NEW YORK – Boston-based diagnostics startup RT MicroDx is aiming to commercialize the first over-the-counter, disposable, saliva-based molecular diagnostic test for strep throat. The company has developed a novel technology to read out an isothermal molecular assay and expects it to be competitive with at-home molecular tests that require reader instruments.
Nathalya Mamane, founder and CEO of RT MicroDx, said in an interview that the firm is purposely targeting strep A as a first application because of a tremendous unmet need.
Sore throats send tens of millions of people to the doctor each year in the US, but group A strep infections cause fewer than 30 percent of sore throats in children and less than 15 percent in adults.
Still, while there are millions of strep throat cases each year in the US, the testing demand is actually much higher. Children with sore throats are frequently tested to rule out group A strep infection because strep throat can lead to complications in kids — including scarlet fever, impetigo, and fatal invasive infections — if not treated with antibiotics.
Testing for strep at the point of care requires a clinician visit, but has the advantage of preventing spread and avoiding unnecessary antibiotic prescribing. The most frequently used strep tests at the point of care are rapid antigen detection tests, or RADTs, which tend to be low cost.
Unfortunately, due to variable sensitivities, negative RADTs in children require confirmatory microbial cultures. Culture after a negative strep test takes about two days and can add a frustrating cost for patients already negotiating the expenses of missed work and school.
Point-of-care molecular tests typically do not need culture confirmation, but they often require reader instruments that can cost between $5,000 and $15,000.
Overall, the estimated total cost of strep throat cases in the US is as high as $539 million per year, although the cost of testing is likely much higher.
At-home testing that would not require culture confirmation for negative results could potentially eliminate many of these costs, and Mamane said she expects that the accuracy of the RT MicroDx OTC molecular test will allow it to be cleared similar to the CLIA-waived point-of-care molecular tests, eliminating the need for a negative at-home result for further testing.
Instrument-free LAMP and saliva
Olivia Mamane, RT MircoDx's bioengineer, is a co-inventor of the solution and also Nathalya Mamane's daughter. She developed the initial concept for the readerless diagnostic assay, and it was then further developed by the firm's entire technical team.
"We don't need any expensive equipment, optical sensing, or even a phone," Olivia Mamane said in an interview. The method takes advantage of the pH drop generated by the LAMP reaction — a byproduct also exploited by New England Biolabs in its colorimetric LAMP kits, for example.
"We've coupled that process to a hydrogel that will dissolve if the pathogen is present," she said. The hydrogel can be incorporated into a lateral flow strip to enhance visibility of the readout and make the assay similar to a familiar pregnancy or COVID rapid test.
"This makes it accessible to customers and also inexpensive," Olivia Mamane said, adding that the LAMP reaction has also shown high confidence for both positive and negative results.
While antigen tests could theoretically be sold OTC someday, the requirement for culturing negative samples is a hurdle.
RADTs also require throat swabs because of their lower sensitivity, and these require a bit of expertise to perform correctly. But because the RT MicroDx technology is molecular, the firm believes that it can get sufficient concentration of bacteria from saliva samples, Nathalya Mamane said.
The concept of using saliva for strep testing is not too far-fetched. While there are no US Food and Drug Administration-cleared molecular tests with a saliva indication, a research team in France is currently running clinical trials to test saliva as a sample type for the Abbott ID Now strep assay. Researchers in Wisconsin have also reported saliva collected on a lollipop and tested using the Roche Liat strep test had high concordance with swab samples. The Wisconsin team is in clinical trials to validate its CandyCollect technology in combination with an RADT. Meanwhile, a research team in Israel has shown PCR of saliva samples collected after the second day of illness had 90 percent sensitivity and 100 percent specificity compared to PCR of throat swabs.
The strep A and OTC MDx diagnostics spaces
Point-of-care, CLIA-waived antigen tests for strep A are available from at least a dozen different manufacturers. CLIA-waived strep A point-of-care molecular tests, meanwhile, are available on the Roche Liat, Abbot ID Now, Cepheid GeneXpert Xpress, and Thermo Fisher Scientific Mesa Biotech Accula systems, for example.
Quidel has a group A strep test in the pipeline for its point-of-care molecular Solana instrument, while startups like LEX, Domus Diagnostics, and Minute Molecular have point-of-care molecular systems in development and have mentioned strep assays as a part of future testing menus.
But according the FDA's OTC test database, there are no antigen tests or molecular tests cleared for over-the-counter use in the US, although this has not prevented RADTs from being sold online.
Currently, a company called Checkable Medical is in clinical trials with a rapid antigen test for strep aiming for OTC clearance, while Becton Dickinson's acquisition of Scanwell Health was purportedly intended to further the development of at-home antigen testing for infectious diseases, including strep.
On the molecular testing side, Cue Health, Lucira Health, Detect, and Aptitude Medical Systems are the only firms with molecular systems that were granted Emergency Use Authorization from the FDA and authorized for home use, specifically for COVID-19 testing.
These technologies also use LAMP, and Cue says it has developed a strep assay, while Detect previously mentioned a strep assay is in early development, and Lucira has a strep test in the pipeline described in its annual report. Anavasi Diagnostics is also potentially developing a strep test for its home-use molecular diagnostic system.
However, all these home-use molecular systems require a reader and cartridges — with the cost of the readers and the consumables a point of differentiation among them — so the readerless RT MicroDx test could provide the firm a competitive advantage in terms of cost.
Compared to the likes of Cue and Lucira, "we are addressing a whole different market," Nathalya Mamane said. "We are going to the masses."
RT MicroDx will begin working with a product development firm in the next few months to perfect its strep testing device, Mamane said, and the company plans to explore an assay for mononucleosis in the future.
While it has been self-funded to date, RT MicroDx is now looking to raise funds to further product development and move into clinical trials.
In the past year, the company has won the Babson Entrepreneurial Thought & Action pitch competition, was a runner-up in the MIT $100k Entrepreneurship Competition, and is up for a MassChallenge award in the social impact category, Mamane said. She also recently won support from the MITRE Social Innovation Mentorship Program, which is providing funding-related mentoring to founders from underrepresented groups.
Mamane noted that access to care is not evenly distributed in the US, with rural areas sometimes lacking clinics. The burden of the total cost of testing is also not even across all socioeconomic groups in the US, and some families suffer disproportionately from missed work and school.
"At the end of the day we are trying to allow diagnostics to be accessible," she said, by bringing testing to where people live. This may also potentially alleviate the strain that strep causes to patients and the healthcare system.
From a bird's-eye view, the pandemic has dramatically expanded at-home infectious disease testing, Mamane said, and this trend seems likely to continue.
"People are ready to have more control, to test at home, and they know how to do it because they have been doing it with COVID," she said.