This article has been updated from a previous version, which incorrectly stated the potential manufacturing price of Great Basin's platform.
By Ben Butkus
Molecular diagnostics startup Great Basin Corporation has developed a cartridge-based, multiplex, sample-to-answer molecular testing platform, and hopes to begin clinical trials for its first two tests for detecting Staphylococcus aureus in blood culture and Clostridium difficile in stool by early summer, the company said this week.
If all goes well, the company, formerly called Great Basin Scientific, will quickly follow its clinical trials with US Food and Drug Administration regulatory filings for the S. aureus and C. difficile tests; then turn its attention to further expanding its menu with assays for S. aureus and methicillin-resistant S. aureus in nasal swabs and fungal pathogens in blood culture.
To support these endeavors, Great Basin in the past year has made several key business decisions that it disclosed this week. First, in May 2010 it closed a $12.1 million Series A financing funded by "private individuals of very high net worth" that have been investors since the company was founded in 2005, President and CEO Ryan Ashton told PCR Insider.
Great Basin also closed $3.9 million in equity financing in October 2008 and raised another $3.9 million in bridge funding in June 2009.
Second, last summer the company moved into a new 19,000-square-foot headquarters in Salt Lake City to consolidate its corporate offices with its R&D facilities, which had previously been split between Salt Lake City and Longmont, Colo., Ashton said.
And lastly, Great Basin added several key executives to its team in 2010, including Andrew Olson, formerly of Signature Genomics, as VP of sales; and Sandra Nielsen, an alum of international media company Pearson, as VP of marketing. The company also added a director of research, director of engineering, and director of product development in 2010.
Great Basin's molecular diagnostics platform incorporates a thin-film biosensor technology licensed from Yale University; a helicase-dependent amplification technology licensed from New England Biolabs spin-off BioHelix; and its own proprietary technology enhancements and analysis software.
The resultant integrated platform comprises disposable cartridges and a benchtop instrument designed to perform inexpensive and fast "sample in, answer out" molecular diagnostic assays cut from the same cloth as the Cepheid GeneXpert system.
"In fact, we look a lot like Cepheid," Ashton said. "From the beginning our goal was to do the same thing that Cepheid's done. Before the GeneXpert even existed, we were looking at the same model, which is that in the case of infectious disease, time to result matters; and second, it's really important to be able to do the test as simply and easily as possible."
Ashton also acknowledged that Cepheid is "gaining a lot of momentum over the last nine to 12 months as they expand their menu and people become persuaded that molecular really is a superior method for doing infectious disease testing under certain circumstances."
For all its similarities to Cepheid and numerous other startups pursuing a similar self-contained cartridge-based molecular testing model, Great Basin believes it can differentiate itself from the competition in two areas: cost and information.
"Our system was designed from the beginning to be much, much [less expensive]" — a result of the isothermal amplification technology employed by the company, Ashton said. "We don't have an expensive thermal cycler in there. We have a simple block in there, and we heat to 65° F, and it can be plus or minus one degree and the reaction works just fine."
An additional money saver is the platform's relatively simple detection system — a silicon chip with a "macroarray" of up to 64 pre-spotted probes of interest that produce spots that are visible to the naked eye when target hybridization occurs. The company's proprietary pattern-recognition software then analyzes what targets are present versus control targets to identify the presence or absence of particular infectious disease markers of interest.
Great Basin has not yet formalized pricing for its system, but Ashton said that the instrument can be manufactured for less than $5,000. In general, Great Basin's tests will be able to be performed in less than an hour, not counting any pre-test Gram stains that must be performed, such as in the case of the staph blood culture test.
Second, "the most important and most powerful advantage is really information," Ashton said. "Because we're using endpoint detection on a chip, we can spot an array with up to 64 [probes] and take a single sample and look at any number of causes for the patient's symptoms."
In the case of a blood-culture test for S. aureus and MRSA, this is important to physicians because "whereas a Cepheid or [Becton-Dickinson] GeneOhm test can tell you whether a patient has MRSA or not; we're going to be able to tell the clinician, 'It's not MRSA — but it is S. lugdunensis, and they actually do have a blood infection. And in the case of Cepheid or BD GeneOhm, all they can say is that there is no MRSA, and that you had better keep culturing all the other possible staphs in case there is a blood infection here."
Overall, there are about a dozen or so species of Staphylococcus that could be important for physicians to identify in addition to the gene for methicillin resistance, Ashton said. "We can also tell them right away whether or not it's a contaminant, like S. epidermitis. The only way that gets into the blood, in all but about 2 percent of the cases, is that the nurse or technician contaminates the blood draw."
The end goal with the staph test, as well as tests for other infectious diseases, "is to have a single test that provides all of the possible answers, or at least as many of them as we can, as to why a patient might be ill — and to do that in a simple, easy-to-use, on-demand way."
Because of the ability of the technology to perform multiplexing, Great Basin will focus primarily on infectious disease testing "where panels matter — respiratory, for instance. So rather than just tell you that you have flu, we'll add [respiratory syncytial virus]; or we'll subtype the flu, so there will be eight or ten or 25 answers per test; that's really where we're taking this."
Great Basin has completed clinical studies around its staph and C. difficile tests in collaboration with researchers from the University of Indiana and ARUP Laboratories. The company is also planning studies with clinical researchers at Northwestern University and Johns Hopkins University in preparation for clinical trials.
"Right now the timeline for a trial on staph is early summer and on C. diff., a few weeks thereafter," Ashton said. "By the end of this year, or early next, we've got two more [tests] that will follow very quickly: a nasal screening test [for S. aureus] that we are very close to doing outside studies on; and a test for fungal pathogens in blood that is probably going to be in clinical trials more like a year from now."
The company's first staph test will likely fall under the CLIA "moderately complex" designation primarily because of the pre-test Gram stain. "The test itself will qualify for [CLIA] waiver, because you just take an unmeasured aliquot of blood out of a bottle, cap it, and put it in the cartridge and machine — that, by definition, we're confident we'd qualify," Ashton said. "I can't say definitively that we would get CLIA waiver, because that's the FDA's judgment to make."
However, Ashton noted that Great Basin's system was designed "absolutely with [CLIA] waiver in mind. Our long-term goal here is to get to the pharmacy. We believe respiratory testing at the pharmacy level is where this is headed, and we need a system that can do that."
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