Coya Therapeutics Publishes Preclinical Findings for COYA 303 in Neuroinflammation
Coya Therapeutics, Inc. (NASDAQ: COYA), a clinical-stage biotechnology company focused on developing biologic therapies designed to enhance regulatory T-cell (Treg) function, has announced the publication of new preclinical findings evaluating COYA 303, an investigational immunomodulatory combination therapy. The research has been published in the International Journal of Molecular Sciences as part of a special issue examining the roles of glucagon-like peptide-1 (GLP-1) receptor agonists in health and disease.
The publication adds to Coya Therapeutics’ growing body of research into therapeutic strategies aimed at addressing inflammation and immune dysregulation associated with serious neurodegenerative diseases. The company is investigating whether combining different mechanisms of immune regulation could provide broader effects than therapies that target a single pathway.
COYA 303 consists of proprietary low-dose interleukin-2 (LD-IL2) combined with a GLP-1 receptor agonist (GLP-1RA). The combination was evaluated in a subacute low-dose lipopolysaccharide (LPS) mouse model, a research model used to investigate inflammatory and immune responses relevant to neurodegenerative disease biology.
The findings showed that treatment with the GLP-1RA and LD-IL2 combination produced significant changes in inflammatory and immune-related markers in both peripheral immune cells and tissues of the central nervous system (CNS). According to Coya, the results support further investigation of the combination in chronic and disease-relevant models.
Investigating a Multi-Targeted Immunomodulatory Approach
Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer’s disease (AD) are complex disorders involving multiple biological mechanisms. Persistent inflammation and immune dysregulation are increasingly recognized as important components of disease biology, although the precise contribution of these processes can vary among diseases and stages.
Coya is developing therapies intended to influence immune regulation by enhancing the activity and function of Tregs. These immune cells play an important role in maintaining immune balance and limiting excessive inflammatory responses.
COYA 303 combines this Treg-focused strategy with a GLP-1 receptor agonist. GLP-1 receptor agonists are widely recognized for their metabolic effects, but research has also investigated their potential effects on inflammatory and immune pathways.
The rationale behind COYA 303 is to simultaneously influence inflammatory myeloid activity and reinforce Treg-mediated immune regulation. Coya believes that targeting these complementary mechanisms could potentially produce broader immunomodulatory effects than either treatment used independently.
The newly published study was designed to examine this concept in an experimental setting where inflammatory signaling had already been initiated.
LPS Mouse Model Used to Evaluate Inflammation
Researchers evaluated COYA 303 in a subacute low-dose LPS mouse model. Lipopolysaccharide is a component of the outer membrane of certain bacteria and is commonly used in laboratory research to stimulate inflammatory immune responses.
In this model, LPS administration can increase pro-inflammatory signaling and activate myeloid cells, creating an environment of immune dysregulation. Such experimental models can be used to explore potential therapeutic mechanisms and assess whether an investigational intervention can modify inflammatory responses.
For the study, researchers evaluated whether combining a GLP-1 receptor agonist with low-dose IL-2 could influence immune activity both outside the brain and within CNS-associated tissues.
An important aspect of the research was the timing of treatment. GLP-1RA and LD-IL2 administration began 24 hours after the initial LPS exposure. This meant that treatment was initiated after inflammatory induction had already begun rather than being administered solely as a preventive intervention.
Coya said the observation of treatment-associated effects under these conditions provides additional support for further evaluation of the combination in models designed to better represent chronic disease processes.
Effects on Peripheral Immune Markers
The study identified significant changes across several immune-related endpoints in animals receiving the combination therapy.
In peripheral immune cells, treatment with GLP-1RA and LD-IL2 resulted in significant reductions in transcript expression associated with the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF).
IL-6 and TNF are important mediators of inflammatory responses and have been studied extensively in the context of immune activation and inflammatory disease. Changes in their expression can provide researchers with information about how an experimental therapy may influence inflammatory signaling.
At the same time, the combination treatment increased expression of arginase-1 (ARG1), a marker associated with certain anti-inflammatory or reparative myeloid cell states.
The combination also increased the expression of several transcripts associated with regulatory T-cell activity and immune modulation. These included interleukin-2 receptor alpha (IL-2Ra, also known as CD25), transforming growth factor beta 1 (TGF-β1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
These findings were reported as being more pronounced with the combination therapy than with the individual monotherapy treatments.
The results suggest that the two components of COYA 303 may influence complementary aspects of the immune response. Rather than acting exclusively on a single inflammatory pathway, the combination produced changes involving both inflammatory myeloid activity and regulatory immune mechanisms.
Changes Observed in Brain Tissue
Researchers also evaluated inflammatory and immune-associated markers in the cerebral cortex and hippocampus.
Within these brain regions, the combination treatment significantly reduced expression of IL-6 and interleukin-1 beta (IL-1β), both of which are associated with pro-inflammatory signaling.
At the same time, treatment increased transcript expression for CD163 and CD206. These markers are associated with M2 macrophages, a macrophage state commonly linked with anti-inflammatory activity, tissue repair and remodeling.
According to the study results, the changes observed in the cortical and hippocampal tissues were more substantial with the combination treatment than with either therapy administered independently.
These findings are relevant to Coya’s interest in neuroinflammation because they suggest that the combination may influence immune-associated processes in both peripheral tissues and areas of the CNS.
However, the findings remain preclinical. Changes in inflammatory transcripts and immune markers in animal models do not by themselves establish clinical efficacy in humans. Additional research will be necessary to determine whether the biological effects observed in this study translate into meaningful therapeutic benefits in patients with neurodegenerative diseases.
