NEW YORK – Dutch diagnostics company Inbiome is launching a new PCR-based molecular platform for diagnosing bacterial infections that it says can be used in lieu of traditional culture, while rivaling newer methods like sequencing in terms of time and cost and other PCR tests in terms of scope.
The firm recently received a European Innovation Council grant worth €5.7 million ($6.1 million), and is planning further clinical validation of its platform while it eyes a US entry as soon as next year.
"It's a molecular technique that has a broad scope like regular culture," said Inbiome CEO Dries Budding of his firm's technology. "Bacterial infections can be caused by thousands of different bacterial species, so we built a molecular technique with an open approach," he said. "You put in a sample; you get out what bacteria are there."
The technology underpinning Inbiome's platform was first developed over a decade ago at VU Medical Center in Amsterdam. It relies on PCR targeting ribosomal DNA, but instead of targeting 16S ribosomal RNA, as is done typically using next-generation sequencing to survey the bacteria present in a sample, Inbiome's approach targets the internal transcribed spacer region. The lengths of spacer regions are variable, and Inbiome has built a resource where it can match these lengths to various species. It also relies on a colorimetric readout, so that it can pick up multiple species in the same sample. All the data is correlated to values in the firm's database, meaning it can report back on the bacteria present in a sample and their abundance.
"We wanted to do something simple that could be implemented in a clinical routine," remarked Budding. "Measuring a length is much easier than measuring a sequence or actually sequencing."
According to Budding, to run the Molecular Culture test, a sample from a person with a suspected infection is delivered to the lab, where routine DNA extraction is done, followed by a PCR reaction. The lengths of the spacer regions are measured using electrophoresis. The data is fed into the cloud where it is analyzed using Inbiome's software. The whole process from sample to answer takes four hours, he said. An analysis costs around €150.
The company's technology has existed and been honed for over a decade. A company called IS Diagnostics was first established to commercialize the technology in 2012, and Budding served as CEO of that firm, but the venture was later wound up and reconfigured as Inbiome in 2019.
"We decided the technology had reached a maturity level that we could actually bring it to market, and that's when we founded Inbiome," said Budding. The company also raised some seed funding that year, built its own lab at Amsterdam Science Park, and started with a core team of six people that has since ballooned to a team of about 27 staffers.
Inbiome was readying its platform for launch in 2020 and doing some contract research for initial partners when the COVID-19 pandemic struck. Running clinical studies was almost an impossibility for Inbiome, and like many other diagnostics firms with PCR expertise and resources, the company quickly repositioned itself to run SARS-CoV-2 tests. "This was a very crazy and busy time," Budding recalled. "But it generated enough revenue to keep us going."
The new EIC award will also support the firm's activities. According to Budding, the EIC project involves a €2.5 million upfront investment, with the remainder of the €5.7 million budget provided as equity. It will support a variety of activities, including an implementation trial of the Molecular Culture platform in a hospital setting, optimizing the Molecular Culture interface for hospital workflows, validating the platform for use with other sample types, introducing antimicrobial resistance testing into the assay, and expanding the company's commercial reach. In purpose, that means the hiring of more personnel devoted to sales and marketing.
As part of the trial, Inbiome will run all samples from the hospital with standard culture in a routine microbiology lab, as well as Molecular Culture in a small lab it will set up beside the routine lab, and in parallel. All results will be outputted the same day, so the company and its partners can observe the impact.
"We can hopefully convince the world that this is real and that the time has come to move on from culture," said Budding of the project.
According to Budding, Inbiome's platform already holds a CE-IVD certificate for use with samples from normally sterile sites, such as joint aspirates, cerebrospinal fluid, pleural punctates, biopsies, and pus. The company is now launching the platform for a subset of customers who will implement it clinically for specific applications, the first of which will be for joint aspirates.
