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Tangen Biosciences Developing Lab-on-a-Disc Isothermal MDx for Point of Care

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NEW YORK – Having recently closed a $9 million Series A equity financing round, startup Tangen Biosciences is developing a portable centrifugal molecular diagnostic test system that leverages isothermal amplification and proprietary sample prep technologies.

With prior funding from the Biomedical Advanced Research and Development Authority (BARDA), the company's first assay under development is for anthrax, but more recently it has also begun work on tests for fungal and other bacterial infections with plans to launch its first products in 2021.

Molecular biologist John Davidson and mechanical engineer John Nobile founded Tangen in Branford, Connecticut after having previously worked together as senior scientists developing the Ion Torrent sequencing system.

At Tangen, "We teamed up to produce what we thought would be a groundbreaking, portable, low-cost, and fast nucleic acid amplification technology that could go out of the clinical lab and into the field," Davidson, Tangen's CSO, said in an interview.

Davidson had been a scientist at Ion Torrent since 2008 and was with the company when it was acquired by Life Technologies in 2010 for $725 million. He then served as senior director of research and development for the Ion Torrent division of Life Tech until 2014. He used his polymerase engineering and molecular biology skills to help develop the Ion Personal Genome Machine, and he was the technical lead for the Ion Proton system.

Nobile, meanwhile, was principle engineer at Ion Torrent beginning in 2009, and subsequently senior staff engineer at Life Tech until 2012.

Yet, although the two scientists were pioneering cutting-edge sequencing technologies, they saw an opportunity in nucleic acid amplification-based testing.

Davidson said the two were aware that sequences for infectious diseases were becoming readily available, but that "there was no fast, low-cost, and powerful way to connect the information from DNA sequencing databases to a clinical product," he said.

So, Tangen set out to produce an instrument that could rapidly detect infectious diseases using sequences that were available freely in databases, with Davidson bringing the nucleic acid amplification experience and Nobile bringing expertise in fluidics and device development.

The two built the initial prototype instrument in 2013, in Nobile's basement, and subsequently secured initial seed funding from Connecticut Innovations, the state's strategic venture capital arm for early-stage technology companies.

The co-founders were targeting tuberculosis as an initial application, however the firm redirected its efforts when it won funding from BARDA in 2017.

Rick Birkmeyer, Tangen's president and CEO since 2018, noted in an interview that the first year of BARDA funding was for $3.2 million, but that the funding had two options associated with it. "We are looking to expand the value of those options by doing additional work," he said.

Davidson said that the original BARDA contract was for an anthrax test directly from blood samples.

More recently, Tangen closed a $9 million Series A equity financing round and announced that it will use the proceeds to develop platform and infectious disease tests for anthrax and Candida fungi detection.

Tangen is Birkmeyer's third startup, he said. He founded Strategic Diagnostics, a company focused on environmental, food, and genetically modified organism testing in 1990. The company went public in 1996, and its market cap rose to more than $200 million, he said. It is now a wholly owned subsidiary of OriGene Technologies.

In 2003, Birkmeyer left Strategic Diagnostics for venture capital, but in 2012 he joined CD Diagnostics, a developer of orthopedic diagnostic technologies for periprosthetic joint infections. By 2016, that firm claimed more than 80 percent of all orthopedic surgeons were using its tests, and the company was ultimately acquired by Zimmer Biomet for an undisclosed amount. Its immunoassay test kit, called Synovasure, was granted de novo premarket approval from the US Food and Drug Administration earlier this year.

Birkmeyer said that Tangen's technology will now "bring the clinical lab to urgent care centers, remote sites, or wherever testing needs to be done."

One of the firm's development strategies is to join with large corporate partners to penetrate the market, Birkmeyer said.  "We are looking to do what we do best — the R&D and manufacturing — and allow our corporate partners to do the sales and marketing," he said.

The core technology of the Tangen instrument incorporates loop-mediated isothermal amplification, or LAMP and a battery-operated spinning disc microfluidic system.

Although LAMP has been around for a long time, Davidson has been able to modify it by incorporating a hot-start step as well as other patented technologies to eliminate false signals, Birkmeyer said.

Combining all these elements in a unit that is constructed as a spinning disc gives a high level of sensitivity. For example, Birkmeyer claimed that for anthrax the device could detect 5 colony forming units per milliliter of blood, where the next best test is in the 50 CFU range, he said. 

"We are detecting anthrax at levels [at which] one can treat, and the patient will survive," Birkmeyer said.

Each disc allows Tangen to run up to 32 different tests on one patient sample. As described in a 2016 review of disc-based microfluidics, multiplexing in this manner is one of the particular advantages that disc technologies bring to point-of-care applications.

The method is also low cost. "With 32 targets, our cost of goods is less than $.35 a target," Birkmeyer said. The firm is also constantly working to reduce the cost of manufacturing.

"We also recognize that not everybody is going to want 32 targets," Birkmeyer added, so the firm is also looking to make discs that have fewer targets and consequently an even lower cost, in the range of $.50 to $1 per target, or approximately $5 per disc.

Sample preparation is a big bottleneck for molecular diagnostics. Tests need to be sensitive enough to detect a few molecules of DNA on a background of millions of human genomes, but still rapid and user-friendly.

"I've been in diagnostics all my life, and the reason molecular has never been able to do better than immunoassays to date is because you have so much contaminating DNA in samples — you're looking for one bacterial cell in the midst of 106 human white cells," explained Birkmeyer. 

Tangen tackles this challenge with patented technology that eliminates the human DNA without loss of pathogen DNA, he said. The technology is the key to Tangen's assay sensitivity, however, and he declined to further describe the recipe for this "magic sauce."

The sample purification step also involves a blood processing unit that the firm calls a BPU. The firm has three versions of the BPU — one in the $6 range that takes a few more steps, a more complex version in the $12 range, and the firm is also working on an instrument that can process five samples at once with a cost to the user in the $2 per sample range, Birkmeyer said.

The firm plans to seek US Food and Drug Administration clearance for its system and assays. Its anthrax test is closest to market, but it is also developing testing for Candida fungi. Tangen is in the process of choosing clinical trial sites now, Birkmeyer said, and expects to enter trials by the end of 2019 for both tests.

Anthrax assays, and especially portable ones, are important to have available in case of a bioterror event, he said. Although the firm would hope its anthrax testing never needs to be used, something like a large botulism outbreak, for example, might also initially require some anthrax testing as part of a differential diagnostic workflow.

Also in the pipeline is an ESKAPE panel— to detect Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species — for hospital-acquired infections and sepsis, as well as an antimicrobial resistance, or AMR, panel.

An initial trial of the Tangen Candida test performed at Rhode Island Hospital examined 79 whole blood patient samples with 1.5 CFU per milliliter of spiked in C. albicans, C. glabrata, C. krusei, or C. parapsilosis, and 3 CFU per ml of C. tropicalis.  The assays had 100 percent sensitivity with the exception of the C. parapsilosis target, which had a sensitivity of 90 percent. The specificity of the tests ranged between 95 percent to 100 percent for the different Candida targets.

The Candida assays will be part of a sepsis panel as well, Birkmeyer said, but there are also other applications for Candida testing, such as in food and pharmaceutical manufacturing.