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Proteomics Expectations Bear Fruit in 2010, But Challenges Remain


This story originally ran on Jan. 6.

By Adam Bonislawski

Compared to the wheeling and dealing days of 2009, which saw big moves like Danaher's purchase of Applied Biosystems/MDS and Agilent's acquisition of Varian, 2010 was a bit on the quiet side.

There were acquisitions, of course, especially in the chromatography space, where AB Sciex purchased Eksigent Technologies' LC portfolio (PM 02/19/2010) and Thermo Fisher Scientific scooped up LC firms Proxeon (PM 04/16/2010) and Dionex (PM 12/17/2010).

But more than a year of blockbuster deals, 2010 was a year in which proteomics' potential was at least partially fulfilled: A long-awaited protein biomarker test finally reached the market; an advance in LC instrumentation began to see widespread adoption; a much-hyped mass-spec technology made its way into the lab; and a pair of high-profile proteome-mapping initiatives hit major milestones.

Diagnostics Sales Start, But Slump

In particular, 2010 saw proteomics-based diagnostics find a foothold after years of struggles and setbacks, with tests from Vermillion, HealthLinx, and Clarient making their way to market.

Vermillion emerged from Chapter 11 bankruptcy in January and began selling its OVA1 ovarian cancer-triage diagnostic two months later. In August, the company reported $45,000 in Q2 sales of the test – its first-ever revenues from the diagnostic – and $114,000 more in OVA1 revenues in Q3 (PM 11/12/2010).

Australia-based HealthLinx, meanwhile, relaunched domestic sales of its OvPlex ovarian cancer test in June after pausing sales in September 2009 when the test's distributor, ARL Pathology, was acquired by Healthscope. It also started sales of the diagnostic in the UK and Singapore and inked OvPlex distribution deals in Israel and South Korea (PM 12/03/2010).

Also coming online was Clarient's protein biomarker-based breast cancer recurrence test Mammostrat, which the company – recently purchased by GE Healthcare – launched in early December (GWDN 10/22/2010).

Yet, as these firms – Vermillion and HealthLinx in particular – discovered, merely getting a diagnostic to market is no guarantee of robust sales. In a document filed with the SEC on Dec. 4, 2009, Vermillion projected 2010 OVA1 sales of $9.7 million – roughly 97,000 tests given current reimbursement rates.

In fact, the company sold an estimated 6,155 OVA1 tests in 2010, far less than projected in the SEC document and fewer even than the more modest prediction of 8,000 to 10,000 OVA1 sales the company initially provided as part of its official 2010 guidance.

Likewise, sales of HealthLinx's OvPlex test fell short of the company's targets. In its earnings report for fiscal 2009, which ended June 30 that year, HealthLinx predicted that by the end of its 2010 fiscal year it would sell 5,000 OvPlex units in the UK, where they debuted in February 2010, and 500 units in Singapore, where they debuted in September 2010..

Such volumes, it noted, would result in total revenues of more than A$350,000 ($342,000). However, in its 2010 annual report, the company recorded just A$12,757 in total product and royalty revenues, and noted that OvPlex sales were "modest." It did not break out unit sales.

By Sept. 30, 2010, HealthLinx had sold just over 100 tests in the UK and just over 50 tests in Singapore, according to its quarterly report.

For both companies, the key to improving sales in 2011 will be convincing physicians of the tests' value – something the firms struggled with in 2010.

During Vermillion's Q3 earnings call, for instance, CEO Gail Page said the company had underestimated the effort required to convince doctors of OVA1's utility and that it planned to refocus its sales force to concentrate more heavily on educating gynecological oncologists about the test.

An article published in July in the Australian newspaper The Age suggested that HealthLinx was running up against a similar problem. In the story, several prominent doctors criticized the lack of data supporting the test, saying that further studies – and, in particular, longitudinal studies – were needed to determine its clinical usefulness.

The authors included Helen Zorbas, CEO of Australia's National Breast and Ovarian Cancer Centre; Michael Quinn, a gynecological oncologist at the Royal Women's Hospital and the University of Melbourne; and Peter Grant, head of the department of gynecological oncology at Melbourne's Mercy Hospital.

Such studies, though, will have to wait, HealthLinx managing director Nick Gatsios suggested to ProteoMonitor. The company is in the midst of a 1,150-subject study aimed at establishing the utility of adding two new biomarkers – AGR2 and HTX010 – to OvPlex's current five-protein panel.

According to the company, initial results indicate adding the proteins could increase the test's accuracy. It plans to release additional data on the inclusion of the new markers in the first or second quarter of this year.

"At the moment we're just focusing on this particular study," Gatsios said. "We've got to get over this study first and then we'll worry about other studies that might be in the pipeline."

Qual-Quan Mass Spec

In terms of instrumentation, "qual-quan" emerged as a catchphrase in mass-spec circles this year, as several instrument makers introduced new mass specs they claimed combine the qualitative abilities of a high-resolution, accurate mass-spec with the quantitative sensitivity of a triple-quadrupole machine (PM 05/28/2010).

Most prominently, AB Sciex released its TripleTOF 5600 machine at the American Society for Mass Spectrometry's annual conference in Salt Lake City, a launch that Andy Boorn, the firm's chief operating officer, told ProteoMonitor was "the most important" in the 26 years he'd been with AB Sciex (PM 05/28/2010).

"It takes two workflows and allows [users] to do it on one workflow," he said, suggesting that the system would, for instance, enable researchers to collect high-resolution full mass-spectra data on a complex protein sample while simultaneously running multiple-reaction monitoring assays.

