INNA-051 is a first-in-class broad-spectrum innate immunomodulator that significantly impacts on the course of a respiratory flu infection
In a press release by the manufacturer, Ena Respiratory, a phase 2a clinical study of INNA-051, when delivered intra-nasally, significantly reduced the duration of flu infection and led to a dose-related trend towards a reduction in symptom duration.
The body’s innate immune system is designed to provide the first line of defence against microbial pathogens via the use of Toll-like receptors (TLR), i.e., microbe recognition receptors present on the surface of cells. There are several types of TLR produced by cells and evidence suggests that three, TLR2, TLR1 and TLR6 (together with an unknown co-receptor), interact with a large variety of microbial ligands. Moreover, any alteration or absence of TLR2 function, correlates with a reduced immune protection against pathogens that possess TLR2 ligands. Given the important role of TLRs in the earliest phase of a host’s immune response, the development of TLR agonists is a promising therapeutic strategy. In fact, work from 2012 showed that the use of a TLR-2 agonist in mice offered protection against influenza.
INNA-051 is a first-in-class, TLR2/6 agonist and was originally tested as a treatment for COVID-19. In earlier work with ferrets infected with the virus, intra-nasal administration of the INNA-51 significantly reduced viral RNA in both the nose and throat by up to 96%. However, with the introduction of COVID-19 vaccines, there was less need for such treatments but the company continued to explore the potential of the drug in the treatment of other viruses and have found that it induced innate immune priming in response to rhinovirus infection.
INNA-051 and influenza
The press release provides top-line data from a randomised trial in which 123 adults were randomised to either two doses of INNA-051 (low and high) or placebo and then challenged with a large dose of H3N2 influenza A virus. Unfortunately, the company reported that interpreting the results were complicated by the lower than expected infection rates in the placebo arm and a larger than predicted prior immunity across all groups. Nevertheless, in post hoc analysis, it was found that participants treated with the higher dose of INNA-051 had a statistically significant shorter duration of infection, as well as a non-significant reduction in the duration of symptoms.
Although INNA-051 is not currently licensed for use outside of clinical trials, the evidence appears to suggest that a prophylactic approach, based on boosting the innate immune system in the nose could be of clinical benefit for those exposed to respiratory viruses.