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NanoString Technologies Hopes to Achieve FDA Clearance for Breast Cancer Test by 2012

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By Justin Petrone

NanoString Technologies has licensed a gene-expression signature from a coalition of university researchers that can be used to classify different breast cancer subtypes, according to a company official.

NanoString CEO Brad Gray told BioArray News this week that the firm intends to have the breast cancer intrinsic subtyping assay on the US market for clinical use in two years.

"We are seeking US Food and Drug Administration approval for an in vitro diagnostic product," Gray said. "We will then distribute a diagnostic version of the nCounter system and the intrinsic subtyping assays to run on it in hospital and pathology labs right near the patient."

NanoString licensed the signature from Bioclassifier, a partnership of four breast cancer experts from Washington University in St. Louis, the British Columbia Cancer Agency, the University of North Carolina at Chapel Hill, and the University of Utah.

The quartet of researchers has created and validated the PAM50 gene signature, a panel of 50 genes that can be used to subtype breast cancers. Specifically, the signature subtypes cancer samples into luminal A, luminal B, HER2-enriched, basal-like, and normal-like, and provides a continuous risk-of-recurrence score based on the similarity of an individual sample to prototypic subtypes.

Founded in 2003, Seattle-based NanoString has focused on serving the life science tools market with its nCounter Analysis System. Developed on technology licensed from the Institute for Systems Biology, the nCounter is designed to enable researchers to measure gene expression in a multiplexed fashion using color-coded molecular barcodes, and single-molecule imaging to detect and count hundreds of unique transcripts in a single reaction.

The nCounter, which has a list price of $235,000, currently supports research applications for gene- and microRNA-expression profiling as well as copy number analysis. According to Gray, the deal with Bioclassifier puts NanoString on the path to being a molecular diagnostics company.

"We have a vision of placing the nCounter in hospital and pathology labs worldwide as the diagnostic system of choice for multiplexed gene-expression signatures for cancer," said Gray, who joined NanoString from Genzyme Genetics in June.

Gray said that the firm is working to gain access to more content, both from existing research customers and researchers who have developed content on other platforms but would like to transfer those markers to the nCounter.

"The vision is to deliver a series of gene-expression assays for solid tumor oncology to hospital and pathology labs," Gray said. "This assay is an excellent first step for us but only a first step for realizing our ambition."

PAM50

Bioclassifier's founders used microarrays to identify and develop the PAM50 gene signature.

According to co-founder Matthew Ellis, director of the breast cancer program at the Washington University School of Medicine in St. Louis, he and the other developers of the PAM50 signature originally envisioned making the panel commercially available on an array or a quantitative PCR platform, but found limitations in both, encouraging the partnership to license PAM50 to NanoString.

The other three partners in Bioclassifier are Charles Perou of the University of North Carolina at Chapel Hill, Torsten Nielsen at the British Columbia Cancer Agency, and Philip Bernard of the University of Utah.

"The problem with microarrays is the manufacturing," Ellis told BioArray News this week. "It would require custom chips, but most custom platforms rely on high-quality RNA," he said. "We wanted an assay that could work on formalin-fixed, paraffin-embedded tissue that was a decade old."

The option to offer PAM50 via a qPCR-based assay also did not work out. In 2009, University Genomics, a firm that preceded Bioclassifier that comprised the same principals, licensed PAM50 to ARUP Laboratories in Salt Lake City to be offered as a laboratory-developed test using a qPCR-based assay.

While that LDT is still scheduled to launch, Bioclassifier found there to be limitations with qPCR, and opted to license the product rights to NanoString instead.

"When we tried to get the same result for the same sample to produce a kit for distributed testing, we found that multisite qPCR was not robust enough," Ellis said. "You have to use liquid-handling robots on multiple wells, multiple times. It's an inefficient way to measure gene expression," he said. "Our idea was to develop an assay that could be used anywhere in the world, so we decided PCR was not going to be the best approach."

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Bioclassifier co-founder Charles Perou said in a statement that the partnership had a "goal to translate our decade of work on the intrinsic subtypes into a distributed test that could help breast cancer patients across the globe" and that NanoString is the "perfect partner … to bring gene-expression profiling into the clinical setting."

Washington University was an early-access site for the nCounter, and Ellis said his familiarity with the platform led him to see it as the "ideal technology" to commercialize PAM50 as a kit.

"With the nCounter, all the reactions take place in one tube, so say goodbye to liquid-handling robots," he said. "There is direct digital counting of molecules and [the system] looked more likely to make it as a distributed kit."

He noted that the "regulatory environment is shifting all the time" and said that Bioclassifier wanted "something that would lead to a full FDA approval."

Gray said the fact that Washington University was an early-access customer illustrates the way new diagnostic opportunities may present themselves to the company.

"The two businesses we are building within NanoString are synergistic," he said. "Our success in building a validation platform has created privileged access to diagnostic content that helps us build our molecular diagnostics business."

The Road to 510(k)

Gray said that NanoString now needs to perform a series of clinical validation studies to demonstrate that its test is clinically useful before submitting the breast cancer intrinsic subtyping assay to the FDA.

To do that, the firm will collaborate with Washington University, the University of British Columbia, and the University of North Carolina at Chapel Hill to "secure access to clinical material from past randomized controlled clinical trials to perform the clinical validation studies required for FDA approval."

Ellis confirmed that the three institutions would help with the studies, and said that Bioclassifier will also assist with some data analysis algorithms.

Earlier this year, NanoString achieved ISO 13485:2003 certification, an International Organization for Standardization guideline for medical devices. NanoString's certification, achieved in May, covers the design, development, production, sales, and service of the nCounter system.

Gray noted that the firm's diagnostic efforts are less than a year old and that the company has established a product development team devoted to developing diagnostic assays for the nCounter system. He called the recent deal with Bioclassifier a "very important tangible step that will help people understand the rigor with which we are approaching diagnostics and the scale of our ambition."

Gray added that there is a "dire need for a platform that has biologically relevant multiplexing capabilities for gene expression and where there is compatibility with FFPE tissue."

Ultimately, he said that NanoString believes it will enable tests to be "done by pathologists who are part of the healthcare system in which the patient is being treated, where tissue doesn't leave the hospital and it only takes 48 hours to come back, and it's on an FDA-approved platform, and can be distributed globally."


Have topics you'd like to see covered in BioArray News? Contact the editor at jpetrone [at] genomeweb [.] com.

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