Rhinovirus infection

Pre-clinical studies for intranasal RIG-101, a first in class RIG-I agonist, demonstrate potent local innate immune stimulation and pan-viral activity against human rhinovirus, influenza and RSV infections. RIG-101 is in development for the pan-viral prevention of RNA virus transmission in asthma patients to inhibit seasonal exacerbations. RIG-101 intranasal (IN) is on track to enter first in human trials in mid-2025. FARMINGTON, Conn., Sept. 09, 2024 (GLOBE NEWSWIRE) -- RIGImmune Inc., a biopharmaceutical research company developing a new class of RNA therapeutics, today announced three oral presentations demonstrating the viral prevention effects of intranasal RIG-101, their lead product development candidate, at the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria. The three oral presentations highlight the impressive results from pre-clinical studies demonstrating that the company’s first in class RIG-I agonist has the ability to rapidly and substantially reduce viral loads by inducing innate immune responses when delivered directly to the respiratory tract. Intranasal RIG-101 is formulated with the company’s novel NEED™ (Nano-Emulsion Enhanced Delivery) platform, a complex designed to deliver a wide range of RNA payloads without the use of lipid nanoparticle encapsulation. The results from these studies and other company experiments demonstrate the potential for RIG-101 to inhibit the transmission of an RNA virus from an infected person to a non-infected individual and could significantly reduce viral infection-related respiratory complications in at-risk patient populations, including the immune-compromised and those with chronic respiratory diseases such as asthma and COPD. “While the nose is an obvious passageway to leverage for infectious disease prevention, inefficient uptake of previous intranasal RNA therapeutics by the nasal epithelial cells has been a barrier to infection prevention,” said the senior author of all three studies, Kazuhiro Ito, Ph.D., principal research fellow of Respiratory Molecular Pharmacology in Genomic and Environmental Medicine Section in National Heart and Lung Institute (NHLI) in the Faculty of Medicine of Imperial College London, and vice president of biology at RIGImmune. “Our study results show that RIG-101, formulated with our proprietary NEED™ technology can induce efficient uptake into the epithelium and is uniquely optimized to activate the innate immune system to fight viral respiratory diseases with local intranasal administration. The NEED™ platform allows us to effectively deliver RNA therapeutic payloads directly to the upper and lower respiratory tract and avoid the use of LNPs, which can damage the respiratory system when given locally.” “We’re excited with the study results presented by Dr. Ito at the 2024 European Respiratory Society. The data from these studies and other work conducted by RIGImmune demonstrate potent pan-viral activity for RIG-101 formulated with our NEED™ technology platform,” said Susan Sobolov, Ph.D., president of RIGImmune. “We have designed NEED™ to enable targeted delivery of a broad range of RNA therapeutics that aligns with the body’s own biological pathways, thereby minimizing toxicity risks. By validating RIG-101 in our NEEDTM formulation technology in these pre-clinical systems that have demonstrated translation to the clinical setting, we are further committed to advancing RIG-101 intranasal to our first-in-human studies in mid-2025.” Description of RIG-101 Study Results Presented at European Respiratory Society Sept 7th – 11th: Title: Pan-antiviral effects of RIG-I agonists (RIG-101) against respiratory syncytial virus and human rhinovirus in nasal epithelium in vitro and mice in vivoOverview Prophylactic intranasal RIG-101 demonstrates potent antiviral activities against human rhinovirus (HRV) and respiratory syncytial virus (RSV), potentially preventing respiratory virus-induced asthma and similar respiratory disorders. Details This study, led by Leah Daly of Imperial College London, showed that RIG-101 was able to induce interferon signaling in fully differentiated human nasal epithelium when delivered the day-prior and day-of viral exposure at apical site in air-liquid interface (ALI).In vivo testing demonstrated statistically significant reductions in HRV1B viral load and neutrophilia compared to pleconaril. Intranasal RIG-101 NEED™ (2mg/ml) was administered 4 and 1 day prior to exposure, with evaluations one day following exposure, and oral pleconaril (200 mg/kg) was administered up to one day prior to viral exposure. Title: Effects of an anti-viral interferon booster, RIG-I agonist (RIG-101), on influenza infection in vitro and in vivo Overview Prophylactic intranasal RIG-101 offers signs of