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Signal Dx Shifts Focus, Targets Amplification Technology for US Market

By Tony Fong

NEW YORK (GenomeWeb News) – Having an innovative technology means little if you can't get your products to your target audience. It's a lesson start-up molecular diagnostics firm Signal Diagnostic had to learn, and as a result, it is now recalibrating its business with a focus on the US and new targets for its technology.

Founded in 2008, the Park City, Utah-based company is leveraging amplification technology that its CEO, Brian Caplin, said offers advantages over PCR. Dubbed Dynamic Flux Amplification, the technology was initially targeted for commercialization in developing countries where health facilities may not be able to afford PCR systems.

While a PCR platform costs more than $10,000 and can reach into the hundreds of thousands of dollars, Signal's DFA technology can be run on a $1,000 thermocycler, Caplin said.

The first test directed at human disease built on DFA is for tuberculosis screening, a disease which by some estimates afflicts only about 5 to 10 percent of the population in the US but as much as 80 percent of some nations in Asia and Africa.

But like other companies before it, Signal ran into multiple obstacles as it tried to gain entry into Third World markets, and after two years of trying with no revenues to show for it, the company is now shifting its attention to the US market. In the process, it is now also figuring out what disease areas it needs to tackle next, since "TB is not very useful here in the US as a test," Caplin told GenomeWeb Daily News this week. Once that decision is made, "we'll probably proceed on developing that into a test."

The DFA technology is a method for amplifying DNA and RNA, and was originally developed at a company called Fluoresentric, which spun out Signal.

While PCR is the gold standard for amplification analyses, one issue with PCR-based techniques is that the use of double-strand DNA-specific dyes used in PCR experiments results in non-specific products "which makes it near impossible to do specific DNA amplification" because the background noise "can compound any interpretation," Caplin said.

Probes can mitigate the problem, but DFA seeks to circumvent this problem and the need for PCR methods completely.

"What we've done is essentially developed a way to get your specific amplification for a positive-negative call for a diagnostic pathogen," he said.

That capability is especially meaningful in places where access to a PCR platform may not exist: Signal was founded to address this need.

"Diagnostic positive or negative calls for pathogen infection really need to be available to a broader level market and not just high-resource laboratories such as those in the United States and Europe," Caplin said.

Citing Uganda as an example, Caplin said that the common detection method there for TB is microscopic screens, but such screens have only 50 percent accuracy.

DFA provides essentially the same specificity as PCR, however, and reduces the time required to identify patients who actually have TB, according to Signal. By doing so, treatment for those who actually have the disease can be started more quickly, and those who don't can be more accurately weeded out so they don't receive unnecessary treatment.

One drawback of the technology is that it is not as sensitive as PCR, Caplin acknowledged. PCR requires tens of copies of a molecule for accurate detection, he said, while DFA requires hundreds of copies of the molecule.

But, he said, for most clinical tests, "it's a non-issue. If you have the disease, you have the disease, and it's usually pretty robust."

And because PCR equipment is not needed, DFA would provide greater access to a high accuracy diagnostic test.

"So if you think about a place like Uganda and Kampala … that's where you're going to get clinical diagnostic testing done," with the DFA technology, he said. But getting a foothold in such markets have proven to be extremely difficult, Caplin said, more so because Signal is still in start-up phase and has only three employees.

"It's just so challenging to even reach out to the third world and get any traction there," Caplin said.

As a result, the firm is now switching its attention to the US market. For the past few months, Signal has been in discussions with undisclosed clinical diagnostics laboratories that have expressed interest in DFA, he said.

The shift away from under-developed nations, though, means the company will need to find new disease markets for its technology.

"The challenge to moving forward with Signal Diagnostics in the US market [is] obviously the targets that we have in the human realm are less relevant in the US than they are in Third World nations," Caplin said. "So we're trying to identify at this point in time which target is the right one to make as our initial launch target as a US product."

He added that the biggest market for the firm's technology is not necessarily human disease either, but my fall into other realms such as veterinary medicine or environmental testing.

In addition to TB, Signal also offers DFA tests for Kennel cough, wine spoilage, bovine TB, and salmonellosis, and food poisoning. The DFA technology is flexible enough that it can be adapted relatively simply for detection of other diseases, according to Caplin. Using hepatitis as an example, he said that the technology can be used to screen for different strains of hepatitis "and get a colorimetric read-out with the specificity that you would otherwise get with a probe-based study."

The technology has worked with every target that Signal has tried to date, "so we feel pretty confident … that any assay that we throw at it, we can develop with relative ease," he said.

The company's work on TB continues, however, and in addition to a general screen for the disease, the company is developing a test for the detection of antibiotic-resistant strains of the bacteria. A follow-on test the firm is developing targets the five most common antibiotics for treating TB — isoniazid, ethambutol, rifampicin (also known as rifampin), pyrazinamide, and streptomycin.

Last week, Signal announced it was granted a US patent for its method of detecting drug-resistant TB. Its technology, the company said in a statement, can produce a TB drug-resistance profile in a few hours, compared to current molecular methods, which take days or weeks.

In the meantime, with no revenues of its own, Signal is subsisting mainly on funding from its parent firm, Fluoresentric.

Since its inception, Signal has raised $70,000 in investment financing, Caplin said. The company plans on another financing round which would be used to identify its next target and then bring it to market.

"Of course, we would love to believe DFA could replace PCR for diagnostic screening purposes," he said, and "the US market would, of course, be ideal, [and] we are in a funding mode to make this a reality."

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