Privately held molecular diagnostics firm PrimeraDx has been forced to downsize as it undergoes a restructuring and attempts to put together a new round of financing to fund future activities, PCR Insider has learned.
Despite the setback, the Mansfield, Mass.-based company in August submitted a package to the US Food and Drug Administration supporting potential approval of ICEPlex, its highly multiplexed PCR-based testing system, and associated assay for Clostridium difficile, President and CEO Matthew McManus told PCR Insider this week.
In addition, PrimeraDx "continues to support its customers and collaborators," McManus said, among them Eli Lilly and Quest Diagnostics, with whom PrimeraDx has separate agreements to develop multiplexed molecular assays to support the clinical development of targeted therapeutics.
"We have had to downsize as we restructure and put a new round of financing into the company," McManus said. "It's a difficult time for diagnostic and device companies to get financing, and we're in the process of restructuring the company … organizationally to trim the burn as we put a new round of financing in place."
McManus declined to disclose how many employees the company had before or after the restructuring.
Two of PrimeraDx's academic collaborators — Belinda Yen-Lieberman of the Cleveland Clinic and Bryce Portier of the Houston Methodist Hospital — were scheduled to provide an overview of how PrimeraDx's could enable multiplex PCR in the clinic at a company-sponsored workshop last week as part of the Association for Molecular Pathology annual meeting in Phoenix, Ariz.
However, given its financial struggles, PrimeraDx was forced to cancel the presentations. Similarly, the company decided not to man a booth in the AMP exhibit hall as it had originally planned.
"We are very tightly controlling expenditures, so we had to cut back on our display booth," McManus said. "With any downsizing there are difficulties."
PrimeraDx was founded in 2005, and it last closed a financing round in 2009, netting $20 million in a Series C from a cadre of investors including CHL Medical Partners, Abingworth, Burrill & Company, InterWest Partners, the Invus Group, and the Malaysian Technology Development Group.
The company's benchtop ICEPlex platform runs an assay technology called scalable target amplification routine, or STAR, which integrates standard endpoint PCR with capillary electrophoresis to simultaneously quantitatively measure multiple target nucleic acids.
The platform continuously samples PCR reactions containing fluorescently labeled primers during sequential cycles of amplification. The amplified products can then be detected by size using capillary electrophoresis, and the amplification kinetics can be reconstructed using real-time PCR algorithms to quantify the amount of material in the initial sample.
The company has maintained that this enables a much higher level of multiplexing than is possible with real-time PCR techniques that use fluorescent probes and, as such, can simultaneous quantify multiple gene targets — a few dozen for practical purposes but a few hundred, theoretically — from a single reaction.
PrimeraDx originally designed the platform for infectious disease assays, but shifted gears in 2012 to increase its focus on oncology and companion diagnostic assays.
PrimeraDx has made strides with the new strategy. Last June it entered into a multiyear agreement with Eli Lilly to develop ICEPlex assays in support of multiple therapeutic development programs. And in March it said it was working with Quest Diagnostics to co-develop and commercialize molecular diagnostic products and services in support of targeted therapeutics. Also, in September 2012 the company won a grant from the National Cancer Institute to develop a gene expression profiling assay that can rapidly detect diffuse large B-cell lymphoma subgroups.
McManus affirmed this week that all of these initiatives are intact.
"Primera is still an operating company," McManus said. "We're still shipping product and collaborating on our companion products. We continue to support our customers and collaborators. We sent out a number of shipments of products last week, and I'm sure we'll continue to this week."
PrimeraDx did have a presence at the AMP meeting in the form of six separate scientific posters.
In one poster, Cleveland Clinic's Yen-Lieberman — along with scientists from Nationwide Children's Hospital, Tampa General Hospital, Ohio State University, and PrimeraDx — presented a poster detailing data from a multicenter prospective clinical trial of ICEPlex C. difficile.
The assay is designed to target the C. difficile tcdB gene (encoding for the toxin B protein), and is performed as a seven-plex PCR reaction including three internal calibration standards, one internal control, and three independent target sites on the toxin B gene.
The researchers compared the ICEPlex test to a cell culture cytotoxicity method for 688 fresh patient samples, and found that ICEPlex demonstrated 91 percent sensitivity and 97 percent specificity.
The trial was intended to support PrimeraDx's FDA submission for ICEPlex and the C. difficile assay. In May, McManus said that the company was hoping to submit the assay to FDA by the end of that quarter, with the idea that winning instrument approval with a relatively simple multiplexed test like C. diff would open the door for the company to more easily gain approval for more complex multiplexed tests on the platform.
McManus told PCR Insder this week that PrimeraDx submitted its package to FDA in August "with what we think are excellent results from the clinical trial." He added that the company in September received notice that the submission was complete and that PrimeraDx has been working with the FDA since. "They have been great to work with, and we're moving forward under interactive review," he said. Overall, he added, the company has made "very good progress … on the regulatory side, hopefully with a final decision in the near future for the C. diff assay."
In another poster, company collaborators from the Mayo Clinic prospectively compared a transplant multiplex viral panel on the ICEPlex system with real-time PCR for detection of cytomegalovirus, Epstein-Barr virus, and BK virus in 292 clinical specimens.
In this study ICEPlex demonstrated sensitivities of 90 percent, 96.7 percent, and 75 percent, and specificities of 97.9 percent, 96.6 percent, and 96.3 percent for the detection of CMV, EBV, and BKV, respectively. The researchers concluded that the ICEPlex viral panel performed comparably to real-time PCR for the three infectious agents, with an overall agreement of 93.8 percent. "Our findings show that the ICEPlex system has the ability to detect multiple targets in the same specimen, which may improve the management of transplant patients," they concluded in their abstract.
On the oncology side, scientists from PrimeraDx and Cleveland Clinic presented analytical verification of a 20-plex ICEPlex diffuse B-cell lymphoma assay; while researchers from the company and the Geisel School of Medicine at Dartmouth presented positive data for an ICEPlex assay designed to detect 13 of the most clinically important KRAS mutations along with four other BRAF mutations in one tube from formalin-fixed, paraffin-embedded tumor samples.
Finally, company scientists presented a poster validating a single-tube multiplex ICEPlex assay for the 13 most frequently encountered cMET point mutations; and another validating a single-tube, 18-target, 21-plex assay for cMET and EGFR copy number variation and cMET gene expression profiling.
"We were very pleased with the technical showing on the scientific side," McManus said. "This is why I continue to be bullish on the company and our prospects — we continue doing things in the diagnostic space that really no other platform can do. We've developed some assays that, to my knowledge, are not possible to do on any other single platform, let alone in a single well. We're excited about that, and we were excited about putting the technical face on it at AMP, but we've had to restrict some of our marketing spend."