With targets from genomics and proteomics technologies now flooding the pharmaceutical R&D pipeline, those proteomics companies that can help pharma develop lead compounds to bind to these targets — rather than just discover more targets — have a leg up lately in getting in the door.
Last week, Astex Technology of Cambridge, UK, and Serenex of Durham, NC, both announced deals with pharmaceutical partners based on technologies that can help them get from targets to leads — in two very different ways. Astex signed a multi-year deal with Schering based on its work with individual crystallized proteins, where it aims to build up strong binders from weakly binding drug fragments. Serenex, meanwhile, signed a smaller agreement with GlaxoSmithKline, using its technique of screening compounds against a subset of proteins in solution simultaneously to determine how selective these compounds are.
Astex’s agreement with Berlin-based Schering will initially span four years and will involve studying several drug targets, mainly in the area of oncology, in particular relating to solid tumors. “It will be a few targets each year,” said Jeremy Carmichael, associate director for business development at Astex, and there will be an option to extend the relationship for another four years. “It’s our first multi-target collaboration,” he added. “It’s our biggest collaboration to date.” Unlike in many pharma deals, there was no pilot study prior to the alliance.
As part of the agreement, Schering will take over all research and development costs relating to the collaboration. While Carmichael would not reveal the value of the deal, he said it is “probably more than” several million euros. In addition, Schering will pay Astex for pre-clinical and clinical milestones and grant the company royalties for sales of products that reach the market.
Schering will be responsible for the clinical development of compounds and has an option to the compounds’ worldwide exclusive marketing rights.
Astex usually either receives the protein from its partner, or purifies and crystallizes the protein in-house. The company then screens the protein with its own drug fragment libraries that contain novel cores and side chains, or with focused fragment sets that have a high probability of binding to certain protein target classes such as kinases, proteases, or phosphatases. “Initially, the fragments that we detect are typically low-affinity,” Carmichael said, often in the mM range, and have a molecular weight of typically 150 Da. “Using that information, we can guide medicinal chemistry to build additional functionality into those fragments.”
The new agreement adds to others Astex has had with AstraZeneca, Mitsubishi Pharma, and an undisclosed pharmaceutical company. It also recently announced a collaboration with the UK’s Institute of Cancer Research, and it is collaborating with AstraZeneca, Aventis Pharmaceuticals, and Mitsubishi Pharma on solving novel cytochrome P450 crystal structures.
As part of an internal discovery program, Astex has developed lead series that are currently available for licensing, said Carmichael, both for oncology target CDK2 and for rheumatoid arthritis target P38.
Schering was unavailable for comment before press time.
Serenex’s deal with GlaxoSmithKline’s Center of Excellence in Drug Discovery, on the other hand, is a technology evaluation agreement that “puts it on the small side,” according to Richard Kent, Serenex’ president and CEO. Kent hopes, though, that it might develop into a larger collaboration later on.
Under the agreement, Serenex will profile compounds provided by Glaxo “to find targets that these compounds bind to that can’t be found as easily using other technologies,” said Kent. Serenex licenses technology developed by its scientific founder Tim Haystead. It captures purine-binding proteins from tissues or cell lines on proprietary ATP affinity columns. This “sub-proteome” of purine-binding proteins is rich in putative drug targets, such as kinases, that span “most therapeutic areas of interest to the pharmaceutical industry,” according to Steven Hall, Serenex’s head of research and development. The company then applies compounds, some of which elute proteins off the column by competing with the affinity resin. Scientists then analyze the eluted proteins by tandem MALDI mass spectrometry, identifying them with a search algorithm developed by Bill Pearson at the University of Virginia, a member of the company’s scientific advisory board.
Since it received $15 million in a Series B round of financing last August, Serenex has been automating each step in this process, which it runs on a standard 96-well format, starting from loading the protein to the mass spectrometry analysis. It is now able to handle up to 1,000 compounds per day. This high-throughput capability, in combination with being able to work with protein in solution, is what sets the company apart from most of its competitors, according to Kent.
Serenex has had prior collaborations with Johnson&Johnson, Chiron, and Pharmacia/ Pfizer, and is currently discussing larger agreements with all of them. One seems to be particularly promising: “[We] expect to have a larger deal agreed upon hopefully within the next two months,” said Kent. The company also recently announced a collaboration with UK-based natural products company Molecular Nature.
In addition, Serenex is pursuing — as far as current resources allow — an internal program to develop compounds that target quinone reductase, a novel rheumatoid arthritis target.
The company plans to grow from currently 27 to 40-50 people by the end of next year. This is slower than originally anticipated, but the slowdown helps “to see expenditures grow in a controlled way in this environment,” said Kent.
GlaxoSmithKline did not respond to several requests for interviews.