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Clinical Genomics Presents Validation Data for Blood-Based Post-Surgical CRC Recurrence Test


NEW YORK (GenomeWeb) – Clinical Genomics recently presented new data that demonstrate that its two-gene blood test for post-surgical monitoring of colorectal cancer recurrence is nearly three times more effective at picking up recurrence than measuring antigen levels, the only other monitoring tool on the market.

Clinical Genomics is a private Sydney-based company that is developing next-generation diagnostic tools for colorectal cancer (CRC). It opened its first offices in the US after acquiring Enterix, a subsidiary of Quest Diagnostics, in 2006. The company began doing research and development work in Australia, where it still has several laboratories, but has since focused its work on evaluating epigenetic changes in tumor DNA, specifically in CRC, which the company identified as an area that needed better diagnostic tools.

CRC is one of the leading causes of cancer-related deaths worldwide, and accounts for more than 600,000 deaths each year. Among individuals undergoing surgical treatment of CRC, recurrence occurs in 30 to 40 percent of all cases, the majority of which present in the first two to three years following initial diagnosis and treatment.

"People don't really die of colon cancer," Lawrence LaPointe, president and CEO of Clinical Genomics, told GenomeWeb. "They die when they have metastatic colon cancer." This was the epiphany that led Clinical Genomics to develop its post-surgical CRC liquid biopsy, he said.

Currently the standard care for post-surgical monitoring for CRC recurrence includes quarterly or semiannual blood-based testing to measure carcinoembryonic antigen (CEA) levels. "[The CEA assay] has been around forever," LaPointe said. Although it can detect cancer recurrence, it has poor sensitivity and specificity, he said.

Instead of measuring CEA levels, Clinical Genomics' liquid biopsy technology detects the presence of two genes, BCAT1 and IKZF1, that are epigenetically modified when someone has CRC. "They become hypermethylated early in the cancer process," LaPointe said. These methylated genes are easy to detect in blood, since circulating tumor DNA leaks into the bloodstream.

Clinical Genomics detects the presence of the genes using PCR technology, although it said that sequencing technology could also be used. The presence of either of those two loci in a patient's blood indicates the presence of cancer which should indicate the need for a CAT scan or colonoscopy at the discretion of the physician.

The company clinically validated its biomarkers in 2012, during the development of its ColoVantage Plasma test, in partnership with the Commonwealth Scientific and Industrial Research Organisation (CSIRO).

The new data were presented in two posters last week at the American Society of Clinical Oncology's Gastrointestinal Cancers Symposium in San Francisco. Each poster represented a different study that looked in two major questions: exactly how Clinical Genomics' post-surgical CRC liquid biopsy compared to the CEA test and what the relationship was between biomarkers present in matched plasma and tissue for patients diagnosed with CRC.

The first study, which compared the liquid biopsy and CEA tests' respective sensitivity and specificity, enrolled 332 patients (31-85 years old). Of those enrolled, 120 patients had confirmed recurrence status (30 recurrences confirmed via imaging or other clinical means; 90 patients with no evidence of recurrence). The authors estimated that overall sensitivity for recurrence detection was 63 percent for methylated BCAT1/IKZF1 versus 23 percent for CEA. They estimated that specificity in the 90 patients with no evidence of disease was 86 percent for methylated BCAT1/IKZF1 versus 96 percent for CEA. No cases with confirmed recurrence were CEA positive only.

The authors concluded that methylated BCAT1/IKFZ1 test positivity is correlated with local and distant recurrence, with 2.7 times as many recurrence cases detected than with the CEA test.

The second study, which compared the biomarkers present in plasma and tissue, looked at matched plasma and tumor tissue samples from 75 patients diagnosed with CRC. The authors determined that methylated BCAT1 and IKZF1 genes were detected in 35 and 36 samples respectively, and at least one gene was methylated in 64 percent of samples. While the authors did not observe that concentration of methylated BCAT1 and IKZF1 DNA in plasma was linked to their concentration in tissue, they did observe a positive correlation between the presence of the methylated gene in plasma and the depth of tumor invasion and lymph node invasion.

The authors said that these results demonstrated that BCAT1 and IKZF1 are highly methylated in CRC tissues with low methylation levels in surrounding non-tumor tissue, which they believe suggests that these methylated genes are highly tumor-specific without a field effect.

LaPointe said that in the US the company first plans to launch its products as a laboratory-developed test and intends to apply for US Food and Drug Administration approval as a LDT. Clinical Genomics plans to have the test ready for operation in its new laboratory in Bridgewater, New Jersey by May of this year. The company also plans to market the product in Australia and in European countries that recognize the CE mark down the line.

Going forward, LaPointe told GenomeWeb that the company plans to focus primarily on the launch of this product and training physicians to use it effectively for the foreseeable future. However, he also mentioned that the company does have a portfolio of biomarkers that will eventually go towards the development of similar diagnostic tools in this area down the line.

"To achieve what we've done to date, Clinical Genomics has [been] funded out of cash flow including contract R&D, revenue from our existing [fecal immunochemical test] and cash rebates from the Australian government from R&D tax concessions," LaPointe noted in a follow-up email to GenomeWeb. "Going forward, the company has been actively exploring external sources of capital through the back half of 2015. We aim to close our first significant external funding round in 2016."