Acute asthma

ETH47 resulted in a dose-dependent increase in target protein expression in the nasal cavity Nasal administration of ETH47 was generally safe and well-tolerated, with no severe adverse events or drug-related adverse events of clinical relevance Full data readout expected in the third quarter of 2024 Following the Phase 1 study, Ethris plans to advance ETH47 for patients with uncontrolled asthma MUNICH--(BUSINESS WIRE)-- Ethris GmbH, a leading biotechnology company pioneering next-generation RNA therapeutics and vaccines, announced today preliminary positive data from its Phase 1 dose escalation clinical trial evaluating the safety, tolerability, and target engagement of lead mRNA candidate ETH47 encoding interferon lambda (IFNλ), in healthy participants. IFNλ has a key role in viral immunity in the respiratory tract. The data indicates that ETH47, administered nasally, was generally safe and well-tolerated, with no severe adverse events or drug-related adverse events of clinical relevance across all dose levels. Initial results also show target engagement and suggest no systemic biodistribution of ETH47. A full data readout is planned for the third quarter of 2024. “These preliminary results are highly encouraging as they provide the first clinical validation of our innovative SNIM®RNA platform and SNaP LNP technology, which allows localized administration directly at virus entry sites and supports the potential of ETH47 as a broadly protective antiviral candidate for respiratory diseases,” said Dr. Thomas Langenickel, Chief Medical Officer of Ethris. “We look forward to sharing comprehensive Phase 1 data later this year as we continue evaluating ETH47 for the treatment of uncontrolled asthma. Furthermore, successful nasal delivery opens up mRNA therapeutics as a new potential modality to treat diseases of the respiratory tract.” 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. Susceptibility to viral infections in asthma is associated with dysregulation of IFNλ in asthmatics. The promising safety and tolerability pro ETH47 observed in the clinical trial, along with its potential to enhance mucosal immune defense and correct low IFNλ levels, could represent a significant advancement in the treatment landscape for uncontrolled asthma. Professor Eric Bateman, MD, Key Opinion Leader and Member of the Board of the Global Initiative for Asthma (GINA) said, “Given the strong association between viral infections, particular with rhinovirus, and asthma exacerbations, Ethris’ mRNA product candidate ETH47, with its unique mechanism of action has the potential to fill a significant gap in the asthma treatment paradigm.” The Phase 1 trial is a randomized, placebo-controlled, double-blind, single-ascending dose design to evaluate the safety and tolerability of ETH47 in healthy participants. ETH47, Ethris’ lead candidate developed using the company’s proprietary technologies was designed to address the unique challenges of delivering mRNA to the lungs, including physiological barriers, low transfection efficiency and delivery vehicle-induced inflammatory responses. This initial data assessment indicates proof of principle with ETH47 and supports its continued development toward human viral challenge studies, including a rhinovirus challenge study in mild asthmatics. 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 platform 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 optimised formulation and nebulisation 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 . View source version on businesswire.com: Contacts For Ethris, please contact: Dr. Philipp Schreppel +49 89 244 153 042 schreppel@ethris.com Source: Ethris GmbH View this news release online at:

