LONDON – Oncimmune Holdings plc has won government funding to apply its autoantibody biomarker technology to develop a COVID-19 immune profiling tool for triaging patients and predicting response to therapies and vaccines in development against the virus.

The company will cross reference serum samples from 3,000 COVID-19 patients against its library of 800 SARS-CoV-2 related antigens and peptides to identify autoantibodies that characterize the range of immune responses to the infection. Access to medical records will enable Oncimmune to determine which of these are biomarkers of specific complications and of severity of disease.

This is not about diagnosing COVID-19 itself, but predicting the likely course of the infection, said Adam Hill, CEO of Oncimmune. “As the COVID-19 pandemic moves from the immediate challenge of developing novel diagnostics, we are now entering a phase where the world needs to better understand this disease in infected patients, in order to optimize therapeutic outcomes,” Hill added.

The test Oncimmune is developing is intended as a research tool for use in clinical trials. There are more than 1,200 drugs in development to treat COVID-19, and one of the key issues to be addressed in assessing their effectiveness – and ensuring the right patients are treated at the right time – is the widely varying severity of disease and the unpredictability of its course, with symptoms ranging from pneumonia, to cardiovascular disease, to kidney failure and neurological deficits.

After analyzing the autoantibody profile of COVID-19 patients, Oncimmune will stratify these into three categories of response to the virus: mild, moderate and severe. That data will form the basis of a panel of autoantibodies that can be used to predict disease severity and response to therapy.

Among other aspects, Hill said it will be possible to identify patients at risk of cytokine release syndrome and to detect cross-reactivity with other coronaviruses.

Evidence has steadily accumulated that the most severe cases of COVID-19 are due to the viral infection triggering an autoimmune response. As one example of the potential value of being able to systematically detect autoantibodies that cause this to happen, in September an international team of scientists reported that 101 of 987 patients with life-threatening COVID-19 pneumonia had autoantibodies that neutralized type 1 interferons.

A subsequent experiment showed that these autoantibodies neutralized the ability of type 1 interferons to block SARS-CoV-2 infection in vitro.

The autoantibodies detected in severely affected patients were not found in 633 individuals with asymptomatic or mild COVID-19 infections and were present only in four of 1,227 healthy people.

Similarly, research carried out at the Charité Hospital in Berlin, found a high frequency of autoantibodies in the cerebrospinal fluid of COVID-19 patients with neurological symptoms.

Studies elsewhere have found different autoantibodies that are associated with thromboembolism and other complications of COVID-19.

Nottingham, U.K.-based Oncimmune has its roots in using autoantibody markers to screen people at risk of developing cancer. These are smokers in the case of lung cancer, and patients with hepatitis B or C, cirrhosis or nonalcoholic steatohepatitis in the case of liver cancer.

Its panels also are used in immune system profiling in clinical trials of cancer immunotherapies, where the company has discovered autoantibodies that are predictive of immune-related adverse events and likely responders to treatment. In addition, the tests are used in clinical trials of autoimmune disease drugs, with the Roche AG unit Genentech recently signing up Oncimmune to assess responses in a lupus study.

Hill told BioWorld that Oncimmune decided to stand back in March when there was a rush to develop COVID-19 diagnostics, because other companies have more suitable technologies. “We knew our peers could do it,” he said.

But in the second phase the challenge has moved on from developing diagnostics to better understanding how to treat COVID-19. Here, Oncimmune has a “unique contribution” to make. “We are experts in a single biomarker class – autoantibodies – as we have demonstrated in cancer,” Hill said. “There are very few others with this expertise.”

While earlier academic research has identified a number of relevant autoantibodies, these have emerged from small patient cohorts. Oncimmune will bring the power of its proven bioinformatics platform to thoroughly profile the autoantibody fingerprint of COVID-19 across 3,000 patients.

The company will access these consented samples and associated medical records through the Medicines Discovery Catapult (MDC), a government-funded national center that provides tools, equipment and expertise to SMEs for the discovery and early development of drugs.

During the pandemic, MDC has taken on the role of coordinating a national network of COVID-19 testing labs. Oncimmune now can draw on MDC’s access to nationwide biobanks, said Chris Molloy, CEO of MCD. “[We will] also be providing expertise in navigating the complex brokering and procurement process for obtaining samples,” Molloy said.

Given this access, Hill expects to be able to put a panel into the hands of academic partners for validation in a couple of months, with a commercial product available in five to six months. Oncimmune already is in discussions with pharma companies about applying the test in clinical studies.

As another output of the project, MDC and Oncimmune will build an extensive, severity-based biorepository and associated registry of clinical data. Over time, Oncimmune intends to apply this to other infectious diseases.

The project will broaden “collective intelligence” on how SARS-CoV-2 exhibits in different patients, said Molloy. That will “lead to stratified and then more tailored therapeutics, according to the varying need,” he said.

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