By Ben Butkus
In an effort to expand the potential market for its multiplex PCR-based molecular testing technology, PrimeraDx has decided to offer it as an open platform to laboratories wishing to develop their own molecular tests, CEO Matthew McManus said in an interview this week.
Thus far, the company has inked collaborative agreements with researchers at the MD Anderson Cancer Center and the Hitchcock Medical Center of Dartmouth Medical College to develop various multi-marker oncology assays; and has sold one of its platforms to Eli Lilly, according to McManus.
In addition, PrimeraDx is pursuing partnerships with other pharmaceutical companies to explore using the platform in companion diagnostic development; as well as readying its own molecular diagnostic — a multiplex assay for Clostridium difficile — for regulatory submittal, a process it hopes to complete by the first quarter of 2012, McManus said.
Based in Mansfield, Mass., privately held PrimeraDx has developed a technology called scalable target amplification routine, or STAR, which integrates standard endpoint PCR with capillary electrophoresis to simultaneously quantitatively measure multiple target nucleic acids.
Many multiplex PCR-CE combination technologies are commercially available, but what makes PrimeraDx's technology different is the fact that it continuously samples PCR reactions during sequential cycles and then separates out the product using CE. This results in data that can be constructed into amplification curves not unlike quantitative real-time PCR.
"It actually is quantitative PCR in real time," McManus said. "But it's not the standard probe-based, real-time systems like TaqMan, where you're looking at fluorescence in the entire reaction volume. It's combining the best of both worlds in terms of the high level of … specificity, sensitivity, and broad linear range [of qRT-PCR], and other technologies just don't have that kind of range when multiplexed."
Besides the STAR technology, PrimeraDx has also developed an instrument platform called ICEPlex for running STAR-based assays. ICEPlex is a standalone, bench-top analyzer that can run up to 96 samples, including controls, and report on up to 60 targets in each sample in under four hours. Software independently controls and monitors instrument function and analyzes data to provide completed determinations at the end of a run, the company said.
ICEPlex "samples at multiple runs over time, so it's actually sampling in real time from the reaction," McManus said. We follow the build-up of fluorescence intensity over time and we plot that against cycle number, and by plotting that you get back to real-time math and it's an amplification curve. We generate that curve for each of the targets over the course of the PCR reaction, so we can multiplex and quantitate a high number of targets in real time."
An added advantage over qRT-PCR, according to McManus, is that ICEPlex and STAR don't use fluorescent probes. "We're just using primer sets for each of the amplicons, so we don't have that competing chemistry. So it's cleaner, and we can multiplex more easily than you can with a probe-based system."
Despite the multiplexing capability of its technology, PrimeraDx spent the first several years of its existence marketing a specific multiplex PCR-based assay for studying viral load in transplant patients. The 14-plex test contains internal calibrators and controls, and simultaneously detects and quantifies levels of viruses such as cytomegalovirus, Epstein-Barr virus, BK virus, and human herpes viruses 6 and 7 in blood.
"We still have that test, and it's sort of in the sweet spot of multiplexing and quantitative," McManus said. "But it's only one of the things we can do, and I think that for us to succeed as a company, we have to demonstrate the value in a number of other areas,"
To that end, when McManus joined the company as CEO last September (PCR Insider, 9/1/10), he helped lead a change in strategy that would try to take advantage of the ICEPlex and STAR technologies in a number of different application areas including mixed microbial panels, oncology, companion diagnostics, and even applied markets like food testing, pharmaceutical quality control, and agricultural biology.
"I think the value of the technology itself had not been paid attention to," McManus said. "We really hadn't rounded out what the platform can do and pushed the edge of the envelope in terms of its capabilities. PCR, from a clinical standpoint … is kind of going to be the bread and butter here for a long time to come in terms of diagnosing and managing patients. We had the ability, and now have demonstrated that ability, to do lots of different things in the space, and just hadn't really paid attention to that."
Of the potential application areas, McManus sees multi-marker oncology molecular testing and companion diagnostic development as perhaps the most promising. To that end, PrimeraDx is pursuing a near-term strategy of offering ICEPlex as an open platform on which CLIA-certified labs can potentially develop their own molecular diagnostic tests.
"The nice thing is that any of those labs that run molecular tests have a good fundamental understanding of PCR," McManus said. "On top of that we have a whole suite of software tools … that help those labs to develop tests for their needs. We place the instrument, sell the consumable cartridge and calibrators and controls to make it easy for them to develop and run their own tests on the machine."
PrimeraDx has already placed platforms and established partnerships with various academic institutions to explore such diagnostic development. Chief among these are individual collaborations with Dartmouth's Hitchcock Medical Center and MD Anderson on various assays in the oncology space; as well as a three-way collaboration with the institutions in the area of lung cancer. McManus also said that PrimeraDx recently sold an ICEPlex to Eli Lilly, although he did not say what type of research the pharma giant will be using it for.
In general, McManus said, partnerships such as these are taking advantage of another key aspect of PrimeraDx's multimodal detection capabilities, which "is really looking at different flavors of target. For instance we have one assay that was developed in partnership with a pharma company that looks at multiple mRNAs, multiple miRNAs, genomic DNA, and size calibrators and quantitation calibrators — separate internal controls — at the same time, in the same reaction well, which gives you much higher quality data by eliminating pipetting errors or different master mixes."
In the meantime, as part of a more intermediate strategy, PrimeraDx plans to also develop its own molecular diagnostic tests and shepherd them through the US Food and Drug Administration approval process. PrimeraDx's first such test, for C. difficile, is about halfway to the submittal stage.
"This is a well-recognized and growing marketplace, and there are some other competitors in the field, but that's OK as well, because it helps us understand how to take our first assay through the FDA," McManus said. "FDA has been a terrific partner to us … and we anticipate submitting a full package with clinical [data] in Q1 of 2012."
The C. diff test is a multiplex assay, "although we can't yet talk about the formulation," McManus said. Although the assay will contain various calibrators and controls that the company believes will provide better data quality than currently marketed tests, McManus admitted that "it's only getting at the very first level of utility for the platform. The other sorts of tests we're working on push it much farther, say in the oncology space, and in the high-plexing infectious disease area."
Lastly, longer term the company hopes to partner with various companies in applied markets — "products in non-regulated spaces," McManus said. "Even if they're regulated by FDA, or the US Department of Agriculture, they're done differently. The ability to multiplex and take a lot of cost out of the equation but provide an even higher quality answer — that's of importance to, broadly, ag bio, food, materials QC and pharmaceutical manufacturing, water supply [testing], forensics, et cetera."
In order to achieve these new goals, PrimeraDx will likely aim to raise money in a Series D financing round beginning sometime this fall, and likely closing early next year. The company has previously disclosed a Series C financing round worth $20 million in 2009; and a Series B round worth $21 million in 2008.
"We've got a very high-quality, experienced investment syndicate" in place, McManus said.
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