NEW YORK ─ Harvard University spinout Torus Biosystems is planning its entry into the market for syndromic multiplex testing, leveraging a platform that combines convection PCR, nanoarrays, and proprietary probes to enable quantitative detection of a broad range of DNA and RNA biomarkers.
Torus is combining the technologies to develop diagnostic testing products for use near patients that would provide results directly from a sample within 30 minutes, its President and CEO Shawn Marcell said in an interview.
The Cambridge, Massachusetts-based company recently licensed probe technology from Harvard University's Office of Technology Development that had been developed at the Wyss Institute for Biologically Inspired Engineering, and it is using complementary technologies developed at Rice University by Torus Cofounder David Zhang and Dmitriy Khodakov, a co-inventor.
The proprietary probes along with nanoarrays and convection qPCR could enable levels of sensitivity and specificity exceeding that of current high-performance PCR-based syndromic panels, according to its developers.
In particular, the use of novel toehold probes enable specificity at the level of a single nucleotide, enhancing the performance of the platform, said Peng Yin, a professor of systems biology at Harvard Medical School, who led the development of the toehold-probe technology and is also a Torus cofounder.
The testing platform consists of a torus-shaped chamber that enables low-power convection-based qPCR and an integrated pre-quenched nanoarray that enables a massively multiplexed readout of results, the firm said.
A toehold is the shape that emerges when probes bind with their targets, Marcell said, adding that anywhere from one to 1,080 dots that have toehold probes embedded in them are printed within the test's chamber to enable multiplex testing. When the platform is testing for disease markers, a sample with reagents flows over the toehold probes in the chamber and initiates the release of fluorophores. Target DNA or RNA are also amplified as they move from a hot zone to a cold zone, providing the basis for convection-based PCR amplification.
All of that occurs in a device about the size of a toaster that would provide sample-to-answer results and enable large multiplex panels, Marcell said.
Its current product prototype uses a single slot for a disposable cartridge that consists of reagents and enables the addition of the sample to the torus-shaped instrument. Torus Biosystems is developing a next-iteration prototype with four slots to enable higher throughput and random-access testing, Marcell said.
He added that the platform can operate using blood, saliva, or urine, which should be beneficial in near-patient testing and enable testing for different conditions. Late in the second quarter of next year, the company expects to initiate clinical studies involving 500 patients or more to validate its first product, a syndromic panel for urinary tract infections that identifies pathogens and drug resistance from urine samples.
The clinical study is being designed to provide a basis for a submission in early 2022 to obtain 510k clearance from the US Food and Drug Administration and a CLIA waiver. The firm will file a parallel application for CE marking that would enable marketing of the product in European countries and others that accept the designation.
The second product in the Torus pipeline, a blood test for sepsis, is being designed to have a large number of target biomarkers for the identification of infectious pathogens, the body's immune response, and drug resistance. Torus anticipates kicking off clinical studies for the product in 2022 and filing applications for regulatory clearances early in 2023.
Beyond that, the firm expects to seek the green light in 2023 for a urine-based panel for sexually transmitted diseases that includes biomarkers to detect chlamydia, gonorrhea, and bacterial vaginosis. In the same year, it anticipates looking for clearance of a nasal swab-based respiratory panel that includes all known respiratory pathogens, including those that are bacterial and also viral, such as SARS-CoV-2.
With these products, Torus is looking to solve some of the challenges it sees with syndromic infectious disease testing. Depending on the application, "multiplexed molecular tests used for syndromic testing can take too long to provide actionable results," Marcell said. "In general," he added, "clinicians can't use the panels to implement broad pathogen identification and antimicrobial resistance testing near patients or get test results in a timely manner."
Torus' technology has the potential to mitigate drawbacks by providing a fast turnaround while testing for a broad range of targets, he added.
The number of known infectious disease pathogens is far greater than those covered by current multiplex panels, and more host immune response and antimicrobial resistance markers need to be incorporated in panels for more comprehensive testing coverage, he said. The firm believes it can incorporate up to 300 target biomarkers in panels consisting of subsets of those biomarkers.
Along with breadth and turnaround time, Torus believes its tests' performance will also draw interest. Internal studies have shown that its technology has a limit of detection of less than 10 genomic copies per sample and specificity at the level of a single nucleotide, Yin noted.
Achieving sensitivity levels of 10 genomic copies per sample rivals that of high-performing PCR-based syndromic panels in the market, Cornelius Clancy, a physician and chief of infectious diseases at the US Department of Veterans Affairs Pittsburgh Healthcare System, said in an interview. According to Clancy, who is not involved in the development of Torus' technology or products, the addition of novel probes and nanoarrays that enable detection at the level of a single nucleotide improves specificity over current PCR tests, and specificity is an area in which molecular testing products need to show improvement.
Though the technology has the potential to enable a large number of biomarkers per panel, too many markers could lead to performance issues, and the firm should therefore try to optimize the number of targets for each test, Clancy said. He also suggested that to achieve traction, Torus should target its test and platform "where clinicians can use it to drive clinical decisions."
Among Torus' future competitors in the syndromic testing market are well-known diagnostic players including BioMérieux, Danaher's Cepheid, GenMark Diagnostics, Luminex, Qiagen, and OpGen. But Marcell believes that the Torus platform's quicker turnaround time, operation near patients, and high performance will provide it with differentiation.
The launch of Torus Biosystems has been in the planning for more than a year, but it began official operations this past March.
Marcell noted that he has experience in commercializing technology as a former CEO of ReadCoor, a spinout of the Wyss Institute that has developed in situ sequencing products based on technology originally developed in George Church's laboratory at Harvard.
Marcell said that the Torus product is being designed so that it can be powered by a battery and plugged into the electrical grid. It will be Wi-Fi and Bluetooth enabled so that that testing data can be sent wirelessly as needed to locations other than where testing is taking place.
"If you want to do drive-through respiratory testing, this would allow you to get swabbed in your car and receive results in less than a half hour," he said. In low-resource and remote settings, where the testing infrastructure, including laboratories and supplies, tend to be scarce, health professionals will be able to run the test as long as there's a way to recharge its battery.
The company expects that its instrument will be made available at $10,000 dollars, which, Marcell noted, is far less expensive than syndromic testing machines.
Torus expects to place early-access tests for research use only using its own sales network. However, for sales and marketing of its commercial diagnostic products, the company may look to collaborate with a commercial-stage diagnostic company that has already established its sales channels.
The firm selected the detection of urinary tract infections for its first product because "the gap between the market need and available solutions is wide," Marcell said. It will target hospital emergency departments for assessment of complicated urinary tract infection cases, as well as convalescent homes where there is a high prevalence of urinary tract infections.
Not all urinary tract infections are going to require a test, and most are diagnosed based on patients' symptoms, Clancy said. However, "there's a large volume of complicated urinary tract infections in healthcare settings that drive antibiotic overuse," he said. "In high-risk patients, these infections also harbor a lot of drug-resistant bacteria, and people who develop recurring infections tend to be older and can have underlying neurologic diseases. The test could target that population because it requires testing accuracy and speed, and there are implications for prescribing suitable antibiotics."