Arialys Therapeutics Publishes Preclinical Data in Nature Communications Supporting ART5803 as a First-in-Class Precision Therapeutic for Anti-NMDA Receptor Autoimmune Neuropsychiatric Disease
'This study underscores the promise of ART5803 to directly address neuropsychiatric disease caused by anti-NMDA receptor-targeting pathogenic antibodies,' said Peter Flynn, Ph.D. President and CEO of Arialys Therapeutics.
Share
'This study underscores the promise of ART5803 to directly address neuropsychiatric disease caused by anti-NMDA receptor-targeting pathogenic antibodies,' said Peter Flynn, Ph.D. President and CEO of Arialys Therapeutics. 'Despite our understanding of the disease mechanism and its severity, ANRE lacks an approved therapy. Further, there is a growing body of data identifying significant levels of anti-NMDA receptor autoantibodies in subpopulations of patients diagnosed with diseases that result in psychosis and dementia.'
'These data provide compelling evidence that ART5803 can directly block the pathogenic effect of autoantibodies that target the NMDA receptor, resulting in a rapid resolution of symptoms,' said Mitsuyuki (Mickey) Matsumoto, Ph.D., Chief Scientific Officer of Arialys Therapeutics and senior author of the paper. 'Our detailed structural and functional analyses confirm that ART5803 precisely inhibits NMDA receptor internalization induced by the pathogenic autoantibodies, while preserving normal receptor function. In addition, our discovery of a potential molecular mimicry mechanism for anti-NMDA receptor autoantibody generation broadens the understanding of disease initiation and may inform future indication expansion for ART5803.'
Anti-NMDA receptor encephalitis (ANRE) is a rare, potentially lethal, poorly managed, and often misdiagnosed neurological disease. ANRE is caused by pathogenic autoantibodies that bind to and crosslink NMDA receptors in the brain, leading to receptor internalization and synaptic dysfunction. The result is a range of debilitating neuropsychiatric symptoms including psychiatric and behavioral alterations, cognitive decline, seizures, coma, and diminished autonomic function. A significant percentage of ANRE patients are pediatric, where NMDA receptor-specific autoantibodies can also result in neurological development deficits. There are no approved therapies for this disease, and current treatments rely on broadly immunosuppressive therapies, which are associated with delayed efficacy and significant side effects.
Recent findings have also identified anti-NMDA receptor autoantibodies in other neurological and psychiatric diseases such as schizophrenia, depression, bipolar disorder, and dementia. Arialys is planning clinical assessment of ART5803 in anti-NMDA receptor autoantibody-positive psychosis patients. The company is also currently testing patient samples using a proprietary high-throughput screen for autoantibodies to identify enriched disease indications and subpopulations for future clinical development.
ART5803 is a humanized, monovalent IgG1 antibody engineered to selectively bind the GluN1 subunit of the NMDA receptor without disrupting receptor function or causing internalization. In this study, ART5803 demonstrated the ability to potently block NMDA receptor internalization in cellular and neuronal models and reversed both molecular and behavioral hallmarks of disease in a novel marmoset model of ANRE. Notably, ART5803 exhibited rapid onset of action and was well tolerated in vivo. The publication also includes a detailed characterization of ART5803's binding epitope, its mechanism of action, and population pharmacokinetic modeling supporting the feasibility of systemic administration in patients.
In addition to demonstrating the therapeutic potential of ART5803, the paper revealed a potential link between infections—specifically Toxoplasma gondii and certain bacterial pathogens—and the generation of pathogenic anti-NMDA receptor autoantibodies. Epitope mapping analysis identified regions of potential molecular mimicry between microbial proteins and the GluN1 subunit of the NMDA receptor, suggesting that infections could serve as environmental triggers for disease initiation. Notably, toxoplasmosis and bacterial infections are well-established risk factors for a range of neuropsychiatric conditions. These findings not only suggest a basis for disease pathogenesis but also support broader therapeutic opportunities for ART5803 across autoimmune neuropsychiatric disorders.
ART5803 is currently being evaluated in a Phase 1 clinical trial in healthy volunteers. In February 2025, Arialys announced completion of all single ascending dose (SAD) cohorts and initiation of multiple ascending dose (MAD) cohorts. The company expects to share initial clinical data in the second half of 2025 and initiate Phase 2 proof-of-concept studies.
