LA JOLLA, Calif.--(BUSINESS WIRE)--Arialys Therapeutics, a clinical-stage biotechnology company pioneering new precision medicines for autoimmune neuropsychiatry, today announced the completion of all five Single Ascending Dose (SAD) cohorts and the initiation of the Multiple Ascending Dose (MAD) cohorts in its ongoing double-blind, placebo-controlled, Phase 1 study of ART5803 in healthy volunteers. Phase 2 proof-of-concept studies in patients suffering from the rare and devastating disease, ANRE, are anticipated to start in the second half of 2025.

Preliminary data from the SAD cohorts indicate that ART5803, a single-armed monoclonal antibody designed to bind the NMDA receptor and inhibit the pathogenic effects of autoantibodies, was well tolerated at all dose levels. ART5803 dosing was escalated across five cohorts, ranging from 3 mg/kg to 100 mg/kg, with no treatment-related dose reductions required and no treatment-related serious adverse events observed.

In addition to the safety assessments, extensive pharmacokinetic (PK) and biodistribution measurements were performed, including multiple cerebrospinal fluid (CSF) samplings from each subject to assess blood brain barrier penetration following intravenous administration of ART5803. PK assessments support the dose and regimen to be evaluated in the MAD portion of the study. Importantly, several of the SAD dose cohorts demonstrated CSF exposures of ART5803 consistent with potentially efficacious CNS levels, as modelled preclinically.

“We are excited to move from SAD to MAD dosing in our Phase 1 study, and we thank the trialists and volunteers for the thorough and efficient assessment of ART5803,” said Peter Flynn, Ph.D., President and CEO of Arialys Therapeutics. “We look forward to further establishing the safety of ART5803 and transitioning to efficacy assessments later this year.”

“We are enthusiastic to see this initial safety and PK profile, including CNS exposure levels for ART5803,” said Sankalp Gokhale, M.D., Chief Medical Officer of Arialys Therapeutics. “We remain on course to bring this novel and potentially efficacious treatment to patients suffering from serious neurological and psychiatric symptoms resulting from anti-NMDAR autoantibodies.”

The ART5803 Phase 1 clinical study is designed as a double-blind, placebo-controlled, first-in-human, single-ascending dose trial in healthy volunteers (ClinicalTrials.gov Identifier: NCT06575153). The study is being conducted in collaboration with Nucleus Network in Melbourne, Australia. The study is evaluating the safety, tolerability, pharmacokinetics (PK), and immunogenicity of ART5803. It has enrolled 40 subjects in the SAD cohorts and is expected to enroll approximately 24 subjects in the MAD cohorts.

Pending safety, tolerability, and PK assessments in healthy volunteers, Arialys anticipates initiating Phase 2 proof-of-concept clinical assessments of ART5803 in the second half of 2025, initially in patients with ANRE.

About ANRE and 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 NMDA receptors (NMDAR), resulting in loss of function and rapid onset of a range of symptoms including psychiatric and behavioral alterations, cognitive decline, seizures and diminished autonomic function. A significant percentage of ANRE patients are pediatric where NMDAR specific autoantibodies can also result in neurological development deficits. Recent findings have also identified anti-NMDAR autoantibodies in other neuropsychiatric diseases such as schizophrenia and dementia. Arialys has used co-crystallographic structural analysis of the autoantibody-NMDAR interaction to design a precision medicine approach to the treatment of neuropsychiatric disease. ART5803 is a clinical-stage therapeutic antibody that competitively blocks the pathogenic autoantibodies and rescues NMDAR function. Arialys has generated compelling preclinical data in higher disease models confirming ART5803 rapidly reverses the behavioral symptoms caused by NMDAR autoantibody pathogenicity in the brain. Arialys has received Orphan Drug Designation from the U.S. FDA for ART5803.

About Arialys Therapeutics

Arialys was founded 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.