Coya Therapeutics' Alzheimer's Candidate: Monthly Dosing Shows Promise in Inflammatory Blood Markers

Coya Therapeutics, Inc. (NASDAQ: COYA), a clinical-stage biotechnology company, has reported encouraging results from a Phase 2 study of low-dose interleukin-2 (LD IL-2) in patients with Alzheimer's disease (AD). The study, conducted at the Houston Methodist Research Institute, demonstrated statistically significant improvements in inflammatory blood markers following monthly dosing of LD IL-2. These findings suggest that LD IL-2 may have potential as a therapeutic approach for AD.

The investigator-initiated, 21-week, double-blind, placebo-controlled, exploratory Phase 2 trial evaluated two dosing regimens of subcutaneous LD IL-2 in 38 participants with AD. The primary endpoint was the incidence and severity of adverse events (AEs), with the secondary endpoint evaluating changes in regulatory T cells (Tregs). Exploratory endpoints assessed changes in cerebrospinal fluid (CSF), AD-related biomarkers, and cognitive status.

The study successfully met its primary and secondary endpoints, demonstrating that treatment with LD IL-2 is safe and well-tolerated in patients with AD. Notably, LD IL-2 showed targeted biological activity, evidenced by a significant expansion of Treg 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 (CSF)-soluble Aβ42 levels, an indicator of amyloid pathology, and showed a promising trend in stabilizing cognitive function, with a clinically meaningful 4.93-point improvement 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 function. The study supports and increases confidence in Treg modulation strategies in neurodegenerative conditions and in advancing LD IL-2 q4wks and LD IL-2 q4wks combination strategies (i.e., COYA 302) in AD and other related diseases.



The monthly dosing regimen of LD IL-2 showed superior results compared to biweekly administration in terms of efficacy and safety. Patients receiving monthly LD IL-2 demonstrated statistically significant reductions in proinflammatory markers CCL2 (p<0.05) and IL-15 (p<0.001), as well as an increase in the anti-inflammatory cytokine IL-4 (p<0.01) compared to placebo. In contrast, the biweekly dosing regimen did not show significant improvements in these markers. Patients receiving monthly LD IL-2 also showed a 4.93-point improvement in the ADAS-Cog score compared to placebo over the 21-week treatment period, indicating clinically relevant cognitive stabilization. The biweekly dosing regimen did not result in a significant improvement in cognitive function.



The improvement in beta amyloid 42 clearance observed in the study is a significant finding that relates to the overall disease progression and potential long-term benefits for patients with Alzheimer's disease. Beta amyloid 42 (Aβ42) is a protein fragment that accumulates in the brain and forms plaques, which are a hallmark of Alzheimer's disease. The clearance of Aβ42 is an important factor in slowing down the progression of the disease. In the study, patients receiving monthly LD IL-2 showed an increase in Aβ42 levels in cerebrospinal fluid (CSF), suggesting increased clearance of amyloid-β. This is a critical factor in disease modification, as the reduction of amyloid plaques can help slow down the progression of cognitive decline in Alzheimer's patients.

The corresponding increase in CSF Aβ42 levels and the 4.93-point improvement in ADAS-Cog scores over 21 weeks are clinically relevant and indicate that LD IL-2 therapy may have long-term benefits for patients with Alzheimer's disease. The ADAS-Cog score is a widely used measure of cognitive function in Alzheimer's patients, and a change of 4 points or more is generally considered meaningful in AD trials. The reversion of anti-inflammatory benefits to baseline after treatment cessation validates the biological activity of the therapy while highlighting the need for maintenance treatment. This suggests that continuous treatment with LD IL-2 may be necessary to maintain the beneficial effects on beta amyloid clearance and cognitive function in the long term.

In conclusion, the monthly dosing regimen of LD IL-2 appears to be more efficacious and safe compared to biweekly administration, with potential benefits for treatment adherence and cost-effectiveness. The combination of increased Aβ42 clearance, stabilized cognitive function, and the need for maintenance treatment suggests that LD IL-2 may play a crucial role in slowing down the progression of the disease and improving the overall quality of life for patients with Alzheimer's disease.