NEW YORK (GenomeWeb) – Less than a year after announcing its plans to enter the point-of-care molecular diagnostics space with an antimicrobial susceptibility test, startup GeneCapture now has its eyes on the infectious disease diagnostic market by integrating its CAPTURE and C-AST analyzers into a rapid, small counter-top portable diagnostic device.
Last week, the firm presented data on the C-AST assay's ability to predict antibiotic resistance in several strains of bacterial pathogens that cause urinary tract infections (UTIs).
GeneCapture CEO and Cofounder Peggy Sammon explained that the firm has planned on developing the C-AST assay for the past two years. However, the team only began extensively working on the assay in the last year or so after prioritizing the CAPTURE assay.Â
"Some physicians we talked to asked us to ID the pathogen, others just wanted the antibiotic resistance profile, and some wanted both," GeneCapture Chief Technology Officer Krishnan Chittur explained. "So this was something that was always on our radar screen, but most of the work that we've done started last year."
The Huntsville, Alabama-based firm is developing the C-AST assay in tandem with the CAPTURE (confirm active pathogens through unamplified RNA expression) pathogen identification platform. According to Sammon, the CAPTURE assay identifies bacterial or fungal pathogen RNA in liquid samples — including blood, urine, and saliva — with a "universal fluorescent marker," applying the firm's proprietary array using a machine-learning algorithm.
Chittur explained that the C-AST technology identifies patient samples with breakpoint concentrations of various drugs that could be used against the bacteria or fungus identified with the CAPTURE assay. The C-AST assay's machine-learning algorithm determines antibiotic sensitivity or resistance by interpreting optical scanning from the sample with different wavelengths.
"We realized that for most infections, knowing the identity of the organism wasn't enough … so we developed the C-AST assay to give us information about the right drugs to use once CAPTURE has identified an organism," Sammon said. "Knowing the type of organism and its concentration allows the C-AST assay to quickly analyze which antibiotics are sensitive or resistant."
Earlier this month, GeneCapture presented data collected from the functioning prototype system for its collaborators at the University of Alabama in Huntsville. The researchers tested four antibiotics — ampicillin (AMP), amoxicillin/clavulanate (AMC), trimethoprim/sulfamethoxazole (SXT), and ciprofloxacin (CIP) — against the nine pathogens responsible for most UTI cases. The group organisms include strains of species like Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus.
The researchers initially evaluated 70 runs comparing 181 drug exposures to no-drug controls. They then evaluated 25 subsequent assays against culture results, focusing on AMP, AMC, SXT, and CIP, with most being tested in duplicate or triplicate.
Sammon noted that the group did not encounter false resistances or false sensitivities using the drugs. She also emphasized that the C-AST assay performed identically to culture results but in a much shorter period of time.
According to Chittur, the C-AST assay can test the effectiveness of various antibiotics against pathogens in between 5 and 75 minutes. However, he highlighted that the time required does not reflect the utility of the drug, but instead the growth speed of the different bacterial species used in the presentation.
Chittur acknowledged that the firm's researchers encountered some challenges while developing the C-AST assay in terms of sensitivity and sample identification, including trouble distinguishing between control samples and samples that were sensitive to the antibiotics.
Sammon mentioned that the researchers also needed to figure out how to label samples and their antibiotic susceptibility using different wavelengths.
"This was interesting because some samples have a color that absorbs certain wavelengths, and so we would really need to be clever about all these different wavelengths that we're using to scan," Sammon explained.
GeneCapture plans to offer both the CAPTURE ID and C-AST assays in clinics and other point-of-care locations, which it believes will help doctors to quickly prescribe the most effective antibiotic for their patients. Sammon believes that the C-AST assay may be useful for drug development to rapidly screen potential new antimicrobials.
"Each of those steps requires a separate cartridge, but we plan to market the two tests in a single instrument," Sammon explained.
Sammon noted that the firm still aims to offer the CAPTURE and C-AST assays each at about $20 per cartridge. However, she acknowledged that the overall cost to run both assays on the portable device will increase to around $40 per sample.
GeneCapture will be entering a crowded space for antimicrobial susceptibility detection with its integrated CAPTURE assay, as several groups have received approval, or currently developing, or offer their own unique platforms to track drug resistance in bacterial and fungal species.
Accelerate Diagnostics PhenoTest BC kit provides ID and AST results for patients suspected of bacteremia or fungemia within seven hours. According to the firm, the kit targets more than 80 percent of pathogens that cause bloodstream infections and more than 90 percent of antibiotics useful in treating those pathogens. The firm plans to begin clinical trials for its lower respiratory tract in Q1 2019.
BioMérieux recently received 510(k) clearance from the FDA for its automated Vitek 2 gram-positive AST assays, which identify and conduct AST of bacteria and yeast. The firm said the results can then be used to determine appropriate antibiotic treatments for patients. In addition, the FDA also recently approved Becton Dickenson's automated Phoenix CPO test, which the firm said can detect carbapenemase producing organisms in less than 36 hours.
Chittur argues that while several companies and universities are developing similar tools, GeneCapture's platform is "a bit more straightforward and simpler, using a technique that provides more direct information about the bacteria."
Rather than using a genotypic approach, GeneCapture's tool looks for the phenotypic element in order to detect "what is actually growing and not growing," Sammon added. She also noted that GeneCapture is currently working with microbiology labs that struggle with sample throughput.
GeneCapture plans on building panels for gastrointestinal and respiratory infections after the firm finishes developing the UTI panels. The firm is also using C-AST on non-bacterial samples, such as with the fungus Candida.
Moving forward, Sammon argued that the firm is now focusing its resources on engineering aspects of the device to simplify usage while maintaining a high sensitivity and specificity.
"We're talking with [microbiology] groups to understand their operational needs, their space, and time limitations, and so we are trying to pull that into the device's design," Sammon said. "Right now, we're looking at pre-manufacturing models, the cost of manufacturing, [and] getting designs for easy disposable cartridges."
Sammon noted that GeneCapture hopes to seek 510(k) clearance from the US Food and Drug Administration for its combined identification and antimicrobial sensitivity test by the end of 2019. In June, the firm received a $1 million Small Business Technology Transfer Research contract from the US Department of Defense to develop a prototype that would quickly identify pathogens in combat zones.
GeneCapture has also appointed Greg Thompson yesterday as its chief operating officer. He will oversee product design, commercialization, and medical device approval for the firm's diagnostic platform.
"The question for our first prototype is how do we make it so simple to use and therefore keep [the assay] at the low price point that we want," Chittur noted. "Our ultimate goal, since the automated cartridge we are developing can process different sample types, is to produce a single cartridge that can ID hundreds of pathogens from the same sample in a single CAPTURE assay."