Immunexpress is a molecular diagnostic company focused on improving outcomes for suspected sepsis patients. In this interview CEO Dr. Rollie Carlson discusses the company’s FDA-cleared sepsis diagnostic test and the value it brings to the healthcare system.
Please describe the story behind the company: What sparked the idea, and how has it evolved so far?
Immunexpress originated in Australia as a biomarker discovery company focused on infectious diseases. When we moved our headquarters to Seattle in 2011, we had identified differences in genetic expression in patients who were suspected of having sepsis, the body’s overwhelming and life-threatening dysregulated immune response to infection that can lead to tissue damage, organ failure, and death.
The clinical presentation of sepsis is often hard to identify early; fever is not always present, and it can often go unrecognized clinically for extended periods Patients suspected of sepsis may be misdiagnosed and could be experiencing a systemic inflammatory response syndrome (SIRS), which presents similarly to sepsis in patients but has a non-infectious origin and is more benign.
Our team is focused on finding a better way to distinguish sepsis from SIRS in patients. The current diagnostic standard is to treat a patient with antibiotics as soon as they present with sepsis-like symptoms. However, since patients with sepsis may not be reacting to a bacterial infection, or those patients could be suffering from SIRS, this drastic over-prescription of antibiotics leads to an overwhelming burden to hospitals, clinicians, payers, and antibiotic stewardship efforts.
To achieve this goal, we began by using microarrays and next generation sequencing to discover genes that were differentially expressed in sepsis and SIRS and then we were able to narrow down the number of these to a gene set to be evaluated in clinical studies.
Immunexpress conducted these studies across eight different sites and ultimately was able to demonstrate performance of our technology, SeptiCyte®, which is based on RNA expression of white blood cells in the host as a response to pathogen infection. We have collaborators at major hospitals and health systems in the U.S., Australia, the Netherlands and the UK.
When it comes to sepsis, every minute counts. For each hour that treatment initiation is delayed after diagnosis, sepsis-related mortality increases by approximately 8%. It was clear that we had to develop a solution that would give rapid, accurate results. However, in the beginning, our diagnostic results took about six to eight hours. We wanted to fit it within the clinical time frame that could potentially save patient lives and therefore matter to a physician. Being able to get accurate results within an hour and get feedback to the physician as quickly as possible is very important to us, and the shortened time frame matters immensely for physicians.
Over the last three years, we have transposed our technology and partnered with Biocartis, S.A., to develop a fully-automated SeptiCyte® cartridge compatible with their Idylla™ platform. The cartridge is designed to have all the requisite reagents included, eliminating the necessity of an operator to use instrumentation associated with three partitioned segments of a molecular laboratory, thus saving crucial minutes.
Blood is drawn from the patient and added to the cartridge; the cartridge is then placed in a tray in the Idylla™ platform; 60 minutes later a result is produced indicating the patient’s probability of sepsis. The footprint of this instrument is very small. One disposable cartridge does all the extractions and PCR reactions necessary to facilitate an accurate report on the probability of sepsis.
In November 2021, Immunexpress announced it had received FDA clearance of the SeptiCyte® RAPID technology and we plan to launch the product across the U.S. in 2022. Biocartis, which manufactures this Idylla™ system, is based in Belgium. We currently have the CE mark in Europe, and their team is marketing the device and platform across Europe.
What is sepsis?
Sepsis is one of the single greatest causes of mortality in U.S. hospitals. It affects over 48 million patients worldwide, and that number has now almost doubled since the beginning of the COVID-19 pandemic because many COVID-19 infections and associated mortalities are due to viral-induced sepsis. Sadly, sepsis is very difficult to diagnose.
Immunexpress conducted initial clinical studies long before COVID and came up with a probability score for sepsis. We have a “high negative predictive value at high positive predictive value,” which means the test can rule in a patient that truly is septic and rule out a patient with a low likelihood of sepsis.
In the past, sepsis was thought to be primarily caused by bacterial infection. Now, we understand that it can be caused by bacterial, viral, fungal, or even protozoa infections.
Because SeptiCyte® RAPID measures the body’s own immune system response to infection (as opposed to detecting the source of the infection), we feel our technology is more applicable to the current health care needs. We’ve measured blood samples from patients infected with various viral and fungal species, and have found a consistent and accurate diagnosis of sepsis.
What are the main challenges that Immunexpress is solving for sepsis patients and their physicians?
