• Serum 4-Hydroxynonenal (4-HNE) levels are significantly increased in ALS patients- the higher the 4-HNE level, the faster the progression and shorter the survival;
• Serum 4-HNE levels are increased in bulbar vs. limb onset ALS patients and correlate with shortened survival in patients with bulbar onset ALS;
• Serum 4-HNE Receiver Operating Curve (ROC) Analysis demonstrates a 100% sensitivity for survival threshold of 21 months, indicating that it is a highly promising candidate biomarker in ALS and an independent monitor of clinical status for the upcoming COYA 302 Ph. 2 clinical trial

HOUSTON / Apr 26, 2024 / Business Wire / Coya Therapeutics, Inc. (Nasdaq: COYA) (“Coya” or the “Company”), a clinical-stage biotechnology company developing biologics intended to enhance regulatory T cell (Treg) function, announces that Dr. Stanley Appel, M.D., Chairman of Coya’s Scientific Advisory Board, and Dr. David Beers, Ph.D., Associate Research Professor of Neurology, Houston Methodist Hospital (HMH), will present biomarker data today as part of a presentation at the 2^nd Annual Johnson Center Symposium in Houston, TX.

The data presented highlights the strong predictive value of oxidative stress biomarker (4-HNE) levels with the rate of disease progression and survival in ALS patients from a longitudinal patient registry cohort.

Summary of Study Results

• A retrospective cohort study was conducted at HMH using longitudinal sera samples collected between January 2018 and December 2022 in 50 adult patients with confirmed sporadic ALS
• Randomly selected sera samples were assayed for 4-HNE levels by standard ELISAs and correlated with clinical outcomes and compared with 4-HNE levels from sera samples of 53 age-matched healthy controls
• Serum 4-HNE levels predictive of survival in ALS patients: 4-HNE levels significantly correlated with survival from onset of disease to death and from diagnosis to death
• Serum 4-HNE levels are elevated at diagnosis in bulbar vs. limb onset ALS: 4-HNE levels are increased in bulbar vs. limb onset ALS patients at diagnosis and parallel the shorter survival of bulbar ALS onset patients from diagnosis to death.
• ROC analysis demonstrates 100% sensitivity for 21 month survival threshold: 100% of patients that had serum levels > 8ug/ml were deceased within the subsequent 21 months, while 2/3 of patients that had serum levels < 8ug/ml were alive 21 months later.

Dr. Stanley Appel, M.D., Chairman of Coya’s SAB, commented: “The demonstration that serum levels of 4-HNE are highly correlated with ALS progression and survival highlights the potential value of this lipid peroxide as a biomarker of disease pathophysiology and as an independent monitor of clinical status.”

4-HNE Relevance in Disease Pathophysiology

Reactive oxygen species (ROS) are generated mainly as byproducts of mitochondrial respiration and are tightly controlled by multiple anti-oxidant mechanisms. In neurodegenerative diseases, such as ALS, when the antioxidant system is overwhelmed by overproduction of ROS, oxidative stress occurs. 4-HNE, an abundant and reactive oxygen species, is thought to exert neuronal toxicity ultimately through formation of toxic protein aggregates, as seen in ALS patients. Additionally, 4-HNE appears to be causally involved in multiple pathophysiologic events associated with disease pathophysiology, including motor neuron death.

About COYA 302

COYA 302 is an investigational and proprietary biologic combination therapy with a dual immunomodulatory mechanism of action intended to enhance the anti-inflammatory function of regulatory T cells (Tregs) and suppress the inflammation produced by activated monocytes and macrophages. COYA 302 is comprised of proprietary low dose interleukin-2 (LD IL-2) and CTLA-4 Ig (abatacept) and is being developed for subcutaneous administration for the treatment of patients with ALS, FTD, PD, and AD. These mechanisms may have additive or synergistic effects.

