Ethris GmbH has dosed the first patient in a Phase 2a clinical trial investigating ETH47, the company's lead mRNA-based antiviral candidate for asthma. The study will assess the ability of intranasal ETH47 to reduce asthma-related symptoms following a rhinovirus challenge in adults with asthma.
ETH47 encodes interferon lambda (IFNλ), a protein crucial for viral immunity in the airways, and is designed to target viral triggers of asthma exacerbations, one of the most common causes of acute symptoms in patients with asthma.
Strong Phase 1 Safety Profile Supports Advancement
The Phase 2a clinical trial (ISRCTN21576805) builds on positive data from the Phase 1 trial (ISRCTN15391202) where ETH47 demonstrated favorable safety and tolerability at all tested doses in healthy volunteers. The Phase 1 trial confirmed targeted activity in the respiratory tract, with robust local induction of IFNλ and activation of antiviral genes, with no systemic exposure to mRNA, IFNλ, or the lipidoid nanoparticle, thereby minimizing the risk of off-target effects.
"Dosing the first patient in our Phase 2a trial for ETH47 marks a defining moment for Ethris, as we advance our lead candidate further into clinical development and continue to validate the potential of Ethris' innovative platform," said Dr. Thomas Langenickel, Chief Medical Officer of Ethris.
Novel Mechanism Targets Viral Triggers Upstream
ETH47 represents a departure from conventional asthma therapies that focus on managing symptoms or reducing inflammation. The mRNA therapy is designed to directly strengthen the body's antiviral defenses in the airways by targeting viral infections upstream.
"ETH47 stands out as a highly promising candidate with a novel mechanism of action designed to directly strengthen the body's antiviral defenses in the airways. By targeting viral infections upstream, ETH47 has the potential to fundamentally change the way asthma is managed and reduce the burden of acute attacks," Langenickel explained.
Sebastian Johnston, Professor of Respiratory Medicine at Imperial College London and Director & Chief Medical Officer of VirTus Respiratory Research Ltd, emphasized the unmet medical need. "After more than three decades investigating the role of respiratory viruses in asthma, it is clear that we need new approaches to address the underlying triggers of asthma exacerbations. Most therapies today focus on managing symptoms or reducing inflammation. There remains a significant unmet need for interventions that directly target viral triggers and boost antiviral defenses in the airways."
Phase 2a Trial Design and Endpoints
The Phase 2a clinical trial is a randomized, double-blind, placebo-controlled study being conducted by VirTus Respiratory Research Ltd at St. Mary's Hospital, London, UK. The study will enroll 50 adult patients with asthma who will undergo a rhinovirus challenge and will then be equally randomized to receive either ETH47 or placebo.
The primary endpoint will evaluate the impact of ETH47 on respiratory symptoms, as measured by the Lower Respiratory Symptoms Score (LRSS) – a commonly used, standardized survey completed by participants twice daily. The primary objective is to assess whether ETH47 can help restore respiratory health in asthmatic patients, bringing them closer to the level observed in healthy individuals.
Technology Platform and Future Development
ETH47 was developed using Ethris' Stabilized Non-Immunogenic mRNA (SNIMRNA) platform and is uniquely designed to be administered locally to the respiratory tract through inhalation or nasal spray using the company's proprietary Stabilized NanoParticle (SNaP) LNP platform. The therapy is designed to induce a mucosal innate immune defense response at virus entry sites as well as inhibit viral replication.
ETH47's versatile, virus- and mutation-independent mode of action has the potential to broadly address seasonal and emerging respiratory virus infections, including virus-driven exacerbation of chronic respiratory diseases such as asthma.
After the successful completion of this trial, Ethris plans to progress ETH47 into a broader Phase 2b study, further evaluating its potential to reduce asthma exacerbations and improve patient outcomes.
