Arialys Therapeutics' precision medicine has shown preclinical potential to address the underlying cause of anti-NMDA receptor encephalitis (ANRE), a rare brain disorder that comes with severe psychiatric and neurological symptoms.
The data, which were published in Nature Communications, showed that Arialys’ candidate ART5803 blocked pathogenic antibodies that target the NMDA receptor and reversed behavioral symptoms in a nonhuman primate model.
It means ART5803 has potential to become a “fast-acting, efficacious, and safe treatment option,” according to the article in Nature. There are currently no approved treatments for ANRE.
The results support the continued development of ART5803, Arialys said. The treatment is already being evaluated using healthy volunteers in phase 1 safety studies, which are expected to read out in the second half of this year. A phase 2 proof-of-concept trial in patients with ANRE and autoimmune psychosis is scheduled to kick off before the end of 2025.
ANRE is a potentially lethal and often misdiagnosed disorder caused by pathogenic autoantibodies that bind to NMDA receptors in the brain, leading to receptor internalization and synaptic dysfunction.
It occurs in roughly 1.5 out of every 1 million people and can strike at any age, though it is more prevalent in young adult women. Patients often first experience symptoms typical of a viral infection before progressing to behavioral, psychiatric and eventually neurological symptoms that can include seizures and cognitive dysfunction.
“Despite our understanding of the disease mechanism and its severity, ANRE lacks an approved therapy,” Arialys CEO Peter Flynn, Ph.D., said in a June 17 release, adding that the data suggest the treatment could be effective in combating other neuropsychiatric disorders.
“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,” Flynn said, referring to conditions such as schizophrenia, depression and bipolar disorder.
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,” according to Arialys. The company is currently testing patient samples for autoantibodies to identify disease indications and subpopulations for future clinical development of the therapy.
Arialys, which specializes in neuropsychiatric disorders driven by autoimmune disease, launched in September 2023 with $58 million in seed financing. Johnson & Johnson Innovation was one of the La Jolla, Calif.-based biotech's backers.