This month, scientists from Inbiome, VU Amsterdam, and Maastricht University Medical Center published a study in the Journal of Clinical Microbiology discussing the use of the test to diagnose bone and joint infections. In it, the authors analyzed fluid samples from patients with suspected joint infections and compared the outcome of the test with conventional culture and found more than 90 percent agreement between both methods. The test also yielded 83 extra bacterial detections, the authors noted, and concluded that Inbiome's test showed "an excellent performance for fast diagnostics."
Assays for bone and joint infections have been targeted by other players, including BioMérieux with its BioFire Joint Infection Panel. Scientists from University Medical Center Groningen discussed a study of the BioFire PCR-based assay, which runs on the BioFire FilmArray 2.0 and BioFire Torch systems, at a conference in Copenhagen, Denmark, last month. The test, which has a turnaround time of about an hour, already gained US Food and Drug Administration clearance and holds a CE-IVD mark. However, it is a targeted panel, including 31 pathogens and eight antimicrobial resistance genes.
There is also Santa Cruz, California-based Pathogenomix which offers Patho-Seq, a targeted, sequencing-based assay that the company says can test for 400 bacterial pathogens to help diagnose sepsis, bacteremia, joint and implant infections, bacterial meningitis, and tick-borne bacterial infections in patients. The FDA granted Patho-Seq breakthrough device designation last year.
This trend on focusing on specific applications for molecular approaches, rather than replacing culture in toto, reflects the reluctance among clinicians to abandon an approach that has been in use since the 19th century, and available via automated platforms since the 1970s.
"We started by approaching hospitals, saying that they could replace everything, but that didn't work and it didn't sell," noted Budding. "That encouraged us to go for an application basis."
Joint infections are an increasing problem among people with artificial joints, and it can take weeks to get results using culture. This leads to either the prescription of broad-spectrum antibiotics, or even surgery to clean out infections. Here, Budding sees an opportunity for Molecular Culture.
"We can get the same results faster with more sensitivity in four hours, and potentially cut the number of operations in half," he said.
There will be other such appeals for adoption of the platform in other applications. According to Budding, Inbiome and its academic partners are planning a series of publications that will showcase the use of Molecular Culture in other sample types, after which the firm will roll out the assay to a broader set of customers. He acknowledged that to reach US customers, the company will need FDA clearance, which the company hopes to obtain in 2024.
Christian von Wintersdorff, a medical molecular biologist at Maastricht UMC, said that his department is using Inbiome's platform in several research projects focused on microbial composition or pathogen detection. According to von Wintersdorff, Inbiome's technology has some advantages over next-generation sequencing, as well as other PCR-based approaches.
In the case of sequencing, the advantages are time related. Molecular Culture can detect "nonviable or hard-to-culture organisms" in a manner similar to 16S rRNA sequencing. Sequencing, however, has a "more complex workflow," he said, and higher bioinformatics burden. Molecular Culture's four-hour turnaround time and reduced informatics requirements make it faster than sequencing, which "creates great opportunities for its use in diagnostics," he said.
Von Wintersdorff also compared the Molecular Culture platform to pathogen-specific PCR tests. Here, an advantage is that the technology is eubacterial and does not only cover a targeted species. Using Molecular Culture therefore provides more information about what bacteria might be causing an infection.
"Traditional eubacterial 16S rRNA PCRs followed by classical Sanger sequencing, while cheap and potentially rapid, are unfortunately not appropriate for characterizing polymicrobial infections and may suffer from insufficient discriminatory power," remarked von Wintersdorff.
Paul Savelkoul, who heads the medical microbiology department at Maastricht UMC, and is a scientific adviser for Inbiome, said in an email that the platform is an example of a "holistic approach in molecular diagnostics" for bacterial infections.
He noted that the Inbiome test includes positive and negative controls to ensure that every clinical sample is optimally processed. And while the amount of data reported back is large, the file is not, making it easier to implement, he said, adding he was able to train a student to use the platform in one week.
He stressed, though, that more studies are necessary to demonstrate the benefit of the platform in other samples. Once convinced, though, laboratories should be able to easily adopt Molecular Culture. The platform "fits into the molecular way of working in most molecular diagnostics labs," said Savelkoul, "making integration not too complicated."