Last summer, Synairgen’s stock skyrocketed by 300% in a study showing that the inhaled form of interferon beta-1a developed to treat COVID-19 reduced the likelihood of patients passing on to a severe form of the virus .
But there was a big shadow over the results: interferon is known to increase levels of the cell surface protein ACE2, which serves as the entry point for SARS-CoV-2, the virus that causes COVID-19. This led to fears that interferon-based treatments would ultimately fail to treat the coronavirus.
Now, researchers led by the University of Southampton, who are working with Synairgen in the development of its drug, have discovered that interferon increases the levels of a short form of ACE2 that prevents SARS-CoV-2 from entering the cells. It may even have a protective effect, the team reported in the journal Nature Genetics.
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The short form of ACE2 discovered by the British researchers lacks a specific binding site that SARS-CoV-2 needs to enter healthy cells. Because this short version of the protein rises in response to interferons – but not SARS-CoV-2 – the researchers think it is somehow involved in the body’s natural immune response to viruses.
“We were excited to discover a new form of ACE2, and became even more interested when we did [realized] that could be protective against SARS-CoV-2 in the respiratory tract rather than an entry point for infection, ”said Professor Jane Lucas, MD, Ph.D. from the University of Southampton, in a statement. Two of the study’s co-authors, Donna Davies, Ph.D., and Ratko Djukanovic, MD, are co-founders and shareholders of Synairgen, which grew out of the university.
Investors applauded Synairgen when preliminary data from its 101-patient study showed that the interferon drug SNG001 reduced the risk of progression to severe COVID-19 by 79% over placebo. An update to those results increased the company’s stock by an additional 30% in November, when the company reported that 75% of patients using SNG001 showed clinical improvement on day 15/16, as measured by a major scale of the World Health Organisation.
The discovery of short ACE2 could affect more than just Synairgen, the authors argued in the new study. Researchers’ ability to distinguish between the two versions of the protein could spark ideas for more advanced coronavirus treatments, they said.
The University of Southampton-led team is now planning further studies to investigate the implications of short ACE2 for the management of COVID-19.
In December, Synairgen announced that it had started a phase 3 study of SNG001 in the UK and that the FDA had granted fast-track status to the drug and approved it for US studies.