Normally, in the hospital, if a physician suspects a patient of suffering from sepsis, the physician would take a blood sample and would receive a diagnosis within 24 to 72 hours after trying to grow the pathogen in a blood culture. But even in a perfect scenario, they only get a result in about 20% of the cases from blood culture. Multiple blood cultures may be ordered for a single patient, which is not very efficient, but nonetheless, is the current standard of care.
Currently, physicians treat patients under the assumption that they are septic. A large Dutch study has shown that 43% of the time, physicians are mistreating patients with administration of antibiotics and insertion of a mainline catheter, only to discover that the diagnosis is not sepsis. For some patients, such as kidney failure patients, antibiotics could be lethal. Our test is designed to solve the dilemma that the physician is confronted with when a patient is looking dangerously ill and the physician doesn’t know the reason.
As far as treatment goes, there’s always a fork in the road. If it is sepsis, physicians would want to know whether it is a viral, fungal, or bacterial pathogen, and whether it’s a resistant organism. The growth of treatment-resistant organisms poses a large issue and is one of the key reasons physicians don’t want to indiscriminately apply antibiotics.
If there’s a reason to believe a patient might have sepsis, using SeptiCyte® RAPID as a normal practice would be quite valuable. Our test is administered in situations in which there is consideration of ICU admission or when a patient exhibits two signs of SIRS, like fever or diarrhea. A patient might already be in the emergency department or ward, or may have come to the ICU for another reason (such as surgery), and the physician may now suspect sepsis (such as post-surgery sepsis).
If the patient is at high risk of sepsis, healthcare providers need to act quickly. If there’s a low risk of sepsis, then they can rule it out with a degree of certainty, and the patient might be ok. Of course, the providers may want to check other risk factors, but our test provides that initial quick response and potentially widens the treatment window.
Physician education is also an important need that has been exacerbated by the pandemic. We’ve been giving educational webinars and virtual seminars about sepsis and particularly about COVID-induced sepsis, which has garnered significant interest from critical care physicians and nurses.
What is the correlation between COVID and sepsis?
Sepsis is the most frequently observed complication of COVID. To make sure our test works with COVID, we included hundreds of COVID-19 patients in our clinical studies. Overall, we’ve evaluated over 500 COVID patients with this technology.
COVID’s burden on hospitals has been profound, specifically the burden on healthcare costs and available resources (ICU hospital beds, for example). Our test is particularly important in the context of the pandemic because you want to use ICU beds for critically ill patients. One of the big dilemmas of the pandemic was the uncertainty around whether patients would progress to severe disease or not. If they have a high risk of sepsis, they should be treated quickly in the ICU and be administered the appropriate treatments.
What would it take for this to become the standard of care?
Our test is the first FDA-cleared diagnostic in the U.S. that can differentiate SIRS from sepsis. We’ve presented our clinical validation at various major medical conferences and have published these data in peer-reviewed publications, as well as been disseminating the unique value proposition of our new technological approach to diagnosing sepsis. We need to make this the standard of care through education and awareness in different hospital systems.
Here in the U.S., different hospitals triage patients using a variety of inclusionary and exclusionary tests and SeptiCyte® RAPID should be included in that bundle of evaluations because it cancan improve patient outcomes.
In the U.S., Medicare CMS measures and rates hospitals by their sepsis patient management. Even within a hospital system, there is huge variability in ratings, and being able to improve and standardize patient management across the system will be a great advantage.
Although the highest cost is, of course, the high mortality rate, the management of sepsis is a significant financial burden for hospitals. By improving sepsis management, hospitals can reduce the length of stay while also reducing the number of other administered therapies.
What are the future plans for Immunexpress?
With FDA clearance, Immunexpress can now provide test cartridges to hospital systems. Our goal is to provide individual hospital systems with a solution to standardize their sepsis response protocols and improve their sepsis management quality scores. For us, that would be a success as it would demonstrate the hope for physician adoption of this technology.
We’re a small company but have been fortunate to have investors that have supported us throughout this journey. To take it to the next level and build up our capabilities, we need additional capital, mainly to support the commercialization of SeptiCyte® RAPID and the development of our next generation test SeptiCyte® RAPID + which will tell whether a sepsis patient has a bacterial or viral (including COVID-19) infection.
From a technology standpoint, early intervention means making the treatment decisions quicker, faster, and more accurate. The more precise diagnostics tools become, the better the management of sepsis will be. That is the promise of precision medicine. That is the promise of SeptiCyte® RAPID.
 Kumar A et al. Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical Care Medicine. 2006;(34):1589-1596.
 Zhou, F., et al. (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. DOI: https://doi.org/10.1016/S0140-6736(20)30566-3