This story originally ran on Dec. 9.
London-based biotech firm Activiomics this week announced an agreement with biopharmaceutical company UCB to apply its mass spec-based phosphoproteomics platform to the study of cell signaling pathways targeted by UCB's therapeutic antibodies.
The deal comes as Activiomics wraps up a project it started in April for drugmaker GlaxoSmithKline to investigate phosphorylation patterns related to inflammatory stimulus and steroid treatment (PM 04/23/2010). It's currently negotiating other agreements for cell signaling analysis work, as well, CEO Mark Warne told ProteoMonitor, including one with a large biopharmaceutical firm that it hopes to announce early next year.
The company also plans early next year to raise around $1 million in venture funding, Warne said, with money to come from existing investor IP Group and an additional venture firm that he declined to name.
Under the UCB agreement, Activiomics will use its TIQUAS – targeted in-depth quantification of cell signaling – platform to analyze UCB's therapeutic antibodies and identify potential protein biomarkers that the drugmaker might use to measure efficacy and stratify patient cohorts in its clinical trials.
TIQUAS is a label-free, mass spec-based approach to quantifying levels of phosphorylated proteins in material like cells or human tissue. Samples are digested and enriched for phosphopeptides, which are then run on an LC-MS/MS platform – Activiomics currently uses a Thermo Fisher LTQ Orbitrap XL and plans to move to an Orbitrap Velos in the next several months – and identified by comparison to peptide databases with software like Mascot. The company's proprietary Pescal software enables researchers to then quantify the identified peptides by automatically extracting the elution profile for these peptides and generating extracted ion chromatograms for each.
Being label- and antibody-free, the platform offers certain advantages relative to other methods for investigating cell-signaling pathways, Neil Torbett, Activiomics' principal scientist and project manager, told ProteoMonitor. For instance, competing SILAC-based approaches aren't applicable to tissue samples, he said, while immunoassay-based platforms rely on antibodies, which means that only kinases for which good antibodies exist can be studied.
Antibody-based methods are typically superior to mass spec approaches in terms of sensitivity, however, and, said George Mason University researcher Emanuel Petricoin – co-developer, with GMU's Lance Liotta, of the reverse phase protein microarray immunoassay commonly used in cell signaling research – TIQUAS might not be sensitive enough to provide a truly comprehensive profile of protein signaling pathways.
"It's a very highly sensitive mass spectrometry platform. It has very cool bioinformatic capabilities on the back end, but from a technological standpoint, it's still a relatively insensitive system," he told ProteoMonitor.
Torbett said the company doesn't have numbers on how sensitive the TIQUAS platform is in term of absolute quantities, but "in terms of the types of phosphopeptides we're able to monitor, we're routinely able to pick up many key signaling enzymes that are known to be of low abundance, so we're reasonably confident we achieve a high sensitivity," he said.
In the GSK project the company examined the effect of a steroid treatment on protein phosphorylation levels in basal epithelial cells undergoing stimulus from pro-inflammatory cytokine tumor necrosis factor-alpha. It identified more than 2,400 phosphopeptides, several dozen of which were differentially regulated in the presence of TNF-stimulation and steroid treatment and which could be tied to signaling pathways in which TNF is known to be present.
The two firms are working on a paper based on the results of the study, which they hope to publish within the next several months, Torbett said.
Having demonstrated the utility of TIQUAS with the GSK work, Activiomics is now looking to apply the platform to more targeted biomarker work, both for outside clients and in-house, Warne said.
"We worked with GSK to prove the applications of the technology," he said. "You'll start to see from the deals that we're working on and that we've just announced that we're starting to work on specific biomarker programs and on some of our own activities in that area, as well."
The UCB agreement is one such example. The company is also in talks with an undisclosed biopharma company about an "oncology-focused discovery program," Torbett said, and plans early next year to begin "proof-of-principle work in the biomarker and diagnostic space" with the aim of identifying predictive protein biomarkers for diseases including breast and kidney cancer.
Activiomics has established relationships with "a breast cancer biobank and leading breast cancer specialists in the UK," as well as "a kidney cancer specialist," Warne said. Those resources will provide expertise as well as clinical samples as the company ventures into biomarker development, he suggested.
The company is also considering expanding the TIQUAS platform to look at modifications beyond phosphorylation, Torbett said, noting that the technology is applicable to essentially any class of modification with good database coverage.
"We're not actively looking right now, but it's something we'd be willing to branch into," he said, citing acetylation and ubiquination as two particular areas of interest.
Despite its ambitions in the biomarker and diagnostics realm, Warne said he doesn't expect the company to shed its services business anytime soon – if ever.
I think there will always be a reasonably heavy sway towards the services business," he said. "We haven't taken very much venture funding, so we're not going to be under pressure from shareholders to produce a multi-billion-dollar outcome in a short time frame. The technology can be applied to a number of different target areas, some of which we have real expertise and others in which we'll almost be providing just a flat fee-for-service [product]."
"If you look at the core of our technology, we're not developing a diagnostic platform here. What we have here is a biomarker [discovery] platform. Any diagnostic to come out of Activiomics' technology is probably not going to be based on a mass spec platform. It's going to be based on multivariate biomarkers that are identified and then turned into something else," he said.
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