NEW YORK – When CRISPR-based diagnostics firm Sherlock Biosciences acquired UK's Sense Biodetection this month, it gained new tools and infrastructure that may accelerate its commercialization plans by as much as two years.
Bryan Dechairo, Sherlock's CEO, said in a recent interview that with the acquisition of Sense Bio, Sherlock now has four chemistries and two platform technologies in its portfolio.
The Watertown, Massachusetts-based firm plans to merge Sense's 10-minute, instrument-free Veros molecular diagnostic platform with its other technologies, ultimately aiming to reach the at-home and global infectious disease markets.
Sherlock's mission is to make accurate molecular diagnostics accessible for people around the world at a price that they can afford, Dechairo said. He and his team had considered Sense Biodetection to be a competitor in this realm and had been monitoring the Cambridge, UK-based company's progress, he added.
The team was intrigued by Sense's low-cost, disposable platform, which already met their target product profile for cost of goods and had been de-risked through obtaining a CE mark and undergoing a 510(k) clinical trial.
Sherlock has proprietary CRISPR chemistries and recently licensed ambient temperature amplification technology, and it has a synthetic biology approach that enables high multiplexing. But, "Sense's proprietary chemistry was the fastest isothermal amplification that I've ever seen," Dechairo said.
The speed of this isothermal chemistry — which Dechairo said is based on strand displacement amplification, or SDA — now potentially opens up both the point-of-care and the over-the-counter space. The newly licensed ambient technology, meanwhile, is based on a chemistry called capped SDA, he added.
"The chemistry on the Veros platform really accelerates Sherlock's ability to commercialize, but the [ambient chemistry] allows us to have a next-generation disposable that has an even lower cost of goods and requires no batteries," Dechairo explained.
Sherlock has been driven to bring diagnostics to patients and also to address global inequities in the availability of diagnostics that lead to suffering and death from treatable diseases. To further its global health aims, the company has collaborated with and been funded by the Bill and Melinda Gates Foundation, FIND, Open Philanthropy, and other nongovernmental organizations.
For both at-home and low-resource settings, the cost of testing is the most critical product criteria, to Dechairo's mind.
Indeed, once inexpensive rapid antigen tests flooded the stores during the COVID-19 pandemic, first movers in the at-home molecular testing space seemed to struggle.
While retail consumers might be intrigued by higher accuracy, price points above $40 may have seemed like too much investment for new technology in an ever-changing health crisis. Tests that require consumers to keep readers in their homes may also struggle for the same reasons.
In the global market, the target price point is even lower. "A disposable format with a very low cost of goods is the key," Dechairo said. While Sherlock has also developed a cartridge-based system with a reader, this is "too expensive for a lot of the global health needs," he said.
And even in the OTC space in high-income countries, Sherlock has targeted a cost of goods under $10 in order to compete with antigen tests, he added.
"Molecular offers higher accuracy than antigen testing and allows you to move into areas outside of infectious disease and immunity … but if people can't afford it, no one will use it."
Next steps
Sense obtained the CE mark for a COVID-19 assay on the Veros and had applied for Emergency Use Authorization. The firm had demonstrated 98 percent accuracy for its isothermal test compared to lab-based testing using assays from Roche and Hologic, Dechairo said, when the agency seemed to shift to prioritizing technologies supported by US federal programs.
Sense subsequently completed the clinical trials for 510(k) submission, and Sherlock now expects to file its Veros device and COVID test this quarter, Dechairo said.
Although POC COVID testing itself is a fairly saturated market, Dechairo said, it is a necessary part of a path to CLIA waiver and OTC clearance. Whether it ultimately makes sense to bring the COVID test to market remains to be determined, Dechairo said.
Sherlock also expects to port its CRISPR-based sexually transmitted infections franchise onto the Veros platform and bring these assays into clinical trials, as well. Such tests may be particularly beneficial for chlamydia and gonorrhea testing in low-resource settings.
Sense has also developed assays for flu A and B and respiratory syncytial virus on the Veros, and these are ready for clinical trials, so the firm will continue to advance these as it monitors COVID and respiratory virus needs over the next year or so, informed by the market situation, Dechairo said.
The Veros has advantages of being extremely rapid and disposable, but Sherlock also has a platform that would be amenable to applications requiring a more robust instrument or a reader to detect results.
"It allows you to detect polymorphisms, do multiplexing, and RNA quantification, which opens up early detection of cancer, and it allows us to open up the prenatal market," he said.
In this way, the firm expects to bring DNA and RNA detection to the market beyond infectious diseases.
