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Immunexpress to Submit Molecular 'Immune Response' Sepsis Assay to FDA in May

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NEW YORK (GenomeWeb) – Immunexpress, a privately held firm that has for several years been developing molecular assay technology to diagnose sepsis, may finally be close to marketing a clinical test in the US.

Having just wrapped up a key clinical trial of its first sepsis assay in around 200 ICU patients, Immunexpress plans to submit the test in May to the US Food and Drug Administration, and hopes it can gain marketing clearance by the end of this year, Immunexpress President and CEO Roslyn Brandon told GenomeWeb this week.

The company believes that its assay can address a "huge unmet clinical need" — namely ruling in or ruling out whether patients have a septic infection within hours of their admittance to a hospital — because it uses the unique approach of detecting biomarkers of host immune response rather than testing for the presence of a specific pathogen, Brandon said.

"The definition of sepsis remains controversial," Brandon said. "We do know it’s a dysfunctional, systemic immune response to an infection. I want to highlight 'immune response' because that distinction forms the basis of how we are different, in that we are focusing almost entirely on that immune response rather than trying to find the pathogen."

Immunexpress was founded in Australia in 2006 to develop and commercialize its so-called SeptiCyte technology, which uses molecular methods such as qPCR to quantify from whole blood specific biomarkers from a patient's immune system. The company formed a US subsidiary in 2010 in Seattle, where it is now headquartered, though it still maintains offices in Brisbane, Australia.

"We've got a pipeline of products based on SeptiCyte, and they are blood tests," Brandon said. "The first product measures four mRNA markers [that are] upregulated or downregulated with the septic response. We know that based on the result from that report that the patient has sepsis or they have systemic inflammatory response syndrome, which is not due to an infection."

Most competing approaches to sepsis diagnosis, including the gold standard of microbiological culture, focus on detecting a specific pathogen. But culture-based methods can take one to two days to perform, during which time a septic infection may easily worsen to kill a patient. Newer molecular methods such as qPCR have proven to be as specific and sensitive as culture, with a much faster turnaround time, but still have inherent limitations in diagnosing a syndrome that can be caused by any number of microorganisms.

"It doesn't matter how fast or sensitive the detection technology is … you have to have the pathogen in the blood sample in the first place," Brandon said. "If it's not there, which is quite regularly — particularly in children because it's related to volume and blood and the severity of the disease — you end up with a lot of false negatives."

Alternatively, Immunexpress' test is able to give clinicians actionable information in 100 percent of cases, Brandon said. "We're saying let's determine first whether this person has a septic immune response," she said. "The physician with the false negative doesn't know if the patient doesn't have sepsis or if they just didn't find the [pathogen]. The immune response is not the whole answer, but it is the first port of call, which can give you a very clear understanding of whether or not it's sepsis."

As such, Immunexpress hopes its test can be used to provide a broad answer about the likelihood of a septic infection to physicians so they can then decide whether or not to begin broad-spectrum antibiotics or to conduct more specific testing for a particular organism.

Currently, Immunexpress' first test can be run on a standard hospital lab RT-qPCR system and provide an answer in about four hours. However, it will be crucial for the company to cut this time down even more, because a septic infection can worsen to a life-threatening condition in a matter of hours.

"We've done extensive quantitative and qualitative market research, particularly in the US, and what we understand is that a physician will hold antibiotic treatment but probably not for much longer than about 60 to 90 minutes," Brandon said.

To that end, Immunexpress is currently working with an unnamed laboratory instrument manufacturer to develop a fully automated sample-to-answer platform that would provide an answer in that time frame. That partner, Brandon noted, will not be BioCartis, with which Immunexpress previously forged a pact to develop the SeptiCyte assay. She declined to provide additional details.

Brandon noted that the company believes its assay would still provide value in terms of antibiotic stewardship if it took a few hours to perform.

"It's not a simple transition," she said. "It has to be quantitative. And one of the challenges is the RNA extraction process. We're really motivated to get that turnaround time down. We really believe that sepsis can kill in hours, and suspected sepsis is very much overtreated, so we're trying to deal with both of those issues."

Brandon said that the company plans to submit its test to the FDA in May, with data from the company's recently completed "Validation of septic gene ExpressioN Using SeptiCyte" (VENUS) trial forming a large part of that submission. This prospective observational cohort study of approximately 200 ICU patients was conducted at two Intermountain Healthcare clinical sites: the Intermountain Medical Center in Murray, Utah, and the Latter Day Saints Hospital in Salt Lake City.

"We've been engaged early with FDA, worked with them for the last two years, and we're putting in our regulatory file next month," Brandon said. She added that there are discussions around the test result being reported in terms of the probability of sepsis, such that "physicians will get an answer and understand what the probability of sepsis is in every patient."

Immunexpress also participated in the "Molecular Diagnosis and Risk Stratification of Sepsis" (MARS) Consortium, an initiative spearheaded by the Dutch government that wrapped up last year. Brandon said that this clinical trial looked at around 8,000 critically ill patients, about 1,000 of which were tested with Immunexpress' technology. The results of this study will be published in a peer-reviewed journal in the coming months.

The company has raised an aggregate of about $40 million over the course of its existence, with its most recent Series B financing round garnering about $12 million. A $6 million tranche of that Series B, completed last May, was led by Switzerland's Debiopharm Group.

Brandon said that Debiopharm is still an investor, and that Immunexpress is now working toward a Series C financing round with the hope of landing between $20 million and $40 million in funds.

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