Background

This immunomodulatory therapy combines low-dose interleukin-2 with an antibody to the cytotoxic T lymphocyte antigen 4 (CTLA4-Ig). Marketed as Abatacept, CTLA4-Ig is used to modulate inflammation in autoimmune diseases. IL-2 is approved for cancer therapy. At low doses, IL-2 increases the activity of regulatory T cells (Tregs) that suppress inflammation. The addition of CTLA4-Ig to low-dose IL-2 is intended to further enhance Treg numbers and function, and lower inflammation.

Deficits in Tregs have been documented in AD, PD, and ALS (e.g., Faridar et al., 2020; Arce-Sillas et al., 2024). On its own, low-dose IL2 has been evaluated in Phase 2 trials in ALS and AD patients, where it increased Tregs and reduced biomarkers of inflammation (see Low Dose Interleukin-2 for details).

No preclinical work is published on COYA 302. According to information on the company website, subcutaneous injections reduced inflammation and microglial activation in affected areas of the substantia nigra and dorsal striatum in a mouse model of Parkinson’s disease (Sep 24 press release).

Coya is also planning to develop an IL-2/glucagon-like peptide-1 receptor antagonist combination for neurodegenerative and autoimmune diseases (Jan 2025 press release).

Findings

In October 2021, an investigator-initiated, open-label study of COYA 302 began at the Houston Methodist Research Institute. The study planned to enroll 10 people with ALS, treat them every two weeks for one year, and assess safety and tolerability. Secondary and exploratory outcomes include Treg function, serum biomarkers of oxidative stress, inflammation, and neurodegeneration, and clinical functioning on the ALSFRS-R scale. Results are published (Thonhoff et al., 2024). Four patients enrolled; they completed the study without serious adverse events. Increases in Treg in number and function occurred over the entire treatment period, and returned to baseline levels after treatment stopped. Biomarkers showed trends to reduction in the first 16 weeks, but were not uniformly changed. ALSFRS-R scores remained stable over 16 weeks; three of four participants had declined by 48 weeks.

In May 2024, the Houston researchers began a small, open-label study testing COYA 302, dosed every two or four weeks, in eight frontotemporal dementia patients. Treatment will run for six months with a primary outcome of safety, and a secondary outcome of blood Treg numbers. Completion is expected in April 2026. As of December 2024, five patients had enrolled (press release). At the March 2024 AD/PD conference, Coya had presented supporting data claiming that Treg function was compromised, and peripheral inflammatory markers were increased, in people with FTD compared to healthy controls (press release).

For details on COYA 302 trials, see clinicaltrials.gov.