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Fusion Genomics Clinically Validating NGS Test for Infectious Disease; Eyes 2020 FDA Submission

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NEW YORK – Fusion Genomics has begun clinical validation of OneTest PathoGenome, a next-generation sequencing assay for infectious disease, through a prospective trial at Toronto's Sunnybrook Research Institute.

The firm may also be in a position later this year to submit two rapid infectious disease syndromic NGS panels for marketing clearance to the US Food and Drug Administration, said Fusion Genomics President and CSO Mohammad Qadir.

To support commercialization of the infectious disease syndromic panels, called OneTest Rapid, the firm has opened a $10 million Series A round that it expects to close around the end of the summer, Qadir said. It anticipates using the financing to support two clinical studies to validate the rapid syndromic panels — one to detect sepsis and a second to detect nosocomial infections.

The most suitable patients for the NGS assays are people who have been in the hospital for about two days, but clinicians have been unable to detect the causes of their illnesses, Qadir said. The firm is developing the assays to also detect known genetic resistance markers associated with pathogens.

Idiopathic infections contracted by these patients are a leading cause of morbidity, mortality, and hospitalizations, due in part to limitations associated with current diagnostic tests, he said, adding that in developed countries, current clinical tests are unable to identify pathogens in about 15 percent of hospitalized patients suspected of having an infection, and that the rates are far higher in resource-poor regions of the world.

British Columbia-based Fusion Genomics' research and clinical assays leverage its OneTest NGS platform. The firm's research-use-only OneTest PathoGenome assay consists of UniPrep, a universal NGS library preparation kit; the firm's QuantumProbes technology for DNA/RNA target enrichment; and FusionCloud, which handles bioinformatics analysis and data management.

The company's QuantumProbes bind to target pathogen genetic material using magnetic beads and synthetic oligonucleotides, enabling preparation of enriched libraries of genetic data.

According to Fusion Genomics, OneTest PathoGenome can detect any of a full spectrum of approximately 1,400 pathogens known to cause human infection. The assay can identify emerging, novel strains to eliminate failures in diagnosis associated with continuously evolving pathogen genomes, and it works on all common sample types, Qadir said.

Of the 1,400 pathogens that the system can interrogate, 398 of them are frequent contributors to hospital-acquired or sepsis infections, he said.

OneTest Rapid, the clinical assay, uses an enhanced version of the quantum probes and optimized UniPrep that can prepare a sample for sequencing in less than four hours, Qadir said.

"The goal is to enable a diagnosis based on sequencing results in the hospital lab within a timeline that aligns well with hospital workflows." He noted that with an eight-hour test turnaround, clinicians in many circumstances would be able to prescribe an appropriate treatment during the same work shift that they initiated testing.

That's especially important, he said, for respiratory diseases as well as patients with nosocomial infections and sepsis where patients' health can deteriorate quickly.

The firm expects to eventually submit several rapid panels for US FDA clearance and CE marking. "Our strategy is to break up groups of related pathogens into syndromic panels, including separate panels for sepsis, nosocomial infections, encephalitis, and meningitis, among others," Qadir said.

It anticipates continuing to market OneTest PathoGenome for infectious disease research.

Organizations have been investigating sequencing to diagnose infectious disease for some time, and a number of other NGS-based tests are starting to show promise, including those from Karius; Aperiomics; the University of California, San Francisco; ARUP Laboratories; and IDbyDNA.

Aperiomics claims it can identify every known bacteria, virus, fungus, and parasite through "deep shotgun metagenomic sequencing," using a database containing more than 37,000 microbes.

Last year, researchers from Karius published an analytical validation of its cell-free microbial DNA sequencing test as well as results from the first 2,000 clinical cases analyzed from its CLIA-certified and CAP-accredited laboratory in Redwood City, California. Analysis of the first 2,000 patient samples tested in the CLIA laboratory showed that more than 85 percent of results were delivered the day after sample receipt, with 53.7 percent of reports identifying one or more microorganisms.

Fusion Genomics' Qadir said he believes that its cleared kits, by enabling receipt of results within eight hours in a hospital, will not only help clinicians diagnose conditions they are currently unable to diagnose, but may also give the firm an advantage over services that require sending out samples for processing in a CLIA-certified laboratory.

With its rapid NGS assay, Fusion Genomics expects to enable infectious disease testing at an initial price of about $300 per test. Qadir said he believes that the firm can drive down the price to $100 per test, which would make the platform cost-competitive on a per test basis with molecular diagnostic assays for infectious diseases that are currently in the market.

A cleared kit available in hospitals would enable testing a select number of samples on demand, which is an alternative to automated laboratory-based tests that usually operate by testing batches of samples, Qadir said. "The moment you need to batch process anything, you've already lost time in receiving a test result," he said.

"It’s great to see metagenomics continue to move to a lower cost and to slightly more relevant timeframes," said Tim Sweeney, CEO of Inflammatix, a company developing its own sepsis tests based on host gene expression profiling. "A test that costs a few hundred dollars and takes eight to 12 hours may be helpful in modulating antibiotic choice for some patients, but of course is far past the initial decision-making in the emergency department or ICU."

Inflammatix claims to be able to identify the presence of bacterial or viral infections and to determine if a patient has or is likely to develop sepsis at the point of care in 30 minutes or less.

"I think that the future diagnostic workflow will almost inevitably begin with a rapid host-response test to determine which patients do and don't have bacterial infections," Sweeney said. "Then reflex follow-on testing can focus on the expensive pathogen-focused tests to identify the strain, which is sometimes useful, and antimicrobial susceptibility, which is the real goal. All that said, for those niches where metagenomic next-generation sequencing (mNGS) makes sense early in the workflow, [including use with endocarditis and bone marrow transplants, among other applications], it's exciting that a solution is coming through FDA and closer to the clinic."

In the clinical trial for OneTest PathoGenome, investigators at Sunnybrook are currently recruiting patients to validate the assay as part of an independent prospective study to diagnose respiratory tract infections. The researchers anticipate testing samples from approximately 800 patients diagnosed with respiratory tract infections and then comparing results to those coming from conventional testing methods. They also anticipate evaluating samples from healthy individuals to help differentiate clinically relevant respiratory pathogens from those that are benign.

Consortium Québécois sur la Découverte du Médicament (CQDM), a group that supports the development of tools and technologies to accelerate the discovery and development of safer and more effective drugs, awarded an unspecified amount of funding for the trial, and Merck is supporting the study as a member of CQDM.

Qadir said that last April, at the annual conference of the Association of Medical Microbiology and Infectious Disease Canada, Sunnybrook researchers described a retrospective study in which they used Fusion Genomics' target hybridization-based NGS assay that can identify 48 viral and bacterial respiratory pathogens.

The group selected 36 archived nasopharyngeal swabs collected from patients who were admitted to Sunnybrook in 2018. It reported that OneTest is accurate for diagnosis of acute respiratory tract infections and had a favorable agreement rate with the Luminex NxTag Respiratory Pathogen Panel. Further, the OneTest platform yielded additional genomic and quantitative data not available using conventional testing methods, the researchers said.

Fusion Genomics, a spinoff from the British Columbia Cancer Agency, has been in business for about five years. The company has raised about $5 million with $1.5 million from angel investors, $2 million from research collaborations, and the rest from government grants.