viral prevention efficacy against influenza infection, and demonstrated increased immune response Details In an oral presentation, researchers, led by Hugo Ombredane, Ph.D. student at Imperial College London, demonstrated that delivering intranasal RIG-101 prophylactically offered significant induction of type I/III interferon signalling and potent antiviral effects against influenza with antiviral effect comparable or superior to oseltamivir in both in vivo and in vitro models.RIG-101 significantly reduced viral load in vivo and in vitro, as well as strongly induced CXCL10, a surrogate marker of antiviral interferon production in vitro and prevented neutrophil accumulation, a sign of inflammation, in the nasal lavage in vivo.For this study, RIG-101 was delivered 4 days and 1 day prior to viral exposure in vitro and 3 days, 1 day and 1 hour prior to viral exposure in vivo, and evaluations were conducted 48 hours post-viral exposure in vitro and 1-5 days post-viral exposure in vivo. Title: Adjutancy effects of a RIG-I agonist (RIG101) on H1N1 HA antigen intranasally vaccinated mice and human nasal epithelium/PBMCs co-culture Overview Adding prophylactic intranasal RIG-101 to the recombinant seasonal influenza hemagglutinin (rHA) vaccine more effectively reduced viral load and inflammation associated with the H1N1 HA subtype of influenza. Details RIG-101 combined with the recombinant seasonal influenza hemagglutinin (rHA) vaccine not only reduced viral load and inflammation associated with H1N1 HA, but also prevented virus-induced body weight loss compared with both HA antigen vaccination alone and the HA antigen vaccine plus CPG-ODN vaccine addition in a preclinical study led by Dr. Shyreen Hassibi of Imperial College London.An in vitro study involved peripheral blood mononuclear cells (PBMCs), which may include lymphocytes monocytes, natural killer cells (NK cells) and dendritic cells, cultured from the nasal cavity, and found that RIG-101 combined with H1N1 HA vaccination clearly enhanced the body’s natural production of immunogobulin M (IgM) antibodies, the first line of defence of the adaptive immune system, compared with H1N1 HA vaccination alone. Presentation e-posters may be accessed on the Company Presentations page under the Corporate News section of the RIGImmune website as well as the European Respiratory Society Congress website. About RIGImmune RIGImmune is a biopharmaceutical research company focused on the development of innovative RNA therapeutics to prevent or treat serious respiratory diseases with high unmet clinical needs. The company was co-founded by the prominent scientists, Drs. Akiko Iwasaki and Anna Pyle from Yale University, to advance the development of a novel class of oligonucleotides called stem-loop RNA therapeutics or “SLRs.” These SLRs were discovered in Dr. Pyle’s laboratory at Yale. In 2022, RIGImmune combined with a UK-based development company named SubIntro to develop non-lipid nanoparticle formulations for the effective delivery of a broad set of nucleic acid payloads directly to the respiratory tract. SubIntro was co-founded by the prominent research scientists and successful respiratory drug and formulation developers, Drs. Garth Rapeport, Kazuhiro Ito, and Jag Shur. RIGImmune’s lead product development candidate is RIG-101, a stem loop RNA therapeutic that targets the RIG-I pathway to enhance the innate immune response against viral respiratory diseases. RIGImmune’s second product development candidate is RIG-301, an mRNA formulated with the NEED™ technology, targeting the CFTR mutation in cystic fibrosis patients. RIGImmune has internally developed a proprietary nano-emulsion delivery technology platform named NEED™ to effectively deliver RNA compounds without the need for lipid nanoparticle encapsulation. About RIG-101RIG-101 is a potent agonist of RIG-I, which results in the induction of the interferon pathway in the respiratory epithelium when administered locally. RIG-101 is formulated with the company’s NEED™ (Nano-Emulsion Enhanced Delivery) technology and will enter a Phase 1/2a clinical program in mid-2025 for the prevention of seasonal viral exacerbations of asthma. RIGImmune is developing RIG-101 for delivery by multiple routes of administration, including intranasal (IN), a solution for inhalation for lower respiratory tract delivery, intra-muscular, and subcutaneous. In the first clinical program for RIG-101, the product development candidate will be administered by the intranasal route for delivery directly to nasal epithelium. Extensive prior research by noted investigators has shown delivery directly to the nasal epithelium can be critical for comprehensive protection from a broad range of respiratory viruses. About NEED™ (Nano-Emulsion Enhanced Delivery)NEED™ is a non-lipid nanoparticle (LNP) formulation platform developed by RIGImmune to effectively deliver RNA directly to the respiratory mucosa and avoid the limitations and potential toxicity concerns associated with LNP delivery systems. The principal novelty of the NEED™ formulation technology is the ability to transform surfactants and natural fatty acids into a proprietary nano-emulsion complex that encapsulates a nucleic acid and protects the payload while controlling particle size and charge, and facilitates intracellular uptake when administered directly to the respiratory epithelium. The first clinical presentation of the NEED™ delivery platform will be an aqueous formulation for the intranasal delivery of RIG-101 to the upper respiratory tract. RIGImmune has shown that NEED™ can also be administered by multiple routes, including a solution for inhalation to the lower respiratory tract, subcutaneous, and intra-muscular. Initial research conducted by the company has shown the NEED™ delivery platform technology could be compatible and effective with a diverse range of RNA and DNA therapeutics. Media Contact:Caren Begun TellMed Strategies908-947-0500 x723Caren.begun@tmstrat.com

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:

LUND, Sweden, Nov. 7, 2023 /PRNewswire/ -- CEO Comment "The positive research results presented during the quarter contribute to us trusting our financial goals for 2026.. Sales in our own markets Sweden, UK and Iceland are doing very well, with a market share in Sweden that is one of the highest for several years. We are discussing constructive ways forward together with our current partners since sales outside of our own markets have been lower than expected. I am very pleased to see how the recent research findings have sparked an interest for Enzymatica and our technology from many different stakeholders around the worl," said Claus Egstrand, CEO, Enzymatica. Significant events during the quarter In August, the Medical University of Innsbruck, Austria, presented the findings from an in vitro study that explored the effect of ColdZyme on human cells infected with the influenza virus. The study shows that ColdZyme disrupts the infection cycle and restricts the spread of the virus to more cells. When ColdZyme was applied to infected cells, the viral load decreased by 99% compared with cells treated solely with saline solution. The researchers believe that ColdZyme would have a similar effect on other respiratory viruses. In September, the University of Kent (United Kingdom) presented the initial findings from an ongoing in vivo study where athletes use ColdZyme or a placebo for symptoms of upper respiratory tract infections. The results show that ColdZyme statistically significantly reduces the quantity of rhinovirus, the most common cause of the common cold. Moreover, individuals who used ColdZyme demonstrated statistically significantly fewer sore throat symptoms compared with individuals who used a placebo. The study, which is designed as a prospective, placebo-controlled, double-blind, and randomized trial, will be completed in the first half of 2024. Significant events after the quarter No significant events have been reported after the quarter. Other events during and after the quarter An abstract regarding the ongoing study at the University of Kent has been accepted for presentation at the 7th International Olympic Committee Conference on the Prevention Injury and Illness in Sport. The abstract will be also published in the British Journal of Sports Medicine. The company is engaged in discussions with its partners regarding the launch in China and Japan. In the light of the recent research findings, optimal product claims and classifications are being evaluated. The expansion of production capacity at the facility in Reykjavik has continued during the year and the facility is now ready to handle an extensive increase in capacity. Lower than expected sales outside of Enzymatica's own markets (Sweden, UK, Iceland) has prompted discussions with the current business partners to explore constructive ways forward. The full report is available on: This information is information that Enzymatica is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out below, at 08:30 a.m. CET on November 7, 2023. For more information, please contact: Claus Egstrand, Chief Executive Officer, Enzymatica AB Phone: +44 7780 22 8385 | Email: [email protected] Stefan Olsson, Communication Manager, Enzymatica AB Phone: +46 708 55 11 85 | Email: [email protected] Enzymatica AB is headquartered in Lund, Sweden, and is listed on Nasdaq First North Growth Market. For more information, please visit . Enzymatica's Certified Adviser is Erik Penser Bank. The following files are available for download: