Molecular diagnostics firm Theranostics Health plans to commercially launch the first of its TheraLink diagnostic assays by the first quarter of next year, company officials told ProteoMonitor this week.
The test will be used to guide therapy in breast cancer patients, said Ron Hencin, Theranostics' vice president of business development, and is intended to supplement and improve upon conventional HER2 testing.
The company is also developing tests for pancreatic and metastatic colorectal cancer, Hencin said, and plans in the near future to pursue a $5 million to $10 million funding round to support work on these and other diagnostics.
Theranostics also announced this week that the US Patent and Trademark Office has issued a patent covering the methods underlying the Theralink tests, which use reverse phase protein arrays to profile and identify dysregulated signaling pathways in cancer patients, enabling physicians to then tailor therapies based on a patient's given pathway activation profile.
Entitled "Combinatorial Therapy for Protein Signaling Diseases" and issued to the US Public Health Service, the patent, number 8,168,568 B1, covers "methods for selecting combination therapies based upon the activation status of disease or cancer-related protein pathways," the company said. Theranostics holds an exclusive license to the patent from the PHS.
Theranostics spun out of the labs of George Mason University researchers Lance Liotta and Emanuel Petricoin – now both members of the firm's scientific advisory board – in 2006 with the aim of commercializing the duo's laser capture microdissection and RPPA technologies.
Since its launch, the company has derived its revenues primarily from fee-for-service work for pharmaceutical firms and has developed validated panels of assays for three undisclosed drugmakers that have used them in clinical trials for several cancer treatments.
The company has also "been moving pretty steadily down the path toward releasing our own diagnostic tests to guide therapies in oncology," Hencin said, noting that the breast cancer tests represent "the initial thrust of that development program."
Theranostics will make the diagnostic available as a laboratory-developed test out of its CLIA laboratory, Hencin said, adding that it has no plans to ultimately submit the product for US Food and Drug Administration approval, although it may pursue that route for future diagnostics.
The company plans to offer the test at first only to a small group of collaborators, he said, with the aim of gathering additional clinical data as it moves toward wider release.
"Initially [the test] will just be going out to select collaborators – people we are currently working with in terms of getting samples for clinical testing," he noted. "It won't be something that you'll be able to order globally, as it were."
From there, the company plans to expand to "other clinical providers within the networks that we have and then to other networks," Hencin said.
One of the company's primary collaborators on its breast cancer work has been Duke University researcher Victoria Seewaldt, director of the prevention program at the university's Comprehensive Cancer Center. In collaboration with Theranostics, Seewaldt has identified a series of breast cancer signatures – each comprising roughly 15 proteins in the Akt/mTOR/PI3K/cSrc, EGFR/MEK/ERK, and HER2/bcl-2 pathways – that could help identify precancerous women at high risk of developing the disease as well as predict the effectiveness in particular patients of preventive agents like tamoxifen (PM 11/12/2010).
Theranostics also recently released commercially its TheraLin fixative, a reagent for preserving patient tissue in phosphoproteomic research. Developed by Petricoin and Liotta and licensed by the company from GMU, TheraLin is intended to solve sample collection issues that have troubled the phosphoproteomic field (PM 9/2/2011).
Because phosphorylation is a highly labile modification, patient samples used in phosphoproteomic-based diagnostics like Theranostics' TheraLink test must be fixed immediately. Formalin fixation, which is the most commonly used method for preserving tissue biopsies, works slowly, taking hours to penetrate and fix a sample. Additionally, the process can reduce the immunohistochemical activity of the proteins in the tissue, and yields of proteins extracted from a sample preserved in this manner are typically poor. Snap-freezing, on the other hand, works quickly, but the equipment needed to process and store these samples is expensive and unavailable in many clinical environments.
TheraLin potentially offers the ease and low cost of formalin fixation combined with the speed and effectiveness of snap freezing. In a 2011 PLoS One study, a team led by Petricoin and Liotta demonstrated that TheraLin preserved protein phosphorylation at a level comparable to snap-freezing.
Since releasing the reagent, Theranostics has sold it "to a small number of our pharma partners and academic collaborators," Hencin said. He added, however, that the fixative is "secondary" to the firm's diagnostic ambitions and that it is unlikely it will pursue large-scale sales of the reagent in the absence of a partner.
"Probably the most significant area for the fixative will be just [its use] in conjunction with our own tests," he said, adding that the company envisioned in the future potentially offering kits "that would include TheraLin, so that in the surgical suite you could take a sample that would go to routine pathology and then a secondary sample that would go in the TheraLin and be sent to us."
Hencin noted, though, that the TheraLink breast cancer test would not require TheraLin-fixed samples but would instead use FFPE tissue.
"For the initial breast cancer test we've pretty much refined our technology so that we will work with [FFPE] samples, so we're not going to require any change to the current workflow from the surgeon to the pathologist to us," he said.
The company has "developed and optimized protocols" for extracting and measuring proteins in FFPE, Theranostics president and CEO Glenn Hoke told ProteoMonitor. He said that because the breast cancer test uses small core needle biopsy samples, the time required for formalin fixation is not as significant a concern as it might be for larger samples.
"In a core needle biopsy, formalin penetrates very rapidly, and that actually does lock down the phosphorylation state of the proteins," he said. "Formalin penetrates at [a rate] of millimeters per hour, and with a core needle biopsy from any direction you're less than a millimeter from the center. That's why we believe that for the breast cancer test we'll be able to work with [FFPE]."