president of medicines discovery and development. CEEDD now boasts 40 programs across 25 disease areas. Examples of partnerships include a stem cell cancer therapy collaboration with Oncomed Pharmaceuticals and a
The small quantities of target protein used make for an efficient process. In the past, the high price of sequencing DNA was by far the biggest expense of using ELT. With the price for sequencing a million base pairs plummeting, the technology is suddenly a cost-effective way of finding starting points for drug design. In their first few years in the GSK fold, the Praecis scientists focused on proving the technological capacity of their DNA-encoded libraries. “We’ve now demonstrated that and are beginning to learn how to apply it and integrate it with more established methods,” said Barry Morgan, GSK’s vice president of molecular discovery research and an inventor of the technology platform.
ONE LESSON IS that ELT produces fewer but higher quality hits than does traditional high-throughput screening (HTS), Morgan said. Furthermore, researchers are finding that ELT can complement HTS. ELT looks at a molecule’s affinity for a target, whereas HTS looks at its ability to affect the function of a target. When combined, the methods are particularly helpful in designing drug deal to improve drug properties BIG RESULTS A candidates for new target classes, using Concert Pharmaceuticals’ DNA-encoded Morgan noted. library fits into deuterium chemistry expertise. Another difference is that HTS a tiny test tube. Praecis provides an example files through a range of single comof how the approach ties into pounds, whereas ELT interrogates a GSK’s ambitions to save costs, relatively small number of scaffolds expand its pipeline, and keep up with leaddecorated with a large number of subing-edge technology. GSK signed on to run structures. As the former Praecis scientists a pilot program with Praecis’ compoundbegin to build libraries using chemicals screening method in 2006. Praecis quickly from GSK’s small-molecule collection, found promising hits for two targets procompounds in ELT libraries start to take vided by GSK, and in early 2007 the British on characteristics of those used in HTS firm acquired it for $55 million. screens. By comparing the results from Praecis’ encoded library technology HTS and ELT campaigns, scientists can (ELT) attaches specially designed DNA bar use pieces of structures to build composite codes to chemical building blocks and then molecules that are highly potent and selecapplies traditional combinatorial chemistry tive, Morgan said. methods to generate enormous libraries. Still, there are targets for which only Each 20 million-compound library takes ELT produces hits and others where HTS three to six months to make but, amazingly, is the only source of hits. Having access to fits in a tiny microcentrifuge tube. The comboth technologies broadens the range of pounds are then simply mixed with an equaltargets GSK can pursue, he noted. ly small tube containing a target protein. Praecis has applied ELT to more than Scientists use affinity chromatography 140 GSK drug targets, including metalloto pull out the resulting hits, but they still enzymes, kinases, cell- or virus-surface reneed to figure out the structure of the molceptors, and protein-protein interactions. ecules bound to the target. For that, the In January, GSK expects to put its first encoded DNA is sequenced, providing a molecule discovered through the novel apreadout of how the molecule was built. proach into clinical trials.—LISA JARVIS
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DECEMBER 13, 2010