Ethris has received $5 million in funding from The Bill & Melinda Gates Foundation to support preparations for ETH47’s Phase 2a study including CMC manufacturing processes ETH47 is Ethris' first-in-class inhaled mRNA-based candidate with the potential to address a broad spectrum of chronic respiratory diseases and emerging respiratory infections and is currently being evaluated in a Phase 1 clinical trial MUNICH--(BUSINESS WIRE)-- Ethris GmbH, a leading biotechnology company pioneering next-generation RNA therapeutics and vaccines, announced today that it has received funding from the Gates Foundation to support the advancement of the company’s lead mRNA-based product candidate, ETH47. This funding of $5 million includes an equity investment component expected to close at the company’s next financing round. The new capital will enable the company to rapidly reach Phase 2 readiness and build out the CMC manufacturing process for the next clinical trial. “Ethris’ lead mRNA-based product candidate ETH47 was designed to have broad antiviral capabilities, placing it in a distinct position to address a range of virus-induced respiratory infections and chronic respiratory diseases. Ethris, supported by the new funding from the Gates Foundation, will accelerate its clinical development, initially targeting asthma exacerbations, an indication with a high unmet medical need where approximately 80% of acute asthma attacks are associated with virus infections. We are grateful for the foundation's support in our mission to combat the global burden of current and emerging respiratory infections by harnessing the full scope of ETH47's virus-agnostic potential,” said Dr. Carsten Rudolph, CEO of Ethris. A Phase 1 study is ongoing with Ethris’ inhaled mRNA candidate ETH47 to evaluate safety, tolerability, and target engagement in healthy participants. A full data readout is planned for the third quarter of 2024. The ETH47 program is also supported by the BayTherapie2020 program, an initiative of the German state of Bavaria. About ETH47 ETH47 is Ethris’ first-in-class mRNA-based product candidate encoding type III interferon (IFN) that was developed using the company’s Stabilized Non-Immunogenic mRNA (SNIM®RNA) platform, and uniquely designed to be administered locally to the lung 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 address virus-driven exacerbation of chronic respiratory diseases like asthma as well as seasonal and emerging respiratory virus infections. About Ethris Ethris, a clinical stage biotech company, has paved a new path from genes to therapeutic proteins, using its proprietary RNA and lipidoid nanoparticle technology platform 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 optimised formulation and nebulisation 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 View source version on businesswire.com: Contacts For Ethris, please contact: Dr. Philipp Schreppel +49 89 244 153 042 schreppel@ethris.com Source: Ethris GmbH View this news release online at:

Understanding how mucus changes, and what it changes in response to, can help diagnose illnesses and develop treatments. Researchers develop a system to grow mucus-producing intestinal cells and study the characteristics of the mucus in different conditions. The process involves growing a layer of intestinal cells on a laboratory plate exposed to air. These cells produce a layer of mucus that the researchers can easily access for testing. Using a magnetic wire, they can measure the consistency of the mucus without affecting its properties, and the platform can explore the effects of pathogens and help develop medications to combat them. As much as we might not want to think about it, mucus is everywhere in our bodies. It coats our airways and our digestive systems and serves as a first line of defense against pathogens, a habitat for our microbiomes, and a conveyor belt for our insides to keep everything moving smoothly. The front-line role of mucus means it is often the site of the first symptoms of infection or disease. Understanding how mucus changes, and what it changes in response to, can help diagnose illnesses and develop treatments. Designing a study to measure the physical properties of mucus, however, is nothing to sneeze at. In APL Bioengineering, by AIP Publishing, researchers from Stanford University developed a system to grow mucus-producing intestinal cells and study the characteristics of the mucus in different conditions. Their platform can explore the effects of pathogens and help develop medications to combat them. Currently, researchers looking to study intestinal mucus commonly use lab animals for their experiments. These animals would be given a pathogen or drug, and researchers would surgically remove the intestinal mucus to study the effects. This process is expensive, complex, and most importantly, deeply unpleasant for the animals. In addition, the researchers say, the act of removing the mucus is likely to change how it behaves, making any obtained results unreliable. "When people collect the mucus from the animal, they'll pipette it off or scrape it off," said author Margaret Braunreuther. "But what we found is that when we pipette the mucus layer from our cell culture, we see a very different behavior after that action. We think that the act of pipetting or scraping this very soft polymeric solution is resulting in more liquidlike behavior." The alternative process developed by the Stanford team involves growing a layer of intestinal cells on a laboratory plate exposed to air. These cells produce a layer of mucus that the researchers can easily access for testing. Using a magnetic wire, they could measure the consistency of the mucus without affecting its properties. "We put this wire on the mucus layer of the live cells, and then we applied a magnetic force to this probe and measured its displacement," said Braunreuther. "From the relationship between the applied force and the magnetic wire displacement, we can then calculate the rheological properties of the material." Using this setup, the team simulated an infection by a parasitic worm to observe how the mucus responds. This study serves as both a practical demonstration of their platform and a glimpse into how these infections could be treated. The group is now exploring even more ways to leverage their approach for better mucus health. "We have a parallel effort to study airway mucus, looking at conditions such as cystic fibrosis and acute asthma," said author Gerald Fuller. "We also started a collaboration with a group in Berlin to develop drugs to restore a healthy mucus response."