Ethris Reports Promising Phase 1 Data for mRNA Candidate ETH47 in Asthma
Ethris GmbH, a pioneering biotechnology company specializing in next-generation RNA therapeutics and vaccines, has unveiled encouraging topline data from the completed Phase 1 clinical trial of its lead mRNA candidate, ETH47. The trial assessed the safety, tolerability, and target engagement of ETH47 in healthy volunteers, marking a major step in the company’s effort to develop a transformative treatment for asthma exacerbations.
ETH47 is designed to address the upstream triggers of asthma exacerbations by encoding interferon lambda (IFNλ), a protein essential for viral immunity in the respiratory tract. The Phase 1 results not only validate Ethris’ targeted RNA therapeutic approach but also provide strong evidence for the potential of ETH47 to produce a downstream cascade of antiviral interferon-stimulated genes following nasal administration.
ETH47: Targeting Asthma at Its Root Cause
Asthma, a chronic inflammatory disease of the airways, is often triggered or worsened by respiratory infections, particularly those caused by rhinoviruses. These infections can initiate an inflammatory cascade that leads to asthma exacerbations, characterized by worsened symptoms such as shortness of breath, wheezing, and coughing. Currently, there are limited options to directly address the viral causes of asthma exacerbations, which is where ETH47 comes in.
ETH47 encodes the protein IFNλ, which plays a crucial role in the immune response to respiratory viruses. By stimulating the production of IFNλ in the respiratory tract, ETH47 has the potential to enhance the body’s antiviral defenses and reduce the severity of viral-induced asthma attacks. This innovative approach positions ETH47 as a potential breakthrough in asthma treatment, particularly for patients who suffer from frequent exacerbations triggered by respiratory infections.
Phase 1 Trial: Safety, Tolerability, and Target Engagement
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The Phase 1 clinical trial of ETH47 was designed to evaluate the safety, tolerability, and pharmacodynamic effects of the therapeutic following nasal administration. A total of 40 healthy participants were included in the study, which aimed to establish a clear understanding of how ETH47 behaves in the human body and whether it can induce the expected immune responses.
Safety and Tolerability
One of the primary objectives of the Phase 1 study was to assess the safety and tolerability of ETH47. The results were promising, with ETH47 being well tolerated at all tested dose levels. Importantly, no serious or severe adverse events were reported, and none of the participants had to discontinue the trial due to adverse effects. Additionally, the study demonstrated that there was no systemic bioavailability of the mRNA, the produced IFNλ protein, or the proprietary lipidoid compound used for delivery. This is significant as it minimizes the risk of off-target effects, ensuring that the therapeutic remains localized to the respiratory tract.
Dose-Dependent Target Engagement
ETH47 demonstrated clear, dose-dependent engagement with its target. The nasal lining fluid of participants showed a robust production of IFNλ, with levels exceeding those predicted to be therapeutically effective. Furthermore, the administration of ETH47 activated the mRNA expression of antiviral interferon-stimulated genes (ISGs) in nasal brush samples. These results confirm that ETH47 is able to elicit the intended pharmacodynamic effects, providing further validation for its proposed mechanism of action.
The activation of ISGs suggests that ETH47 may effectively stimulate an antiviral immune response in the respiratory tract, which could reduce the risk and severity of asthma exacerbations caused by viral infections. The ability to precisely target the nasal lining offers the advantage of localized treatment, minimizing systemic exposure and potential side effects.
Future Directions: Phase 2a Rhinovirus Challenge Study
Building on the encouraging Phase 1 results, Ethris is moving forward with plans for a Phase 2a clinical trial. The company has filed a Clinical Trial Application (CTA) for a rhinovirus challenge study, which is expected to begin in the second quarter of 2025. This study will evaluate the ability of ETH47 to reduce lower respiratory symptoms in asthma patients following rhinovirus infection.