The publication was completed in collaboration with researchers from Astellas Pharma Inc., University of California, Davis, Kitasato University School of Medicine, and Vanadro LLC.
About Arialys Therapeutics
Arialys was founded by investors Avalon Bioventures, Catalys Pacific and MPM to meaningfully expand the treatment possibilities for neuropsychiatric disorders driven by autoimmune disease. Using a combination of highly sensitive autoantibody detection, patient sampling and receptor structural biology, Arialys has developed a first-in-class precision therapy to specifically block pathogenic autoantibodies in the brain. Arialys is headquartered in La Jolla, California. For more information, visit www.arialysrx.com.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Business Wire
4 minutes ago
- Business Wire
Azafaros Announces Initiation of two Global Phase 3 studies with Nizubaglustat in Niemann-Pick disease Type C (NPC) and GM1/GM2 gangliosidoses, respectively
LEIDEN, Netherlands--(BUSINESS WIRE)-- Azafaros, a company focused on developing treatments for the unmet needs of patients with rare lysosomal storage disorders, today announced that the first patient has been dosed in the company's pivotal, multicenter Phase 3 clinical program to evaluate the safety and efficacy of the company's lead asset, nizubaglustat, in patients with Niemann-Pick disease Type C (NPC) and GM1/GM2 gangliosidoses. 'The dosing of the first patient in our Phase 3 program with nizubaglustat is a significant achievement for Azafaros, and a huge step forward in our efforts to bring new, disease modifying treatments to patients with these seriously debilitating diseases,' Share The initiation of the two Phase 3 studies (NCT07054515) represents a major milestone in Azafaros' commitment to addressing the urgent unmet medical needs of children affected by these devastating neurodegenerative disorders. The Phase 3 program consists of two studies targeting the late-infantile and juvenile-onset forms of NPC, and GM1/GM2 gangliosidoses. The studies aim to assess the potential of nizubaglustat to alter disease progression and improve functional outcomes in these patient populations. Today's news follows the recent, successful completion of an oversubscribed series B financing, raising €132M to support the acceleration of nizubaglustat and the expansion of the company's pipeline to other indications. 'The dosing of the first patient in our Phase 3 program with nizubaglustat is a significant achievement for Azafaros and a huge step forward in our efforts to bring new, disease modifying treatments to patients with these seriously debilitating diseases,' said Stefano Portolano, Chief Executive Officer at Azafaros. 'We are deeply grateful to the patients, families, clinicians, and advocacy groups who are partnering with us to advance this promising therapy.' About the NAVIGATE trial The two 18-month randomized 2 to 1, double-blind, placebo-controlled trials will recruit patients at approximately 35 sites across 15 countries worldwide, including in the US, Europe and Latin America. The studies are expected to enroll around 70 patients. The primary endpoint for both trials is the change from baseline to Month 18 in the Scale for the Assessment and Rating of Ataxia (SARA), with both total and functional SARA scores evaluated. For more information on the Phase 3 program, please visit To enquire about trial participation, email: medinfo@ (if a professional) or patientadvocacy@ (if a patient or caregiver). To protect privacy, avoid including identifying information in the initial message. About nizubaglustat Nizubaglustat is a small molecule, orally available and brain penetrant azasugar with a unique dual mode of action, developed as a potential treatment for rare lysosomal storage disorders with neurological involvement, including GM1 and GM2 gangliosidoses and Niemann-Pick disease type C (NPC). Nizubaglustat has received Rare Pediatric Disease Designations (RPDD) for the treatment of GM1 and GM2 gangliosidoses and NPC, Orphan Drug Designations (ODD) for GM1 and GM2 gangliosidosis (Sandhoff and Tay-Sachs Diseases) and NPC, as well as Fast Track Designation and IND clearance for GM1/GM2 gangliosidoses and NPC from the US Food and Drug Administration (FDA). Additionally, nizubaglustat has been awarded Orphan Medicinal Product Designation (OMPD) for the treatment of GM1 and GM2 gangliosidoses by the European Medicines Agency (EMA) and Innovation Passport for the treatment of GM1 and GM2 gangliosidoses from the UK Medicines and Healthcare Products Regulatory Agency (MHRA). About GM1 and GM2 gangliosidoses GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are lysosomal storage disorders caused by the accumulation of GM1 or GM2 gangliosides respectively, in the central nervous system (CNS). This results in progressive and severe neurological impairment and premature death. These diseases