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Wave 80 Aims to Begin Clinical Trials this Year for POC MDx System, HIV Viral Load Assay

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Bay Area molecular diagnostics shop Wave 80 Biosciences is gearing up to evaluate its first product — a semi-quantitative HIV viral load assay that runs on the company's cartridge-based, near-patient, sample-to-answer testing system — in full-scale clinical trials by the end of this year, company officials said recently.

Depending on the outcome of those trials, Wave 80 hopes to then commercialize its product sometime in the first half of next year in resource-poor areas of the world as a tool to help clinics monitor and tailor antiretroviral therapies and improve outcomes in HIV patients.

Eventually, Wave 80 also hopes to commercialize its assay and platform in the US, and the company is developing a fully quantitative version of the test as well as assays for other infectious diseases such as hepatitis B, chlamydia, and gonorrhea.

Daniel Laser, Wave 80's president and CEO, and Shan Gao, senior chemical engineer at the company, discussed these goals and the recent progress of the company's platform with PCR Insider in advance of a presentation delivered by Gao at the Knowledge Foundation's Sample Prep conference held earlier this month in San Diego.

Founded in 2003, Wave 80 resides in a combined laboratory/office facility near the Mission Bay campus of the University of California at San Francisco. Over the last decade the company developed a type of electro-osomotic flow technology called slit capillary array fluidic actuators, or SCAFA, to carry out chemical and biochemical reactions at the milligram-to-gram scale.

When used in disposable cartridges such as the ones Wave 80 is developing for its flagship testing system, called Eoscape, the SCAFA technology provides several advantages over other actively powered fluid transport methods that serve as the basis for competing lab-on-a-chip technologies.

"This is a set of small chips that we build into our disposable cartridges that provide active fluid transport," Laser said. "They don't just move fluids around, but are very effective at accelerating various assay processes. That applies to both the downstream, or assay, part of the cartridge, and the upstream, or sample prep part."

More specifically, Laser described SCAFA as "a particular implementation of electro-osmotic-based fluid actuation. It's direct transduction from electrical power into fluid power, so we have some specific ways of making chips that are inexpensive enough to build into disposable cartridges, but also have a very high fluid power generation capability. That fluid power is generated directly from electrical power, so there is no other intermediate — for example, a solenoid that acts on a diaphragm that then pushes fluid around."

With this technology in hand, Wave 80 then began assembling additional technologies around it as part of an effort to develop its point-of-care nucleic acid testing system to monitor participants in HIV vaccine trials — an effort that blossomed into a $7.5 million contract awarded in 2009 from the National Institutes of Health to develop a system to monitor viral load in HIV patients receiving antiretroviral therapies in low-resource settings.

One of those components is a solid phase extraction technology developed in the laboratory of Catherine Klapperich at Boston University.

Last year PCR Insider reported on the Klapperich lab's single-use microfluidic chip to extract, PCR amplify, and detect RNA from influenza A virus with a high degree of sensitivity (PCR Insider, 4/5/2012).

Klapperich and colleagues used specially designed SPE columns to extract and purify RNA samples for downstream analysis in their chip and have also licensed it to various companies, such as BioHelix (recently acquired by Quidel), for use in their molecular testing systems. Klapperich also noted at the time that Wave 80 was evaluating the technology.

Laser told PCR Insider recently that the company has "found the technology to be very useful," particularly when coupled with SCAFA, although he declined to disclose whether Wave 80 had licensed the SPE technology from BU.

"Klapperich's lab is developing a monolayer SPE, focusing more on the formulation and … materials side … but we are focusing on trying to make the whole process into a cartridge format," Wave 80's Gao said, recapping her presentation at the Sample Prep conference.

"We are working to reduce the reagents we use, increase the [RNA] recovery rate, and make sure the RNA purified from the monolayers will be compatible with our assay," Gao added.

For instance, Gao said, the SPE monolayers capture precipitated RNA, are washed, and then dried for subsequent dissolution in water and elution of the RNA. The Klapperich lab was using air to dry out the monolayers, but "this is not really feasible in our cartridge format, so instead we are using heat, which is a very achievable method in the cartridge format. It turns out this also increased the recovery rate quite a lot, like killing two birds with one stone."

Another component technology of the Eoscape platform is a proprietary bipartite luminescent signaling system developed by Laser and others at Wave 80.

According to Laser, the bipartite luminescent signaling system "combines the best attributes of chemiluminescent and fluorescent signaling in that it has a low background, but also the advantage of external excitation." Laser declined to provide additional details about the method due to intellectual property concerns.

In general, then, the Eoscape workflow comprises the "upstream" sample prep using SPE, a controlled-replication isothermal amplification of target RNA, and detection using the bipartite luminescent signaling technology — all driven through the cartridge by the SCAFA technology, which "makes it all go," Laser said. "Those three things together are what form the underpinnings of the viral load product that we now have in late-stage development," he added.

According to the company's website, the current product uses 100-µl whole blood or plasma samples, typically from a fingerstick or a heelstick, and quantitates HIV RNA in less than 50 minutes from sample input. The results are displayed on an integrated 18-cm touchscreen display and over a variety of electronic communications protocols, including HL7, SMS, and an optional attached printer.

Laser noted that the $7.5 million contract from the NIH's National Institute of Allergy and Infectious Diseases stipulates the development of a semi-quantitative system that would differentiate between patients with viral loads of greater than 1,000 copies/ml of blood — a threshold that is widely accepted as indicating when patients should potentially be switched from one antiretroviral therapy to another.

"We also plan to later release a version that is fully quantitative," Laser said. "The reason we're putting the [semi-]quantitative one on the market earlier … is that the fully quantitative system requires a little more training for the lab technician running the test. Neither requires very significant training, but with any nucleic acid test, no matter what the setting it's used in, there is a certain amount of calibration and control that needs to be done by a trained lab technician. For the fully quantitative system, that requirement is just a little bit more than the World Health Organization and other relevant bodies think is appropriate for [high-disease burdened countries]."

Laser added that "by releasing this slightly simpler system now we can solve this very important problem of ID'ing failure of first-line anti-retrovirals — that's the real pressing need."

Wave 80 has completed the first limited trials of the product and is currently working to move into full-scale clinical trials this year, Laser said. After that, "everything depends on the regulatory process, and that can be uncertain," he added. "But we'd certainly like to get this product out into the clinics where it can start to improve HIV patient outcomes as soon as possible. And we'd like for that to be end of this year beginning of next year at the latest."

The company will follow either the CE marking process or a new pre-qualification process being developed by the WHO in order to speed access of potentially life-saving technologies to resource-poor areas of the world. In either case, Wave 80 will focus first on marketing its product in high-disease burdened countries, including areas of sub-Saharan Africa, the Caribbean, Latin America, and Asia.

"The longstanding emphasis of the company has been on these HDBCs where the unmet need for nucleic acid testing is the greatest," Laser said. "That said, we do have a chlamydia and gonorrhea nucleic acid test in the pipeline that we feel addresses an unmet need in the US market."

Further, he noted, evidence is increasing that the rate of HIV transmission is dramatically higher in the first few weeks after a patient contracts the virus. As such, an inexpensive, fast, and simple test could go a long way toward curbing spread of the virus in the US, as well.

Laser said that Wave 80 has primarily been subsisting on the NIAID grant and a few other smaller grants and contracts. "We do have some private-sector funding, but don't make that public," he added. "We are a small private company, so we are always seeking funding."

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