Our screening tests aim at finding cancer at early stages before symptoms occur and are carried out conveniently on body fluids such as blood plasma or urine. We actively pursue three cancer screening test development programs in colorectal, prostate, and lung cancer.

Our cancer screening tests rely on the sensitive detection of tumor DNA shed into the blood stream, urine or other body fluids the tumors are exposed to. This DNA differs little from DNA of healthy tissue in its sequence but has a cancer-specific DNA methylation pattern in certain genes. Epigenomics’ sensitive assay technologies detect these patterns in specific genes and thus require only DNA fragments shed from very few cells of the tumor into body fluids as a diagnostic biomarker.

How will or future screening test be applied?
Taken in the doctor's office, the blood or urine samples will be analyzed in diagnostic laboratories. Here, IVD test kits that will be developed and commercialized by our diagnostics industry partners will be used to detect tumor DNA in the samples based on our proprietary DNA methylation biomarkers. The doctor will inform the patient and, if necessary, advise on follow-up procedures.

Characteristics and Market Potentials of Cancer Screening Tests

Our most advanced test in development is a blood-based colorectal cancer screening test which allows for the early detection of colorectal cancer by measuring DNA methylation biomarkers in plasma.

In a clinical study in December 2006, we demonstrated that by measuring a DNA methylation biomarker panel that included our proprietary biomarker Septin 9 in blood plasma, we could detect 66% of all colorectal cancers (i.e. a sensitivity of 66%) at a high specificity of 93% (i. e. only 7% false positive test results). This result was achieved by improving the sample processing workflow from the previous year’s studies by adding a repeated measurement of the marker. With this new workflow, the leading marker Septin 9 alone detected up to 70% of the colorectal cancers at a slightly higher false positive rate (specificity of 90%) or, if optimized for a low false positive rate of 3% (specificity 97%), 63% of the cancers.

Between January 2007 and early July 2007 we have been working to further optimize the assay procedure for this test for transfer into a reference laboratory and placement on high throughput molecular diagnostic platforms of potential IVD partners for global development and commercialization. In a technical study completed in early July 2007, we demonstrated that the newly established optimized assay procedure analytically performs equally or better to the previously used research workflow.

Annual colorectal cancer screening is recommended in the USA for all individuals above the age of 50 which, if applied more broadly, would include up to 300 million people in major market countries. The current standard test is a stool-based test, the so called Fecal Occult Blood Test ("FOBT"), with - in our view - a relatively low sensitivity and low convenience for the patient. The compliance rate for FOBT is estimated to be only 16% in the U.S. In addition, an invasive endoscopic procedure such as colonoscopy is available for early detection of colorectal cancer. In our view, its nature, cost, and availability for mass screening make it impractical as a broad, population-wide primary screening procedure. The goal of the American Cancer Society is to have a compliance rate of above 75% in the relevant age group to allow early detection. The clinical benefit of early detection is significant given that colorectal cancer detected at an early stage has a 90% five-year-survival rate.

Our colorectal cancer screening test is blood-based and has, in our view, a higher sensitivity than the most widely used FOBT. Clinical experts believe that such a blood-based screening test could drive compliance and reduce mortality from this cancer by detecting more cancers at earlier stages. We estimate that the market for a blood-based colorectal cancer screening IVD test kit could have a volume of more than € 3 billion in peak sales potential for diagnostics companies in the major markets (U.S., Europe, Japan).

We expect this test to be launched as a testing service in centralized reference laboratories in 2008*. For the subsequent broad global commercialization as an IVD test kit which can be used by any clinical diagnostic laboratory with molecular diagnostics capabilities we pursue a non-exclusive licensing and partnering strategy aiming for partnerships with various diagnostics companies. Our strategic partner Abbott Molecular will be the first diagnostic company to develop and commercialize our colorectal cancer early detection test. Abbott will transfer our test for the early detection of colorectal cancer on their molecular diagnostic m2000 system and anticipates a market launch in Europe in 2009 followed by filing for U.S. regulatory submission for approval in 2010.   

* Current Epigenomics management estimate for earliest possible launch.

The objective of our prostate cancer screening test program is to develop a urine-based screening test for men over 50 years of age that is more specific than the currently most widely used PSA ("Prostate Specific Antigen") testing or can be used as a diagnostic follow-on for men with PSA elevated to 2.5 ng/ml or more. PSA as a tumor biomarker has a moderate specificity, i. e. it is also elevated in a number of benign prostate conditions leading to anxiety in patients, repeated PSA testing, a number of unnecessary prostate biopsies in men without prostate cancer and an increase in the costs associated with these follow-up procedures.

In December 2006, in a first study on blood plasma and urine from prostate cancer patients and healthy controls, we demonstrated that our assays allow for the detection of cancers with a sensitivity of up to 74% at a specificity of 96% (i. e. only 4% false positive results in healthy men) using a single biomarker. The study also demonstrated that urine is the most suitable analyte for the detection of prostate cancer based on DNA methylation biomarkers. In September 2007 we confirmed in another study on prospectively collected urine samples the feasibility of a urine-based prostate cancer test. It is our intend to further optimize our biomarker panel with a focus on biomarkers that can distinguish prostate cancer from the non-cancerous prostate conditions. To this end we have identified 61 novel biomarkers that statistically significantly distinguish prostate cancer tissue from BPH tissue. Of these, the 38 most promising were selected for further evaluation in tissue followed by clinical studies with prospectively collected urine samples and workflows further optimized for this sample type based on the recently established improved assay procedure for our blood-based screening tests.

Prostate cancer screening tests target men aged 50 or older with average risk of developing this cancer and men aged 45 and older in certain risk groups, together above 150 million men in the major markets (U.S., Europe, Japan). We estimate that the peak sales potential for a prostate cancer screening IVD test kit that performed competitively to current screening procedures but is superior in specificity for the cancer is above €1 billion for IVD companies in the major markets (U.S., Europe and Japan).

In 2006, we initiated a cancer screening test development program for the early detection of lung cancer. We believe that non-invasive or minimally invasive screening tests for lung cancer with high sensitivity and specificity that can be applied to large populations in a convenient, safe, and cost effective way are needed urgently. Today, diagnosis mostly relies on diagnostic imaging procedures such as x-rays, Computer Tomography (CT) or Positron Emission Tomography (PET) followed in some cases by invasive bronchoscopy for definitive diagnosis. As these procedures are not suitable for screening, they are used once a patient reports symptoms that could be indicative of lung cancer. But symptoms occur late and the majority of lung cancer cases are diagnosed in stages too advanced for effective treatment.

In a first study in 2006 we identified numerous candidate biomarkers specific for lung cancer. In a clinical study completed in June 2007, we demonstrated that one of these candidate biomarkers discriminates non-small cell lung cancer (NSCLC) from controls with non-cancerous lung diseases with a sensitivity of 69% at a specificity of 91% when measured in blood plasma. This proprietary biomarker will now be used as the lead biomarker in our lung cancer screening test development program. We are now working on optimizing the biomarker panel for this test and will run further clinical studies.

We estimate the peak sales potential in the major markets (USA, Europe and Japan) for a lung cancer screening test with a high risk target population of about 90 million smokers to reach €800 million for IVD companies and if extended to the general population aged 50 or older of more than €2 billion.

These products are 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.