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Startup Angstrom Bio Plans Saliva-Based COVID-19 Nucleic Acid Test on Nanopore Sequencing Platform

This story has been updated to correct Angstrom Bio's collaborator at TeVido BioDevices, Laura Bosworth.

NEW YORK — An Austin, Texas-based startup has pivoted to SARS-CoV-2 diagnostic testing and plans to launch a nanopore sequencing-based COVID-19 diagnostic test.

Angstrom Bio, founded in 2019 by a group of scientists and executives that have launched at least three drug discovery startups together, have developed a SARS-CoV-2 nucleic acid assay that runs on Oxford Nanopore Technologies' MinIon and GridIon instruments. The technology, which the firm calls AMPD, combines a library prep step that introduces 10- to 20-bp barcodes on PCR products with bioinformatics to demultiplex reads and perform error correction on the nanopore platform.

"We're replacing qPCR with something that has far greater bandwidth," said Angstrom Bio Cofounder and Chief Strategy Officer Forrest Cox. The method can perform thousands of tests at once, he said, and Angstrom Bio has plans for it to do much more than that, including an assay for other respiratory infections.

The company's SARS-CoV-2 test uses saliva samples, can be turned around in 24 hours, and will be launched as a laboratory-developed test. Cox declined to be specific about the test's sensitivity and specificity. "We're currently finalizing the limit of detection ahead of filing with [the US Food and Drug Administration]" for Emergency Use Authorization in mid-December, he said. "We anticipate having best-in-class sensitivity and specificity."

Company officials said they partnered with Laura Bosworth at TeVido BioDevices to help develop and validate the test. The company is also collaborating with Nelson Michael, director of the US Military HIV Research Program at the Walter Reed Army Institute of Research, giving them access to COVID-19 patient samples. Michael confirmed through a spokesperson that he is collaborating with Angstrom, but declined to answer additional questions, citing his schedule. Bosworth did not respond to request for comment.

Founded in 2019, Angstrom Bio's original goal was to develop antibody therapeutics using machine learning algorithms, CEO Carlos Santos said, but after the onset of the COVID-19 pandemic, the team reevaluated its position. With other firms pursuing therapeutic or neutralizing antibodies to SARS-CoV-2, they decided to instead address diagnostic testing. "The way the industry was structured was not conducive to scaling," Cox said. By the end of May, the firm had completed its pivot to become a diagnostics company.

Angstrom Bio has raised a friends and family financing round, but officials declined to say how much it has raised. The company is "actively raising money right now" specifically to develop diagnostics, Cox said. The firm's cofounders also include David States, a former professor at the University of Texas Health Science Center; COO and CTO Jonathan Feldmann, and VP of R&D Josue Moran. Angstrom Bio plans to increase headcount after completing its next funding round.

Angstrom Bio's test will join a growing number of saliva-based assays that are finally gaining acceptance. Last month, the US Department of Health and Human Services announced that it would use Fluidigm's Advanta Dx SARS-CoV-2 RT-PCR assay as part of a federal "surge testing" program. In recent months, saliva-based tests from Qiagen's NeuMoDx subsidiary and PerkinElmer have gained CE Marking. And Mammoth Biosciences has signed commercialization agreements with MilliporeSigma and Hamilton Company for its DETECTR BOOST platform, which is compatible with saliva samples.

Early studies suggested that saliva samples led to lower assay sensitivity than swabs. But rapid turnaround time and ease of collecting samples have replaced ultra-high sensitivity as priorities and momentum will build for saliva-based COVID-19 testing, said Dawn Dudley, a senior scientist at the University of Wisconsin-Madison department of pathology and laboratory medicine. "There is a learning curve, however, to get this relatively difficult sample type to work in different assay types," she wrote in an email. "We have learned quite a bit as scientific community about how to make saliva work better, but each assay must adapt in unique ways to do so."

Angstrom Bio's test can work off both direct saliva and purified RNA from saliva. The EUA filing will include a "novel purification step" that "avoids many of the problems we've seen with bead-based extractions," Cox said. "We think this is a nice midpoint between bead-based and direct-PCR approaches."

The test's primer design and bioinformatics are proprietary, Cox said, adding that the AMPD pipeline "derives thousands of amplicons per positive result that allow for unambiguous barcode recovery and accurate patient ID determination," Cox said. Though he believes improvements in base calling on the nanopore platform have been overlooked, Cox suggested that they are not the driving factor for AMPD's accuracy and confidence metrics.

Oxford Nanopore has launched its own assay for SARS-CoV-2, dubbed LamPore COVID-19, which combines loop-mediated isothermal amplification and nanopore sequencing and is CE marked for in vitro diagnostic use on the GridIon. "We don't overlap with their aims," Cox said, adding that the two firms are in discussions about furthering their relationship. Oxford Nanopore has been "very open, very collaborative," and "unbelievably supportive," Santos said.

Angstrom Bio is currently running proof-of-concept studies in Austin, with plans to launch commercial testing there by the end of the year. The firm plans to add influenza testing to its assay and has designs on adding respiratory syncytial virus and even bacterial species later on.

"In Austin, we'll be scaling to a couple thousand results per day in pilot scale, but that's not meant to be reflective of the final throughput," Cox said. The firm has set a goal of being able to do 1 million tests per day. Cox noted the company faces the same supply chain challenges as the rest of the diagnostics testing industry.

Angstrom Bio is preparing to file for EUA soon, though Cox said the firm believes it won't necessarily need one to offer its tests. "It's worth trying to secure," he said. "We'd like to be able to compare ourselves to rest of tests available on sensitivity or limit of detection."

The company is in talks with potential testing partners and customers. "We're most interested in finding organizations with existing capacity and infrastructure in deploying a higher-throughput solution for testing," Cox said.  "We're really focused on employers, businesses, and the public sector for operational resumption, continuity, and safety."

"Our anticipation is that not only will COVID-19 be with us for quite some time, but there is a new category here that's setting a floor on demand for testing," he said.