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Curetis Subsidiary Ares Ramping Up NGS Antibiotic Resistance Testing Business

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NEW YORK (GenomeWeb) – Ares Genetics, a two-year old subsidiary of Curetis, is progressing in its plans to develop antibiotic resistance testing. The firm recently won funding to set up a research project and new lab space from which it will offer next-generation sequencing-based diagnostic services and products, and it has also begun a collaboration with a German pharmaceutical company to use its antibiotic resistance databases for drug development.

Ares is also now seeking US venture capital for a Series A financing with an eye toward offering antimicrobial resistance testing services and, ultimately, kitted assays, in Europe as well as through its US hub in San Diego or a US partner lab.

Ares, a subsidiary of Holzgerlingen, Germany-headquartered Curetis, sprouted from a large database Curetis acquired from Siemens in 2017. The database originally contained DNA sequences of more than 11,000 bacterial strains and sensitivity data for 21 antibiotics, and Ares has since expanded it, according to Curetis Chief Business Officer and Ares Managing Director Achim Plum.

Curetis announced earlier this month that Ares has initiated a €1.3 million ($1.5 million) development project co-funded by the Vienna Business Agency, a supporter of the Vienna Biocenter which houses Ares' offices. The funds are for a project called “assay development and artificial intelligence to diagnose antibiotic resistant infections,” dubbed Triple-A.

The Ares resistance test is called the Universal Pathogenome Assay, or ARESupa. It is a single NGS-based diagnostic test that can detect any pathogen and associated drug resistances from any type of patient sample, according to the firm.

The database, called ARESdb, covers genotype-phenotype relationships of resistance markers "very comprehensively," according to Ares Genetics CEO Andreas Posch, formerly a research scientist at Siemens.

Yet, "Antibiotic resistance is continuously evolving, so that is where our AI approach comes into play," Posch said.

The firm has designed an AI approach that curates and expands the existing database with sequence information generated in house and obtained from publications in order "to rapidly translate all the novel and emerging markers into diagnostic solutions," Posch said.

Plum noted that the firm is able to give a quantitative assessment of antibiotic resistance. Specifically, by analyzing sequencing and other data versus alongside its database, Ares can provide comprehensive reports linking detected genetic profiles to positive predictive value for bacterial antibiotic resistance.

Although microbial culture followed by phenotypic susceptibility testing can often accomplish the same goal, generally this approach takes days or weeks, and it has trouble with co-infections and anaerobic bacteria or other unculturable organisms.

"With turn-around times for NGS coming down, you really have a chance here to give a comprehensive picture that is actionable for the physician in a much shorter time," Plum said.

The method has achieved up to 98 percent accuracy in internal studies in identifying resistance from NGS data, Posch emphasized. "I think that is a very valuable insight for clinicians,” he said particularly for indications and applications where there may be turnaround time advantages over culture, such as severe hospital-acquired infections and prosthetic joint infections, but that also don’t require extremely fast turnaround times on the order of a few hours.

For prosthetic joint infections, for example, guidelines recommend two weeks of culture to capture the slimy biofilm-forming bacteria that tend to cause these infections.

"After two weeks, sometimes you just have one colony on the plate, and wonder, 'Is that contamination I captured from the lab or is that real?'," Plum said. In this case, molecular technologies may be the only way to detect a pathogen at all.

The new funding from the Vienna Business Agency will now support taking an in silico version of ARESupa to a lab prototype, as well as setting up a dedicated R&D and diagnostic service laboratory space called ARESlab in Vienna for in-house test development and initial commercialization in Europe.

The business plan also entails having a reference lab in the US, although that could be its own lab or a partner lab, Plum said. "We have to get the test in the hands of the users as soon as possible, but eventually we will plan to turn that into an IVD-based test that is a broader solution, where data generation is more locally done but interpretation will happen through our cloud-based decision support system," he said. The firm believes the reference lab model is well proven in the US and is a significant market, he said.

Plum further noted that many pharmaceutical companies are moving out of new antibiotic development, since antibiotics are "a very tricky business model," and the burden is shifting to diagnostics to make the best use of already-available antibiotics.

Ares announced recently that it has begun a collaboration with pharmaceutical company Sandoz to develop a digital platform using ARESdb to support repurposing of existing antibiotics to better treat infections with multidrug-resistant pathogens. Ultimately, this collaboration will also involve the design of new antibiotics that will be less prone to encountering resistance. The collaboration originated from an R&D program called the Digital Microbe, which was supported by the Austrian Research Promotion Agency, Posch said.

Importantly, as previously reported, Curetis also expects that work at Ares will lead both to new standalone products as well as add genetic resistance markers to the firm's PCR-based multiplex molecular diagnostics system, called Unyvero.

"You can think of ARESdb as informing both PCR-based diagnostics for Curetis but also NGS-based tests and services for Ares," Posch explained.

Curetis' lower respiratory tract infection assay, called the Unyvero LRT Panel, detects 19 bacteria and 10 resistance markers in a sample-to-answer workflow. It was cleared by the US Food and Drug Administration, along with the test system, in April last year.

"We got initial clearance for tracheal aspirate samples and are now working on a label claim extension for broncholavage samples," Plum said, noting that this strategy was devised in agreement with the FDA in order to speed up the clearance process for the initial indication.

The firm also has five applications that are CE-IVD marked, including the LRT panel, an implant and tissue infection test, a blood culture cartridge, a test for intra-abdominal infections, and one for urinary tract infections, Plum said.

For the US, the firm officially launched the LRT panel in June last year, and has so far begun in-depth conversations with stakeholders at 140 of the 1,000 targeted hospitals, Plum said.

"We have numerous locations in contract negotiations, we have shipped the first systems, and we have many that will start with some sort of evaluation of the technology, looking at workflow implementation," he said. The firm plans to give an update soon on uptake, he added.

In the US the firm is planning a joint infection cartridge as its next product. However, "It is still a market-development phase for all these applications," he said, adding that this seems to be the case generally across the board in the molecular microbiology market.

By way of analogy, Plum noted that fifteen years ago pathology was just beginning to embrace molecular techniques, and pathologists would say, "What I can't see through my microscope is not real."

Now, however, it is standard to use molecular technologies in pathology. "We see the same thing happening at this moment in microbiology, that it is turning more and more molecular," he said. This, in the end, will complement microbial culture techniques, but it can also provide some results more quickly, and in some situations, may be the only way to obtain a result.

Plum also said that a multi-stakeholder approach is particularly important in the molecular microbiology market.

"It is one thing to convince the lab director of a system's performance and benefits ... but you don't create demand by allowing a microbiologist to offer it; you need to talk to the clinicians about clinical benefits, and to the hospital administration about how it can help to save the hospital money," he said. In addition, in the US in particular, a key stakeholder is the antibiotic stewardship teams.

"That explains why sales cycles [in molecular microbiology] are fairly long — because you need to get all those stakeholders on board — but that is true for any other solution in the inpatient segment that we are in," Plum said.

Finally, for resistance markers in particular, education is sometimes needed before doctors can use the information that the tests are generating, Plum noted.

Toward this end, the Ares team has developed an intuitive, web-based, interactive knowledge base for the markers on the Unyvero panels that the firm intends to provide to clinicians soon. In this way, they can put in the marker name that they found with Unyvero, and they will get all the information from ARESdb. "They get all the insights … so they have all the knowledge on the marker, along with the clinical implications, at their fingertips," Plum said.

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