• The open-label study evaluated the safety and tolerability, biological activity, blood biomarkers and preliminary efficacy of low-dose interleukin 2 (ld IL-2) in 8 patients with Alzheimer’s disease (AD). The academic study was conducted by Dr. Appel and Dr. Faridar at the Houston Methodist Hospital.
• The additional clinical data show a significant decrease in biomarker levels known to be associated with neuroinflammation in AD patients further supporting the initial positive results of the study. Blood levels of CCL4 (CC motif chemokine ligand 4), FLT3LG (FMS-related tyrosine kinase 3 ligand) and TNFα (tumor necrosis factor alpha) were consistently lower following administration of ld IL-2.
• Coya’s investigational ld IL-2 for subcutaneous administration has been designed to enhance the function of regulatory T cells (Tregs) in vivo and it is being developed for the treatment of neurodegenerative and autoimmune diseases, as monotherapy or in combination with other immunomodulatory agents.
• Previously released data showed that treatment with ld IL-2 resulted in a statistically significant improvement in cognitive function, as measured by the Mini-Mental State Examination test (MMSE). In addition, no cognitive decline was observed when it was measured by the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), and the Clinical Dementia Rating-Sum of Boxes scale (CDR-SB).
• Over the course of the study, ld IL-2 demonstrated biological activity by restoring peripheral Treg function and numbers and significantly lowering the blood levels of other well-characterized proinflammatory cytokines and chemokines, such as IL-15 (interleukin 15), CCL2 (monocyte chemoattractant protein-1) and CCL11 (CC motif chemokine ligand 11).
• Treatment with ld IL-2 administered subcutaneously appeared to be safe and well tolerated in patients with AD.
• An ongoing phase 2, double blind, placebo controlled trial (funded by the Gates foundation and Alzheimer’s Association) in approximately 46 patients with mild to moderate AD is almost fully enrolled and should report top line results in July, 2024.

HOUSTON / Jul 17, 2023 / Business Wire / Coya Therapeutics, Inc. (NASDAQ: COYA) (“Coya” or the “Company”), a clinical-stage biotechnology company developing multiple therapeutic platforms intended to enhance Treg function, including biologics and cell therapies, today reported results from an open-label proof-of-concept clinical study for ld IL-2 in patients with AD. Results of the study were presented July 16, 2023, at the Alzheimer’s Association International Conference (AAIC) in Amsterdam, Netherlands. The poster can be accessed here.

The study enrolled 8 patients with confirmed presence of brain amyloid pathology and baseline MMSE scores between 12 and 25. The patients were treated with five-day-courses of subcutaneous ld IL-2 for four monthly cycles and were followed for two months post-treatment. Treg function and numbers, serum biomarkers of inflammation, safety and tolerability, and cognitive functioning as measured by the ADAS-Cog, CDR-SB and MMSE assessment tools were evaluated.

The additional blood biomarker data showing a significant decrease in the blood levels of the proinflammatory cytokines and chemokines CCL4, FLT3LG and TNFα in AD patients treated with ld IL-2 strengthen the positive results Coya has previously announced in May 2023.

Coya previously reported that the treatment with ld IL-2 significantly expanded Treg population and function. At baseline, the mean (SD) percentage of Tregs was 4.55 (1.97) and was almost double at the end of the treatment [8.68 (2.99), p=0.0004]. Mean (SD) Treg suppressive function was 46.61% (7.74) at baseline, and significantly increased to 79.5 % (20.55) at the end of treatment (p=0.003).

In addition, evaluation of cognitive function showed that administration of ld IL-2 resulted in a statistically significant improvement in mean MMSE scores during the treatment phase, compared to mean MMSE score at baseline (p=0.015). Consistent with the positive trend in MMSE score, mean scores in ADAS-Cog and CDR-SB scales did not significantly change at the end of treatment with COYA 301, compared to pre-treatment baseline scores, indicating no cognitive decline as measured by these validated instruments.

Overall, administration of ld-IL-2 appeared to be safe and well tolerated. The most common adverse events were mild injection-site reactions and mild leukopenia. No serious adverse events were reported, and no patient discontinued the study.

Following the encouraging results of this open-label proof-of-concept study, a Phase 2 double-blind, placebo-controlled study in approximately 46 patients with mild-to-moderate AD is being conducted at the Houston Methodist Hospital and as of today, is almost fully enrolled with 38 patients in the study. The well-controlled clinical study will evaluate the safety and tolerability, Teg function, blood biomarkers of neuroinflammation, and efficacy of two dose regimens of ld IL-2 compared to placebo, over a 30-week period. Top-line results are anticipated in July 2024. The study is funded by the Gates Foundation and the Alzheimer’s Association.

Stanley Appel, M.D., Professor at Houston Methodist and Chair of Coya’s Scientific Advisory Board commented, “Our research studies documenting a significant reduction of Treg neuroprotective functions in AD led to our use of low dose IL-2 to enhance Treg numbers and suppressive functions. Our 8 patient study in AD was safe and well tolerated, decreased pro-inflammatory signaling, and suggested a beneficial clinical effect. We are optimistic that this approach, now being tested in a larger double-blind placebo-controlled study, may help address the unmet needs of our deserving AD patients.”

About Alzheimer’s Disease

Alzheimer's disease is the most common cause of dementia, a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. Alzheimer's disease accounts for up to 80% of dementia cases, affecting an estimated 5.7 million Americans. In more than 90% of people with Alzheimer’s, symptoms do not appear until after age 60. The incidence of the disease increases with age and doubles every 5 years beyond age 65. Alzheimer's is a progressive disease, where dementia symptoms gradually worsen over a number of years. In its early stages, memory loss is mild, but with late-stage Alzheimer's, individuals lose the ability to carry on a conversation and respond to their environment. It is the sixth leading cause of death among all adults and the fifth leading cause for those aged 65 or older. On average, a person with Alzheimer's lives 4 to 8 years after diagnosis but can live as long as 20 years, depending on other factors. ^1,2

References

1. Alzheimer’s Association (www.alz.org).
2. Centers for Disease Control and Prevention (www.cdc.gov).

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 a 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’s 300 Series product candidates, COYA 301 and COYA 302, are biologic therapies intended to enhance Treg function and expand Treg numbers. COYA 301 is a cytokine biologic for subcutaneous administration intended to enhance Treg function and expand Treg numbers in vivo, and COYA 302 is a biologic combination for subcutaneous and/or intravenous administration intended to enhance Treg function while depleting T effector function and activated macrophages. These two mechanisms may be additive or synergistic in suppressing inflammation. For more information about Coya, please visit www.coyatherapeutics.com

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