Data demonstrates halting of disease progression in patients with Amyotrophic Lateral Sclerosis (ALS) at 24 weeks (6 months) and a consistent reduction in inflammation, oxidative stress, and enhanced Regulatory T cell (Treg) number and suppressive function in patients who were administered a combination of CTLA4-Ig Fusion Protein (CTLA4-Ig) and Low Dose Interleukin-2 (LD IL-2);

Prior to initiating treatment, patients were declining at an average rate of -1.1 points per month on the ALSFRS-R rating scale- At the end of 6 months of treatment, the mean rate of change on the ALSFRS-R was +0.04 points per month.

Coya Therapeutics, Inc. (NASDAQ: COYA) (“Coya” or the “Company”), a clinical-stage biotechnology company developing biologic intended to enhance regulatory T cell (Treg) function, announces the publication of a peer-reviewed manuscript titled, “A Phase 1 Proof-of-Concept Study Evaluating Safety, Tolerability, and Biological Marker Responses with Combination Therapy of CTLA4-Ig and Interleukin-2 in Amyotrophic Lateral Sclerosis,” in the medical journal Frontiers in Neurology. The publication can be viewed here.

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Disease progression remained relatively unchanged during the first 6 months of CTLA4-Ig/LD IL-2 treatment (Graphic: Business Wire)

Dr. Stanley Appel, MD, Edwards Distinguished Endowed Chair for ALS and Director, Johnson Center for Cellular Therapeutics at Houston Methodist stated, “The ability of the combination therapy to halt clinical progression in ALS for 24 weeks provides an important proof of concept for the protective role of Tregs while simultaneously suppressing inflammation. What is most gratifying is the concomitant reduction of the lipid peroxide 4-HNE as well as inflammatory cytokines. This study provides the basis for a large-scale double-blind placebo-controlled trial to establish potential therapeutic efficacy for ALS patients.”

Dr. Howard H. Berman, CEO of Coya Therapeutics, stated: “This publication illustrates a promising clinical signal of a novel biologic combination immunotherapy in ALS, a truly devastating condition with high unmet need. Our development of our ALS program continues, and Coya remains on track to file its Investigational New Drug Application (IND) with the Food and Drug Administration (FDA) for its proposed randomized double blind placebo controlled study for LD IL-2 + CTLA4-Ig in ALS this month (June, 2024). Concurrently, our strong balance sheet ensures that we have adequate capital to execute on this upcoming study.”

In this open-label study, four participants with ALS received subcutaneous injections of commercial LD IL-2 (1x10⁶ IU/injection/day) for 5 consecutive days every 2 weeks and one subcutaneous injection of CTLA4-Ig (125 mg/mL/injection) every 2 weeks for a total of 24 treatment cycles during the 48-week treatment period. Study participants were followed for additional 8 weeks after treatment with LD IL-2 / CTLA4-Ig. Three participants were sporadic ALS while 1 participant (#1) had mutant C9ORF72-mediated ALS, and 3 participants had respiratory insufficiency according to a qualifying low maximal inspiratory pressure (MIP) value (≤ 60 cm H2O), 2 of which were already being treated with noninvasive ventilation. Prior to initiating treatment, patients had a documented average disease progression of -1.1 points per month in the ALSFRS-R score.

Summary of Results:

Safety and tolerability of CTLA4-Ig/LD IL-2 treatment: Treatment was well tolerated among all patients. There were no serious adverse events and only mild treatment emergent adverse events, and all patients completed the study.

Treg Suppressive Function: Treg suppressive function was significantly increased compared to baseline at weeks 16, 24 and 48 and returned to baseline levels at 6 weeks after the final course of treatment (washout)

Clinical Progression: For all 4 participants, the mean rate of change in the ALSFRS-R over the first 24 weeks was stable (+0.04 points/month). During this time period, the ALSFRS-R improved by 4 points in participant #1, improved by 3 points in participant #2, was unchanged in participant #3, and decreased by 6 points in participant #4. Participant #4 experienced a 4-point decrease at week 4, but then remained relatively stable from weeks 4 to 24. Over the 48-week treatment period, the average rate of change in the ALSFRS-R was -0.13 points/month.

Biological Marker Changes: Biological markers of oxidative stress (4-HNE and ox-LDL), inflammation (IL-18), and structural degeneration (Nf-L) were assessed at baseline and throughout the course of the study. During the first 16 weeks of treatment, 3 participants showed a decreasing trend of 4-HNE, all 4 participants showed decreasing trend of ox-LDL, 3 participants showed a decreasing trend of IL-18, and 2 participants showed decreasing trend in Nf-L. These trends corresponded with the participants lack of observable disease progression during this time.

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 CTLA4-Ig and is being developed for subcutaneous administration for the treatment of patients with ALS, FTD, and PD. 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 CTLA4-Ig in a small cohort of patients with ALS conducted at the Houston Methodist Research Institute (Houston, Texas) 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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