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IncellDx Advancing Toward Filing for FDA Clearance of HPV Test

By Tony Fong

NEW YORK (GenomeWeb News) – A Silicon Valley firm using technology that allows for molecular biology-based research without having to destroy the cell is preparing to apply for clearance from the US Food and Drug Administration for its two lead products.

Last week, IncellDx said it had closed a Series A financing, raising $3 million in order to fund a clinical trial for its human papillomavirus test, for which it intends to seek FDA clearance, and to commercialize its other products. That follows an announcement a month earlier of a supply agreement with Accuri Cytometers for use of its HPV OncoTect E6, E7 mRNA test on Accuri's C6 flow cytometer instrument.

Headquartered in Menlo Park, Calif., the firm was founded about a decade ago, and while some of its tests and other products are available in certain parts of the world, as well as for the research-use only and laboratory-use only sectors, the HPV OncoTect would be IncellDx's first FDA-cleared test, if the company is successful. The test is CE-IVD marked in Europe.

IncellDx also plans to conduct a clinical trial for its test for HIV tropism in advance of an FDA application.

Bruce Patterson, an associate professor of pathology at the Stanford University School of Medicine and Co-founder and CEO of IncellDx, declined to detail the company's plan for the OncoTect trials, but told GenomeWeb Daily News that the firm has identified potential sites and submitted its study design to the FDA.

IncellDx's lead technology, developed by Patterson while he was at Northwestern University, is called simultaneous ultrasensitive subpopulation staining/hybridization in situ, or SUSHI. In short, SUSHI is a method to get IncellDx's reagents into a cell in order to amplify signals.

The issue with molecular biology, Patterson said, has been that technologies such as PCR, destroys the cells, "so you get this soup of genes typically from a mixture of normal and abnormal cells," which hides the abnormal ones that are most interesting to researchers.

SUSHI, however, allows for the detection of DNA and RNA in a cell without destroying it, which in turn allows the company to look at the cell's protein content, so that a genomic and proteomic analysis can be done simultaneously, resulting in more robust phenotypic data, according to Patterson.

SUSHI, the company said, enables the measurement of two separate components, the level of the target in each cell and the total percentage of cells expressing that target. The technology, Patterson added, is limited by only the number of colors available in flow cytometry.

While research is now slowly moving toward using both genomic and proteomic methods, rather than one or the other, Patterson said that the SUSHI technique does not involve cell lysis — which can destroy proteins — as some genomics methods do.

Some methods allow preservation of proteins and nucleic acids, but the "beauty of our technology" is that it enables proteomic and genomic information to be retrieved at the same time, he said.

The technology led to the development of assays and kits offered by IncellDx for HIV, Epstein Barr, and Hepatitis C. Its HPV OncoTect, however, is what IncellDx is hedging its future on, at least in the near term.

Patterson estimated the US market for HPV tests to be between $300 million and $400 million, and the global market is estimated at $2 billion.

The value of HPV testing and the market, he added, can be measured by two deals completed in the past few years. In June 2007, Qiagen bought Digene for $1.6 billion. Digene's core technology was an FDA-cleared HPV test.

A year later, Hologic acquired Third Wave for $580 million mainly on the promise of two molecular tests that Third Wave had that were in the process of getting FDA clearance. The tests, called Cervista HPV HR and Cervista HPV 16/18, were cleared in March 2009.

Patterson would not say that IncellDx's strategy is to be acquired by a larger firm, but said that an HPV test "puts us in a different space in terms of market cap … HPV is really the Holy Grail of molecular diagnostics because of the market size and because of some of the valuations it's created for companies in the past."

The main advantage offered by the HPV OncoTect, is its specificity, he said. Tests marketed by other firms have high sensitivity, greater than 90 percent, but a much lower specificity for pre-cervical cancer or cancer lesions, according to Patterson. The result is that a significant number of women needlessly undergo colposcopies, which while considered the gold standard in the US for diagnosing cervical abnormalities after a Pap smear, can have complications and is expensive.

Meanwhile, Pap smears have high specificity but lower sensitivity, he said. According to a 2003 study, a conventional Pap smear has about 94 percent specificity and 72 percent sensitivity for cervical cancer. The OncoTect test, Patterson said, achieves both high sensitivity and specificity.

The company is preparing three studies involving 12,000 patients for publication, but Patterson said that the HPV OncoTect test achieves sensitivity of greater than 90 percent and specificity of greater than 80 percent, because it detects the presence of lesions of pre-cervical and cervical cancer, "whereas the other tests detect risks of getting the lesion."

The test achieves its higher specificity because it is the only one, according to Patterson, that quantifies the two genes that are encoded by HPV — E6 and E7. Other tests only genotype HPV, he said.

"The hallmark of cervical cancer is when a cell makes a lot of these genes, so that's exactly what we're detecting. So it's much more specific for the process of cancer, and it's not a test that just says 'Yes' or 'No' you have a high-risk HPV that could cause cancer," Patterson said.

IncellDx believes the test can eventually be used as both a general screen as well as a stratification tool for determining which patients who have low-grade Pap smears will progress to a higher-grade pre-cervical cancer lesion or cervical lesion. However, it will probably apply for FDA clearance for only one indication, though Patterson declined to say which one IncellDx is leaning toward.

He also declined to comment on the nature of any conversations IncellDx may have had with the agency.

The company was originally founded as a technology firm but there was never any interest in commercializing the SUSHI technology as a service, Patterson said. Because of the CLIA model that exists in the US, the market would be too limited since many countries prohibit sending clinical samples elsewhere, he said.

The $3 million Series A was the first attempt by IncellDx to raise funds from outside the company and was done exclusively with angel investors. In addition to funding the HPV clinical trial, the company plans to use funds for a clinical trial for its HIV tropism test, which may be used to determine whether a patient may be a candidate for CCR5 inhibitors.

The company plans to file for FDA clearance for the test after it does so for the HPV test.

Other assays under development by IncellDx include one for cytomegalovirus — a marker for organ transplant rejection — ovarian cancer, and breast cancer.

Last month, the company also announced a deal with Accuri to combine the SUSHI technique with Accuri's flow cytometers. The deal, Patterson said, "allows us to have our own platform, so we can sell a complete solution with our assays and a small, affordable instrument."

The platform is available in two formats, one that does three colors at a time, called BlueFish because it uses a blue laser, which retails for "under $40,000," Patterson said. The other uses a gold laser which uses four colors and is thus called GoldFish, which sells for "under $45,000."

Patterson declined to disclose IncellDx's sales figures but said, "Needless to say, we're growing rapidly."

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