Coya Therapeutics says Phase 2 LD-1L-2 study met primary, secondary endpoints

Coya Therapeutics (COYA) announced that results from the placebo-controlled Phase 2 clinical trial of LD IL-2 in patients with mild to moderate Alzheimer’s Disease were announced at the 17th Clinical Trials on Alzheimer’s Disease Conference in Madrid, Spain. The study was led by Dr. Alireza Faridar and Dr. Stanley Appel from the Houston Methodist Research Institute. Dr. Appel is a member of Coya’s Scientific Advisory Board. The study received funding from the Alzheimer’s Association, the Gates Foundation, and the National Institute on Aging, with additional support from Coya. The investigator-initiated, randomized, double-blind, placebo-controlled Phase 2 trial evaluated two dosing regimens of subcutaneous low-dose interleukin-2 in 38 participants with Alzheimer’s disease that were between the ages of 50 to 86 and had Mini-Mental State Examination scores ranging from 12 to 26. Of the 38 total participants, 22 were randomized in a 1:1 ratio to receive either 5 days of LD IL-2 or placebo every 4 weeks for 21 weeks. An additional 16 participants were randomized in a 2:1 ratio to receive 5-day cycles of LD IL-2 every 2 weeks or placebo for the same 21-week duration. All participants were monitored for 9 weeks post-treatment, resulting in a total study period of 30 weeks. Demographics and baseline disease characteristics were comparable among the treatment groups. The primary endpoint was the incidence and severity of adverse events, with the secondary endpoint evaluating changes in Tregs. Exploratory endpoints assessed changes in cerebrospinal fluid, AD-related biomarkers, and cognitive status. The study successfully met its primary and secondary endpoints, demonstrating that treatment with low-dose interleukin-2 is safe and well-tolerated in patients with Alzheimer’s disease. Notably, LD IL-2 showed targeted biological activity, evidenced by a significant expansion of regulatory T cell populations in the LD IL-2 q4wks group without any off-target effects on other peripheral lymphocytes. Additionally, the q4wks regimen led to significant improvements in cerebrospinal fluid-soluble Abeta42 levels, an indicator of amyloid pathology, and showed a promising trend in stabilizing cognitive function, with a clinically meaningful 4.93-point improvement1 in the ADAS-Cog14 score compared to placebo. In contrast, the q2wks group, representing the higher total dose cohort, did not exhibit benefits in exploratory endpoints, underscoring the importance of appropriate IL-2 dosing for maintaining Treg functionality and its associated effects on CSF biomarkers and cognitive outcomes. LD IL-2 q2wks dosing also resulted in a reduction of Foxp3 expression, a critical marker of Treg functionality. While these unstable Tregs continue to show suppressive immune response in vitro, they may lose their immunomodulatory functions in vivo, potentially explaining the dose impact on Treg populations and associated exploratory endpoints. As a result of these data, the company will likely advance LD IL-2 q4wks. Shares of Coya Therapeutics are up 1% in pre-market trading.