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With $3.2M, DioGenix Planning Prospective Trial Completion in 2014, CLIA Bid for MS Sequencing Test

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DioGenix plans to use $3.2 million raised in a private financing earlier this month to support the ongoing prospective clinical trial of its targeted next-generation sequencing-based multiple sclerosis test, MS Precise.

In addition, the Gaithersburg, Md.-based company has established a new central lab facility, for which it plans to seek CLIA certification to commercialize MS Precise as a laboratory-developed test.

MS Precise, which is based on research by Nancy Monson at the University of Texas Southwestern that DioGenix has exclusively licensed, relies on targeted sequencing of patients' B-cell genomes to look for patterns indicative of MS versus other immune-mediated neurological diseases.

DioGenix's ongoing trial is intended to validate the ability of the assay to identify patients with MS at their first clinical presentation more accurately than current clinical assessment methods.

DioGenix President and CEO Larry Tiffany told Clinical Sequencing News that after analyzing data from a small number of patients, it looks like the trial is "on the right track," and without potential issues like site-to-site variability.

He declined to provide additional details about interim results from the study, but noted that they were encouraging enough to give the current investors confidence to support the trial going forward.

According to DioGenix, in a previous, mostly retrospective study of its cerebrospinal fluid targeted sequencing approach, the test performed with double the specificity and about the same sensitivity as current methods for testing CSF such as oligoclonal banding.

The company's ongoing prospective study intends to follow about 150 patients suspected of having MS and compare the results of MS Precise with patients' eventual diagnosis using standard clinical procedures.

While the firm expects a CSF sequencing-based test to be its flagship product, Tiffany said DioGenix is also sampling blood from all patients in the current trial with the potential of also developing a blood-based MS test, as well as sequencing control subjects to potentially identify targets that could be used in tests for other neurological diseases.

"We've actually started to see that there may be DNA signatures that are interesting for other neurological diseases," he said. "We'd have to validate those separately, but we are starting to see the potential to expand the product pipeline."

While the primary goal of the trial is to compare diagnoses determined by MS Precise to those resulting from a standard clinical workflow, which can take up to several months, Tiffany said the company is also collecting data over even longer time periods, to hopefully determine whether the test can accurately diagnose patients who present an even more difficult diagnostic challenge to current clinical tools.

"Some of the patients [in the trial] will not be clear cut, which is why we have to over-enroll, but we are excited about that actually," Tiffany said, "because we have data on all these patients – some may not be able to be diagnosed in the short term, but over time as their disease becomes more obvious — whether MS or another neurologic disease — we are hoping our early scores are going to be pretty predictive of what eventually happens."

According to Tiffany, the money DioGenix recently raised is enough to see the company through completion of the trial some time next year, although it is also planning to raise additional funds.

"What we see is that this money really takes us through late in 2014 — right to that point of being able to make the test available to patients," he said.

He added that the company would consider raising additional money next year once it has results from the study, but that the most recent funding allows DioGenix to "complete and submit the study to peer-reviewed journals … to expand out our current lab capabilities and get ready to submit [for] CLIA [certification], and get the lab ready for making the test available" as an LDT, he added.

In anticipation of this, the company also recently established an in-house development lab, which will, when the trial is successfully completed, be transitioned to a CLIA facility.

"In the early days of DioGenix, we wanted to be as capitally efficient as possible, so instead of having our own lab capabilities in house, we used outsourced CROs and genomics services providers," Tiffany said. "But as development of the test went on, that started giving us a greater deal of confidence and knew we were eventually going to set up a lab."

In moving forward with the prospective trial, Tiffany said the company's targeted sequencing methods have not changed substantially, but Diogenix is considering whether it will stick with the Roche 454 sequencing platform it began with, or switch to a competing technology.

"Frankly, the NGS part of this is not where the secret sauce is, it's just the workhorse," he said. "So we are thinking about and looking into what NGS platforms might be of interest to the company. We started on Roche 454 because of its technological advantages, but now some of the competitors have caught up in terms of read lengths, consistency, and quality."

As Diogenix's prospective trial has progressed over the year, it has expanded to 13 recruiting sites from an initial eight partners. Earlier this year, Tiffany said that the company hoped that this network of participating centers would later transition to become the company's first commercial customers.