The colorectal cancer dilemma. Colorectal cancer is highly curable. More than 90% of patients survive if the cancer is diagnosed at an early stage when it is still localized. This may be a surprising fact as this dreaded disease is among the most frequent causes of death in the industrialized world. In the U.S. – for which statistical data is most easily available – about 154,000 people are diagnosed with the disease every year and about 52,000 people die of this cancer in the same period. This makes colorectal cancer one of the most frequent and most deadly cancers. The dilemma: The majority of colorectal cancers are diagnosed in advanced stages when they already show symptoms lowering the chances of survival to less than 10% once the cancer has already spread to distant organs. These numbers clearly show that early diagnosis can potentially save more lives than any new drug for this cancer ever could.

Colorectal cancer screening test: The medical need

Convenient cancer screening tests are needed. But catching colorectal cancer in its earliest stages requires systematic screening of the asymptomatic average risk population with suitable diagnostic procedures. Screening guidelines in the U.S. recommend an annual fecal occult blood test (FOBT) – a laboratory test that is performed on stool samples usually taken at home and sent in by each patient to check for blood – and an invasive colonoscopy requiring extensive bowel preparation every five to ten years for the average risk population aged 50 years and older. Other countries have similar screening guidelines. Despite these guidelines, only a minority of the target population participates in regular colorectal cancer screening. Thus, annual FOBT tests are only performed by 16% of the individuals aged 50 years and older and only 36% attend a colonoscopy every five to ten years. The most widely accepted reason for this low compliance is the lack of convenience. The American Cancer Society identified screening compliance as the major issue in colorectal cancer and is committed to drive compliance up to 75% by 2015. Reaching this goal will require novel screening tests that are competitive with the best available noninvasive test in the discrimination between cancer patients and healthy individuals but convenient enough to ensure broad acceptance in the target group.

Epigenomics’ colorectal cancer blood test: Competitive performance and unmatched convenience. Our colorectal cancer screening test in development is ideally positioned to address this need. The test relies on measuring the methylated DNA of the gene Septin 9 as a biomarker in blood plasma. In numerous prospective case control studies with about 3,000 clinical samples from cancer patients, matched healthy individuals and other critical control samples we have created an unprecedented body of evidence that this DNA methylation biomarker indicates the presence of colorectal cancer of all stages and in all locations. As early as 2006, we demonstrated that with a research assay optimized for detecting minute amounts of methylated Septin 9 DNA in plasma, we can correctly identify up to 70% of the patients with stage I-III colorectal cancer (i.e. 70% sensitivity) at a specificity of 90% (i.e. 10% false positive test results). If further optimized for a low false positive rate of only 3%, we could identify 63% of the cancer cases correctly.

This performance outcompetes standard FOBTs by far and is highly competitive with or potentially superior to more advanced screening tests on the market like immunological FOBTs (iFOBT) and tests designed to detect cancer DNA in stool. While performance is highly competitive, we believe that its convenience is unparalleled. All our test requires is a simple routine blood draw taken in the doctor’s office. While stool tests for colorectal cancer screening gained little acceptance in the target group, clinical experts believe that a blood test has the potential to drive compliance. Typically, diagnostic blood tests therefore achieve compliance in the 90% range when prescribed or recommended by the doctor. This harbors the opportunity to substantially increase the number of colorectal cancers diagnosed at early stages and eventually reduce mortality from this cancer.

Establishing a case for colorectal cancer screening. There are two important prerequisites for the successful commercialization of a cancer screening test: First, an assay procedure that is suitable for routine high-throughput testing and second, clinical data that support the utility of the test in a true screening population with regard to benefit to the patient and health economic benefit. In 2007, we dedicated much of our work to optimizing the assay procedure to measure our biomarker Septin 9 under clinical routine conditions. This improved assay procedure has not only cleared the way for licensing the Septin 9 biomarker to diagnostic industry partners and reference laboratories, but enables us to perform a multi-center study to characterize Septin 9 clinical performance and health economic benefit in a U.S. colorectal cancer screening guideline-eligible population. The PRESEPT study is planned to start in 2008 and will be run by an independent principal investigator. Study protocol and design have been developed together with our Medical Advisory Board of leading U.S. clinicians. For this study, we will collect blood plasma samples from several thousand individuals attending routine screening colonoscopies at several clinical sites. In these samples we will measure the Septin 9 DNA methylation biomarker and correlate the results with the colonoscopy finding as a gold standard for definitive colorectal cancer diagnosis.

Our path to commercialization. Addressing the huge cancer screening markets needs potent diagnostics industry partners. We have adopted a nonexclusive licensing strategy for the commercialization of our cancer screening tests directed at IVD companies for test kit development and broad worldwide commercialization as well as reference laboratories for early market introduction in selected geographies.

As a first IVD partner, Abbott Molecular obtained a nonexclusive worldwide license to our Septin 9 biomarker for early detection of colorectal cancer in blood in September 2007. We expect that Abbott Molecular now adapts the Septin 9 test to its m2000 molecular diagnostics instrument platform, develops the test kit and runs the necessary clinical trial. Also, Abbott Molecular will seek regulatory approval for the combination of the Septin 9 colorectal cancer test and its m2000 platform. A market launch of a CE-marked test kit in Europe is anticipated for 2009 followed by filing for regulatory approval for a test kit launch in the U.S. in 2010. While Abbott Molecular is spearheading the market introduction of the Septin 9 colorectal cancer IVD test, we expect to close further licensing agreements for this test in the future.

For fast market access we also started licensing the Septin 9 biomarker and the underlying technology to reference laboratories in the U.S. and in Europe for the commercialization laboratory-validated tests (LDT) which could be offered starting from this year. This will give patients and doctors first access to our colorectal cancer test and provide the first commercial proof of concept. As a first reference laboratory, Quest Diagnostics Inc., the leading provider of diagnostic testing, information and services in the U.S., obtained nonexclusive rights to Septin 9 in February 2008.

This products is not available for sale in the United States. The analytical and performance characteristics of any product to be eventually sold in the U.S. based on this technology have not been established.