Overview
Arialys Therapeutics is advancing the field of neurological treatment by targeting autoimmune neuropsychiatric diseases. With $58 million in seed financing, the company has the support of several key investors. Founding investors include Avalon BioVentures, Catalys Pacific, MPM BioImpact, Johnson & Johnson Innovation—JJDC, Inc., and Alexandria Venture Investments. Located in La Jolla, California, this biotechnology company is focusing its efforts on developing ART5803, a therapeutic antibody designed to treat autoimmune encephalitis.
ART5803 is a compound that aims to bind and block pathogenic autoantibodies affecting the central nervous system. Anti-NMDA receptor encephalitis (ANRE) is the primary target of this therapy. ANRE, a type of autoimmune encephalitis, is caused by antibodies that trigger the internalization of NMDA receptors, leading to severe symptoms like seizures and psychosis. ART5803 was acquired from Astellas Pharma, which had made notable progress in preclinical studies. The deal was finalized in 2022.
Current Treatments and Challenges
Typically, ANRE is treated with immunosuppressive therapies like steroids and plasmapheresis. If these first-line treatments are ineffective, second-line treatments such as rituximab and cyclophosphamide are used. Despite these options, about half of the patients do not fully recover, showing persistent neurological symptoms. ART5803 shows promise as a more effective alternative.
Key Facts about ANRE:
- Incidence: Approximately 2,000–3,000 cases in the U.S. each year.
- Gender Disparity: Women are four times more likely to be affected.
- Age Factor: More prevalent in people under 40 years old.
A pivotal risk factor for ANRE in women is ovarian teratomas, which express NMDA receptors. These receptors are usually only found in the brain, causing the immune system to recognize them as foreign when they appear in teratomas. This misidentification leads to the production of harmful autoantibodies.
Lichter explains that other triggers might include infections. One example is the Toxoplasma gondii parasite, which also poses a risk for schizophrenia. Fetuses exposed to ANRE during pregnancy have a substantially higher risk, around seven-fold, of developing the disease. Initial symptoms often resemble common viral infections but can quickly escalate to more severe issues like movement disorders and hallucinations.
ART5803 Development and Preclinical Studies
ART5803’s development is based on encouraging results from preclinical studies conducted by Astellas Pharma. These studies tested the drug’s efficacy in marmosets affected by ANRE. Marmosets infected with a cloned human antibody showed a significant recovery within two weeks of receiving ART5803. Traditionally, CNS drugs take much longer to show results, but ART5803 demonstrated a rapid response, which is significant and promising.
Arialys Therapeutics has replicated these outcomes using different marmoset colonies and protocols. The company’s scientists observed even more robust responses, with improvements noted within a week post-treatment. This quick response suggests ART5803 could offer faster relief for patients suffering from ANRE.
Future Plans and Goals
Arialys Therapeutics is preparing to transition from stealth mode to more public operations. The company’s timeline for the drug involves selecting healthy volunteers for testing ART5803 by the fourth quarter of 2024. The goal is to move on to clinical trials involving encephalitis patients in the first half of 2025. Arialys has already secured orphan drug designation from the U.S. Food and Drug Administration (FDA) for treating ANRE, which could speed up the development process.
In addition to ANRE, the company plans to conduct a trial focusing on autoimmune psychosis in the second half of 2025. Approximately 5% of schizophrenia patients have autoantibodies against NMDA receptors, suggesting ART5803 might also help those individuals.
Other Ongoing Projects
Beyond ART5803, Arialys has initiated an internal discovery program to identify other pathogenic autoantibodies and develop new drugs targeting them. This program aims to build a portfolio of therapeutic candidates addressing various autoimmune neuropsychiatric conditions. The company is working on a backup treatment for ANRE that offers better brain penetration, ensuring preparedness for future clinical needs.
Potential Conditions Benefiting from Arialys’ Research:
- Schizophrenia: Up to 5% of patients may have NMDA receptor autoantibodies.
- Dementia
- Bipolar Disorder
- Severe Depression
Each of these conditions could have a subset of patients who might benefit from targeted treatments developed by Arialys, significantly broadening the market for the company’s therapeutic solutions.
Funding and Leadership
Jay Lichter, PhD, a key figure in Arialys’ leadership, brings significant expertise to the project. As president and CEO, as well as managing partner at Avalon BioVentures, Lichter emphasizes the transformative potential of understanding autoimmune activity in neuropsychiatric diseases.
The collaboration and investment from notable funders such as Avalan BioVentures, Catalys Pacific, MPM BioImpact, and Johnson & Johnson Innovation—JJDC, Inc., help fuel this progress. These investments illustrate confidence in Arialys’ research and the potential impact of their therapies on the neurological market.
PubTable – ART5803 Key Details
| Detail | Information |
|---|---|
| Lead Candidate | ART5803 |
| Disease Target | Anti-NMDA Receptor Encephalitis |
| Type | Single-arm antibody |
| Funding Secured | $58 million in seed financing |
| Investors | Avalon BioVentures, Catalys Pacific, MPM BioImpact, Johnson & Johnson Innovation—JJDC, Inc., Alexandria Venture Investments |
| Preclinical Study Method | Tested on marmosets |
| Preclinical Results | Recovery within two weeks |
| First Patient Trials | Expected Q4 2024 |
| FDA Designation | Orphan Drug for ANRE |
Arialys Therapeutics continues to innovate in treating autoimmune neuropsychiatric diseases. With ART5803 leading the way and additional projects in the pipeline, the company is poised to make significant contributions to the field.
