40-fold lower virus load compared to placebo on Day 2, at the peak of viral replication

Exposure-response relationship observed, with greater interferon lambda (IFNλ) exposure associated with greater antiviral and clinical effects, supporting dose optimization in the next study

Consistent clinical signals, with numerical reductions in lower respiratory symptoms, mild exacerbations, colds and rescue medication use compared to placebo

ETH47 was safe and well tolerated

Ethris GmbH, a clinical-stage biotechnology company pioneering next-generation RNA therapeutics and vaccines, announced positive topline results from its Phase 2a human rhinovirus (RV) challenge trial of ETH47 in adults with mild-to-moderate asthma (ISRCTN21576805). ETH47 is a nasally administered mRNA therapeutic candidate designed to induce local expression of interferon lambda (IFNλ), a key part of the innate immune response and antiviral mediator in the airway. Respiratory viral infections are a leading trigger of asthma exacerbations.

A single nasal dose of ETH47 was safe, well tolerated and showed antiviral activity, with consistent numerical trend improvements versus placebo in lower respiratory symptom score (LRSS), mild exacerbations, upper respiratory symptoms (Jackson Cold Score, JCS), cold prevention and rescue medication use. In an exploratory analysis, effects were consistently greater in participants with higher IFNλ exposure, indicating a clear exposure-response relationship.

“These results confirm ETH47’s mechanism of action and target engagement in asthma patients,” said Carsten Rudolph, PhD, Co-founder and Chief Executive Officer of Ethris. “We gave a single dose in this first patient study and still observed consistent signals on top of standard-of-care inhaled therapy. The clear relationship between exposure and effect will inform dose and regimen optimization in the next study. That trial will focus on asthma patients as well as those with chronic obstructive pulmonary disease (COPD), who also carry a high burden of virus-triggered exacerbations.”

Sebastian Johnston, Professor of Respiratory Medicine at Imperial College London and Director & Chief Medical Officer of VirTus Respiratory Research Ltd, added, “Viral infections remain a major driver of asthma exacerbations, yet today’s treatments don’t directly address the virus. It’s encouraging that an approach designed to boost the airway’s own antiviral defenses reduced viral replication and showed consistent signals across symptoms and rescue medication use in a rhinovirus challenge clinical model. These benefits were observed in patients already receiving maintenance inhaled corticosteroid therapy, supporting the potential of ETH47 as an add-on to standard of care. I look forward to seeing how these results develop in larger studies.”

Ethris is advancing the near-term development of ETH47 on several fronts. To further investigate the exposure-response relationship, the company plans a multiple-dose (Phase 1 MAD) study in patients with asthma and COPD, a Phase 2a rhinovirus challenge study in patients with COPD, as well as Phase 2b field studies in patients with asthma and COPD. In parallel, Ethris is developing a spray-dried dry powder formulation of ETH47 to support room-temperature stability and ease of use.

Key results

ETH47 was safe and well tolerated in asthma patients with no severe or serious adverse events, no systemic exposure, and no induction of anti-DMG-PEG antibodies after single nasal administration.

Nasal administration of ETH47 led to local expression of IFNλ in almost all dosed participants 6 hours after dosing, confirming target engagement.

ETH47 demonstrated antiviral activity, including a 40-fold reduction in virus load on day 2, the peak of viral replication; a subgroup analysis demonstrated a >100-fold reduction on days 2 and 3, as well as a 19-fold lower peak virus load in patients with higher IFNλ expression.  

ETH47 showed a consistent numerical trend towards improvements in the LRSS versus placebo, with a larger difference observed in the subgroup analysis of patients with higher IFNλ expression.

ETH47 showed a 14% reduction of peak LRSS and a 58% reduction of AUC compared to placebo; in the high IFNλ patient subset, a 46% reduction of peak LRSS was observed.

Lung function (spirometry) measures showed numerical trends for improvement versus placebo, particularly in the high IFNλ subset.

The proportion of participants with mild exacerbations (LRSS increase of ≥2 points) was 30% lower when defined over two consecutive days and 56% lower over three days.

JCS AUC was 53% lower and the proportion of participants developing a cold was 37% lower.

Respiratory treatment-emergent adverse events (TEAEs) related to the challenge were 73% lower and rescue medication use 65% lower in the ETH47 group compared to placebo.