In February of 2023, Coya announced results from a proof-of-concept, open-label clinical study evaluating commercially available LD IL-2 and CTLA-4 Ig in a small cohort of patients with ALS conducted at the Houston Methodist Hospital by Stanley Appel, M.D., Jason Thonhoff, M.D., Ph.D., and David Beers, Ph.D.. This study was the first-of-its-kind evaluating this dual-mechanism immunotherapy for the treatment of ALS. Patients in the study received investigational treatment for 48 consecutive weeks and were evaluated for safety and tolerability, Treg function, serum biomarkers of oxidative stress and inflammation, and clinical functioning as measured by the ALSFRS-R scale.

During the 48-week treatment period, the therapy was well tolerated. The most common adverse event was mild injection-site reactions. No patient discontinued the study, and no deaths or other serious adverse events were reported.

Patients' disease progression was measured using the ALSFRS-R scale, a validated rating tool for monitoring the progression of disability in patients with ALS. The mean (±SD) ALSFRS-R scores at week 24 (33.75 ±3.3) and week 48 (32 ±7.8) after initiation of treatment were not statistically different compared to the ALSFRS-R score at baseline (33.5 ±5.9), suggesting significant amelioration in the progression of the disease over the 48-week treatment period.

Treg suppressive function, expressed as percentage of inhibition of proinflammatory T cell proliferation, showed a statistically significant increase over the course of the treatment period and was significantly reduced at the end of the 8-week washout post-treatment period. Treg suppressive function at 24 weeks (79.9 ±9.6) and 48 weeks (89.5 ±4.1) were significantly higher compared to baseline (62.1 ±8.1) (p<0.01), suggesting enhanced and durable Treg suppressive function over the course of treatment. In contrast, Treg suppressive function (mean ±SD) was significantly decreased at the end of the 8-week washout period compared to end-of-treatment at week 48 (70.3 ±8.1 vs. 89.5 ±4.1, p <0.05).

The study also evaluated serum biomarkers of inflammation, oxidative stress, and lipid peroxides. The available data up to 16 weeks after initiation of treatment suggest a decrease in these biomarker levels, which is consistent with the observed enhancement of Treg function. The evaluation of the full biomarker data is ongoing.

COYA 302 is an investigational product not yet approved by the FDA or any other regulatory agency.

About Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare neurological disease that affects motor neurons, the nerve cells in the brain and spinal cord that control voluntary muscle movement. About 20,000 people live with ALS in the United States and approximately 5,000 new cases are diagnosed every year. The disease is progressive, meaning the symptoms get worse over time. The functional status of ALS patients declines about 1 point per month on average, as measured by the Revised ALS Function Rating Scale¹, or ALSFRS-R, a validated tool to monitor the progression of the disease.

ALS has no cure, and the currently approved drug treatments provide limited benefit to patients. ALS is a type of motor neuron disease. As motor neurons degenerate and die, they stop sending messages to the muscles, which causes the muscles to weaken, start to twitch (fasciculations), and waste away (atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements. Most people with ALS die from respiratory failure, usually within three to five years from when the symptoms first appear.²

References

1. Atassi N, et al. The PRO-ACT database: design, initial analyses, and predictive features. Neurology, 2014;83:1719–1725. doi: 10.1212/WNL.0000000000000951.
2. National Institutes of Health (NIH) Website (https://www.ninds.nih.gov), accessed on January 8, 2024.

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, and 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.

COYA 302 – the Company’s lead biologic investigational product or "Pipeline in a Product" – is a proprietary combination of COYA 301 (Coya’s proprietary LD IL-2) and CTLA4-Ig for subcutaneous administration with a unique dual mechanism of action that is now being developed for the treatment of Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, and Alzheimer’s Disease. Its multi-targeted approach enhances the number and anti-inflammatory function of Tregs and simultaneously lowers the expression of activated microglia and the secretion of pro-inflammatory mediators. This synergistic mechanism may lead to the re-establishment of immune balance and amelioration of inflammation in a sustained and durable manner that may not be achieved by either low-dose IL-2 or CTLA4-Ig alone.

For more information about Coya, please visit www.coyatherapeutics.com

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