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Cellzome Gets a Dose of Viagra As Former Pharma Exec Takes Charge

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As proteomics companies search for a way to unlock the doors of big pharma, it probably wouldn’t hurt to have someone around who knows the combination, or so the theory goes. Cellzome is the latest proteomics company to pick up on this, and in a big way. Last week, the Heidelberg, Germany-based company announced that it had recruited David Brown, the former head of global discovery at Roche, to take over the company’s leadership as CEO.

Cellzome — which has forged its reputation on technology developed at the European Molecular Biology Laboratory for deciphering protein-protein interactions, and mass spectrometry expertise acquired from GlaxoSmithKline — is predictably thrilled. Charles Cohen, the company’s former CEO who will remain with the company as chairman of its supervisory board, said in a statement that Brown’s leadership and know-how would “take Cellzome to a new level.”

But first off, Brown needs to help Cellzome figure out where that next level actually lies. His task at the moment, he told ProteoMonitor, is to sit down with the company’s directors for two days and divulge his knowledge of big pharma’s actual needs, as well as determine parameters for deciding which drug development projects Cellzome will attempt to bring to market alone.

“The first thing [the directors] want to learn from me is big pharma’s needs, and then the second thing is how we position this in a business sense,” he said. [Thirdly, we’re figuring out] what we want to partner and what we want to keep ourselves, because we don’t want to give away the crown jewels.”

With 28 years of experience working at four of the top 10 big pharma companies in the world, including GlaxoWellcome, Zeneca, and Pfizer — where he was co-inventor on the patent for Viagra — Brown should have a wealth of knowledge to share with Cellzome’s management. But his high-ranking job at Roche, where he oversaw 2,000 scientists, didn’t make him hesitant to jump at the chance to join Cellzome. In fact, he made the decision to leave Roche in the course of a “short decision-making process” of six to eight weeks, he added.

His inspiration, he said, came from reading Cellzome’s paper published in Nature in January, and the premonition that their approach might provide Roche with a way to boost its own productivity by partnering with Cellzome. Brown led a Roche team that paid a visit to Cellzome earlier this summer to follow up on that idea, and came away thinking he just might decide to join the company instead, knowing it was looking for a CEO.

Brown said he thought Cellzome’s technology had the potential to speed up the process of discovering drugs, “and it was really that realization that made me think very hard about ‘Do I want to stay in big pharma or do I want to try to transform the productivity of the industry?’” he said. “It was a little bit idealistic, I suppose, but there was no reason not to have a go at it if you know what the problems are and you think Cellzome has the technology to do it.”

New Applications For Cellzome’s Technology

Although Brown was impressed with Cellzome’s technology when he read its Nature paper describing its efforts to untangle the networks of protein-protein interactions in yeast, he said he had more respect for the company’s potential when he learned upon visiting Cellzome that it had developed additional applications in drug discovery for its platform. In addition to targeting protein-protein interactions in yeast and mammalian cells, Cellzome has also adapted its “pull-down” technology to probing protein-drug interactions in a variety of ways, Brown said.

One way this could be useful to pharma, he said, is in searching for additional medical applications for drugs already approved and on the market. By using a small molecule drug as a probe to fish in mammalian cells for its protein binding partners, the company can identify additional targets involved in diseases unrelated to the one for which the drug was approved, Brown said. Similarly, using a drug with an unknown mechanism as a probe for drug-protein interactions could also lead to insights into how to design a drug with greater specificity for the original drug’s intended target. Furthermore, Brown said Cellzome has the ability to go after drugs deemed safe in humans but that failed final efficacy trials, in an attempt to identify targets for the drug unrelated to its originally intended therapeutic purpose.

But what impressed Brown the most is the potential for using Cellzome’s pull-down techniques for investigating the interactions between “pharmacophores,” or template small molecule drugs, and proteins fished from a sample. “Purely in a drug discovery sense, you can use privileged structures, or pharmacophores, which most companies have, go fishing with those in cells, pick out new targets they interact with, and then you’ve got both target and lead in a single step,” he said. “This is really exciting, [because] it addresses two big issues the pharma industry has.”

Cellzome has also made progress in translating its yeast protein-protein interaction studies into mammalian systems, most notably in experiments targeting the transduction system of TNF-a, a cytokine associated with rheumatoid arthritis. Brown said Cellzome has identified 45 new proteins interacting with TNF-a, and the company is working through them to determine which ones might serve as effective drug targets.

Initially Cautious, Now Emboldened

Although Cellzome has yet to sign a pharmaceutical partner to a research deal, Brown said this is primarily because the company took a cautious approach to selling itself. The policy under Cohen, the former CEO, was to wait until Cellzome researchers had completed their proof-of-concept studies, and were absolutely sure of the technology’s implications before embarking on marketing expeditions, Brown said.

And of the pharma companies who have expressed interest in talking with Cellzome, all have discussed the potential of Cellzome’s platform for investigating protein-protein interactions, Brown added. The company has yet to advertise its capabilities for studying drug-protein interactions, and “my expectation is that it will raise enormous interest and we will find a lot of people very interested in talking to us about it.”

But others are not so sure Cellzome’s strategy for pulling down drug-protein interactions is necessarily unique. Other companies, such as Serenex, have targeted these types of interactions exclusively in their approaches to big pharma, and MDS Proteomics, whose scientists authored a paper in Nature describing an approach related to Cellzome’s for studying protein-protein interactions, says it also has similar capabilities for discovering new protein targets for existing drugs or drug-like molecules.

“That’s actually one of our core platforms,” said Mike Moran, chief scientific officer of MDS Proteomics in Toronto. Moran added that in addition to studying drug-protein interactions, MDSP has platforms for probing protein-protein interactions, differential profiling of cell-surface proteins, and profiling global phosphorylation levels.

Funding for Drug Discovery

Competition notwithstanding, Brown is also optimistic about Cellzome’s chances for getting its own drug-discovery program off the ground. While technology development will take place primarily in the company’s Heidelberg facility near EMBL, Cellzome’s North London laboratory, acquired a year ago from GSK for a 2.9 percent stake in Cellzome, will house the company’s chemists and pharmacologists, he said. And as a jump start, Cellzome plans within 18 months to acquire rights to bring in house a phase I lead compound for Cellzome to try taking to market.

Already Brown has hired Robert Williams to take the position of vice president for drug discovery. Williams, who previously held positions at Prolifix, a UK-based company acquired by TopaTarget, and GSK, will join Cellzome Oct. 1.

To fund these endeavors, Brown said Cellzome is in the midst of a series C round of financing with help from venture capital firm Invesco Funds. Brown said he hopes the current fun-raising round will raise $30 million, in addition to the $40 million already raised that will carry Cellzome “into next year,” Brown said.

“My understanding is that [the VCs] want us to be quite aggressive in building this company,” Brown said. “[They want us] not just to think about how to survive over two years, but how to transform this into a multi-hundred million dollar company as fast as we can.”

— JSM

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