NEW YORK ─ Following the recent CE marking of its point-of-care platform with a SARS-CoV-2 assay, QuantuMDx expects that during the next year it will complete the development of a highly multiplexed, rapid RT-PCR system for syndromic testing.
The Newcastle upon Tyne, UK-based firm said its point-of-care test will detect DNA and RNA associated with numerous infectious diseases as well as genetic mutations reflective of drug resistance, providing test results in 30 minutes.
Last month, the company obtained CE-IVD marking for a SARS-CoV-2 assay running on a rapid, portable RT-PCR platform, called Q-POC, that it has been developing for around 13 years.
The company expects its instrument and SARS-CoV-2 assay can make a difference in the ongoing fight against SARS-CoV-2, given its rapid turnaround time, ability to compete on price and performance with current PCR tests at the point of care, and its better performance than lateral flow-based antigen tests, Jonathan O'Halloran, QuantuMDx's cofounder and CEO, said in an interview.
Further, the company plans to launch a multiplex syndromic test early next year that will enable the detection of SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus.
O'Halloran began developing the point-of-care testing system in his garage in Sussex, UK, in 2008 and moved the firm to South Africa after obtaining £3 million ($4.2 million) in development funding from the South African government.
"That's when we locked down the specifications for the device as a true point-of-care system, meaning it can be used beside patients in the field, or in settings such as doctor's offices or hot labs in accident and emergency departments," O'Halloran said.
The final Q-POC configuration will be used within a wide range of settings that also include ICUs, birthing centers, clinics, and pharmacies, according to QuantuMDx.
The company is running studies associated with most of these use cases so that it can further validate the performance of the device and show how it can help businesses open up following the pandemic, O'Halloran said.
Its goal to launch an instrument for use next to patients meant designing and developing a system to withstand tough and disparate operating conditions, including wide swings in temperature, in different countries. QuantuMDx further developed the system to use lyophilized reagents that can be stored at room temperature, to run on battery power, and to prevent dust from interfering with testing.
The firm also wanted to develop a system that was differentiated from other point-of-care testing instruments on the market, O'Halloran said. "All of this meant that our development cycle was longer than you would normally expect," and the development team opted for a highly multiplexed device that can detect genetic mutations associated with drug resistance as well as pathogens that cause disease, he added.
The system's RT-PCR technology is different from that of traditional RT-PCR. "Unlike conventional PCR, where you heat and cool the sample and reagents using a heat block or Peltier block, we use two different temperature zones and move the PCR master mix back and forth between the zones 40 to 50 times for rapid cycling," O'Halloran said. "Then the reaction mix with all of its amplicons flows over the microarray."
In its ongoing development of Q-POC, the firm is using standard TaqMan probes and primers from Thermo Fisher Scientific for new assays that will enable the instrument to detect DNA and RNA associated with up to 70 pathogens, or amplify a number of those pathogens and also detect drug resistance mutations, O'Halloran said.
The company's newly CE-marked SARS-CoV-2 assay runs on an early version of Q-POC that QuantuMDx, internally, calls a minimum viable product. However, the current Q-POC system and SARS-CoV-2 assay provide a sound basis for the future evolution of the platform, the firm said.
The test targets the N and S gene plus the Orf1 region within the SARS-CoV-2 genome, providing redundancy and improved detection of strain variants, according to QuantuMDx, which said it demonstrated 96.9 percent sensitivity and 98.3 percent specificity in a recent preliminary evaluation at St. George's NHS Foundation Trust, London.
In a MedRxiv preprint published last month, the study investigators said the Q-POC test "would enable rapid diagnosis and clinical triage in acute care and other settings," and was particularly sensitive, specific, and rapid at a reference cycle threshold cutoff value of 35.
Sanjeev Krishna, a study author and professor at St. George's, University of London, said that he has been familiar with QuantuMDx for many years and believes the firm is now delivering on its vision. Its test enables the building of "a molecular laboratory that is within easy reach of anyone, and one that can transform how to manage important diseases with accurate diagnostic information when and where it is needed," Krishna said.
No preparation is needed before the sample is collected and transferred to the device, which is important for point-of-care testing, he said. "There are so many high-risk circumstances where we need to know someone’s COVID-19 status, whether it is taking a patient to the emergency room, delivering a child, or dealing with international travelers," he added.
O'Halloran also noted that the current combination of instrument and assay for SARS-CoV-2 detection does not require RNA extraction. "We go directly to a heat lysis and reverse transcription to rapid PCR, which enables sample-to-answer testing with a turnaround of 30 minutes," O'Halloran said. "At present, we have a six-plex instrument but next year that will expand to a 70-plex panel for detection."
He expects that the final instrument, which will include extraction and the microarray, will be available with CE marking early next year.
