Q&A: Inhaled mRNA therapy may help combat seasonal, emerging respiratory viruses

Key takeaways:

• An inhaled mRNA-based drug will be tested as a treatment and prophylaxis for respiratory viral infections.
• A phase 1 trial will assess the drug’s safety, tolerability, pharmacokinetics and target engagement.

The U.K. Medicines and Healthcare products Regulatory Agency recently approved a phase 1 study that will test an inhaled mRNA-based drug as a treatment and prophylaxis of respiratory viral infections, according to a press release.

In this trial, healthy participants will receive ETH47 (Ethris) through inhalation or nasal spray.

According to the manufacturer-issued release, two key elements of the product include its anticipated ability to create a mucosal innate immune defense response at virus entry points and stop viral replication.

Healio spoke with Carsten Rudolph, PhD, CEO of Ethris, to learn more about ETH47, the phase 1 clinical trial and the impact ETH47 will have on clinicians if study results are positive.

Healio: How prevalent are respiratory viral infections in Europe? Which are you hoping to address with this therapy?

Rudolph: As we enter the colder winter months, it’s important to recognize the seasonal increase of respiratory viruses especially for the vulnerable population of patients with an underlying respiratory disease, eg, asthma or COPD. Each year, influenza alone infects approximately 10% to 30% of Europe’s population, leading to hundreds of thousands of hospitalizations, and up to 70,000 deaths. In addition to influenza, ETH47 could potentially address respiratory syncytial virus (RSV), SARS-CoV-2 and other beta-coronavirus variants, and other seasonal and emerging respiratory viruses.

Healio: How does ETH47 work? How does it fight against seasonal respiratory virus infections?

Rudolph: ETH47 is a first-in-class mRNA-based product candidate that we are evaluating as an early intervention treatment and prophylaxis for seasonal and emerging respiratory viral infections.

ETH47 represents a differentiated approach by delivering Ethris’ proprietary type III interferon (IFN)-encoding mRNA via inhalation or nasal spray administration. Type III IFNs act as immunomodulators — they trigger an innate immune defense on the mucosal barriers where viruses enter and inhibit viral replication.

Consequently, ETH47 has the potential to combat a range of seasonal and emerging respiratory viruses, including those that exacerbate chronic respiratory diseases such as asthma and COPD. These include influenza, SARS-CoV-2, RSV, other beta-coronavirus variants and other seasonal and emerging respiratory viruses. Further, ETH47 has the potential to prevent severe disease following respiratory viral infections among patient populations at high risk such as immunocompromised patients or patients with chronic respiratory diseases including asthma.

In the current study, we’re starting with healthy volunteers and will later study influenza in healthy volunteers, but the drug has the potential to address a number of respiratory viruses.

Healio: What are the goals for the clinical trial?

Rudolph: The goal of the current trial is to evaluate ETH47’s safety, tolerability, pharmacokinetics and target engagement in healthy adults following nasal and inhaled administration of ETH47 and select the dose for a subsequent human virus challenge study.

Healio: If the results are positive, how will this product impact clinicians?

Rudolph: If ETH47 results are positive, it could be a game-changer for clinicians, representing a new tool in our arsenal to treat and prevent against a broad spectrum of respiratory virus infections, especially for patients who we know are most vulnerable to serious complications from respiratory illnesses.

Unlike existing antiviral therapeutics, ETH47 acts on the host, therefore it exerts broad activity that is independent of a specific virus or virus variant. As a nasal spray, ETH47 could potentially provide prophylaxis against a range of respiratory viruses by inducing host immunity. This approach would allow clinicians to reduce morbidity and mortality from respiratory virus infections, especially in those patients most vulnerable to infection.

Healio: How could ETH47 potentially help patients with asthma or COPD?

Rudolph: Despite the availability of biologics, unmet needs in successfully treating asthma exacerbations remain. We know that viral infections contribute to a substantial percentage (40% to 80%) of asthma exacerbations. By providing host immunity on mucosal barriers and inhibiting viral replication, ETH47 could provide broad protection against virus-driven exacerbations among vulnerable patient populations with chronic respiratory disease, including those with asthma and COPD. This could provide a powerful tool in limiting the frequency and severity of exacerbations, and ultimately reduce morbidity and mortality in these patients.

Reference:

• Ethris announces approval of phase I clinical study for ETH47, a first-in-class inhaled mRNA for respiratory viral infections. https://www.ethris.com/news/eth47-cta-approval/. Published Nov. 28, 2023. Accessed Nov. 28, 2023.