NEW YORK – Inflammatix is expanding into the SARS-CoV-2 testing market with a platform that uses gene expression patterns of a patient's immune response to COVID-19. Unlike current technology used in the diagnosis of COVID-19, the test uses machine learning to develop algorithms that detect the presence of infection and predict disease severity.
The Burlingame, California-based startup, a spinout of Stanford University, is developing the test using $1.1 million in funding from the US Department of Defense's Defense Advanced Research Projects Agency (DARPA). It is currently participating in clinical studies and anticipates applying for Emergency Use Authorization from the US Food and Drug Administration to launch a test for US-based high-complexity laboratories during the first half of next year.
Inflammatix doesn't intend to compete with current tests, including RT-PCR and antigen tests that detect the presence of active infection and antibody tests that detect past infection, but it believes that its test can provide additional, valuable information for clinicians.
If its gene expression, host-response test obtains EUA, clinicians will be able to use it to gauge the severity of the condition and the likelihood that a patient will require a mechanical ventilator, Tim Sweeney, the firm's CEO and cofounder, said in an interview.
The molecular diagnostic firm's CoVerity COVID-19 Severity test and its platform, Myrna, eliminate RNA extraction, a step that is time consuming and can hamper the implementation of testing due to a shortage of reagents.
"We expect CoVerity to attain EUA as an adjunct test for risk stratification of patients presenting to hospital with confirmed COVID-19," Sweeney said.
The test leverages a set of six host-response gene-expression biomarkers to generate a risk score that clinicians could use to make better choices about how to treat patients.
Inflammatix is developing its test to run on current thermocyclers used for SARS-CoV-2 testing in high-complexity laboratories so that testing could be quickly scaled up for broad use, Sweeney added. The test's turnaround time is expected to be less than two hours.
Sweeney said Inflammatix intends to first launch the SARS-CoV-2 test to a limited number of hospitals to gauge interest and to enable clinicians to become more aware of the "power of the host response."
The company anticipates it will take time to prove the utility of a new technology, convince clinicians, and have its platform broadly accepted in the US and internationally, he added.
Assuming customers become interested in CoVerity, Inflammatix would then scale up the production of kits, Sweeney said, adding, "Our aim is to target an initial group of customers so that they can become more familiar with how host-response testing works. We also want them to be aware that we can develop algorithms that are able to interpret multiple RNA signatures and generate useful and stable clinical scores."
The startup is also focused on continuing to develop and launch a 30-minute gene expression-based immune response test, InSep, that distinguishes viral from bacterial infections and is targeted toward clinicians diagnosing sepsis.
Inflammatix plans to launch InSep, formerly called HostDx Sepsis, as a cartridge-based rapid isothermal assay running on Myrna during the second half of next year.
In development for about four years, InSep produces three clinical scores ─ the likelihood of bacterial infection; the likelihood of viral infection; and the severity of the condition, including the risk of a patient requiring intensive care or dying. Because the bacterial and viral scores are separate, the test would also identify a non-infectious inflammation ─ that is neither bacterial nor viral ─ which is also a "strong differentiator," Sweeney said.
Inflammatix is conducting clinical studies for both CoVerity and InSep, and in the second half of next year anticipates launching InSep with an FDA EUA in the US and with CE marking in Europe and other regions that accept such designation.
The firm said that InSep could be used to diagnose the presence of a bacterial or viral infection in patients with suspected COVID-19. "Patients with an InSep-confirmed viral infection could be treated as presumptive COVID-19 until PCR confirmation, whereas those who are InSep-negative for a viral infection could proceed down separate treatment paths," Sweeney said.
Meantime, CoVerity has demonstrated an area under the curve (AUC) of .89 for distinguishing patients that went on to requiring mechanical ventilation within 30 days, Sweeney said. However, to be comfortable using the CoVerity score, clinicians will want to see a number of studies reflecting the test's performance, Sweeney noted. "We have a little over 1,000 patients with COVID-19 enrolled in multiple clinical sites so that we can obtain results and publish the clinical data in peer-reviewed publications," he added.
Overall, Inflammatix is currently engaged in about 30 clinical validation studies worldwide, including studies to evaluate InSep and CoVerity. Studies for InSep span a range of acute infections and primary care and hospital settings. The studies are ongoing in the US, Europe, Australia, and other countries, Sweeney said, adding, "That is necessary because acute infections and sepsis are a major problem in many regions."
Sweeney said that InSep has shown high levels of performance in clinical studies so far. Its bacterial score is broken into four bands ─ reflecting a very low, low, moderate, and high probability of having a bacterial infection. "At the lowest and highest bands, we are seeing sensitivities and specificities of 95 percent to 99 percent, depending on which blinded, prospective study we are looking at," he said.
To diagnose a patient suspected of sepsis, clinicians can use a number of tests to support their clinical assessments. These include a complete blood cell count as well as an assessment of protein biomarkers such as C-reactive protein and procalcitonin, which has received a number of regulatory approvals in recent years.
However, current tests don't provide the level of insights sometimes needed to diagnose patients with sepsis that can be obtained using the gene expression tests, said Nathan Shapiro, an emergency medicine physician at Beth Israel Deaconess Medical Center, who is helping lead the clinical validation of the Inflammatix sepsis test.
One of the advantages of a test that "identifies and measures quantities of transcriptional mRNA is that you can look for patterns," Shapiro said. "Certain infectious agents have specific patterns, and so, you might be able to use a pattern to look at how the body is responding. Based on the body's response, you can then say the infection is likely a virus or more likely a bacterial infection."
A gene expression test also provides added clinical utility for COVID-19 testing, he said. "An RT-PCR test for SARS-CoV-2 tells you whether the infection that causes COVID-19 is present or not, but it won't tell you much more," Shapiro said. "You might be able to detect levels of the virus but that is typically not reliably related to the patient's level of sickness. You could do a similar PCR test to detect bacteria, such as Streptococcal bacteria, which is a common cause of pneumonia, and while you will know whether the bacteria is present or not, you can't see how the immune system is responding."
In January, Inflammatix announced that it had raised $32 million in Series C financing to advance its rapid tests through commercial launch in Europe and the US.
The Series C funding came on the heels of the firm inking a long-term, cost-sharing contract in November 2019 with the US Department of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA). The contract is worth up to $72 million based on achieving certain milestones. It enables Inflammatix to continue the development of a HostDx-Fever test, renamed ViraBac-EZ, to rapidly diagnose the severity of fever at the point of care. The firm expects to launch a rapid test in a few years that operates from a fingerstick blood sample instead of a venipuncture, which is used for its nearer-term tests.
Inflammatix has engaged with external partners for the manufacturing of its tests. It plans to hire an internal sales team but could also collaborate with distributors to target specific market segments and countries, Sweeney said. The firm is not disclosing pricing for its instrument or tests until pricing studies have been completed, he added.
Ephraim Tsalik, a cofounder of Durham, North Carolina-based Predigen, said in an interview that his firm is also developing gene expression, host-response tests. He said that the company, a Duke University spinout, aims to apply for EUA for a combined host-response and pathogen identification test for SARS-CoV-2 testing next year. "Our other priority is a host-response test to differentiate bacterial and viral infection at the point of care, which we expect will utilize a traditional FDA regulatory pathway and be ready for launch at the end of 2022," Tsalik said.
Shapiro noted that gene expression, host-response technologies could be developed to conduct a large number of tests on a single platform. "The bigger machines used in academic research can interrogate tens of thousands of different gene transcripts, whereas point-of-care devices that are being brought to the bedside could interrogate up to a few dozen assays," he said.