mostly affect infants and children, and no disease-modifying treatments are currently available. About Niemann-Pick disease Type C (NPC) Niemann-Pick disease Type C is a progressive, life-limiting, neurological, lysosomal storage disorder, caused by mutations in the NPC1 or NPC2 gene and aberrant endosomal-lysosomal trafficking, leading to the accumulation of various lipids, including gangliosides in the CNS. The onset of disease can happen throughout the lifespan of an affected individual, from prenatal life through adulthood. About Azafaros Azafaros is a clinical-stage company founded in 2018 with a deep understanding of rare genetic disease mechanisms using compound discoveries made by scientists at Leiden University and Amsterdam UMC and is led by a team of highly experienced industry experts. Azafaros aims to build a pipeline of disease-modifying therapeutics to offer new treatment options to patients and their families. By applying its knowledge, network and courage, the Azafaros team challenges traditional development pathways to rapidly bring new drugs to the rare disease patients who need them. Azafaros is supported by leading healthcare investors including Forbion, Jeito Capital, Seroba, Pictet Group, BioGeneration Ventures (BGV), BioMedPartners, Asahi Kasei Pharma Ventures, and Schroders Capital.
Business Wire
4 minutes ago
- Business Wire
Genentech and Roche Present New Insights in Alzheimer's Disease Research Across Its Diagnostics and Pharmaceutical Portfolios at AAIC
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) announced today that new data from its Alzheimer's development portfolio is being presented at the Alzheimer's Association International Conference (AAIC) in Toronto, Canada (July 27-30). These data exemplify the comprehensive approach Roche is taking in addressing Alzheimer's across the entire patient journey. Featured oral presentations include the latest results from the ongoing Phase Ib/IIa Brainshuttle™ AD study, which continue to support rapid and robust reduction of amyloid plaques, and design of the Phase III TRONTIER 1 and 2 studies of investigational trontinemab for early symptomatic Alzheimer's disease, with initiation planned later this year. As part of its growing Alzheimer's development program, Roche announced today its plans for an additional Phase III trial to investigate trontinemab in preclinical Alzheimer's disease. The trial will focus on individuals at risk of cognitive decline, with the goal of potentially delaying or preventing the progression of the disease to symptomatic stages. 'Alzheimer's disease represents one of the greatest challenges in healthcare today and tackling it requires early detection and effective therapeutics,' said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. 'Trontinemab is designed to target a key driver of Alzheimer's disease biology more effectively in the brain. Combining new treatment avenues with advanced diagnostics may enable earlier and potentially more effective intervention. With plans for Phase III trials in both early symptomatic and preclinical Alzheimer's disease, we are advancing science with the goal of delaying—and ultimately preventing—progression of this devastating condition.' Late-breaking oral and poster presentations highlight the potential of Roche's Elecsys ® pTau217 as a reliable and accessible blood-based biomarker test, providing comparable results to PET scan and cerebrospinal fluid (CSF) diagnostics for rule-in and rule-out diagnosis of amyloid pathology, a hallmark of Alzheimer's disease, across care settings. The test, which received Breakthrough Device Designation from the U.S. Food and Drug Administration last year, will also be utilized in Roche's TRONTIER studies. 'Blood based testing for Alzheimer's disease has the potential to greatly improve patient access and decrease the time to definitive disease diagnosis,' said Matt Sause, CEO of Roche Diagnostics. 'Our data show that the Elecsys pTau217 test performs comparably to PET scans but can be performed with a simple blood draw and analyzed in a routine clinical laboratory. This has the potential to transform the diagnosis of Alzheimer's and provide clear answers to caregivers, patients, and their families.' Up to 75% of people living with symptoms of Alzheimer's disease globally have not been diagnosed, and those who have, waited an average of 2.8 years, and even less have received any form of treatment. Diagnostics play a crucial role in addressing the global challenge of Alzheimer's, not only to detect and identify people with the disease early, even before the first symptoms, but also to rule out those who may or may not benefit from specific treatments. Pharmaceuticals In a 90-minute Featured Research session, designs were shared for the Phase III studies, TRONTIER 1 and 2, which will initiate later this year, investigating the efficacy and safety of investigational trontinemab