"But you have to start with low-cost disposables," Dechairo said.
Manufacturing and tech advantages
Sense's biomanufacturing expertise brings a lot to the table, Dechairo said.
The company manufactures its own lysis solutions, for example. It has also developed a carbon particle-based lateral flow strip that yields a black-and-white result, rather than the sometimes-vague red strips on typical tests. The company manufactures these itself in Cambridge, UK.
In the acquisition, Sherlock also picked up Sense's novel lyophilization process, a step Sherlock had previously needed to outsource.
The Sense lyophilization method creates beads that don't deform with pressure or humidity, Dechairo said. "They are perfect spheres that can bounce on a table, but the minute you add liquid they dissolve immediately," he added.
The future global health menu for Sherlock's CRISPR technology might include tuberculosis, Dechairo said. Similar to a team at Tulane that has developed a blood-based tuberculosis infection assay using CRISPR, Sherlock Cofounder Deborah Hung is working on a TB assay for the firm's platforms, he said. However, the Sherlock approach is to use tongue swabs, which is a novel approach that has lately intrigued many in the TB global health space.
Sense Bio had been supported by Koch Disruptive Technologies, an investment firm associated with Koch Industries, and had former president and CEO of Roche Molecular Systems Heiner Dreismann and former Cepheid CEO John Bishop as members of its board of directors.
Dechairo said Sherlock will continue to consult these experts in the field, but the board of Sherlock will remain the same at this time. "And we have great investors behind us," he said, including Novalis, Illumina Ventures, Mike Rubin of Northpond Ventures, and David Walt, a founder of Illumina and Quanterix.
Sherlock is also currently in conversations regarding funding opportunities at RADx and CARB-X and others, Dechairo said.
Update on the POC MDx space
The pandemic clearly accelerated point-of-care testing. Now that consumers are comfortable with 15-minute rapid antigen assay, speeding up isothermal molecular amplification reactions would potentially make them even more acceptable in the home and at the point of care.
Commercial point-of-care systems using Loop-mediated isothermal amplification (LAMP) and reverse transcriptase-LAMP include platforms from Lucira Health, Cue Health, Talis Biomedical, Detect, Anavasi, and Aptitude Medical Systems.
Many of these require reader devices that could potentially increase the costs and limit their use to clinical and high-resource settings. If consumers are willing to invest in reader devices, however, handheld PCR systems could also potentially be used in the home, such as one being developed by Co-Diagnostics for this purpose.
Disposable, or single-use molecular diagnostic technologies, on the other hand, are targeting a different use case and price point. These include PCR-based tests from Visby Medical and startup Nuclein, and a LAMP-based system developed by Domus Diagnostics that is potentially disposable and claims a $2 cost of goods.
LAMP tests are being developed for rapid point-of-care testing of everything from strep throat to Kaposi's sarcoma and schistosomiasis. Firms like GeneMe, a Gdansk, Poland-based company, are among the groups that have found ways to improve the limit of detection of LAMP reactions, while a team at the University of California, Santa Barbara recently improved the chemistry by eliminating primer-dimer formation.
Among other isothermal technologies, recombinase polymerase amplification (RPA) reactions — which run at body temperature — have been adapted for rapid diagnostics by firms like Midge Medical, while a team in Birmingham, UK, developed a 10-minute isothermal method called reverse transcription-free exponential amplification reaction, or RTF-EXPAR, that was recently licensed by Innova Medical Group.
Meanwhile, researchers at Tulane University, Johns Hopkins, and others are also finding new ways to combine isothermal chemistries with CRISPR technologies.
A legacy
Sense Biodetection was originally founded in 2014 by brothers Ralph and Harry Lamble. Inspired by the death of their brother from cancer at a young age, the Lambles wanted to develop rapid point-of-care testing for early cancer detection.
"Ralph and his team engineered the Veros platform, which is the lowest-cost disposable molecular platform out there," Dechairo said. "It took eight years to get to what our engineers, prior to the acquisition, thought was one of the most amazing technologies that they've seen in a device."
On the chemistry side, Harry Lamble "was the brains behind the SDA methodology," which Dechairo said is not licensed from an academic institution but rather was his own intellectual property.
"To have two brothers who create amazing chemistry and engineering, and package that together to create a company to solve something that impacted their other brother, that is a legacy that we want to embrace and continue," Dechairo said.
Bringing CRISPR onto that platform may also now enable high levels of sensitivity and specificity, which is important in the oncology market.
"We will be able to bring that oncology dream to fruition now that we are together," Dechairo said.