Ian Bolland caught up with Dr. Rolland Carlson, CEO of Immunexpress, to talk about a molecular diagnostic, SeptiCyte RAPID, which is used to detect sepsis and offers the potential to triage severe COVID-19 patients in the emergency department.
Briefly, tell us more about Immunexpress – how did the idea to start the company come about?
Immunexpress was the result of compelling proof-of-concept research in animal models. Our researchers, who were veterinarians, were focused on studying an induced endotoxemia model, which is a sepsis-like condition. The team performed time-course analyses of peripheral blood gene expression as the animals developed endotoxemia and saw profound differential gene expression. From these initial studies, and due to the similar disease profiles, we believed that a gene expression signature could be identified in humans for differentiating sepsis from non-infectious systemic inflammation.
In addition to these initial promising scientific results, there is a massive unmet need for an improved approach to sepsis diagnostics in humans and there is a large potential market. Over 1.7 million Americans develop sepsis each year and an even larger number are suspected of sepsis. Therefore, the idea to start Immunexpress came from a solution meeting a market need.
Can you tell us more about SeptiCyte RAPID? Why is the rapid diagnosis of sepsis so important?
SeptiCyte RAPID is a blood-based gene signature assay that can discriminate sepsis from non-infectious systemic inflammation with a high negative predictive value or high positive predictive value. Our test results indicate if there is a high probability that a suspected sepsis patient does (high positive prediction) or does not (high negative predication) have sepsis. The test uses an easily accessible whole blood sample where circulating leukocytes act as reporters for the immune status of the rest of the body, providing detailed information on a patient’s immune status. The test gives healthcare providers results in about an hour. This can expedite clinical decision making and has the potential to improve patient outcomes.
With every hour delay in diagnosing severe sepsis there is an 8% increased risk of mortality, so an accurate, early, rapid test to rule in or rule out sepsis fulfills a critical unmet need for early identification and appropriate intervention for this life-threatening condition.
How was this test developed?
SeptiCyte RAPID biomarkers were discovered using complex bioinformatic analyses of peripheral blood gene expression of a large number of patients that we were confident had either non-infectious systemic inflammation or sepsis. The biomarkers were then validated using other datasets and patient populations to ensure good diagnostic performance including specificity and high positive and negative predictive value. The test has been validated in two formats, as a kit called SeptiCyte LAB which is FDA cleared, and as a cartridge called SeptiCyte RAPID.
How does the test measure immune response?
SeptiCyte RAPID is based on the measurement of the RNA quantity of genes found in peripheral blood leukocytes. As a person’s immune system responds to infection, some genes are up-regulated (increased gene expression leads to increased cellular RNA levels) and some are down-regulated. SeptiCyte RAPID measures the up-regulated genes and the down-regulated genes using Reverse Transcription-quantitative Polymerase Chain Reaction also known as RT-qPCR. A ratio of these RT-qPCR measurements provides a SeptiScore which is a number between 0 and 15. The higher the SeptiScore the higher the probability that a patient has sepsis.
It seems like the test has seen a lot of development as we’ve come to know more about COVID-19, can you talk about that further?
SeptiCyte RAPID can differentiate systemic inflammation from bacterial, viral, and fungal sepsis. Even before the COVID-19 pandemic, we had demonstrated that SeptiCyte RAPID differentiated patients with systemic inflammation from those with sepsis caused by many different types of viruses, including influenza, respiratory syncytial virus, dengue and Ebola. There is strong literature support that severe COVID-19 is in fact viral sepsis. We believe SeptiCyte RAPID may be used to diagnose sepsis in severe COVID-19 cases, and that it can be used to differentiate between mild/moderate and severe COVID-19.
Can this kind of testing be done at scale and quickly?
One of the key benefits of SeptiCyte RAPID is that the test has a fast turnaround time of one hour. It is run on the Idylla platform, a fully automated real-time PCR system made by Immunexpress’ partner Biocartis NV. Biocartis currently has over 1,300 Idylla instruments installed throughout the world. Although the sample is run one sample per cartridge on the Idylla platform, it can be scaled up to run as many as eight cartridges at a time on a random-access basis. The platform has a small footprint which can be used in remote locations and requires minimal lab technician expertise. The platform is easy to operate with less than five minutes of technician hands-on-time required to set up a test.
How is the test manufactured?
SeptiCyte RAPID is manufactured in a single-use cartridge format. The manufacturing process is highly specialised because the cartridge is fully self-contained, fully automated, sealed and disposable. The cartridge contains all reagents necessary for sample extraction, PCR amplification followed by readout of quantitative test results determined by the Idylla instrument. Manufacturing is performed under rigorous quality assurance and release protocols to ensure reliability. The cartridge, which runs on the Biocartis NV Idylla platform, is QR coded to provide test-specific information and results tailored for Immunexpress SeptiCyte RAPID.
What steps are needed for the commercialisation of SeptiCyte RAPID globally? What is your supply chain and commercial strategy?
We have a strategic global launch plan, which is influenced by regulatory considerations, market opportunity, and capability to support both commercially and technically in regions around the globe, either directly or with distributors. The initial launch is in Europe, where we have CE mark and a Distribution Agreement with Biocartis NV. In the U.S., we will sell directly to hospitals once we receive 510K FDA clearance, however, for those interested in early access to SeptiCyte RAPID we offer early access programs for evaluation. We will assess each region according to the considerations noted previously.