in people with early Alzheimer's disease. The primary endpoint will measure the change in cognition and function based on the Clinical Dementia Rating – Sum of Boxes scale after 18 months of treatment. Secondary endpoints will include assessments of cognition, function, behavioral symptoms, and quality of life. A pre-screening study, TRAVELLER, based on a brief clinical assessment and a plasma biomarker, which will be identified using the Elecsys pTau217 test, has also been initiated, to enable broader community outreach and extend access to these trials to more diverse populations representative of Alzheimer's disease. New data on the latest results for trontinemab from the completed dose-expansion part of the 1.8 mg/kg and 3.6 mg/kg cohorts from the ongoing Phase Ib/IIa Brainshuttle AD study continued to show rapid and robust reduction of amyloid plaques in the brain as measured by amyloid positron emission tomography (PET). In the 3.6 mg/kg cohort, trontinemab reduced amyloid levels below the 24 centiloid positivity threshold in 91% of participants (n=49/54) after 28 weeks of treatment; 72% (n=39/54) achieved deep clearance below 11 centiloids. These data were reinforced by early and significant reductions in fluid biomarkers of Alzheimer's disease, including total tau, phosphorylated Tau (pTau)181, pTau217, and neurogranin measured in CSF and continues to show a favourable safety and tolerability profile. Amyloid-related imaging abnormalities-edema/effusion (ARIA-E) continued to be observed in <5% of participants (blinded data; N=4/149 across 1.8 and 3.6 mg/kg dose cohorts). All cases were radiographically mild, one was associated with mild and transient symptoms. Diagnostics Roche will present data on a new study comparing the pTau217/Ab42 plasma ratio to the high-throughput, fully automated Elecsys pTau217 assay. The presentation will report on the accuracy of these tools in detecting amyloid pathology. Together with the high throughput and full automation of the assay, these data will assess the potential of Elecsys pTau217 as an accurate standalone rule-in and rule-out test that could be scaled up for broad implementation in routine clinical practice worldwide. Additionally, results from a cohort-based model of healthcare utilization in the U.S. demonstrated that using the Elecsys ® pTau181 blood-based rule-out test in primary care scenarios improved diagnostic accuracy and reduced resource use compared with the current standard-of-care clinical, cognitive and imaging tests. If made available in primary care settings, the Roche Elecsys ® pTau181 blood test has the potential to reliably avoid the need for further confirmatory testing in nearly all people who receive a negative result. This will avoid the need for these people to undergo unnecessary testing using CSF or PET, which often come with long wait times and high cost, resulting in further delays to diagnosis and cost to healthcare systems. About trontinemab Trontinemab is an investigational Brainshuttle bispecific 2+1 amyloid-beta targeting monoclonal antibody specifically engineered for enhanced access to the brain to enable rapid reduction of amyloid in people with Alzheimer's disease. Trontinemab is designed for the efficient transport across the blood-brain barrier to target aggregated forms of amyloid beta and remove amyloid plaques in the brain. The uniqueness of trontinemab is based on Roche's proprietary Brainshuttle technology combining an amyloid beta-binding antibody with a transferring receptor (TfR1) shuttle module. As a result, high central nervous system (CNS) exposure of trontinemab may be achieved at low doses, leading to a rapid and deep amyloid clearance. Due to its unique properties, trontinemab might unlock the full potential of disease-modifying monoclonal antibodies by effectively penetrating the brain and potentially leading to slowing of disease progression. About Roche in Alzheimer's Disease With more than two decades of scientific research in Alzheimer's disease, Roche is working towards a day when we can detect and treat the disease early, in order to slow down, stop or even prevent its progression to preserve what makes people who they are. Today, the company's Alzheimer's disease portfolio spans investigational medicines for different targets, types and stages of the disease, including trontinemab. On the diagnostics side, it also includes approved and investigational tools, including digital and blood-based tests and CSF assays, aiming to more effectively detect, diagnose and monitor the disease. Yet the global challenges of Alzheimer's disease go well beyond the capabilities of science, and making a meaningful impact requires collaboration both within the Alzheimer's community and outside of healthcare. Roche will continue to work together with numerous partners with the hope to transform millions of lives. About Genentech in Neuroscience Neuroscience is a major focus of research and development at Genentech. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases. Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer's disease, Huntington's disease, Parkinson's disease and Duchenne muscular dystrophy. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit
