Precision Therapeutic Options for Autoimmune Neuropsychiatric Disease

Untapped Mechanism, Vast Potential

The study of autoimmune activity has historically focused on diseases of peripheral tissues and organs. We now know that autoantibodies can target the brain causing severe neurological and psychiatric diseases. Founded to explore the latest discoveries in autoimmune neuropsychiatry, Arialys Therapeutics is developing new precision medicines to specifically block the effect of pathogenic autoantibodies in the brain and meaningfully expand the treatment possibilities for neuropsychiatric disorders driven by autoimmune disease.

Precision Therapies for Autoimmune Neuropsychiatric Diseases 

Pathogenic autoantibodies that target receptors in the brain and drive neurological and psychiatric symptoms were first discovered in 2007. The most common target of these autoantibodies is the NMDA receptor (NMDAR), a molecule vital for neuron synapse activity and normal cognition, learning memory and autonomic function. Anti-NMDAR autoantibodies have now been detected in patients suffering from a myriad of neuropsychiatric conditions including encephalitis, schizophrenia, schizoaffective disorder, dementia, stroke and cancer-related cognitive impairment. Arialys has used structural analysis of the autoantibody-NMDAR interactions to design precision medicines for the treatment of neuropsychiatric disease.

ART5803: a Lead Therapeutic for ANRE

Anti-NMDA receptor encephalitis (ANRE) is the most common form of autoimmune encephalitis. ANRE is a potentially lethal, poorly managed and often misdiagnosed neurological disease as detailed in the book, Brain on Fire. 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.

ART5803 is a clinical-stage therapeutic antibody that competitively blocks 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 is now investigating the clinical potential of ART5803 in ANRE and other neuropsychiatric diseases where NMDAR autoantibodies have been detected.