In this Phase 2a trial, asthma patients will be exposed to rhinovirus, the most common viral trigger for asthma exacerbations. The study will assess whether treatment with ETH47 can prevent or mitigate the onset of exacerbations and reduce the severity of symptoms following infection. This trial is a crucial next step in determining the therapeutic potential of ETH47 in a real-world patient population, providing key insights into its efficacy and safety in asthma patients.
The results from the Phase 2a study could further solidify ETH47’s potential as a novel treatment option for asthma patients, particularly those who experience frequent exacerbations due to viral infections. If successful, ETH47 could become a game-changer in the management of asthma, offering a new approach to tackling one of the most common causes of flare-ups.
A New Era for RNA Therapeutics in Respiratory Diseases
Ethris’ Phase 1 data for ETH47 is a significant milestone not just for the company but also for the field of RNA therapeutics. RNA-based treatments have shown great promise in recent years, especially with the success of mRNA vaccines for COVID-19. Ethris is now expanding the potential applications of this technology to respiratory diseases such as asthma, with a novel approach that directly targets viral-induced exacerbations.
The ability to deliver RNA therapeutics directly to the respiratory tract represents a major breakthrough in the treatment of respiratory diseases. Through its proprietary SNIM® and SNaP® technology platforms, Ethris has developed an innovative delivery system that enables the efficient and localized delivery of mRNA therapies to the nose and lungs. This targeted delivery system enhances the therapeutic effects of ETH47 while minimizing the risk of systemic side effects, making it a promising candidate for treating asthma and other respiratory conditions.
Commitment to Transforming Asthma Care
Ethris is committed to advancing ETH47 through clinical development with the goal of transforming the care of asthma patients. The positive Phase 1 data provides a strong foundation for further clinical trials, and the company is excited about the potential of ETH47 to become a breakthrough treatment for asthma exacerbations caused by viral infections.
Dr. Thomas Langenickel, Chief Medical Officer at Ethris, expressed his enthusiasm for the future of ETH47, stating, “This significant milestone demonstrates the ability of our technology to deliver precisely designed mRNA candidates to the respiratory tract, facilitating the production of the encoded protein and engagement with the intended target. We look forward to advancing ETH47 into Phase 2 trials in 2025 and remain committed to exploring its potential to transform care for patients with asthma and broader respiratory conditions.”
With continued advancements in RNA-based therapies and the promising results from its clinical trials, Ethris is poised to make a lasting impact on the treatment of asthma and other respiratory diseases, bringing hope to patients who currently have limited options for managing their condition. The future looks bright for ETH47, and its potential to change the landscape of asthma treatment is just beginning to unfold.
About ETH47
ETH47 is Ethris’ first-in-class mRNA-based product candidate encoding interferon lambda (IFNλ) that was developed using the company’s Stabilized Non-Immunogenic mRNA (SNIM®RNA) platform, and uniquely designed to be administered locally to the respiratory tract through inhalation or nasal spray using Ethris’ proprietary Stabilized NanoParticle (SNaP®) LNP platform. ETH47 is meant 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.
About Uncontrolled Asthma
Uncontrolled asthma is a significant burden for patients, including 4.4 million moderate to severe asthma patients in the US alone. Approximately 80% of acute asthma attacks (exacerbations) are associated with virus infections. Asthma exacerbations cause excessive inflammation and mucus hyperproduction. They remain a significant burden for patients, leading to increased healthcare costs and decreased quality of life. ETH47’s innovative mechanism of action aims to prevent those exacerbations at their source, potentially improving outcomes for millions of patients worldwide.
About Ethris
Ethris, a clinical-stage biotechnology company, has paved a new path from genes to therapeutic proteins, using its proprietary RNA and lipidoid nanoparticle technology platforms to discover, design and develop innovative therapies. With more than a decade as an mRNA pioneer, Ethris is a global leader in delivering stabilized mRNAs directly to the respiratory system via optimized formulation and nebulization technologies. The company is rapidly advancing its mRNA pipeline of immuno-modulation, protein replacement therapies, and differentiated vaccines, with the ultimate goal of improving patients’ lives.
For more information, visit www.ethris.com