Business Wire
4 hours ago
- Business Wire
GTJAI Achieved 'Carbon Neutrality' at Operational Level for the Third Consecutive Year
HONG KONG--(BUSINESS WIRE)-- Guotai Junan International Holdings Limited ('GTJAI' or the 'Company', stock code: a company of Guotai Haitong Group, is pleased to announce that while actively saving energy and reducing emissions, it has successfully offset its Scope 1 and Scope 2 carbon emissions totaling 609.29 tons of carbon dioxide equivalent for the year 2024 by subscribing to the carbon credits issued under the international Verified Carbon Standard (VCS). This marks the third consecutive year that GTJAI has achieved 'carbon neutrality' at the operational level, demonstrating the Company's leading practice and commitment to green operation. The carbon credits come from 'Guoluo Grassland Sustainable Management Project' located in Guoluo Tibetan Autonomous Prefecture, Qinghai Province, China. It is dedicated to the restoration of degraded grassland ecosystems, based on the holistic nature of the ecosystems, in line with the concept of ecological civilization construction, and to effectively respond to the challenges of climate change. The project is also the first grassland carbon project in China receiving both VCS certification and the Climate, Community and Biodiversity Standards (CCB) - CCB-Biodiversity Gold Level certification. In recent years, GTJAI has been continuously reducing its operational carbon footprint through systematic energy saving and emission reduction initiatives, which is the core support for the achievement of 'carbon neutrality', including vigorously implementing energy-saving renovation of office space, deepening digitalization and paperless transformation, and implementing stringent waste management (100% safe recycling of hazardous waste by 2024). Solid internal emission reduction efforts, combined with carbon offsetting through high-quality carbon credits, enabled the Company to achieve 'carbon neutrality' at the operational level. Adhering to the core philosophy of 'finance for the country, finance for the people, finance for the good', GTJAI has always placed sustainable development at the core of its corporate strategy. The Company is committed to supporting the real economy through financial services while facilitating the green transformation of its corporate clients. In 2024, the Company successfully completed 90 sustainable finance projects covering green bonds, sustainable bonds and green sector IPOs with a total issuance volume of HK$179.8 billion, significantly broadening the financing pipeline for the green industry. Meanwhile, the private equity sector is actively engaged in the sustainability sector, with more than half of its investments focusing on ESG-related industries. Looking ahead, GTJAI will deepen the level of ESG governance, fully integrate ESG factors into its operations and management processes, further leverage its professional strengths and enhance the level of green financial services capabilities. Through innovative products and services, GTJAI will proactively contribute to the realization of the country's 'dual carbon' goal and promote the high-quality development of the economy and society. About GTJAI Guotai Junan International ('GTJAI', Stock Code: a company of Guotai Haitong Group, is the market leader and first mover for internationalization of Chinese Securities Company as well as the first Chinese securities broker listed on the Main Board of The Hong Kong Stock Exchange through initial public offering. Based in Hong Kong with subsidiaries in Singapore, Vietnam and Macau, GTJAI's business covers major markets around the world, offering high-quality and diversified comprehensive financial services for clients' overseas asset allocation. Core business includes brokerage, corporate finance, asset management, loans and financing, financial products, which cover three dimensions including individual finance (wealth management), institutional finance (institutional investor services and corporate finance) and investment management. GTJAI has been assigned 'Baa2' and 'BBB+' long term issuer rating from Moody and Standard & Poor respectively, as well as an MSCI ESG 'A' rating, Wind ESG 'A' rating and SynTao Green Finance 'A' rating in ESG. Additionally, its S&P Global ESG score leads 84% of its global peers. The controlling shareholder, Guotai Haitong Securities (Stock Code: is the comprehensive financial provider with a long-term, sustainable and overall leading position in the China's capital markets. For more information about GTJAI, please visit
