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Phosphoproteomics Startup Focuses on Cell-Signaling Pathways, Signs Deal with GSK

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This story originally ran on April 22.

A new proteomics firm that uses what it says is a novel method for analyzing and interpreting cell signaling pathways has opened shop in London and signed its first agreement with GlaxoSmithKline to investigate inflammatory signaling mechanisms.

The company, Activiomics, is a spinout from the Institute of Cancer at Barts and the London School of Medicine and Dentistry at Queen Mary, University of London.

It was formed in February to commercialize the technology, which combines phosphoproteomics, mass spectrometry, and a proprietary database and software to investigate cell signaling pathways faster and cheaper than other methods, according to a company official.

The technology, called TIQUAS, for targeted in-depth quantification of cell signaling, can be used for biomarker identification and target validation. It was developed by Pedro Cutillas and Bart Vanhaesebroeck, researchers at the Institute of Cancer at Barts and the London School of Medicine and Dentistry.

Last week, Activiomics announced a collaboration with GSK's Respiratory Centre of Excellence for Drug Discovery. Terms of the deal were not disclosed, and Activiomics' interim CEO Mark declined to detail the work it will do for GSK. However, he told ProteoMonitor that Activiomics will use TIQUAS to analyze novel inflammatory pathways.

Other deals with pharma and biotech firms are in the pipeline, he added, though he declined to discuss them. And while Activiomics' focus in the short term is on providing services to companies such as GSK, in the long term, the company will be conducting its own biomarker discovery and validation efforts.

TIQUAS operates on the idea that by "looking at phosphopeptides, we could get a much better understanding of how cell signaling pathways [work], and actually by identifying the specific interactions between each of the proteins in a cell signaling pathway," Warne said.

At the heart of the technology is proprietary software developed by Cutillas, called Pescal, and the TIQUAS database of phosphopeptides and targets, which was culled "from a whole range of different cellular samples," Warne said.

The process starts with a cellular sample from a client. Activiomics digests the sample with a protease to get peptide fragments. Mass-spec analysis using phosphopeptide beads follow, and the results are then cross-compared with data contained in Activiomics' database.

The Pescal software acts as an interface between the database and LC-MS data generated from experimental samples

The workflow allows Activiomics "to identify specific phosphopeptides, and the mass spectrometry run allows you to quantify their existence," Warne said. "And then you use those, in essence, [for] biomarker discovery or drug profiling."

Because TIQUAS is label- and antibody-free, the technology offers several advantages over existing methods for analyzing cell-signaling pathways, according to Warne.

First, it doesn't depend on the existence of antibodies, whereas most other cell signaling pathway strategies use either antibodies or fluorescence labels to look at individual phosphopeptides, Warne said.

The issue with antibody-based methods is that antibodies have never been raised for many proteins and peptides.

"And there are large numbers of kinases that you can't raise an antibody against, which means you are unable to study those individual peptides, and you won't necessarily know that they're even part of the cell-signaling pathway," Warne said.

Because the TIQUAS technology does not require antibodies, researchers can get a "full, unambiguous … view of a particular cell-signaling pathway at a quantitative level."

TIQUAS also differs from other methodologies because they are qualitative rather than quantitative, which limits the kind of data they can generate. For instance, in qualitative studies, results between different experiments cannot be correlated, Warne said.

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According to Neil Torbett, principal scientist and project manager at Activiomics, other methods used to quantify phosphopeptides, such as MS/MS-based approaches, are "relatively stochastic … [and] you end up quantifying what you're given. Using the phosphopeptide database as a standard enables you to cross-compare samples in a more efficient way."

”Until now, really being able to compare the same phosphopeptides between experimental samples has been quite difficult," he added. "This is where we see the breakthrough in our technology."

Activiomics, he said, can currently profile up to 4,000 phosphopeptides from its database.

In a paper published in 2007, Cutillas and Vanhaesebroeck used TIQUAS to quantitatively analyze five mouse proteomes. Matching 8,800 MS/MS peptide spectra to 1,500 proteins, they generated 44,000 independent data points to profile the 1,000 most abundant proteins in mouse tissues.

That dataset provided "a quantitative profile of the fundamental proteome of a mouse, identifies the major similarities and differences between organ-specific proteomes, and serves as a paradigm of how label-free quantitative MS can be used to characterize the phenotype of mammalian primary tissues at the molecular level," the scientists wrote in the study's abstract.

Start-up funding for Activiomics comes from the IP Group, a London-based firm that commercializes IP held by academic institutions. Warne, who is partnership director at the IP Group, declined to disclose the amount of the investment into Activiomics, but described it as a "modest investment."

The IP Group appointed Warne as interim CEO of Activiomics while it seeks a full-time CEO. It will probably hire one after the company completes a biomarker-validation study and determines what skill sets the new CEO will need to take Activiomics forward, Warne said.

In the current, first stage of its existence, Activiomics will depend in large part on its service business. In the latter part of the last decade, numerous proteomics service firms went bust as the initial buzz surrounding proteomics gave way to the harsh reality that it could be another decade before the science led to revenue.

Warne said that while pharmas and biotechs are not currently rushing back into the proteomics space, a few more recent factors may work in favor of proteomics services firms. These include pressure felt by biotech firms to prove that they "are doing something unique that has value not only for themselves but for pharmaceutical companies."

That, said Warne, could spur the biotech and pharma industries to increase their investment in proteomics-based research. For instance, services such as those provided by Activiomics could help drug makers develop companion diagnostics to support therapeutic candidates, Warne added.

"What's clear is we fit within a particular framework. We'll provide some things that will be very beneficial to other companies, but we're not going to look to take over the world," he said. "Not every technology that comes out is going to change everything, but it's going to add real value to particular programs."

As part of its current business model, Activiomics plans to split its resources equally between its services and in-house biomarker-research efforts. But further out, Warne said, the company's sustainability will depend on its ability to find and validate new disease biomarkers.

"I think that that's what will generate the highest value for the venture capital shareholders," Warne said. "There's a certain inevitability to that."

He said that Activiomics is not providing information about biomarker discovery work it is currently doing, but said that it is currently conducting a validation study "in the biomarker space."

While partnerships with pharma and biotech will probably always remain part of Activiomics' business model, "if Activiomics is successful in the biomarker space, only part of it will derive from the technology that's come from the university," Warne said. "There will be other skill sets that will need to be brought on board to take that further forward, and then you'll be looking at a different proposition."

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