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NX Prenatal Undertaking Pair of Studies to Refine Exosome-Based Proteomic Test for Preterm Birth


NEW YORK(GenomeWeb) – Prenatal diagnostics firm NX Prenatal is developing an exosome-based proteomic test for identifying pregnant women at risk of preterm delivery.

In a paper published in the May issue of the American Journal of Perinatology, the company identified 18 proteins that appeared useful in predicting a woman's risk of preterm delivery, and it is now involved in two additional studies aimed at winnowing those proteins down to panels of around eight to 12 markers, NX Prenatal CEO Brian Brohman, told GenomeWeb.

Brohman declined to provide a timeline for launch of the test, but he said that he expected the company would launch the first generation of the test on a mass spec platform, which would make it among the first proteomic diagnostics firms to do so. Integrated Diagnostics brought the first such test to market with the launch of its Xpresys Lung test in 2013. Sera Prognostics plans this year to launch its PreTRM proteomic test for assessing risk of preterm delivery on a multiple-reaction monitoring mass spec-based platform.

Brohman said he believes that launching on a mass spec platform holds several advantages. NX Prenatal has used shotgun style mass spec followed by targeted MRM-style analysis for development of its preterm delivery test, and so keeping it on a mass spec platform would allow the company to skip development of an immunoassay version.

Additionally, he noted, mass spec avoids the problems of cross-reactivity and interference that can crop up when multiplexing immunoassays.

Of course, development of mass spec-based protein tests comes with its own set of issues, which the field has slowly been working out over the course of the last decade. One of the most prominent issues is that mass spec is typically less sensitive than antibody-based tests, meaning that low-abundance proteins can be difficult to measure.

Researchers have adopted a variety of approaches to get around this issue, but each comes with its own drawbacks. For instance, antibody enrichment of target proteins or peptides to supplement the mass spec's sensitivity adds sample prep steps that can increase the complexity and variability of an assay. Running longer LC gradients, on the other hand, can reduce throughput, which is a key element of commercial clinical assays.

One potential advantage of NX Prenatal's approach, Brohman said, is that by focusing on proteins contained in exosomes, the company is looking at an enriched sample, which could help with sensitivity.

Exosomes are membrane-bound particles released by cells that contain molecular content including proteins and nucleic acids from their cell of origin. A number of researchers are exploring these vesicles as part of biomarker development work, the idea being that their contents could shed light on the function and status of their source tissue.

In the AJP study, researchers including NX Prenatal Co-founder and CSO Alan Ezrin used a Thermo Fisher Scientific LTQ Orbitrap XL to look at exosomes collected from 48 pregnant women at 15 to 17 weeks of gestation, analyzing them for markers that could distinguish subjects (n=24) who ultimately delivered at or after 37 weeks of gestation from those who delivered at or before 34 weeks of gestation.

This analysis identified 99 potential markers, which the researchers then winnowed down to 18 markers for further exploration. NX Prenatal is now undertaking two additional studies to further refine this set, Brohman said. He noted that using markers from the 18-plex panel the company has distinguished between women who would deliver preterm and at-term with accuracy in the 80 percent range.

Beyond simply predicting risk of preterm birth, the researchers also hope to use the markers to better understand different subgroups of the at-risk population, Brohman said.

"For example, a patient who is at risk because of placental insufficiency — do they represent a different type of biomarker profile than a patient who may be undergoing an imbalance of certain inflammatory processes?" he said. "Right now what we are doing is looking at those various types of clinical utility."

Based in Louisville, Kentucky, NX Prenatal is a spinout of parent company NX Pharmagen, which Brohman and Ezrin launched to commercialize exosome-based diagnostics more generally, with a focus on oncology and prenatal medicine. They established NX Prenatal to house NX Pharmagen's prenatal assets after deciding that working through a more focused entity would help with commercialization efforts. In addition to Brohman and Ezrin, the company counts former Vermillion CEO Gail Page as executive chairperson.

"It became clear to us that the experts and advisors and clinicians and market were different in addressing questions of pregnancy as opposed to cancer and that there was relatively little synergy between those efforts," Brohman said. "There is synergy at the platform level in terms of how you take a bodily fluid sample and obtain a relevant exosome fraction to study. But in terms of the market and your commercialization and development plans, they really are different business opportunities altogether."

"A lot of times investors would rather have you focused on one particular market," he added. "So that does come into play. It's a little cleaner."

NX Prenatal is currently funded by what Brohman characterized as "a group of experienced private life science investors." He declined to comment on any plans to raise new funding.

He likewise declined to provide a potential timeline for launch of the preterm birth test. He said that the company has not yet decided whether it will offer it as a laboratory-developed test or pursue US Food and Drug Administration clearance, but, he said, "Our studies are designed to be powered and rigorous enough to pursue either regulatory path."

When the company's test does reach the market, it will most likely face competition from Sera Prognostics PreTRM preterm delivery risk test, which Sera plans to launch this year.

Based on intellectual property licensed from the University of Utah and Brigham Young University, Sera's preterm birth panel consists of three proprietary peptides plus six additional proteins, which the company measures early in a patient's second trimester.