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Orion Genomics Licenses Epigenetic Marker From JHU to Develop Early-Stage CRC Test

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This article has been updated from a previous version to clarify the nature of the original research agreement between Orion and Johns Hopkins.
 
Johns Hopkins University has granted Orion Genomics an exclusive worldwide license to commercialize tests that can identify patients at risk for colorectal cancer, Orion said this week.
 
The license will enable Orion to study loss of imprinting of the insulin-like growth factor 2 gene and allow it to develop a blood-based test that would identify at-risk patients at a much younger age than current tests so they can be screened for the disease at its earliest stages using existing techniques.
 
In addition, Orion hopes to further develop the colorectal cancer test in collaboration with Johns Hopkins, as well as tests for other cancers based on IGF2 imprinting abnormalities with different academic and non-profit research institutions, a company executive said this week.
 
The license is based on a suite of pending and issued patents awarded to JHU and covering inventions made by Andrew Feinberg, a professor of molecular medicine and of medicine, oncology, and molecular biology and genetics at Johns Hopkins.
 
Orion’s relationship with Feinberg’s laboratory dates back to July 2005, when the company began collaborating with his lab to better understand the role of DNA methylation in colon cancer, to enable the development of a simple early-detection cancer diagnostic.
 
That collaboration is ongoing, but in the meantime, Orion became interested in separate discoveries that Feinberg made involving IGF2 loss of imprinting, Orion President and CEO Nathan Lakey told BTW this week.
 
“It’s a natural next step for quite a longstanding relationship we have with Andy Feinberg,” Lakey said.
 
“[His] lab used our platform technologies in epigenetics to understand some of the molecular causes of cancer,” Lakey continued. “Through that relationship we’ve grown close, and recently opted to license patents that he holds covering loss of imprinting on IGF2 … to commercialize a blood-based test that we hope will identify individuals at an increased risk of getting colon cancer.”
 
Financial terms of Orion’s licensing agreement have not been disclosed. An Orion spokesperson said that the company did not provide financial support for the original research agreement.
 
Other tests exist for diagnosing the presence of colorectal cancer, including a stool-based DNA test from Exact Sciences “that has done well in studies,” Lakey said.
 
In addition, several other earlier stage tests for determining the risk of colorectal cancer exist or are in development. Just this week, Moffitt Cancer Center granted a worldwide, exclusive license to Xceed Molecular to a gene signature for colon cancer that Xceed will attempt to turn into a diagnostic test that would use biopsy tissue from colonoscopies (see News Briefs, this issue, for more details).
 

“It makes sense that perhaps if you have loss of imprinting, your colon ages epigenetically faster than those who don’t have it, and that’s why they may get cancer at an earlier age.”

Other tests, however, only identify individuals at risk of getting hereditary colorectal cancer syndromes, Lakey said. “Those syndromes account for two to three percent of all colorectal cancer cases. So there are no molecular tests to ID people who are at risk for sporadic colorectal cancer.
 
“The problem is that it is really expensive to screen everybody,” Lakey added. “Individuals that are determined to be of average risk start screening at age 50. And we think that those with this loss of imprinting are likely to get the disease earlier in their life. So if they wait to start screening until they are 50, disease may have already started and advanced.”
 
According to Lakey, in most people the maternal IGF2 allele is silenced but the paternal allele is expressed, meaning that overall IGF2 either isn’t expressed or is expressed at very low levels.
 
In IGF2 loss of imprinting, the maternal allele is expressed due to an abnormality, causing an overall greater expression of the gene, which is linked to cell division and growth.
 
“Studies have shown that people with loss of imprinting of IGF2 have more dividing cells in their colon,” Lakey said. “It makes sense that perhaps if you have loss of imprinting, your colon ages epigenetically faster than those who don’t have it, and that’s why they may get cancer at an earlier age.”
 
Loss of imprinting of IGF2 has in fact been shown to be associated with a variety of diseases, including multiple cancer types, but the link to colorectal cancer is “the most advanced,” according to Lakey.
 
Ten percent of the population, he added, carries IGF2 loss of imprinting in their blood. “Roughly 40 percent of colon cancers have loss of imprinting of IGF2,” Lakey said.
 
The marker’s promise as the basis for an early-detection blood test stems from a pair of retrospective studies – one conducted by Feinberg and colleagues and published in Science in March 2003; and the other conducted by researchers at the National Cancer Institute and published in March 2004 in the Journal of the National Cancer Institute.
 
Combined, these studies investigated more than 200 patients and showed that individuals who developed colorectal cancer or polyps were more than five times likelier than cancer-free individuals to have loss of imprinting.
 
In addition to a large body of retrospective studies, a prospective trial is now underway as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial through the Division of Cancer Prevention at NCI.
 
This study is examining the results of various screening tests given to 154,938 healthy men and women aged 55 to 74 at the time of enrollment from September 1992 to July 2001.
 
“Some of them who were healthy went on to get colon cancer or polyps,” Lakey said. “The IGF2 loss of imprinting is now being evaluated in those blood samples to make a prospective link.”
 
Lakey said that Orion expects these studies will confirm what was found in other retrospective studies. “This, we believe, will be the last piece of evidence that is necessary to have a successful application at the FDA, and to convince the professional organizations that it is a good idea to shift resources for screening toward people who are positive for this biomarker.”
 
If it has its druthers, Orion will develop the test with Feinberg’s lab, but it will also begin to explore loss of imprinting of IGF2 in other cancers and diseases.
 
“That’s our hope — that we would work with his lab,” Lakey said. “At present, we have a license in this area and a different [research] collaboration. There are also several other labs that are studying this gene. As our test becomes more sensitive and specific, our aim is to enable all kinds of research linking this abnormality with disease.”