It had been quiet around Cellzome since last September, when former Roche Pharma executive David Brown joined the company as president and CEO. But last week, Cellzome broke its silence with a bang, announcing that it had raised €30 million ($31.8 million) in a Series C round from Invesco Private Capital and nine other VC companies. At least investors, it seems, trust that the company is well on its way to morph from an academic spin-off with an interesting proteomics technology into a drug discovery firm with potential for profits.
Early last year, Cellzome, a spin-off from EMBL in Heidelberg, made a splash with a publication in Nature detailing its ability to characterize protein complexes in yeast by mass spectrometry. Later on, it presented data at conferences showing that it was able to study protein complexes — which often coincide with functional pathways — in mammalian cells as well.
But since September, Cellzome has changed more than its website, according to Brown: “We have completely changed the focus inside the company.” In addition to mapping pathways to discover new targets, “we have pushed very hard at developing our second technology, the drug pull-down technology,” he said. This method uses compounds, such as drugs or drug-like molecules, tethered to a solid support via a linker to pull down interacting proteins from cells or tissues, which are then identified by mass spectrometry. This approach, which is reminiscent of what others have dubbed “chemical genomics,” reverses the way pharma companies usually proceed, by screening for targets, not leads, said Brown.
Cellzome is hoping to use the new technology in two ways: by taking existing drugs and finding additional uses for them, and by starting with drug-like molecules to discover promising drug-lead pairs. According to Francesco De Rubertis, a partner with Index Ventures, a Cellzome investor, the new technology has not been completely validated yet, but “most of the pieces have been proven.”
The known-drug option appears to be the more straightforward route to profits. “The molecule is already optimized for use in humans,” said Brown, who formerly headed up Roche’s global discovery efforts. “When you find another use, you can put it straight back into phase I clinical trials, very fast, within months.” Cellzome, he said, has already started filing patents on second medical uses for drugs. In addition, the company is “within weeks” of signing an agreement with an undisclosed provider of a number of approved drugs, Brown added, which would give it a share in the intellectual property if it helped find a second use for them.
A similar approach, at least in principle, is used by Activx Biosciences in La Jolla, Calif., which started a collaboration with Japanese biotech company Sosei in January to find new disease indications for existing drugs or drugs that have failed in clinical trials (see ProteoMonitor 1-13-03). However, Cellzome’s method is unique in combining the drug pull-down technology with its pathway mapping technology, Brown said.
For starting out with drug-like molecules, Cellzome has sifted through large numbers of compounds from commercial providers, using computational filters followed by manual assessments by chemists, to find those that appear to be “drug-like.” The next step is to “go fishing in the proteome” for known or new targets, said Brown. The protein complex mapping technology will help put new targets into the context of a pathway, which might be of relevance to a certain disease. The lead-like molecules that come with the targets could then be optimized into drugs, which may take up to two years, Brown said.
In terms of disease areas, Cellzome has chosen to focus on Alzheimer’s disease, inflammation, fungal diseases, and cancer, Brown said, adding that these choices were driven by unmet clinical needs, commercial potential, and internal expertise. Attesting to its new emphasis on chemistry, Cellzome has been hiring chemists and pharmacologists into its UK site.
The company is hoping to advance some of its projects to clinical trials itself, in areas “where we can get an initial indication of efficacy on a relatively short timescale and at a reasonable cost,” Brown said. In other areas such as Alzheimer’s, where clinical trials are more complicated, it will seek partnerships with pharmaceutical companies. Negotiations with pharmas and large biotech firms started at the end of December, and Brown hopes to sign a deal by the end of this year. Just last week, he was touring the US for ten days to visit potential partners on both coasts.
The lack of such a deal is what sets Cellzome apart from its competitors in the proteomics world, such as GeneProt, Oxford GlycoSciences, or MDS Proteomics. Besides providing additional cash, a deal would serve as an important market validation. “It’s a signal that a big pharma partner is willing to touch money to use the company’s technology,” said Jörg Ruppert, an investment manager with Heidelberg Innovation, which has €2.2 million of total investments in Cellzome, including €250,000 from the latest round. While Cellzome has an excellent reputation for its science, “it will be important for them to show that they are also a company that can strike excellent deals,” he said. Equally important is that Cellzome advances lead compounds to early phase clinical trials, according to De Rubertis, whose company has invested a total of $11 million in Cellzome. “What we want to see is that these guys are able to discover drugs in a different way,” he said. “That is the most important single feature for the long-term viability of the company, a top-performing [drug discovery] engine.”