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Evotec to Use PhosphoScout Platform in Oncology Biomarker Alliance with Roche


By Bernadette Toner

Just over two months after closing its purchase of Kinaxo Biotechnologies, Evotec announced last week that it will use the newly acquired PhosphoScout phosphoproteomics platform to identify biomarkers for oncology drugs in Roche's pipeline.

The deal marks the first pharma alliance for Hamburg, Germany-based Evotec since it acquired Kinaxo in mid-April in a deal worth up to €16 million ($23 million) — an initial purchase price of €12 million paid in cash and stock and a potential performance payment of €4 million.

Evotec said it will use the mass spec-based PhosphoScout platform to discover protein phosphorylation markers that can be used to identify patients likely to respond to targeted cancer drugs. Roche will be responsible for conducting clinical trials and "assessing the development of companion diagnostics for patient stratification," Evotec said.

Under the initial three-year term of the alliance, Evotec and Roche will use the platform to conduct "multiple" biomarker programs for therapeutic antibodies as well as small-molecule inhibitors. Evotec will receive up-front and success-based payments for each program.

The companies did not disclose the financial terms or other details of the agreement.

Kinaxo has been working with Roche since 2009 to use PhoshoScout to identify biomarkers for oncology treatments, but Evotec CEO Werner Lanthaler told ProteoMonitor that the deal announced last week is not simply an extension of that collaboration. While Kinaxo's work was performed as more of a service agreement, the new pact is "a novel framework" that involves the "strategic development of biomarkers together with Roche," he said, though he was not able to disclose further details of the nature of the partnership.

Nevertheless, he described the agreement as an important "validation" of the Kinaxo technology. "This isn't something where they signed up to play around a bit," he said. "They signed up to do strategic product development here."

PhosphoScout is based on LC-MS/MS on Thermo Fisher Scientific's LTQ Orbitrap Velos. The key is a phosphopeptide enrichment step that uses strong cationic exchange chromatography in combination with immobilized metal affinity chromatography or TiO2. Mass spec data is analyzed with the MaxQuant quantitative proteomics software developed in the lab of Max Planck Institute researcher Matthias Mann

According to the company, PhosphoScout can perform proteome-wide analysis of phosphorylation signals on any cell line or tissue and can measure the relative quantity of more than 15,000 phosphorylation sites in a single experiment.

The company uses the technology to monitor global changes in the cellular phosphoproteome in response to drug treatment — an approach that it said can shed light on the mechanism of action of targeted drugs, as well as enable the discovery of predictive biomarkers.

Kinaxo has used PhosphoScout in a number of drug development collaborations and signed agreements for the use of the technology with AstraZeneca and Takeda Pharmaceuticals just prior to closing the acquisition deal with Evotec earlier this year. Kinaxo's other pharma clients include Johnson & Johnson, Dalichi-Sankyo, Bristol-Myers Squibb, Bayer, Eisai, and Boehringer Ingelheim.

"The compelling thing about the PhosphoScout technology is that it's truly unbiased," Lanthaler said. "You basically find unbiased system-wide profiles of signaling pathways," which provides "a better systematic view of what could be the ultimate starting point for a biomarker."

Lanthaler noted that Evotec is working to make PhosphoScout "part of integrated drug-discovery alliances where it is only one part of our offering."

Indeed, Evotec acquired Kinaxo because it felt that its capabilities in target deconvolution, mode-of-action analysis, and biomarker discovery were complementary to its own portfolio of drug-discovery services, which include small-molecule screening, fragment drug discovery, medicinal chemistry, and in vitro and in vivo pharmacology. The acquisition also gave Evotec a strong presence in oncology and additional expertise in kinase profiling.

"Strategically, we come from the drug discovery angle and the med-chem angle into kinases and new drug targets in kinases, so adding here high-end mass spectrometry on a proteomics basis as we can do it with Kinaxo brings all these platforms together and makes it very comprehensive, very systematic, and very unbiased in how you can move oncology projects forward," Lanthaler said.

He said that Kinaxo is now "fully integrated" into Evotec. The company has maintained Kinaxo's facility in Munich, Germany as a "center of excellence" for phosphoproteomics and chemical proteomics. Kinaxo had 25 employees as of the acquisition and Lanthaler said that Evotec has "kept the team together" even as it has "slowly started the integration process into our existing alliances."

Evotec's pharma clients include Boehringer Ingelheim, CHDI, Genentech, MedImmune, AstraZeneca, Novartis, and Ono Pharmaceutical. Lanthaler said the company has identified partners who would be interested in using the Kinaxo technology in a similar way that Roche is, but he declined to provide further details.

It's likely, however, that any such agreements would focus on cancer. While Lanthaler noted that there would be no technical limitations to applying the PhosphoScout platform to other indications, he said the firm believes there will be more than enough opportunity within oncology for the time being.

While Evotec may consider extending the technology beyond cancer drugs down the road, "in the short range it's good enough to learn and get better with what we have started in kinases and oncology," he said.

Evotec projects that the Kinaxo business will generate 2011 revenues of approximately €2.5 million ($3.6 million), which would represent about 13 percent of the Evotec's total 2010 revenue. The company estimates that the business will grow at a rate of more than 30 percent year over year.

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