Last summer, shares of Synairgen skyrocketed 300% on a study showing its inhaled form of interferon beta-1a being developed to treat COVID-19 lessened the chance that patients would progress to a severe form of the virus.
But there was a major shadow hanging 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. That sparked fears that interferon-based treatments would ultimately fail in the treatment of the coronavirus.
Now, researchers led by the University of Southampton, which is collaborating with Synairgen in the development of its drug, have discovered that interferon raises levels of a short form of ACE2 that doesn’t allow SARS-CoV-2 to enter cells. In fact, it may have a protective effect, the team reported in the journal Nature Genetics.
The short form of ACE2 that the U.K. researchers discovered lacks a particular 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 to SARS-CoV-2—the researchers believe 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 [realized] that may be protective against SARS-CoV-2 in the airways rather than an entry site for infection,” said University of Southampton professor Jane Lucas, M.D., Ph.D., in a statement. Two of the study’s co-authors, Donna Davies, Ph.D., and Ratko Djukanovic, M.D., are co-founders and shareholders of Synairgen, which was spun out of the university.
Investors applauded Synairgen when preliminary data from its 101-patient trial showed that its interferon drug, SNG001, lowered the risk of progression to severe COVID-19 by 79% over placebo. An update to those results lifted the company’s shares another 30% in November, when the company reported that 75% of patients taking SNG001 showed a clinical improvement at Day 15/16, as measured by a key World Health Organization scale.
The discovery of short ACE2 could have implications for more than just Synairgen, the authors argued in the new study. The ability for researchers to distinguish between the two versions of the protein could spark ideas for more sophisticated coronavirus treatments, they said.
The University of Southampton-led team is now planning further studies to investigate the implications of short ACE2 on the management of COVID-19.
In December, Synairgen announced that it had started a phase 3 trial of SNG001 in the U.K. and that the FDA awarded fast-track status to the drug and cleared it for U.S. studies.