NEW YORK ─ With data indicating its Nanotrap technology could help boost the sensitivity of molecular assays for SARS-CoV-S, Ceres Nanosciences is looking to move into testing for the virus.
The company is currently working with a number of labs to incorporate its Nanotrap reagents into their SARS-CoV-2 testing and is in discussion with several in vitro diagnostic vendors about integrating the Nanotrap technology as part of their molecular testing systems, said Robbie Barbero, Ceres' chief business officer.
Nanotraps are hydrogel nanoparticles functionalized with internal affinity baits to enrich target analytes for downstream analysis. Originally developed by researchers at George Mason University including company cofounders Emanuel Petricoin and Lance Liotta, the nanoparticles bind targets of interest, concentrating them inside the nanoparticles and protecting them from degradation, thereby improving the sensitivity of the ultimate clinical detection method.
Ceres has been focused on infectious disease since its founding, with its initial lead product being a test for Lyme disease that used the Nanotraps to concentrate the surface protein A of Borrelia, the tick-borne organism that causes Lyme disease.
Last fall, the company launched a version of the Nanotraps intended for capturing whole viruses, which Barbero said was the result of several years of work funded by the Defense Advanced Research Projects Agency. Ceres received $980,000 from DARPA in 2016 to support work using the reagents to capture immune markers and $750,000 in 2017 to develop the particles for use in tests for Zika and other infectious diseases.
Ceres launched the virus capture Nanotraps with the aim of focusing on respiratory viruses given that "respiratory virus testing has always been a big market and an area where we perceive there to be a real benefit of improved sensitivity," Barbero said, noting that the company planned to target areas like flu testing and syndromic respiratory testing.
When SARS-CoV-2 appeared shortly after the launch, it presented an obvious and urgent opportunity for the company's technology. Estimates of the sensitivity of molecular SARS-Cov-2 testing vary (and are dependent on factors including the sample type, a patient's viral load, and when in the course of infection a sample is taken), but some researchers have put the sensitivity of many of the available assays at around 70 percent.
Ceres believes its nanoparticles can boost test sensitivity by concentrating SARS-CoV-2 prior to PCR analysis. In a preprint published last month in bioRxiv, company researchers used the Nanotraps to process 49 samples previously analyzed using either Abbott's RealTime SARS-CoV-2 test or the Cepheid Xpert Xpress SARS-CoV-2. In the study, the researchers found that the assays run with the Nanotraps identified all 17 positives initially identified by the tests. It also detected low levels of the virus in four samples that had previously been identified as negative.
The researchers also saw roughly threefold improvements in Ct values in samples with low viral loads when using the Nanotrap enrichment, though this improvement was not seen consistently in samples with high viral loads, suggesting, the researchers noted, that the particles may become saturated in samples with high virus levels.
The researchers also used dilutions of the positive SARS-CoV-2 samples to test how the reagents performed in these samples. They found that use of the Nanotraps substantially improved detection of the virus in the diluted samples and that roughly the same amount of virus was recovered from Nanotrap assays in both a 5ml and 10ml dilution, indicating that the reagents concentrated the full amount of the virus present.
The results, Barbero said, suggest the particles could be useful in several respects, most notably for boosting sensitivity in assays that don't use an RNA extraction step, which has proved a major bottleneck in SARS-CoV-2 testing, and for pooled testing, which some have suggested as an approach to address test capacity challenges.
"Our particles can basically recover the performance [lost by skipping RNA extraction], so that is one area where, in the very short term, we play well in that we can get around that supply chain limitation," he said.
With regard to pooling, Barbero noted that pools of multiple patient samples will be too large in volume for existing assays and so labs will need to take just a fraction of the pooled sample for testing, which will further dilute any viral particles present.
"And if you are already worried about false negatives, now you are compounded that by doing another dilution," he said, adding that using Nanotraps to concentrate the virus present in the samples could allow labs to process the pooled samples to a usable volume without losing sensitivity.
Barbero said that a number of labs are currently working to incorporate the reagents into their testing and that the company expects it to be in use by the end of the summer, though he declined to name the labs. He said that it would be the labs' responsibility to generate whatever data was needed to modify their Emergency Use Authorization submissions to the US Food and Drug Administration to incorporate use of the Nanotraps.
More generally, Barbero said Ceres had stepped back from its original plans to develop its own in-house diagnostics. The company had previously offered its Lyme disease test out of GMU's CLIA lab as a laboratory-developed test and planned to develop it as a point-of-care assay. The POC Lyme assay received breakthrough device designation from the FDA in 2018.
Barbero said the company had partnered with a reference lab that was relaunching the Lyme test this summer but that beyond this, it was now focused solely on providing the Nanotrap reagents to researchers and clinicians as opposed to test development.
Barbero said that Nanotrap reagents added around five to 10 minutes to assay times and are fully compatible with existing lab automation. He said the company was currently looking at different options to scale production of the particles including increasing capacity within its existing facilities as well as potentially adding new production space.
"When we launched the product in the fall we had a production capacity that was less than 5,000 units [with one unit equal to one test] per day because that is where we thought we needed to be at that time," he said.
In the last three months, Ceres has increased production capacity by tenfold and plans to increased current capacity by another tenfold to twentyfold in the next three months, Barbero said.
He said that while previously customers would typically come with requests for several thousand units, more recently potential customers have come asking about orders of hundreds of thousands of units per day.
"Everybody is looking at these [infection] numbers and saying, how fast can I get to the biggest number of tests possible," he said.