In an H1 earnings call in July, Danaher CEO Lawrence Culp said the company anticipated mid-single-digit revenue growth in its AB Sciex division in 2010, driven in part by sales of the new machine, which began shipping in September (PM 07/23/2010).

Waters also released a qual-quan instrument at ASMS – its Xevo G2 QTof. And while neither Agilent nor Thermo Fisher introduced such devices, executives from both companies made certain to emphasize the qual-quan capabilities of existing machines in their portfolios.

For instance, Thermo Fisher's Ian Jardine said the company had been delivering "simultaneous qual-quan measurements on all of our instruments all of the time" for the past two years, and Agilent's Gus Salem cited the qual-quan abilities of the company's 6540 UHD Q-TOF machine, which it released in June of 2009.

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Salem downplayed the notion that the new machines might eliminate the need for dedicated quantitative instruments like triple quadrupoles, however, telling ProteoMonitor that Agilent viewed qual-quan as "an additive capability."

"You may do that qual-quan experiment up-front because you now have that capability, but if you were going to develop a truly quantitative protein assay, and you had done all of the right work to define all the appropriate peptides, you'd probably end up executing that on a routine basis on a triple quad," he said.

Lorne Taylor, director of the Ontario Proteomics Methods Centre at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, who used the TripleTOF in advance of its release, seconded Salem's remarks, telling ProteoMonitor that although he was impressed by the 5600's quantitative capabilities, his lab would continue using triple-quads for high-sensitivity work.

Another early adopter, Mark Molloy, director of Sydney's Australian Proteome Analysis Facility, which recently purchased a TripleTOF, told ProteoMonitor that in preliminary studies using the machine as part of iTRAQ workflows, his lab had been able to acquire roughly 30 percent to 40 percent more peptides than with other Q-TOF systems (PM 09/24/2010).

The Spread of UPLC

Also of note on the instrumentation front was the emergence of ultra-performance liquid chromatography, with Waters and Agilent in particular experiencing significant growth in this area.

Key to this growth was the trend by vendors toward making their UPLC systems backwards compatible with HPLC instruments, thereby easing anxieties that existing HPLC users – particularly those running regulated testing assays like pharmaceutical QA-QC protocols – had with regard to shifting their LC work to a new platform.

During Waters' Q3 earnings call in October, CEO Douglas Berthiaume said he believed the "broad conversion" of HPLC systems to UPLC systems may represent "the largest business-growth opportunity in analytical instrumentation."

He added that the company's Acquity H-Class UPLC platform, which debuted in February to provide back-compatibility to its HPLC customers, was "helping to initiate a long-awaited replacement cycle … that has the potential to augment LC system growth over a multi-year period" (PM 10/29/2010).

At the HPLC 2010 meeting in June, LC vendor Dionex said it was adding UHPLC capability to all of its basic automated and standard HPLC platforms under the name UHPLC+. Agilent also focused on UPLC-HPLC compatibility at the meeting, introducing its new 1200 Infinity Series, comprising the 1220 Inifinity LC, the 1260 Infinity LC, and an enhanced version of the 1290 Infinity LC, which the company first released in April of 2009.

In an online presentation accompanying the 1200 series launch, Michael Frank, product manager of HPLC systems and solutions at Agilent, said that in 2011 the company will release software enabling the 1290 to emulate any other system from Agilent's 1100 and 1200 product lines, allowing total method reproducibility across the platforms (PM 05/25/2010).

SRMAtlas Reaches Completion

2010 also saw two high-profile proteome-mapping initiatives hit major milestones.

At the Human Proteome Organization's annual meeting in September, scientists from the Institute of Systems Biology and the Swiss Federal Institute of Technology announced they had completed an initial single-reaction monitoring mass-spec map of the human proteome (PM 09/24/2010).

The map, which was built with $2.7 million in direct funds under the American Recovery and Reinvestment Act and €2.7 million ($4.1 million) from the European Research Council, comprises more than 170,000 single reaction monitoring assays – one each for at least five proteotypic peptides for each of the 20,300 human genes currently annotated as protein-encoding.

Its purpose is to offer proteomics researchers a set of standardized SRM assays they can use to investigate proteins of interest, eliminating the need for scientists to develop their own assays from scratch.

The project, which launched in October 2009, is now in its second phase, which will last an additional 12 months and aims to increase the number of peptides included in the atlas to between roughly 250,000 and 300,000.

Human Protein Atlas Hits Halfway Mark

November brought another proteome-mapping achievement, as scientists led by Mathias Uhlen, professor of microbiology at Stockholm's Royal Institute of Technology, released the seventh version of the Human Protein Atlas database, providing localization and expression data on 10,000 human proteins (PM 11/19/2010). The release marked the halfway point of the project, which plans to characterize 20,000 human proteins.

Launched in 2003, the Protein Atlas includes, for each characterized protein, information on its sub-cellular localization; data on its expression patterns in 46 organs and 20 different types of cancer; and information on what cell lines it's expressed in.

The open-access database is a tool for basic research, Uhlen told ProteoMonitor, providing "a knowledge base for people studying human proteins, to see what proteins are mitochondrial, what proteins are in the nucleus, and so on." It should also aid applied work like protein biomarker research and the discovery of potential new drug targets, he added.

At their current rate of eight to 10 proteins a day, the researchers should reach their goal of mapping 20,000 human proteins sometime in 2015, Uhlen said, with the project possibly continuing on to map different protein isoforms after the initial draft is completed.

Have topics you'd like to see covered in ProteoMonitor? Contact the editor at abonislawski [at] genomeweb [.] com.