RIG-I

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

Pet dogs were enrolled in a study with the permission of their owners. A personalized mRNA-based cancer vaccine for glioblastoma with an “onion-like” delivery mechanism can prolong survival both in dogs and humans, the results of a small study have suggested.  In an article published May 1 in Cell, researchers from the University of Florida (UF) and a spinout biotech, iOncologi, shared results from seven years’ worth of experiments culminating in a first-of-its-kind phase 1 trial in four patients and 10 pet dogs who had developed brain cancer spontaneously. The human patients survived or lived without disease for “longer than expected,” according to a press release, although it noted that it is too early in the trial to analyze the vaccine’s clinical effects. Meanwhile, the dogs lived for a median of 139 days, far longer than the typical 30- to 60-day survival time.   The findings drew the attention of Eric Topol, M.D., Ph.D., founder of the Scripps Research Translational Institute. He was not affiliated with the study.  “Glioblastomas are among the most aggressive and fatal cancers,” Topol commented in a post on X, formerly known as Twitter. “After marked success treating 10 dogs … [the vaccine] induced a striking anti-tumor response.”  The vaccine’s design is a marked departure from others of its kind. Typically, mRNA vaccines ferry their payload in lipid nanoparticles that target Toll-like receptors on immune cells, a type of receptor that activates the adaptive immune response. For most applications, like mRNA-based COVID-19 vaccines, the mRNA inside the particles is transcribed into proteins that train the immune system to react to a disease, but it isn’t targeted to a specific patient.  In contrast, the new vaccines wrap either mRNA or RNA based on a patient’s tumor in a complex of several lipid nanoparticles called RNA lipid particle aggregates (RNA-LPAs), a tactic that disguises it to look like a virus. Rather than engaging Toll-like receptors, they activate a protein called RIG-I in stromal cells, a type of stem cell found in tissues throughout the body as well as the tumor microenvironment. When injected into the bloodstream, this stimulates the release of a large number of cytokines and chemokines along with dendritic cells and lymphocytes, training the immune system to go after the patient’s cancer.  “Instead of us injecting single particles, we’re injecting clusters of particles that are wrapping around each other like onions, like a bag full of onions,” Elias Sayour, M.D., Ph.D., senior author, said in the release. “The reason we’ve done that in the context of cancer is these clusters alert the immune system in a much more profound way than single particles would.” The strategy overcomes one of cancer vaccines’ biggest obstacles: eliciting a strong immune response, UF researchers Christina von Roemeling, Ph.D., and John Ligon, M.D., both authors on the study, explained in a separate article they penned for The Conversation. Injecting them systemically, rather than directly into the skin, muscle or tumor itself, perpetuates the effect.  “From [the bloodstream], they travel to organs throughout the body involved in the immune response to teach the body to fight against cancer,” von Roemeling and Ligon said in their article. “By doing so, we’ve found that the immune system launches a near-immediate and powerful response.” They saw blood markers associated with immune activation within just six hours; the tumors were turned from “cold”, or impenetrable by the immune system, to “hot” within just 48 hours, according to the press release.  All that immune activity does come with the risk of side effects, the degree of which aren’t yet clear from the early studies. That’s one limitation the researchers will be on the lookout for as they move into an expanded phase 1 study that will include up to 24 pediatric and adult patients.  Once they’ve established dosing, the researchers will enroll 25 pediatric patients for phase 2. They also hope to test the vaccine alongside other immunotherapies, as early evidence from their experiments suggests a combination approach might be worth pursuing, Sayour said in the release.  “I am hopeful for how this could now synergize with other immunotherapies and perhaps unlock those immunotherapies,” he said.

GAITHERSBURG, Md., April 18, 2024 /PRNewswire/ -- YS Biopharma Co., Ltd. (Nasdaq: YS) ("YS Biopharma" or the "Company"), a global biopharmaceutical company dedicated to discovering, developing, manufacturing, and delivering new generations of vaccines and therapeutic biologics for infectious diseases and cancer, today announced that its YS-HBV-002 immunotherapeutic vaccine, designed to treat patients suffering from chronic hepatitis B virus ("HBV") infection, has been granted clinical trial approval by the Philippine Food and Drug Administration ("PFDA"). In light of the approval, the Company is preparing to initiate a Phase I clinical trial for YS-HBV-002 in the Philippines, which is expected to begin in June 2024. Chronic HBV infection is a major global health concern, with an estimated 254 million people suffering from the condition, with 1.2 million new infections each year, according to the World Health Organization (WHO). Those infected are at higher risk for cirrhosis, liver failure, and liver cancer, with between 15%-40% of chronic HBV patients afflicted with one or more of these conditions. In 2022, HBV infection resulted in an estimated 1.1 million deaths, mostly from cirrhosis and hepatocellular carcinoma (primary liver cancer). Chronic HBV infections occur in both developing and developed countries, constituting a significant unaddressed public health threat. At present, the efficacy of existing anti-viral treatment paradigms is limited, and no cure for chronic HBV has yet been developed. Despite the availability of preventive vaccines for hepatitis B infection, there remains an urgent need for effective therapies for individuals who are already infected and have progressed to chronic stages of infection. Dr. David Shao, Director, President, and CEO of YS Biopharma, commented, "The approval of YS-HBV-002 by the Philippines FDA and Ethics Committee represents a significant milestone in our efforts to develop innovative therapies for chronic hepatitis B infection. At present, there is no effective vaccine treatment option for patients suffering from chronic HBV, leaving them at higher risk for other conditions affecting the liver and significantly hampering their quality of life. With our recent approval and upcoming clinical study, we hope to provide these patients with a safe and effective solution to combat this significant unaddressed public health threat. As always, we plan to conduct the clinical trial to the highest safety and ethical standards, and we are eager to take the next step towards delivering these much-needed treatment options to chronic HBV patients." The Phase I clinical trial for YS-HBV-002 will mark an important milestone in addressing this unmet medical need. This trial will employ a double-blind, randomized, placebo-controlled, dose-escalation approach, and aims to evaluate the safety, immunogenicity, and efficacy of YS-HBV-002 among adult patients diagnosed with chronic HBV infection. By targeting both humoral and cellular immune responses, YS-HBV-002 has the potential to disrupt immune tolerance mechanisms and facilitate the treatment of chronic HBV infection in patients. About YS-HBV-002 YS-HBV-002 is a new generation of therapeutic HBV vaccine based on the proprietary technology and clinical results of YS-HBV-001, the first generation of HBV vaccine in the pipeline of YS Biopharma. YS-HBV-002 is formulated with several key components, including recombinant core and surface hepatitis B antigens, and YS Biopharma's proprietary PIKA adjuvant. This carefully designed set of components has the potential to activate both innate and adaptive immune responses in patients, thereby generating a more robust and targeted response to the virus. The re-establishment of a desirable and comprehensive immune response is the first step towards the eradication of chronic HBV infection from the body. About YS Biopharma YS Biopharma is a global biopharmaceutical company dedicated to discovering, developing, manufacturing, and commercializing new generations of vaccines and therapeutic biologics for infectious diseases and cancer. It has developed a proprietary PIKA® immunomodulating technology platform and a series of preventive and therapeutic biologics with a potential for improved Rabies, Coronavirus, Hepatitis B, Influenza, and Shingles vaccines. YS Biopharma operates in China, the United States, Singapore and the Philippines, and is led by a management team that combines rich local expertise and global experience in the bio-pharmaceutical industry. For more information, please visit . 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