A single nasal dose of ETH47, an investigational messenger RNA (mRNA) therapy encoding interferon lambda (IFNλ), reduced peak rhinovirus load 40-fold and showed a numerical trend toward lower respiratory symptoms vs placebo in adults with asthma, according to topline phase 2a data announced by Ethris on November 5, 2026.1
The primary endpoint, lower respiratory symptom score (LRSS), showed what Ethris described as a "consistent numerical trend" toward improvement, and the company did not report P values or CIs for any outcome.1 ETH47 is designed to induce local IFNλ expression in the airway to bolster innate antiviral defense, targeting virus-triggered exacerbations not directly addressed by current maintenance therapy.1 In a phase 1 study of 40 healthy volunteers, ETH47 produced dose-dependent IFNλ in nasal lining fluid with no systemic exposure.2
"Viral infections remain a major driver of asthma exacerbations, yet today's treatments don't directly address the virus," said Sebastian Johnston, MBBS, PhD, professor of respiratory medicine, Imperial College London, and director and chief medical officer, VirTus Respiratory Research.1
ETH47 effects on viral load and LRSS in the rhinovirus challenge model
The randomized, placebo-controlled trial (ISRCTN21576805) enrolled 50 adults aged 18 to 65 years with symptomatic asthma receiving inhaled corticosteroids, with or without a long-acting β2-agonist.1 Participants received a single nasal dose of ETH47 or placebo 1 day before challenge with rhinovirus A16 and were followed through day 42 at the Imperial Clinical Respiratory Research Unit and the Medicines Evaluation Unit in the UK.1 The release did not report the ETH47 dose or the number of participants in each arm.
According to Ethris, ETH47 reduced viral load 40-fold at day 2, the time of peak replication.1 Peak LRSS was 14% lower and LRSS area under the curve (AUC) was 58% lower with ETH47 vs placebo.1
Episodes meeting a mild exacerbation definition, an LRSS rise of at least 2 points, were 30% lower when sustained over 2 consecutive days and 56% lower over 3 days.1 Jackson Cold Score AUC was 53% lower, and the proportion of participants developing a cold was 37% lower.1
ETH47 safety and exploratory IFNλ exposure-response findings
Ethris reported no severe or serious adverse events (AEs), no systemic exposure, and no anti-DMG-PEG antibodies after the single nasal dose.1 Local IFNλ expression was detected in nearly all dosed participants at 6 hours.1
Challenge-related respiratory treatment-emergent AEs were 73% lower and rescue medication use was 65% lower with ETH47.1 Spirometry showed numerical improvements, according to the company.1
In an exploratory exposure-response analysis, effects were greater in participants with higher IFNλ exposure, including a more than 100-fold viral load reduction on days 2 and 3, a 19-fold lower peak viral load, and a 46% lower peak LRSS.1 The release did not state how many participants were in this subgroup or how higher exposure was defined.
"The clear relationship between exposure and effect will inform dose and regimen optimization in the next study," said Carsten Rudolph, PhD, cofounder and chief executive officer, Ethris.1
Ethris plans a multiple-ascending-dose phase 1 study in patients with asthma and chronic obstructive pulmonary disease (COPD), a phase 2a rhinovirus challenge study in COPD, and phase 2b field studies in both populations.1 The company is also developing a spray-dried dry powder formulation designed for room-temperature stability.1
References
Ethris. Ethris reports positive topline phase 2a data for nasal mRNA candidate ETH47 in asthma patients challenged with rhinovirus. Published November 5, 2026. Accessed November 5, 2026. https://www.globenewswire.com/news-release/2026/11/05/3396091/0/en/ethris-reports-positive-topline-phase-2a-data-for-nasal-mrna-candidate-eth47-in-asthma-patients-challenged-with-rhinovirus.html
Ethris. Ethris presents positive topline phase 1 data with mRNA lead candidate ETH47 for uncontrolled asthma. Published January 30, 2025. Accessed November 5, 2026. https://www.businesswire.com/news/home/20250130943965/en/Ethris-Presents-Positive-Topline-Phase-1-Data-with-mRNA-Lead-Candidate-ETH47-for-Uncontrolled-Asthma
