Combination therapy demonstrates 'synergistic anti-inflammatory effects'

Coya’s biologic therapeutic aims to suppress chronic inflammation by targeting two key immune pathways simultaneously.

A new paper published in the Journal of NeuroImmune Pharmacology and Therapeutics highlights the potential of Coya Therapeutics’ latest combination therapeutic to modulate the immune response in inflammatory and neurological conditions. Coya develops combination biologics that address chronic inflammatory and neurodegenerative diseases with regulatory T cell (Treg) dysfunction and persistent inflammation at their core.

Tregs are critical in maintaining immune balance and preventing excessive inflammation. In neurodegenerative diseases characterized by persistent immune activation, Tregs often exhibit dysfunction, resulting in chronic inflammation and oxidative stress.

The study, conducted at the Houston Methodist Research Institute, evaluated the synergistic effects of COYA 303, a dual-component biologic therapy combining low-dose interleukin-2 (also known as COYA 301) with a GLP-1 receptor agonist. The investigational treatment aims to enhance Treg function and suppress chronic inflammation by addressing two key immune pathways simultaneously.

Dr Fred Grossman is Chief Medical Officer of Coya Therapeutics.

LD IL-2 preferentially binds the IL-2 receptor alpha, which is highly expressed on Tregs, enhancing their suppressive capabilities. GLP-1RAs, which are already used clinically for metabolic disorders, also interact with the immune system and are known to influence myeloid and regulatory immune cell populations due to their receptor distribution.

The study demonstrated that the combined use of the drugs in COYA 303 significantly enhanced Treg suppressive function beyond what was observed with either agent alone. When tested in an in vitro system using immune cells from healthy human donors, LD IL-2 alone increased Treg suppression of pro-inflammatory myeloid cells by 15%, while GLP-1RA alone achieved a 20% enhancement. In contrast, COYA 303 led to a 42% increase in suppressive function, a statistically significant improvement that indicates a potential synergy between the two components.

“We believe COYA 303 could offer a differentiated and synergistic approach to addressing multiple conditions, including in neurodegenerative conditions such as Alzheimer’s Disease, in which GLP-1 RAs have recently shown promise,” said Coya CEO Dr Arun Swaminathan. “We believe the potential of this proprietary combination could lead to value-creating opportunities and may open up a new avenue of research within the GLP-1RA drug class.”

Furthermore, the study showed that COYA 303 also improved Treg survival by modulating apoptotic (cell death) pathways. The study found that COYA 303 reduced the expression of the pro-apoptotic markers, while increasing the expression of survival-related genes. Tregs treated with the combination exhibited elevated markers associated with suppressive capacity and stability.

In addition to its effects on Tregs, COYA 303 demonstrated the ability to downregulate inflammatory mediators in myeloid cells. The combination therapy suppressed IL-6 and TNF transcripts while promoting expression of ARG1, a marker associated with anti-inflammatory myeloid activity. These effects were associated with reduced IL-6 production and decreased proliferation of responder T cells, suggesting a broader immunoregulatory impact.

“We believe the encouraging results of this study provide support for our multi-targeted combination approach as a potentially viable treatment option for serious and life-threatening conditions of high unmet need driven by chronic inflammation and Treg dysfunction, for which currently available treatments provide limited benefits,” said Coya CMO Dr Fred Grossman.