Sample-preparation firm Expression Pathology announced two developments this week that could help build its diagnostic pipeline.
The Gaithersburg, Md.-based company said that it has received a $6.5 million investment from a drug maker, which it said it plans to use to continue developing pharmacogenomic clinical assays on its flagship technology.
The firm also announced that it and NextGen Sciences have developed a protein biomarker assay method they claim can provide rapid, reproducible, quantitative measurements of protein expression in formalin-fixed, paraffin-embedded tissue samples.
The investment, from biotechnology and therapeutics firm Abraxis Biosciences, is designed to help Expression Pathology develop assays based on its Liquid Tissue MS protocol and protein biomarkers found in FFPE tissue that would be able to identify patients likely to respond to cancer drugs, including those developed by Abraxis.
"Our goal is to develop assays that relate to specific drug targets and drug modes of action so that patient tumors can be more accurately characterized as to which drugs are more likely to work," Casey Eitner, president and CEO of Expression Pathology, told ProteoMonitor this week.
The field is wide open, he added, since "there are a plethora of new drugs coming out for which there are no companion diagnostics."
According to Eitner, the investment gives Expression Pathology two things: the financial means to build out its technology and "a strategic partner" for potential diagnostics development down the road.
Abraxis has a "very, very keen focus on personalized medicine-based drug development," Eitner said. And while Expression Pathology has other academic and pharmaceutical partners that he declined to identify, Abraxis has drug-development programs for which his company's technology can interrogate tissue for protein biomarkers and drug targets.
The technology, he said, can then be used to develop specific assays to measure proteins that are especially interesting to Abraxis.
In a statement, Lex Van der Ploeg, senior vice president of integrative medicine and translational science at Abraxis, said his firm is "looking forward to harnessing the technology and clinical assays in its development and diagnostic programs, and to benefiting from the value, which is being created by growing interest from biopharmaceutical companies and academic research groups who are increasingly seeking to access Expression Pathology's technologies to accelerate their own research and drug development."
Research into FFPE tissue, whose appropriateness is limited to diseases in which solid tissue samples can be used, jibes with Expression Pathology's cancer focus. However, the company is also interested in identifying drug-toxicity biomarkers, Eitner said. A small number of pharma firms has determined that the company's technology can be applied for such work but has not proceeded beyond that, he added.
Improving on Immunohistochemistry?
Expression Pathology's business is built on two technologies: the Liquid Tissue MS protocol and the Director Laser Microdissection Slides. The Abraxis investment and the joint announcement with NextGen relate to the Liquid Tissue technology, a method for solubilizing and capturing the total protein content of microdissected FFPE tissue. Starting with about 30,000 cells, the technology can identify more than 2,000 proteins from such samples using LC-MS/MS analyses.
In January, Expression Pathology was granted US Patent No. 7,473,532 covering its Liquid Tissue sample-preparation method along with other sample-prep methods for protein analysis.
While FFPE tissue is widely used in light-microscopy research, it is much less commonly used in proteomics experiments, in which immunohistochemistry is the method of choice for identifying tissue proteins. However, one limitation of immunohistochemistry is that FFPE tissue samples create crosslinks that make proteins insoluble, and therefore unsuitable for routine biochemical analysis.
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By comparison, Expression Pathology's technologies uses heat buffers and enzymatic digestion to undo the crosslinking in the tissues.
Last June, Expression Pathology received $148,000 in a Phase I Small Business Innovation Research grant from the National Cancer Institute to use its technologies to identify protein biomarkers in primary breast cancer tissue that differentially express during early-stage metastasis [See PM 06/19/08]. Yet despite the potential of the technology, Eitner acknowledged that reception to it from the research community has been moribund.
"It's been a long haul," he said this week. "Anytime you introduce a new technology that can do something that couldn't be done before — especially something that requires you to connect tissues with microdissection [and] with mass spectrometry — it's a new paradigm."
However, interest is slowly gaining, particularly in the technology's ability to design "a mass spec-based quantitation of specific proteins" in FFPE, he said. At this week's American Association for Cancer Research meeting in Denver, attendees have queried him about that capability, he added.
"So, I think we're really starting to see a nice reception to it," Eitner said.
Meanwhile, the assay method Expression Pathology developed with NextGen resulted from a collaboration begun last summer between the two firms for biomarker services in FFPE samples [See PM 07/03/08]. As part of those services, customers can send in FFPE tissue samples to either company, and Expression Pathology will process the tissue while NextGen will identify and quantify protein levels.
The new assay method uses Expression Pathology's Liquid Tissue reagents and protocols to solubilize the entire protein content from FFPE tissue. NextGen then assays the proteins using multiple-reaction monitoring.
According to an Expression Pathology's statement, the results correlate with those obtained by immunohistochemistry methods, but the newly developed technique is faster, more straightforward, and provides "accurate and quantitative measurement of protein biomarkers."
The utility of the approach was first demonstrated with the Her2 protein, a biomarker for breast cancer, and "the development of this assay shows that FFPE tissue can be used for direct measurement of clinically important protein biomarkers by mass spectrometry-based tools," NextGen CEO Michael Pisano said in the joint statement.
In March, his firm sold its electrophoresis business to Sigma-Aldrich to complete its transformation into a biomarker-discovery and -validation firm [See PM 03/05/09]. This week, Pisano told ProteoMonitor in an e-mail that as NextGen continues building its new business model, part of its strategy is to "combine our own expertise with that of other companies to offer services to customers (such as the analysis of FFPE sample) that were previously unavailable.
"The FFPE services extend the reach of our offering into areas of pathology and pre-clinical discovery of tissue biomarkers," he said.
Because MRM assays can be multiplexed, assays in which multiple proteins are measured simultaneously can be developed, which his firm and Expression Pathology are doing, Pisano said.
Eitner said that tests, including FISH, already are able to detect and measure Her2 levels and Expression Pathology is now interested in "to take [its] technology and apply it to biomarkers for which immunohistochemistry or FISH or any of the existing methods don't w