NEW YORK – MeMed, an Israeli company with a focus on developing assays that gauge immune response to infectious diseases, is developing two new tests that could help select treatments for COVID-19 patients.
Both tests are related to its flagship point-of-care platform, which identifies whether a patient is suffering from a viral or bacterial infection. Called MeMed BV, the test analyzes the expression signature of three blood-born host immune response proteins. The chemiluminescence immunoassay achieved a CE-IVD mark this year and is available for clinical use on its point-of-care platform, MeMed Key.
MeMed BV relies on three markers — TRAIL, CRP, and IP-10 — to distinguish between bacterial and viral infections. And it is this last marker, IP-10, that the Haifa-based company believes can be used to make treatment decisions for patients suffering from SARS-CoV-2. The company discussed findings from a study that assessed the use of its test for guiding treatment of COVID-19 patients in a poster at the annual meeting of the American Association for Clinical Chemistry, held online this month.
In the poster, the company and partners at Rabin Medical Center in Israel showed how they used the firm's test over the course of a month to measure interferon gamma induced protein 10 (IP-10) levels in 52 SARS-CoV-2 patients, half of whom progressed to severe COVID-19.
They found that severe patients had higher IP-10 levels compared to non-severe patients, who had moderate levels of the protein in their blood. Those severe patients treated more aggressively with corticosteroids meantime saw their IP-10 levels fall to moderate levels, underlying a reduction in the severity of their disease.
Based on the findings, MeMed believes its test can be used to identify which COVID-19 patients require more aggressive treatment with corticosteroids. "Real-time IP-10 measurements help identify COVID-19 patients in a hyperinflammatory state, specifically those not responding to standard corticosteroid regimens, who may require more aggressive treatment," the authors wrote, although they concluded that further studies are warranted.
"About 10 percent of COVID-19 patients will deteriorate due to what is called hyperinflammation," noted MeMed CEO and co-founder Eran Eden. "The body's response goes haywire and causes damage to the body itself," he said. "So, we asked in this study, could we use our technology to determine if someone had hyperinflammation, and then if that information could be used to dampen the response in a personalized manner."
Using inflammatory biomarkers to guide treatment decisions is a core concept for MeMed. Eden established the firm with CTO Kfir Oved in 2009 and it has since grown to 55 full-time employees, plus about 30 part-timers. MeMed introduced the first generation of its MeMed BV test in an ELISA formatin 2015 across Europe and Israel. Then, with the development of the point-of-need MeMed Key platform, it secured a CE-IVD mark for both earlier this year.
Since achieving the CE-IVD mark, MeMed has intensified its commercial activities. It inked a deal with DiaSorin, the Italian diagnostics multinational, for instance, to allow the latter to offer MeMed BV on its 5,000-strong installed base of Liaison analyzers worldwide. MeMed continues to offer the test on the MeMed Key instrument directly.
The firm has also embarked on a clinical study involving more than 1,000 subjects of MeMed BV and its MeMed Key instrument in the US in collaboration with Johns Hopkins University, Boston Children's Hospital, and other partners. According to Eden, MeMed is also currently establishing an office in Boston to support a planned expansion in the US, which will include seeking a US Food and Drug Administration clearance for its test and platform next year.
Then COVID-19 broke
All of these plans were in motion when the COVID-19 pandemic struck. But given its expertise and breadth of experience in designing tests for monitoring immune response in order to guide treatments, the latest and quite deadly infectious disease seemed a natural extension for MeMed.
Noting the relationship with DiaSorin, Eden said the company kept a close eye on the spread of COVID-19 in Italy, where cases spiked dramatically in the spring. According to the World Health Organization, there have been close to 1.9 million cases since the pandemic began in Italy, a country of 60 million, and 66,000 deaths. In Israel, out of a population of 8.9 million there have been about 360,000 cases and 3,000 deaths.
"We were monitoring everything that was happening in Italy very closely," said Eden. "We asked how we could help."
Applying its IP-10 assay to make more educated decisions regarding corticosteroids therefore became an immediate goal for the company. "IP-10 has been studied for about 20 years, and it's a protein that goes up when you have viral infections," said Eden. "Since COVID-19 broke, there seems to be a high correlation between high levels of IP-10 and severe outcome," he said.
Given the outcome of the study presented at AACC, he also noted that it is possible for more clinicians to use its test to track IP-10 levels in COVID-19 patients, especially since the marker, along with CRP and TRAIL, was cleared as part of the MeMed BV test and MeMed Key platform.
Building on these results, MeMed is now running programs for two new tests in parallel. First, the company is developing MeMed COVID-19 Severity, which measures host-immune proteins coupled with machine learning. The product's aim is to aid in the early identification of whether a COVID-19 patient is likely to have a severe outcome or not, and, in doing so, help guide whether to escalate treatment. The second program is focused on real-time monitoring of IP-10 for tracking hyperinflammation, assessing the potential of MeMed's technology to aid in personalizing treatment using corticosteroids. Both tests run within minutes on the MeMed Key platform, Eden said.
"We have provided the technology as part of an early-access program to multiple centers, and they are starting to use that to more closely study the relationship between IP-10 and severity and IP-10 and corticosteroid treatment," said Eden. "We expect that these results will be reproduced by other groups, and this might become an important tool in terms of enabling more personalized treatment with corticosteroids."
While this work continues, MeMed is also exploring the use of TRAIL, another MeMed BV marker, for assessing the severity of disease in COVID-19 patients, Eden noted. "TRAIL goes up when you have a viral infection and goes down when you have a bacterial infection," he said. "It is extremely low when something bad is about to happen." He noted that TRAIL works quite well to determine which COVID-19 patients will develop severe disease.
"We are working to lock down the final COVID-19 signature," said Eden. He declined to provide a timeline for when a CE-IVD mark might be obtained. "The regulatory process is obviously something we don't have control over."
As with many diagnostics firms, MeMed's learning curve during the COVID-19 pandemic has been steep, Eden said. Decisions that used to take months were made during weeks. Studies that might have taken years were carried out in months. Yet that experience has left the firm well-positioned to meet future challenges, he said.
"We are creating very specific, COVID-19-tailored technologies that we can later use for the next pandemic, or the next non-pandemic situation, and can be broadly generalizable," said Eden.
Tahel Ilan-Ber, director of medical affairs at MeMed, agreed with Eden's forecast, noting the work the firm has done on IP-10 related to hyperinflammatory direction "opens up a lot of doors in clinical medicine," including in the oncology field.
"A lot of cancer patients will experience what is called a cytokine release syndrome, and IP-10 could potentially be an interesting marker to look at in those patients," said Ilan-Ber. "I think COVID-19 opened doors and gave us this wealth of data as to how IP-10 works in a very large, different, heterogenous subset of patients," she said. "There are a lot of next steps that can be explored with that data that we have collected."