Correlogic Systems was “oblivious” to the NIH- and FDA-approved consulting deals by Emanuel Petricoin and Lance Liotta that last week were called into question by a US Congressional ethics probe, Correlogic’s president and CEO, Peter Levine, told ProteoMonitor this week.
“Suffice it to say it was pretty apparent to others in the industry that Biospect was a direct competitor of Correlogic, but I was oblivious to it frankly — I had no idea that any consulting was going on,” Levine said. The conflict “was brought to my attention by others in the industry, [and] I then brought it to the attention of our research partners,” he said.
Correlogic’s relationship with Petricoin and Liotta started in April 2002, when the company developed a CRADA research collaboration with the NCI-FDA Clinical Proteomics program, of which Petricoin and Liotta are co-principal investigators. While this CRADA agreement has finished, these revelations about the researchers’ consulting activities have not caused Correlogic to end negotiations with the NCI for another CRADA that would encompass clinical trials — trials that Petricoin and Liotta say they are already in the preliminary stages of conducting (see PM 2-13-04, 2-20-04). Levine said he didn’t know when the negotiations for the new CRADA would be completed. “I was surprised that it’s gone on as long as it has,” he said.
The US Congressional Subcommittee on Oversight and Investigations questioned Petricoin and Liotta during hearings last week on broader NIH ethics concerns (see PM 5-21-04). The hearings examined consulting activities that the pair was conducting with South San Francisco. Calif.-based start-up Biospect, now known as Predicant Biosciences, which were approved by the NIH and FDA. The chairman of the subcommittee alleged that the activities should never have been approved, because they represented a conflict of interest with Petricoin’s and Liotta’s official government-funded contract with Correlogic: Predicant is also a proteomics biomarker company, and Correlogic was not told of the consulting deal. Liotta and Petricoin denied that they were aware of any conflict. “My understanding was that Correlogic was a software company, in contrast with Biospect, that I understood to be a scientific instrument company,” Liotta said during the hearings. He said that he ended the relationship with Predicant when he had information that this status may have changed.
Predicant now describes its mission as “developing an integrated system incorporating proprietary separation, detection and informatics technologies to provide reliable, reproducible, and sensitive measurements for protein pattern discovery and clinical assays.” The company would not get more specific about its activities, but a source that asked not to be named indicated that the company was focusing on systems development and diagnostics development.
At the ASMS conference in Nashville, Tenn., this week, Predicant presented one lecture, entitled, “Multiplexed Orthogonal Time-of-Flight Mass Spectrometry,” which described an orthogonal TOF mass spec its researchers had designed.
Predicant declined to comment on the hearings. “Predicant doesn’t have a relationship with Chip [Petricoin] or Lance [Liotta] anymore, so there’s nothing for them to comment on,” company spokesperson Rick Roose, from Predicant’s outside PR firm WeissCom Partners, told ProteoMonitor this week.
Meanwhile, PerkinElmer announced at the ASMS conference this week that Petricoin and Liotta had approached PerkinElmer in October 2003 about establishing a separate CRADA for biomarker screening based on the carrier protein approach put forth by Timothy Veenstra and Thomas Conrad at SAIC-Frederick (see PM 11-28-03), and using PerkinElmer’s proTOF mass spec platform (see article p. 1). The company accepted, and the CRADA is expected to be completed “sometime in late summer,” according to Mary Lopez, business leader for analytical proteomics at PerkinElmer. “Once the research platform is in place, we may elect to go the diagnostic route but we have not made any commitments or decisions on this for now,” Lopez told ProteoMonitor in an e-mail message. She said that the company is on the lookout for a software provider that provides “a solution that is right now commercially available that will interface with our technology platform.”
Levine said that, separately from its CRADAs, Correlogic still has an ongoing license agreement with both the NCI and the FDA for the underlying process in Correlogic’s pattern recognition software — a process that was coinvented by Petricoin, Liotta, and two scientists from Correlogic. This license, he said, gives Correlogic the exclusive right to commercialize a test based on the invention.
“In a joint invention, both parties can practice the invention, or one side can license rights to the other,” Levine said. “For commercialization purposes, those rights were licensed to Correlogic.”
