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With 4K Tumor Genomes Analyzed, N of One Discusses Challenges, Lessons Learned, and Future Plans

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Last month, genetic analysis and interpretation firm N of One said that it had interpreted sequence data from over 4,000 tumors, including from whole genomes, exomes, and targeted panels.

Founded in 2008, the company has 30 employees and its customers include diagnostic companies, cancer centers, and other healthcare providers. It also has a small direct patient business, where individual oncologists refer patients directly to N of One, CEO Chris Cournoyer told Clinical Sequencing News.

Its clients do the sequencing and variant calling, while N of One takes that data, interprets it and generates a clinical report that can be returned to the physician. The company uses a proprietary analysis framework, which it calls PrecisionWorks, for curation. It also has its own database, MarkerMine.

Already in 2013, N of One has generated 2,237 clinical interpretation reports, more than the 1,830 reports it produced in all of 2012. And Cournoyer added that the firm expects to "more than double" the number of reports it produces in 2013 over its 2012 levels.

As reported by sister publication Pharmacogenomics Reporter, it is providing interpretation for Fox Chase Cancer Center's CancerCode-45 test, which relies on Life Technologies' Ion AmpliSeq cancer panel to analyze 45 genes associated with prognosis or targeted treatments (PGx Reporter 2/27/2013).

Additionally, it provides interpretation for Foundation Medicine's sequencing-based test that analyzes more than 200 cancer genes and has partnered with Clarient to develop a website informing cancer patients about targeted treatments.

From the 4,000 clinical reports it has generated, Cournoyer said that in more than 70 percent of the cases, therapeutic options were found beyond the current standard of care.

Additionally, the company has been able to track the patients that utilized its service as part of its direct patient business. Within this subset of several hundred patients, Cournoyer said that in 35 percent of cases, the report led to the physician making an immediate change to the patient's treatment strategy.

"If our small sample of a couple hundred patients is representative, and there's no reason to think they're not, then we're making a dramatic impact," she said.

Additionally, of the 25 percent of the patients in the cohort that said they were interested in pursuing a clinical trial, the report identified available trials for 96 percent of those patients. The enrollment rate for patients that expressed interest in a clinical trial was 38 percent, and 9.5 percent for the entire cohort, above the national enrollment rate of 3 percent.

Whether the increase in clinical trial enrollment and changes to treatment strategies are actually leading to improved survival rates still remains to be seen. "But there are also many other additional benefits in terms of options to other therapies and other types of improved outcomes," like fewer drug side effects, or reduced drug costs, said Jennifer Levin-Carter, N of One's chief medical officer and founder.

Cournoyer said that the firm has been in discussions with some of its cancer center clients to follow patients over time to determine the impact on survival and quality of life.

While the firm has analyzed data from small panels all the way up to whole genomes, Cournoyer said that whether or not clinically actionable information is found is not necessarily dependent on the amount of sequencing. "The smaller panels are effective," she said. "It really depends on the cancer — the disease and the stage," she said. "There is some debate in the industry and different institutions are taking different perspectives," she said, "but we're seeing clinically actionable results across the entire spectrum."

N of One has a fee-for-service business model, so it will charge clients a fixed rate per report for the length of the specific contract. Each contract is negotiated separately and prices vary, depending on the complexity of the test and the anticipated number of samples.

The report itself will provide the molecular drivers as well as the data provided by the laboratory, including information on the particular molecular change or mutation, and then its relevance to the disease, its significance, relevant biological information, as well as the clinical and scientific evidence behind the annotation and the evidence that points to its involvement in a specific therapeutic strategy.

The report is not just a straight one-to-one match-up between mutations and therapies, however. "When you have multiple mutations in tumors, you have to understand how they play together," said Cournoyer.

For instance, a tumor could have mutations that point to an effective therapy, but it would also be important to understand whether the patient also had mutations that confer resistance to any therapies, as well, to enable the physician to make the best decision.

Turnaround time for a single report can range anywhere from a couple of hours to a few days, Cournoyer said. The company relies on its "wealth of knowledge" that it has built up in its database and is also continually adding new data to the database to make sure the annotations are up to date.

While the company has thus far been primarily focused on cancer, Levin-Carter said that the company is also looking to provide clinical interpretation for other diseases, like rare disease.

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