Limited Effects With Monotherapy
Another notable aspect of the study was the difference between combination treatment and individual therapies.
According to Coya, monotherapy with either the GLP-1 receptor agonist or low-dose IL-2 produced relatively limited changes across the evaluated endpoints. In contrast, the combination generated clearer and more consistent effects across multiple inflammatory and regulatory markers.
This observation provides support for the company’s multi-targeted approach. By combining agents that may influence different components of immune regulation, Coya is investigating whether it can achieve a broader biological response.
The findings also provide a rationale for additional studies designed to examine the durability and significance of these effects in models that more closely reflect chronic neurodegenerative disease.
Coya Highlights Potential for Neurodegenerative Disease Applications
Fred Grossman, DO, FAPA, President and Chief Medical Officer of Coya Therapeutics, said the findings reinforce the company’s interest in combination immunomodulatory strategies for serious neurodegenerative disorders.
“We are encouraged by these preclinical findings, which we believe demonstrate the therapeutic potential of immunomodulatory combinations for the treatment of serious neurodegenerative diseases characterized by sustained inflammation,” Grossman said.
He noted that diseases such as ALS, FTD and Alzheimer’s disease involve complex biological mechanisms and may require treatment approaches capable of influencing multiple pathways.
“These results continue to reinforce our belief that complex neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s disease (AD) are best addressed through a combination approach,” Grossman said.
He also emphasized the need for additional research in chronic and disease-relevant models to better understand the potential of the strategy.
Importance of Further Research
The publication of the COYA 303 findings provides Coya with additional preclinical evidence as it evaluates potential immunomodulatory strategies for neurodegenerative disease.
The company plans to use future studies to further investigate the mechanisms underlying the combination’s effects and determine whether similar responses can be observed in experimental models that more closely replicate chronic disease conditions.
Such studies will be important because neurodegenerative diseases develop over extended periods and involve complex interactions among neurons, immune cells, glial cells and other biological systems. Acute or subacute inflammatory models can provide useful mechanistic information, but they cannot fully reproduce the complexity of human disease.
Further research will therefore be required to assess whether the observed reductions in inflammatory markers and increases in regulatory immune markers can translate into changes in disease-related outcomes.
Study Conducted Through Houston Methodist Collaboration
The study was conducted by Dr. Stanley Appel, Dr. Aaron Thome and other researchers at the Houston Methodist Neurological Institute. The research was funded by Coya through a sponsored research agreement with the Houston Methodist Hospital Research Institute.
The collaboration reflects Coya’s ongoing work with academic researchers to investigate the role of immune regulation in neurological disorders and evaluate potential therapeutic approaches.
The publication in the International Journal of Molecular Sciences also places the findings within a broader scientific discussion regarding the potential immunomodulatory effects of GLP-1 receptor agonists. The special issue in which the article appears focuses on emerging applications of GLP-1 receptor agonists beyond their established metabolic uses.
The newly published findings represent another step in Coya Therapeutics’ efforts to develop therapies targeting immune dysfunction associated with neurodegenerative disease.
COYA 303 is designed around the combination of two distinct therapeutic approaches: low-dose IL-2, intended to support regulatory T-cell activity, and a GLP-1 receptor agonist, which may influence inflammatory and metabolic pathways.
In the LPS mouse model, the combination produced changes across peripheral immune cells as well as cortical and hippocampal tissues. The observed reductions in pro-inflammatory markers, together with increases in markers associated with regulatory T cells and potentially anti-inflammatory myeloid states, provide a biological basis for further investigation.
The fact that treatment began after inflammatory activation had already occurred is another element Coya considers relevant to the program. Nevertheless, the company recognizes that additional studies are needed, particularly in chronic disease models, to establish whether these effects can be sustained and whether they have meaningful implications for neurodegenerative disease progression.
As Coya continues its research, future findings will help clarify the therapeutic potential of COYA 303 and the broader concept of combination immunomodulation. The company’s approach reflects a growing interest in addressing neurodegenerative diseases through strategies that target not only neuronal processes but also the immune and inflammatory pathways that may contribute to disease biology.
For now, the publication provides preclinical evidence supporting continued evaluation of COYA 303. Additional research will be essential to determine whether the combination can ultimately advance from experimental models into clinical development and potentially offer a new treatment strategy for patients affected by serious inflammation-associated neurodegenerative diseases.
About COYA 303
COYA 303 is an investigational proprietary biologic combination of low-dose IL-2 and a glucagon-like-peptide-1 receptor agonist (GLP-1RA) designed for subcutaneous administration. In preclinical studies, COYA 303 has demonstrated a dual immunomodulatory mechanism of action targeting regulatory T cells (Tregs) and pro-inflammatory myeloid cells.
About Coya Therapeutics, Inc.
Headquartered in Houston, TX, Coya Therapeutics, Inc. (Nasdaq: COYA) is a clinical-stage biotechnology company developing proprietary treatments focused on the biology and potential therapeutic advantages of regulatory T cells (“Tregs”) to target systemic inflammation and neuroinflammation. Dysfunctional Tregs underlie numerous conditions, including neurodegenerative, metabolic, and autoimmune diseases. This cellular dysfunction may lead to sustained inflammation and oxidative stress resulting in lack of homeostasis of the immune system.
Coya’s investigational product candidate pipeline leverages multiple therapeutic modalities aimed at restoring the anti-inflammatory and immunomodulatory functions of Tregs. Coya’s therapeutic platforms include Treg-enhancing biologics, Treg-derived exosomes, and autologous Treg cell therapy.