Investigational COYA 302 Shows Feasibility, Preliminary Efficacy in Small Trial of Frontotemporal Dementia

Recently announced data from a small-scale, investigator-initiated trial showed that treatment with COYA 302 (Coya Therapeutics), a combination of low-dose interleukin-2 (IL2) plus CTLA-4 Ig, met its target engagement and led to stable cognitive outcomes in patients with frontotemporal dementia (FTD) over a 6-month period. Coya expects to move the investigational agent into more controlled phase 2 studies to further understand its therapeutic effects.^1,2

The trial featured 9 patients with FTD who received subcutaneous CTLA4-IgG, along with a 5-day course of low-dose IL-2 every 4 weeks for a treatment period lasting 22 weeks in total. Although not powered for significance, results revealed relatively unchanged scores on Montreal Cognitive Assessment (MoCA), a cognitive outcome, over the 22-week period (baseline: 13.5; week 22: 14). While there were slightly higher Clinical Dementia Rating-Frontotemporal Lobe Dementia (CDR-FTLD) scores at week 22, these were still considered unchanged relative to baseline (baseline: 4.8; week 22: 5.5).

“We believe these results suggest the potential for COYA 302 as a therapeutic option for patients with FTD,” Arun Swaminathan, chief executive officer at Coya, said in a statement. “We look forward to advancing COYA 302 in a well-controlled phase 2 clinical trial in patients with FTD.”

COYA 302, a biologic combination therapy, is designed to enhance the anti-inflammatory function of regulatory T cells (Tregs) and suppress the inflammation produced by activated monocytes and macrophages. The role of Tregs in FTD has been uncovered more in recent years, with a 2022 publication noting that these cells are compromised in this patient population. In addition to FTD, COYA 302 is being evaluated in patients with amyotrophic lateral sclerosis (ALS), through a phase 2 trial called ALSTARS (NCT07161999).

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Across the 22-week treatment period, investigators observed rapid and sustained enhancement of Treg biology, with multiple markers showing significant improvement as early as 2 weeks after dosing. Most notably, Treg suppressive function increased significantly by week 2 and remained consistently amplified through week 22, suggesting a durable shift toward a more immunoregulatory phenotype rather than a transient immunologic effect.

In the small-scale study, Treg percentage followed a similar trajectory, separating from baseline within 2 weeks and staying significantly elevated for the duration of treatment, indicating an expansion or enrichment of the Treg compartment. In parallel, CD25 mean fluorescence intensity (MFI), a marker closely tied to IL-2 receptor signaling and Treg activation, was significantly increased by week 2 and remained elevated through week 22, supporting sustained functional responsiveness of these cells. Finally, FOXP3 MFI, reflecting upregulation of the transcription factor central to Treg identity and stability, also rose significantly within 2 weeks of dosing.

In terms of safety, the most common adverse events (AEs) included erythema at injection site (33.3%), gastrointestinal symptoms (22.2%), and musculoskeletal pain (22.2%), all of which were mild in severity. Hives, which had 3 events occurring in 1 patient, was the only AE considered related to the intervention. Other documented AEs included hypokalemia, URI, UTI, urinary retention, headache, hypoglycemia, dental infection, sinus infection, feeding tube dysfunction, fatigue, aspiration pneumonia, and chest pain, each of which occurred in 1 participant.

“We believe this study continues to add evidence that restoring Treg numbers and function has the potential to translate to clinically meaningful effects across multiple neurodegenerative diseases,” Fred Grossman, chief medical officer at Coya, said in a statement.¹

More recently, the FDA accepted Coya’s investigational new drug application (IND) for COYA 302 for the treatment of FTD.³ To date, FTD remains the most common form of dementia in people under the age of 65, affecting nearly 60,000 Americans. To date, there are no FDA-approved therapies for FTD that target the underlying pathology of the disease, further stressing the need for more treatment options.

REFERENCES
1. Coya Therapeutics Announces Results of Investigator-Initiated Study of LD IL-2 and CTLA4-Ig Demonstrating Treg Enhancement and Cognitive Stability in Frontotemporal Dementia Patients. News release. January 8, 2026. Accessed January 15, 2026. https://www.businesswire.com/news/home/20260108513635/en/Coya-Therapeutics-Announces-Results-of-Investigator-Initiated-Study-of-LD-IL-2-and-CTLA4-Ig-Demonstrating-Treg-Enhancement-and-Cognitive-Stability-in-Frontotemporal-Dementia-Patients
2. Faridar A. Low Dose Interleukin-2 Plus Abatacept Feasibility Trial in Patients With Frontotemporal Dementia. Coya Therapeutics. Published January 8, 2026. Accessed January 15, 2026. https://s201.q4cdn.com/307844724/files/doc_presentations/2026/Jan/07/Coya-FTD-IIT-Study-slides-2026-01-08.pdf
3. Coya Therapeutics Announces U.S. FDA Acceptance of Investigational New Drug (IND) Application for COYA 302 for the Treatment of Frontotemporal Dementia (FTD). Coya Therapeutics. January 5, 2026. Accessed January 15, 2026. https://www.businesswire.com/news/home/20260105080790/en/Coya-Therapeutics-Announces-U.S.-FDA-Acceptance-of-Investigational-New-Drug-IND-Application-for-COYA-302-for-the-Treatment-of-Frontotemporal-Dementia-FTD