To achieve that, QuantuMDx has designed its Q-POC instrument to include a space that enables the integration of a 226-spot microarray for pathogen identification and quantitation, and to provide a scan for drug resistance mutations.
The company is developing a syndromic test that detects SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus and a separate assay that detects human papillomavirus nucleic acids associated with head, neck, and cervical cancers. Both types of tests will run on the minimum viable product version of the instrument.
As QuantuMDx continues to develop its final instrument, it is also integrating a sexually transmitted disease panel to run on it, which will detect chlamydia, gonorrhea, trichomonas, and Mycoplasma genitalium, as well as mutations associated with drug resistance.
O'Halloran believes its molecular test is a natural fit for STD testing because of the rising prevalence of infections and drug resistance. Such a test could be used to provide the correct therapy to patients before they leave the clinic, he noted.
Additionally, moving to the final product configuration and adding assays will be a seamless transition for customers because the system is modular, making it easy to add new tests, O'Halloran said.
QuantuMDx has also worked hard to keep down the cost of its system and tests, he said. A 30-minute SARS-CoV-2 test using Q-POC is priced at about £30 and reflects the potential price for additional tests using the system, he said. However, specific prices depend on the volumes of ordered tests and agreements with individual customers.
The firm offers its customers an option to purchase an instrument or sign a reagent rental agreement that enables receiving the instrument for free. It is not disclosing specific pricing for the instrument when it is purchased separate from the reagent rental agreement.
The firm is partnering with a network of distributors for its sales and marketing activities in Europe. In the UK, it is employing a direct sales approach and working to obtain reimbursement with the National Health Service and be part of the Department of Health Dynamic Purchasing System.
Submissions for US Food and Drug Administration clearance for its platform and tests are among its plans, but a timeline is not yet available. The company is in discussions with contract research organizations to initiate studies with a view to eventually obtaining US clearances, but wants to see traction in Europe before focusing more of its attention on the US, O'Halloran said.
Though the firm has received CE marking, new regulations remain on track to be implemented in May 2022, though there is growing sentiment to delay them, and firms launching new tests in the EU will have to make sure they comply with those regulations. On deadline, QuantuMDx had not responded to a question regarding any preparations it may need to make in advance of potential new regulations.
In the past year, the company's production footprint has increased dramatically. Last December, the firm announced it had invested more than £11 million to scale up production of Q-POC. The company is partnering with Cogent Technology, which operates an 80,000-square-foot facility in Felixstowe, UK, and has capacity to produce 800 Q-POC instruments per month.
QuantuMDx is also working with Danish firm RD Support to initiate manufacturing in Copenhagen for Q-POC disposable cassettes. The production line has a capacity to produce 200,000 tests per year.
Further, the point-of-care test developer is working with Singapore-based Univac, which has built a production line that can manufacture 2 million QuantuMDx cassettes per year.
QuantuMDx's journey as a startup began with investments from friends and family members and later included angel investors, family-owned physician offices, strategic investors, and venture capital investors, O'Halloran said.
The company raised £11 million ($15.1 million) in March to support manufacturing and commercial scale-up of Q-POC. It had previously raised £16 million in UK government funding to accelerate the development and scale-up of the system in response to the COVID-19 pandemic, as well as £10 million in a convertible loan notes offering.
In May, the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, or CARB-X, awarded up to $3.7 million to Australian diagnostic test developer SpeeDx to develop a rapid point-of-care test to diagnose Chlamydia trachomatis and Neisseria gonorrhoeae infections and to determine the antibiotic susceptibility of gonorrhea infections while running on the QuantuMDx Q-POC portable PCR device.
The objective is to develop a simple-to-use 60-minute assay that can identify the best oral antibiotic from among those available in low- and middle-income countries. A project to assess the feasibility of porting SpeeDx assays to the instrument from QuantuMDx was funded by the Foundation for Innovative New Diagnostics in 2019.
SpeeDx chose the Q-POC platform partly because of its rapid turnaround time and that it enables the development of a molecular susceptibility test, which is "a hint at things to come" for QuantuMDx, O'Halloran said.
O'Halloran noted a number of near-patient multiplex systems as competitors in European countries, including Hologic's Novodiag system, Qiagen's Qiastat-Dx, BioMérieux's BioFire Diagnostics' FilmArray, Bosch's Vivalytic, and Curetis' Unyvero.
A number of additional fully integrated, rapid, and small PCR and qPCR benchtop systems are also available, including the Roche Liat, Meridian Bioscience Revogene, Binx io, and Quidel Savanna. The Abbott IDNow COVID-19 rapid isothermal amplification assay detects COVID-19 in 13 minutes or less at the point of care.
Nonetheless, many of the current multiplex systems are characterized by longer turnaround times and are more expensive than Q-POC. "For the first time, we'll have a battery-powered device that can perform high multiplexing at the point of care in 30 minutes, sold at a price point that isn't going to break the bank," Halloran said.