NEW YORK (GenomeWeb) – London-based DNAe has been operating under the radar for years, but it expects to start clinical trials next year for a diagnostic test based on semiconductor DNA analysis that it believes will provide rapid, accurate results at the point of need for bloodstream pathogens that could lead to sepsis.
The company's first product, which will use PCR as part of the firm's Genalysis instrument, could be on the market in Europe in the middle of 2017 and in the US in early 2018, and future products using the same semiconductor DNA technology, but with a next-generation sequencing platform, could be in clinical settings for bloodstream pathogen testing in around two years.
The company's technology, which measures DNA on a semiconductor chip, is a key enabling feature of the its current and future products.
"A piece of gold in the middle of the chip senses different bases within DNA that allows us to read the fingerprint of either a pathogen or human DNA depending on what we put on to it," Steve Allen, DNAe's chief executive officer, told GenomeWeb.
The sensing chip is embedded inside a sealed, disposable cartridge. When the user inserts a blood sample inside the cartridge, nothing can contact it, which is important for avoiding contamination and achieving test accuracy, according to DNAe.
The firm, founded in 2003, focused its strategy on R&D and licensing for about 10 years. The company's founders invented semiconductor sequencing, which is the basis of Ion Torrent, Thermo Fisher Scientific's sequencing technology, Allen said, and Thermo Fisher has a limited, non-exclusive license to some of the firm's intellectual property from which DNAe receives royalties.
But in recent years, the company has altered its strategy and moved away from R&D and licensing towards developing its own products.
"Clearly, with Illumina, Thermo Fisher, and others in the market, we had no interest in becoming yet another whole-genome sequencing company," Allen said, "and we focused instead on using the scalability and the fact that we can miniaturize the analytical part of the DNA sequence analysis to build a much more user-friendly, rapid, point-of-need instrument, which is similar to the evolution of mainframe computers to PCs and laptops, where we bring the power of sequencing to the clinical point of need."
Allen, along with Nick McCooke, DNAe's chief business officer, led the development of Solexa's whole-genome analyzer. Illumina purchased the company for $600 million in 2006 and made the Solexa technology the centerpiece of its early sequencing platforms.
DNAe said it expects that its first products, utilizing PCR as part of its Genalysis instrument, will be used in labs that require a short turnaround time and are close to the emergency room, rather than in large central labs.
"Although the technology and system can go into physician's offices or other points of need, our initial focus is hospitals," Sam Reed, president of DNAe's US office, told GenomeWeb. "The differentiation from where sequencing is today and what we are looking to achieve is that we are not limited to use in the major academic centers, or the major centralized or reference labs. We're talking about something that can be used in any hospital, small or large, that doesn't necessarily have all of the capabilities of a centralized lab."
In 2015, DNAe acquired NanoMR, a company that provided a pathogen-capture capability, giving it the ability to develop a test that would provide sample-to-result capabilities from blood.
"We realized quite early on that if we were to achieve our dream of getting a test that worked from sample to result, we would need an enabling sample preparation technology," Allen said. "Among the differentiating factors we were looking to achieve was a technology that would provide a wide breadth of capture for the many different pathogens, including bacteria and fungi, that the system would need to be able to identify to detect the vast majority of bloodstream infections, and also provide very low limits of detection," he added. "We wanted to match the best of what a blood culture could do and go down to one colony-forming unit per milliliter, which is the limit of detection of blood culture methods, and in both of those areas the NanoMR technology stood out."
The DNAe technology measures signals from isolated hydrogen ions that are produced when nucleotides are incorporated during sequence detection. Above the chip are micrometer-sized structures that allow the flow of reagents, and wells that allow reactions. Ion-sensitive field-effect transistors on the chip are responsible for measuring hydrogen ion signals.
"It's an incredibly simple way of detecting DNA sequences, and it does not need all of the complication of optics or chemical modification with fluorescent probes that some of the other technologies require," Allen said.
With a couple of exceptions, including a test for Candida produced by T2 Biosystems and a test for multiple bloodstream infections produced by Abbott, most blood-based diagnostic tests are run after a blood culture procedure.
"Despite what [competing companies] quote in terms of turnaround time, you have to add approximately 24 hours before that to run the blood culture," Reed said. "The total turnaround time for most of those tests is, therefore, much longer plus they are usually run in a centralized facility and sometimes remote from the patient." Being blood-culture independent is significant, especially for conditions such as sepsis, which benefit from rapid detection, he added.
A number of companies including Roche, BioMerieux, T2Biosystems, OpGen, and Accelerate Diagnostics are either developing or have available systems to detect pathogens that could lead to sepsis. In addition to the obvious benefits to patients from the viewpoint of saving lives, "there's plenty of evidence that shows you can make big savings in healthcare costs, and a lot of that comes from a reduction in the length of the hospital stay and particularly the intensive care stay, which has a real impact on cost," McCooke told GenomeWeb.
DNAe is developing an economic model that demonstrates the health and economic benefits of more effectively treating sepsis using its technology, McCooke said. Although he did not elaborate on the details of the economic model, McCooke said it will allow DNAe to engage with potential customers and customize it for them, based on parameters such as incidence frequencies, and show them the budget impact at an institutional level.
Reimbursement will be relatively straightforward, he said, in the sense that hospitals will be responsible for being paid for the test and services they provide, and they will decide which tests to use. "If we can show that the technology will have a significantly positive budget impact, then it really is in economic terms a no-brainer for them to adopt it," McCooke said.
DNAe said it also has a roadmap for its product pipeline with two connected but different platforms. Its first bloodstream-based test product, which uses a PCR platform, is in the prototype phase and close to clinical trials. The company, in parallel, is developing a next-generation sequencing platform, and the semiconductor DNA analysis technology enables both platforms.
DNAe expects to begin clinical trials for bloodstream infections and sepsis around the middle of next year and aims to achieve 510(k) clearance from the US Food and Drug Administration toward the end of 2017 or early in 2018. The company will introduce the product in Europe with a CE mark at around the same time that it initiates clinical trials in the US.
The next-generation clinical sequencing product is at an earlier stage of development and could be ready in about two years, DNAe said. After launching the product for bloodstream infections, the firm has plans to enter the oncology market with a liquid biopsy test.
"In oncology, the opportunity is potentially huge," McCooke said. "Speed probably does not have the same prerogative as it does in bloodstream infections, especially in cases such as sepsis where it is obviously vital, but when you look carefully at opportunities in cancer there really are cases where you want to get a test result back really quickly.
"At the moment you have processes in place where you won't get results back for weeks to a DNA-based test for cancer," he explained. "So, we are looking at an opportunity again to be able to cut that turnaround time and to be able to place instruments where they are not currently located, which adds to the fast turnaround."
The DNAe team said that it believes the potential for the company in doing bloodstream infection tests alone is worth several hundred million dollars per year.