Arialys Therapeutics Begins Phase 1 Trial of ART5803 for Autoimmune Neuropsychiatric Diseases

In La Jolla, California, on October 10, 2024, Arialys Therapeutics, a biotech company at the clinical stage, announced the commencement of dosing healthy volunteers in its inaugural clinical trial for ART5803. This therapeutic monoclonal antibody candidate is engineered to counteract detrimental autoantibodies that target the NMDA receptor (NMDAR). These autoantibodies are responsible for anti-NMDAR encephalitis (ANRE), a serious and currently untreatable rare disease. Additionally, these autoantibodies have been linked to other neuropsychiatric conditions, including schizophrenia and dementia. Arialys Therapeutics plans to begin a Phase 2a clinical study of ART5803 for ANRE in late 2025.

Peter Flynn, Ph.D., President and CEO of Arialys Therapeutics, expressed excitement about the clinical development of ART5803, noting its potential as a groundbreaking precision therapeutic. He stated that alongside efforts for ANRE, the company is examining the levels of autoantibodies and the therapeutic potential of ART5803 in patients with various neuropsychiatric disorders like schizophrenia and dementia.

The Phase 1 clinical trial of ART5803 is a double-blind, placebo-controlled, single-ascending dose study in healthy individuals (ClinicalTrials.gov Identifier: NCT06575153). This study, conducted in partnership with Nucleus Network in Melbourne, Australia, aims to assess the safety, tolerability, and pharmacokinetics (PK) of ART5803. Approximately 40 participants are expected to enroll in the trial.

If the initial assessments of safety, tolerability, and PK in healthy volunteers are favorable, Arialys plans to start a Phase 2a proof-of-concept clinical trial for ART5803 in the latter half of 2025, focusing first on ANRE patients.

ANRE, or anti-NMDA receptor encephalitis, is a rare, life-threatening disease that is often misdiagnosed and poorly managed. It is caused by harmful autoantibodies that bind to NMDA receptors, leading to a loss of receptor function and a rapid onset of symptoms such as psychiatric and behavioral changes, cognitive decline, seizures, and reduced autonomic function. A considerable number of ANRE patients are children, where these autoantibodies can also impede neurological development. Recent research has found these autoantibodies in other neuropsychiatric conditions like schizophrenia and dementia.

Arialys Therapeutics has utilized co-crystallographic structural analysis of the interaction between the autoantibody and the NMDAR to create a precision medicine strategy for treating neuropsychiatric diseases. ART5803 is designed to competitively block the harmful autoantibodies and restore NMDAR function. Preclinical studies have shown promising results, with ART5803 rapidly reversing behavioral symptoms caused by the autoantibodies in higher disease models. The U.S. FDA has granted Orphan Drug Designation to ART5803.

Arialys Therapeutics was established to significantly enhance treatment options for neuropsychiatric disorders stemming from autoimmune diseases. By integrating advanced autoantibody detection, patient sampling, and receptor structural biology, Arialys has developed a pioneering precision medicine to specifically inhibit harmful autoantibodies in the brain. The company is based in La Jolla, California.