With the rights to commercialization in hand, Correlogic struck up agreements in November 2002 with diagnostic reference laboratories Quest and LabCorp. The nature of the agreement, Levine said, “was and is to bring to market the first application of both the technology we developed with the FDA-NCI, and to bring to market an ovarian cancer test.” The three companies set about testing and validating the ovarian cancer test for release as a home brew, a specification that would not normally require FDA approval. He added that the US government had actually approved the agreement, “because part of the agreement involves licensed technology from the federal government.”
FDA Guinea Pig
What came next was somewhat unexpected, Levine said. “I didn’t think that this was going to be an easy road, but there have been a remarkable number of obstacles out of left field that I never could have anticipated,” he laughed. “It’s truly for a good cause, though — I’m really pleased to be doing it.”
Correlogic — as the first company to try to commercialize a proteomics-pattern based diagnostic — has clearly been the experimental guinea pig for this new test. In February and March, the FDA — which has never set standards for approval of a proteomics pattern-based diagnostic — sent a series of letters to Correlogic, LabCorp, and Quest warning them that the test they wanted to market as a home brew might be subject to FDA regulation as a medical device. The letters asked the companies to come in and talk with the FDA about what action might be necessary (see PM 2-27-04, 3-5-04, 3-12-04).
At the time that the letters arrived, LabCorp had been intending to release the first version of the ovarian cancer test, which it was calling OvaCheck, on April 1st. But the move by the FDA put the companies into what Levine called a “holding pattern.” Levine said that Correlogic met with the FDA several weeks ago, and that discussions are ongoing. In terms of when a test might finally make it to the market, “it’s difficult to have any way to predict how long that may take.” He would not go into further detail about the discussions, except to call them “productive.” Outside experts have estimated it will take at least six months to bring the product to market if official FDA approval is required (see PM 2-27-04).
In the meantime, Correlogic, Quest, and LabCorp are continuing to conduct validation experiments on the ovarian test. “We’re going on reviewing everything that we’ve done, [and] analyzing more samples,” Levine said. “There are so many different areas of ovarian and other cancers that we haven’t yet begun to work on in the level of detail that we’d like to … so there’s always tons of work to be done, even on ovarian cancer that’s had so much progress.” Levine said that when conducting validation experiments, Correlogic collects the samples, aliquots them, and shares the aliquots with Quest and LabCorp. All three companies process the same samples, and then “we send the spectra back and forth and continue building new models,” he said, that take into account such issues as sample handling artifacts that might be introduced by using different tubes during sample collection. While all three companies produce their own spectra, however, Levine emphasized that in both validation studies and in a real-life testing process, Correlogic always conducts the analyses itself, using its software, at the Correlogic site. “We have not distributed the analytical part of the test — that’s all kept here at Correlogic,” Levine said.
Beyond Ovarian Cancer
Correlogic may to much of the world be synonymous with OvaCheck, but Levine said that the company is actually working on applying its algorithm to a number of different cancers, as well as to vasculitis, prenatal conditions, and other disorders. A month ago, the company entered into a collaboration on breast cancer with the Walter Reed Army Medical Center and the Windber Research Institute. The company also has agreements with other NIH institutes, with the Foundation for Blood Research, with Advion BioSciences, and with academic institutes such as the University of California, Irvine, and the University of North Carolina, Chapel Hill. Correlogic has additionally “been actively pursuing other governmental joint research opportunities,” Levine said.
Levine also said he does not want the company to be associated only with its famous pattern recognition algorithm. In addition to its original Proteome Quest, the company has developed Proteome Dx software, which is both a “collection and analytical system,” according to Levine. “When the original [Lancet] paper first published on biomarker patterns for ovarian cancer, there really wasn’t a software system per se — there was a series of algorithms,” he said. “What we’ve done is develop that into a comprehensive software system, that not only incorporates analytical tools on the bioinformatics side, but also we’ve developed a software system for actual processing of samples.” Levine said that since the Lancet paper, the company has been “honing in” on developing sample prep and mass spec platforms that would produce better results when used with the original algorithm, which it has also worked on improving. “While we’ve done remarkably well in the early going, what became apparent is if you want to have something wonderful coming out, you have to have something better going in,” he said.
What Correlogic has learned the hard way in the past two years, Levine said, is the same lesson that most biomarker scientists have learned: “It’s one thing to do one experiment and publish a paper. It’s another thing to bring it to the market.”