NEW YORK (GenomeWeb News) – Looking to enter the fast-growing non-invasive prenatal diagnostics space, CellScape is eyeing a second-half 2014 commercial launch of its test, which detects for fetal aneuploidies, and more importantly, genetic disorders that currently require invasive methods for detection.
Called the Clarity test, Newark, Calif.-based CellScape's product is for investigational use only at the moment, but the company has validated its technology and by early 2014 it anticipates having an operational CLIA laboratory, which would allow it to process large-scale clinical samples and conduct a clinical study, company Co-Founder Karen Drexler told GenomeWeb Daily News recently.
When Clarity launches, it would move CellScape into the increasingly competitive NIPD testing market that so far is dominated by Sequenom. Other firms operating in the space in the US include Ariosa Diagnostics, Verinata Health, now part of Illumina, and Natera. Firms outside of the US include LifeCodexx, which licenses IP from Sequenom, in Germany, as well as BGI and Berry Genomics in China.
While tests from those firms predominantly test for Down syndrome and other fetal aneuploidies, the value proposition of Clarity, Drexler said, is that its capabilities will be closer to tests, such as amniocentesis and chorionic villus sampling, which detect chromosomal abnormalities beyond aneuploidies.
CellScape was founded four years ago with the goal of developing a test that would isolate fetal cells in such a way that DNA would remain viable and a genetic analysis method could be then be performed. The firm's Clarity test works by extracting and then amplifying the DNA from fetal cells, which is followed by analysis with chromosomal microarrays.
Drexler said that CellScape originally had used fluorescent in situ hybridization-based technology for its test, similar to what another firm called KellBenX is doing. CellScape had a test for identifying whole chromosome aneuploidies, but it eventually decided the test "didn't take advantage of the power of having access to the whole genome," Drexler said, adding that a FISH-based approach "just wasn't comprehensive enough." While it could detect whole chromosome aneuploidies "we just didn't feel that met the market need."
An investor in the firm had been hearing about a study underway that would point to the use of chromosomal microarrays as an optimal technology for what CellScape was trying to do. In August 2011, the company made the switch to the technology.
That study turned out to be one published late last year in the New England Journal of Medicine, which indicated chromosomal microarrays could have advantages over traditional karyotyping and should become the standard for prenatal diagnostics. The lead author on the study, Ronald Wapner, is now a clinical advisor to CellScape.
While market leaders Sequenom, Ariosa, Verinata, and Natera use next-gen sequencing as the technological foundation for their tests, Drexler said, "we believe today that to get copy number variants — which is what you're looking at with the microdeletion syndromes — that the microarrays are the best platforms."
Citing the Wapner study, she added that microdeletion syndromes are not only more prevalent than fetal aneuploidies but also are "more devastating." And unlike companies currently in the NIPD space, CellScape's focus will be on microdeletions, though the Clarity test will also detect aneuploidies.
Because of current limitations to amplification methods, the company anticipates Clarity will provide about 80 percent coverage of an amniocentesis when it launches. "Amplification is not yet perfect," Drexler said, and when single cells or small numbers of cells are involved, noise can be introduced in the process. She didn't provide any details on the amplification methods the firm employs.
As amplification technologies improve, though, CellScape's technology will improve as well, Drexler said. For now, CellScape needs to use a targeted array that looks for the top 20 to 40 microdeletion syndromes that are relevant to prenatal medicine. CellScape's microarrays are produced by Agilent Technologies.
Despite not being able to completely replicate the results of an amniocentesis, Drexler said she has no doubts that Clarity would serve a clinical need. "I'm so beyond comfortable" with launching the test at its current capabilities, she said.
"You look at what the cell-free companies have done — they have taken the market by storm with a test that is basically for Down syndrome," Drexler said. She estimated that tests such as Sequenom's MaterniT21 Plus cover about 30 percent of what an amniocentesis covers. Clarity would cover more than twice that, which she called "a huge advance."
Its technology will also allow CellScape to look across the entire "backbone" of the genome at a 5 to 10 Mb resolution to pick up defects that are still smaller than can be detected by karyotyping, she said.
Additionally, CellScape has developed a patent-pending method of separating fetal cells from maternal cells. Aside from saying that the method involves biomarkers and an analysis method and has been verified extensively using other technologies, Drexler declined to elaborate on the in-house developed method.
With molecular diagnostics increasingly leaning toward next-generation sequencing, the company has begun feasibility testing around that technology with its first project employing targeted sequencing to investigate specific regions of the genome known to be responsible for Mendelian disorders. CellScape anticipates it will be able to launch a single-gene disorder sequencing-based test within a year after the launch of the initial microarray-based Clarity test.
That technology would detect inherited traits such as sickle-cell disease and Tay-Sachs disease, for which a chromosomal microarray is not suitable. Such a sequencing-based test, however, would require a different amplification optimization method.
"It turns out that the ideal fragment length for sequencing vs. microarray is different," Drexler said, adding that CellScape is currently evaluating multiple next-generation sequencing platforms.
Upon launch, Drexler anticipates the potential market size for Clarity to be all 4 million live births annually in the US. Initially, CellScape would market the test as a screen and it would recommend that Clarity findings be confirmed by invasive testing. As more data is generated, the test "has the potential certainly to be considered a diagnostic test," Drexler said.
That is still a few years into the future, though, and for now CellScape is moving cautiously in its commercialization efforts. It recently hired a chief medical officer as well as a geneticist who Drexler said has been developing relationships with "key clinicians." A reimbursement expert is working with the firm also to create a health economic model for Clarity.
"So, from that standpoint, we have been doing market-ready niche work with some of the key opinion leaders," she said. But until Clarity is closer to market launch, the company doesn't want to carry the costs of maintaining a commercial infrastructure.
Along with Drexler, who now serves as CellScape's executive chairman, the company's other founders are Bhairavi Parikh, the company's current CEO, and James Stone, who currently is developing the hardware platform for Clarity.
The initial investor into the company was XSeed Capital, which also participated in a second round of investments into the firm, along with angel investors. The last funding round was led by an institutional investor, whom Drexler declined to identify. She also declined to say how much in total funding CellScape has secured.
The company is in the process of raising additional capital, which it intends to use to help launch Clarity, she said.