NEW YORK (GenomeWeb News) – Start-up KellBenX is positioning itself as the David among the Goliaths of the non-invasive prenatal diagnostics space by building a test that it said can detect fetal chromosomal abnormalities beyond aneuploidies.
The Great River, NY-based company doesn't plan to launch its test until late 2014 or early 2015, but when and if it does, it would go up against NIPD tests offered by Sequenom, Verinata Health, and Ariosa Diagnostics, as well as a test that will be offered in the near-future by Natera. While those firms would have a leg up on KellBenX as established technologies, its advantage is that it can detect microdeletions, chromosomal translocations, and perform single-gene analysis, KellBenX Co-Founder and CEO Hassan Bennani told GenomeWeb Daily News recently on the sidelines of the 31st Annual JP Morgan Healthcare Conference in San Francisco.
In addition, the company anticipates launching a test as early as the end of this year that would allow physicians to evaluate a woman's risk of having a preterm birth. The test would be able to do so even before the woman is pregnant, Bennani said.
For its NIPD product, KellBenX is leveraging intellectual property around an antibody called 4B9 that it licensed from AdnaGen to develop a blood-based assay that can separate rare fetal cells in maternal blood. 4B9 recognizes and binds to an epitope expressed by a type of nucleated fetal nucleated red blood cell, or fNRBC.
Used on a fetal cell capture platform that the firm also is developing, the assay, the name of which Benanni declined to disclose, can identify and enrich fNRBC. The target can then be analyzed by other technologies such as sequencing, PCR, fluorescent in situ hybridization, and immunohistochemistry to identify chromosomal abnormalities in a fetus.
The advantage of KellBenX's approach over existing NIPD tests, according to the company, is that it can detect more aneuploidies because its method is based on intact DNA. Tests such as Sequenom's MaterniT21 Plus, Bennani said, use a cell-free approach that relies on small fragments of DNA. The method results in low concentrations of fetal DNA, limiting the number of aneuploidies and other abnormalities that can be detected.
MaterniT21 Plus currently can detect trisomies 21, 18, and 13, for example. In comparison, KellBenX's test has demonstrated the ability to detect those aneuploidies, as well as sex chromosome aneuploidies, and more, he said.
At JP Morgan, though, Sequenom said it plans to add X and Y chromosome aneuploidy detection to its test, and Verinata's test called Verifi already has that capability.
Regardless, Bennani said KellBenX's technology can detect fetal chromosomal abnormalities other than aneuploidies because having access to the intact cells "gives us the intact DNA [so] we can do all aneuploidies, all microdeletions, [chromosomal] translocations, [and] single-gene analysis … the same way they do with amniocentesis and [chorionic villus sampling] today."
Co-Founder Leonard Kellner added that KellBenX is using the whole genome of the fetus, so the DNA "is more enriched, it has no missing components."
While it has been known for decades that fNRBC circulate in maternal blood, leveraging that information for diagnostic purposes has been impossible until only recently, KellBenX said, because no one had an antibody that could bind specifically to fNRBC.
"The challenge has been extricating that," Thomas Auth, an advisor to and a board member of KellBenX, said.
In 2009 AdnaGen was granted the patent in the European Union to the 4B9 antibody, its corresponding hybridoma, and antigens. The following year it received the US patent to the technology.
So far, KellBenX has validated its technology with FISH assays, PCR, and staining methods. In addition to its internal validation, collaborators in Italy, Russia, and China have also been carrying out validation work and so far have been able to match KellBenX's success.
The company plans to publish its validation study, carried out on 500 patients, in about six months, Bennani said. It also has submitted a manuscript to a peer-reviewed journal that he said he anticipates will be published in a few months.
Poster abstracts have also been submitted to the Society for Fetal-Maternal Medicine and the American College of Obstetricians and Gynecologists for presentations at their annual meetings.
A Competitive and Contentious Market
When and if KellBenX's peer-review study is published, the firm would move to launch its NIPD as a laboratory-developed test on a FISH format, Bennani said. In doing so, it seeks a spot in one of the hottest and most contentious segments of the diagnostics space dominated by Sequenom, followed by Ariosa. Verinata is a distant third according to some estimates, but with its recent acquisition by Illumina and a marketing agreement with PerkinElmer it is poised to increase its footprint.
In addition to a growing number of competitors, the space has been highly litigious with several lawsuits and challenges to patent issuances filed by the companies against each other.
Because KellBenX holds the exclusive global license to the 4B9 antibody and associated technology, it will be spared from the litigation issues that other firms in the space are navigating, company officials said.
As for other firms in the NIPD market, Bennani said that he doesn't see KellBenX competing against them as much as surpassing them. "We want to go beyond" what firms such as Sequenom provide "and offer something more valuable to the doctor," he said.
Sequenom did not respond to several requests seeking comment on what plans it may have to add capabilities beyond aneuploidy testing to its product portfolio.
Meanwhile, a spokesperson for Verinata said in an e-mail to GWDN, "We've only said that we will include items in our future test that are clinically relevant," and a Natera spokesman said that the firm anticipates adding pre-implantation genetic diagnosis and pre-implantation screening capabilities to its test in the future.
"The underlying technology for [Natera's] test has the capability to test for Mendelian disorders — we use the same technology for single-gene disorders for our PGD/PGS products," he said.
Ariosa told GWDN that it is working to expand its test menu in prenatal "for those areas of highest clinical importance as well as investigation into other medical areas outside of prenatal testing."
A final price has not yet been determined for the KellBenX test, but Bennani said that it would be comparable to Ariosa's Harmony test, which is priced at about $800. Depending on what a doctor orders, the KellBenX test may also be cheaper.
An Ob/Gyn may want to test only for aneuploidies, for example, and KellBenX would price its test differently from a test requested by a maternal-fetal medicine doctor interested only in microdeletions or translocations.
The test is intended as a diagnostic tool, not as a screening device. Bennani said that it can be used for high-, medium- and low-risk pregnancies, but the firm may introduce it first to target the high-risk population and then to all expectant mothers as "doctors build … confidence in the test."
Other NIPD tests on the market are sequencing-based, but KellBenX will not make a decision about using that technology for its test until it receives more data in the coming weeks from validation studies, Bennani said.
In the meantime, the company is also developing a blood-based test for determining a woman's risk for preterm birth. Fetal fibronectin is the current standard method for evaluating preterm birth risk, but because the test is given later during a pregnancy — at 22 weeks to 35 weeks of pregnancy — a doctor cannot use it to help guide the use of a preventive therapeutic.
Bennani said that his firm's test can be used before a woman is even pregnant, however, so steps, such as progesterone therapy, can begin early on to prevent an early birth. The firm has licensed three protein biomarkers, IL-10, IL-13, and IL 1Ra, from Cedars-Sinai Medical Center and is developing an assay around them that potentially would have as its market every woman who is thinking about becoming pregnant. Auth added that the vision is that a woman would have the test performed as part of a routine doctor's visit.
KellBenX expects to finish a 250-patient validation study for the test within the next two months, and then submit it for publication, Bennani said. Upon publication, the company would have it independently validated by others, including the March of Dimes, and if all goes according to plan, the test could hit the market later this year or early next year as an LDT.
The firm is in discussions with an existing CLIA lab about possible partnerships and also is weighing building its own laboratory.
To date, KellBenX, founded in 2010, has raised $5 million from angel investors, and is now speaking with investors for additional financing as it eyes possible commercialization of its products, Bennani said.