NEW YORK – Selux Diagnostics is targeting the first half of next year for US Food and Drug Administration approval and subsequent launch of its Next Generation Phenotyping (NGP) system for rapid antimicrobial susceptibility testing (AST) after recently completing a clinical trial showing that the platform could rapidly phenotype a plethora of bacterial pathogens.
The Boston-based company has also recently received an influx of funding to support these efforts. Selux announced in June that it received an additional $14.6 million milestone payment from the US Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA). The initial award, worth up to $45 million, was adjusted upward by BARDA as well, to $60.8 million. Selux previously received milestone payments of $11.4 million in 2019, and $9.6 million in 2020.
And in September, Selux was awarded approximately $1 million in Commercial Readiness Pilot Small Business Innovation Research funding from the National Institutes of Health to commercialize its NGP platform. The firm said the support will be used in part to scale manufacturing in order to lower costs.
Selux's core technology involves the labeling and imaging of cultured bacteria combined with artificial intelligence-based interpretation in order to rapidly determine antibiotic susceptibility and the minimum concentration of antibiotic needed.
The NGP system is agnostic to the bacterial identification part of the workflow — rapid ID can be run in parallel with AST and minimum inhibitory concentration (MIC) testing using Selux's tech, either with rapid PCR-based or MALDI-ToF systems.
Steve Lufkin, Selux's CEO, said in a recent interview that increased laboratory adoption of faster bacterial identification systems — such as blood-culture ID panels for liquid cultures or MALDI-ToF for solid cultures — has shone a light on the fact that susceptibility testing is really slow.
Traditional AST involves waiting for bacteria to multiply in a liquid or solid culture, then splitting them out and applying different antibiotics at different concentrations.
Laboratory systems that can do this in an automated way include BioMérieux's Vitek 2, Becton Dickinson's Phoenix, Beckman Coulter's MicroScan, and Thermo Fisher Scientific's Sensititre.
Rapid AST systems are also being commercialized by firms like Accelerate Diagnostics, Affinity Biosensors, Avails Medical, Gradientech, Q-Linea, and First Light Biosciences, while a system from Specific Diagnostics will be distributed in Europe by BioMérieux.
The Selux NGP system requires an upfront Gram stain to select the appropriate AST 384-well plate prefilled with bacterial label and dilutions of antibiotic.
Once the ID results are available, the system can also report and interpret the MIC, but, "That is going to be available within the window while we are doing the susceptibility testing," Lufkin said.
Overall, same-shift AST results can enable labs to "close the gap" between when rapid ID results are available and when AST and MIC are ready, which in turn "is going to have a big clinical impact," Lufkin said.
That impact is measured in clinical outcomes, such as length of patient stay, or reduction in rates of other infections acquired in the hospital.
Still, "Those are things we are going to have to prove out in the marketplace once we get clearance," Lufkin said.
Support for the idea that there will be clinical utility, however, comes from outcomes data on competing technologies, like the Accelerate Pheno, which performs both rapid ID and AST.
That system has been shown to reduce the time it takes for a patient to be put on the correct antibiotic, although other significant clinical outcomes have been elusive, in part due to complexities of septic patients and a possible need for supportive antibiotic stewardship efforts. Accelerate is also developing an AST-only system.
Lufkin said that while speed matters, "You also need to have a broad antibiotic menu so you can eliminate reflex testing, and you have to have the ability to work from all sample types," which are qualities the NGP possesses.
The throughput of the Selux NGP is 80 to 100 samples per shift, Lufkin said, which, when combined with all the other attributes, might allow it to be competitive with legacy automated systems. That said, the Selux NGP also mimics the easy-to-use workflows of these systems. "We are not trying to ask a technician to do something completely different," Lufkin said.
The high throughput of the NGP might also lead to a more rapid validation in the lab than lower throughput systems, Lufkin said.
Lufkin said Selux is also developing technology to speed up the time to a positive signal in a blood culture bottle, adding that this work is also supported by its BARDA funding.
"The key is to get to the 10 percent of blood culture bottles that are actually positive as quickly as possible," he said. Commercial blood culture systems were developed in an era when microbiology labs were sited within the hospital, but these days more samples are transported elsewhere for testing, he said, with some large hospital systems even creating their own courier forces to transport samples to a central lab.
So, Selux is developing a technology called Grow-on-the-Go, Lufkin said, that "keeps the bugs happy while they are coming to the lab" so detection can happen sooner.
That work is earlier stage but is part of the firm's larger vision of how microbiology labs can evolve over time, he said.
The firm recently presented proof-of-concept data on the NGP in the form of posters at the American Society for Microbiology meeting.
In one evaluation of 350 clinical isolates, the firm showed greater than 90 percent agreement with a reference method for both Gram-negative and Gram-positive samples.
In another evaluation, 50 samples comprising 12 major species of non-fastidious bacteria were processed on the NGP, and each sample was tested against 20 antibiotics representative of major antibiotic classes. The Selux platform showed agreement of 96 percent for all bug-drug combinations and no less than 92 percent for any one combination.
In the latter evaluation, results were obtained between about five and seven hours, including the time for automated sample preparation from blood bottles, and were accurate even for patients who had been administered IV antibiotics before blood draws.
And, in a study published last month in the journal Anesthesia & Surgery, authors at New York Medical College and Weill Cornell Medical School evaluated more than a dozen studies of sepsis patients, using the data to generate a model.
They concluded that going from conventional AST to a rapid AST system with the specifications of the Selux NGP could save more than $1,600 per sepsis case, or approximately 7 percent of total average admission costs due entirely to improved length of stay.
"When scaled to the hospital level, this represents $5.65 million saved per 100,000 total hospital admissions," wrote the authors, who also acknowledged receiving funding from Selux to support their research.
Breakthrough designation, expansion
Selux has submitted its NGP system to the FDA for solid culture AST, but also recently received breakthrough device designation last month for its system using liquid culture samples, specifically positive blood culture and sterile body fluid samples.
That recognition by the FDA is "another stamp" on the firm's technology, Lufkin said.
Initiated in 2018, the Breakthrough Devices Program offers manufacturers an opportunity to interact with the FDA during the premarket review phase, which the agency maintains allows it to more quickly provide feedback, identify areas of agreement, and prioritize review.
Although the FDA does not publish a list of all designated devices, a spokesperson said that the agency's Center for Diagnostics and Radiological Health has granted 561 Breakthrough Device designations since the program began, with 32 publicly disclosed after attaining market authorization from the agency.
Breakthrough designation requires novelty, uniqueness, and potential to impact patient care, and Lufkin said Selux's success at hitting technical milestones over the past few years likely led its application to rise to the top.
To further support the NGP launch, this month Selux brought John Wilson as chief commercial officer. Wilson spent the last decade at GenMark Diagnostics. The company has also been expanding its commercial infrastructure, Lufkin said, and is recruiting software and engineering talent as well as sales, service, technical support, and application specialists.
Lufkin said the firm is going for a targeted, strategic launch, with an in-house commercial organization to support it, so the firm is not looking to partner at this time.
It will be targeting labs that are performing more than 20,000 ASTs per year to inform inpatient care, but it also has future designs on outpatient settings using a smaller menu of antibiotics, Lufkin said.