German molecular diagnostics firm Epigenomics is seeking a diagnostic partner to commercialize a microarray-based assay it has developed to assess the risk of recurrence of prostate cancer.
Achim Plum, vice president of corporate development at Epigenomics, told BioArray News this week that the prostate cancer assay, which profiles DNA methylation of the gene PITX2, is the first of Epigenomics' tests that is run on an array platform. It is also the first test that the company is looking to market rather through a partner than on its own.
While Epigenomics, which maintains a close relationship with Affymetrix, has used the array vendor's GeneChips in its biomarker discovery programs, the first two tests to come out of its pipeline have both been finalized as RT-PCR-based assays.
In October 2009, Epigenomics launched the first of these tests, its Epi proColon early detection assay, which detects aberrantly methylated DNA of the v2 region of the Septin9 gene in blood plasma, enabling early-stage colorectal cancer diagnosis. Next quarter, the company will debut Epi proLung, which measures the methylation of the gene SHOX2 to diagnose early-stage lung cancer.
The new prostate cancer test, though, is different from these two in terms of technology platform. "We use arrays two ways: first as a discovery technology that allows us to find biomarkers," Plum said. For the colorectal and lung cancer projects, Epigenomics used a custom-designed GeneChip that is not available for general sale, he said. In the case of prostate cancer, though, Epigenomics decided to proceed with a GeneChip-based diagnostic assay to look at DNA methylation in PITX2.
"At the time we began developing this test, we did not have access to RT-PCR license-wise, so we opted for an array because it was comparatively attractive on business terms and also we were thinking in terms of a whole portfolio of tissue-based tests and wanted to use a platform with multi-marker capabilities," Plum said. "With an array, you can add as many controls as you like," he added. "By having lots of redundancies we can develop sophisticated control concepts that you would have a hard time doing with a PCR approach."
Epigenomics and collaborators at the University of Zurich, the University of Erlangen in Germany, and the Virginia Mason Medical Center in Seattle recently described the development of the assay in the Journal of Molecular Diagnostics. Plum said the academic researchers provided access to patient samples and clinical expertise for the study, while Epigenomics supplied the assay.
As the authors note in the paper, which was published online on March 19, DNA methylation of PITX2 has been established in several studies as a prognostic biomarker for breast and prostate cancer. For the study, the PITX2 biomarker was transferred to a customized Affy array referred to as the Epichip PITX2. The Affy platform was chosen with a "strategic view on the future, in which complex multiplexed assays are likely to play an important role in molecular pathology," the authors wrote.
The PITX2 assay described in the study measures DNA methylation at a single gene locus, but "future assays in prostate cancer diagnosis may rely on more than one DNA methylation biomarker, and therefore may require multiplexing capabilities," the authors wrote.
"The advantage of a microarray-based platform is further exemplified by the possibility to add different types of control oligonucleotides that indicate inappropriate hybridization conditions or incomplete bisulfite-conversion of the genomic DNA," they added.
Determination of PITX2 methylation in formalin-fixed, paraffin-embedded tissue samples from a cohort of 157 prostatectomy patients resulted in "an excellent level of concordance of the clinical classification, as well as the measured output between the research assay and the Epichip PITX2," the authors wrote. They deemed the Epichip PITX2 a "reliable diagnostic tool for assessing the methylation status of PITX2, enabling an improved outcome prediction in cancer patients following radical prostatectomy."
According to the paper, the Epichip PITX2 array contains three distinct classes of probes: a first group of 21 detection probes that are used to measure the methylation signal; a second group of methylation-unspecific probes targeting partially and completely converted DNA; and probes that are used for the assessment of background hybridization derived from Arabidopsis thaliana.
Epigenomics signed an agreement with Affy in 2006 that enables it to develop, market, and sell tests that run on the GeneChip platform.
While Epigenomics sells its own Epi proColon test, for instance, it has also outlicensed the Septin9 biomarker used for that test. So far, the company has signed non-exclusive deals with Abbott Molecular, Quest Diagnostics, and ARUP Laboratories to commercialize the marker for use on their own platforms. Japan's Sysmex currently has an R&D license to the marker and is developing an assay using it. Once the assay is developed, the company will likely negotiate an in vitro diagnostic license with Epigenomics.
"Our company has a dual business model: we commercialize products ourselves and give non-exclusive licenses to others to commercialize the tests, too," said Plum. "That way we can capture more of the market through a consortium of partners." With the prostate assay, though, Epigenomics would prefer that a partner sell the test instead.
"With our own products, we need to focus on very few indications, and colorectal cancer and lung cancer are already a lot for small company," he said. "Whether we might go forward with an exclusive, co-exclusive or non-exclusive license will depend on the terms and the preferences of our future partners," Plum added.
It is unclear if the current version of the prostate cancer test will make it to market on the Affy platform. Plum said that the array-based test is "fully developed" and predicted it would take "very little" to release it as CE-IVD-marked product for clinical use in Europe.
If the company's prospective partner preferred to take it to market on an RT-PCR platform, though, "that's surely something we can discuss," Plum said. "We have done studies with the PITX2 biomarker showing concordance between both technologies."