HOUSTON--(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 the direct CNS anti-inflammatory effect of subcutaneously administered COYA 302 in a preclinical inflammatory associated mouse model of Parkinson’s Disease (PD)..

休斯顿--（商业新闻短讯）--Coya Therapeutics，Inc.（纳斯达克：Coya）（“Coya”或“公司”）是一家临床阶段的生物技术公司，开发旨在增强调节性T细胞（Treg）功能的生物制剂，宣布皮下注射Coya 302在帕金森病（PD）临床前炎症相关小鼠模型中的直接中枢神经系统抗炎作用。。

Coya’s Chief Business Officer and incoming Chief Executive Officer Arun Swaminathan, Ph.D. stated: “We believe that the ability of peripherally administered biologics (COYA 302) that potently and directly ameliorate the inflammatory milieu in the brain translates to strategies to suppress CNS neuro-inflammation beyond PD, including other inflammatory mediated neurodegenerative diseases such as Alzheimer’s disease (AD) and Frontotemporal Dementia (FTD).”.

Coya首席商务官兼新任首席执行官Arun Swaminathan博士表示：“我们认为，外周给药生物制剂（Coya 302）能够有效和直接改善大脑中的炎症环境，从而转化为抑制PD以外的中枢神经系统神经炎症的策略，包括其他炎症介导的神经退行性疾病，如阿尔茨海默氏病（AD）和额颞叶痴呆（FTD）。”。

Parkinson’s disease is characterized by the selective loss of dopaminergic neurons in brain regions responsible for motor control (nigrostriatal pathway), while inflammation and immune dysfunction from the associated loss of systemic Treg function are currently recognized as critical mediators of disease and subsequent progression of PD.

帕金森氏病的特征是负责运动控制（黑质纹状体通路）的大脑区域中多巴胺能神经元的选择性丧失，而全身Treg功能丧失引起的炎症和免疫功能障碍目前被认为是疾病和随后PD进展的关键介体。

Targeting the sustained proinflammatory mechanisms that progress the disease and enhance immunosuppressive cells, such as Tregs, may have the potential to provide disease-modifying benefits in patients with PD..

针对疾病进展和增强免疫抑制细胞（如Tregs）的持续促炎机制，可能有可能为PD患者提供改善疾病的益处。。

In an inflammatory mouse model of PD, subcutaneous injections of COYA 302 significantly reduced inflammation and microglial activation in nigrostriatal brain regions responsible for motor control (dorsal striatum and substantia nigra). Microglial activation is an important mediator of PD and plays an important role in PD pathology and neurodegeneration.

。小胶质细胞激活是PD的重要介质，在PD病理学和神经变性中起重要作用。

Microglial inhibition may hold promise as a therapeutic strategy to delay the progression of PD. Additionally, subcutaneous injections of COYA 302 resulted in reductions in astrocyte numbers and their activation (astrogliosis) in the nigrostriatal pathway. It is known that pathogenic astrocyte activation leads to neurodegeneration in PD, and mitigating its damage may be another therapeutic target.

小胶质细胞抑制可能有望作为延缓PD进展的治疗策略。此外，皮下注射COYA 302导致黑质纹状体途径中星形胶质细胞数量减少及其活化（星形胶质细胞增生）。已知致病性星形胶质细胞活化导致PD中的神经变性，减轻其损伤可能是另一种治疗靶标。

COYA 302’s direct effect in reducing neuroinflammatory constituents known to drive neurodegeneration is promising and warrants clinical translation into additional preclinical models and, ultimately, into patients. The Company anticipates presenting and/or publishing these data in a peer reviewing setting..

COYA 302在减少已知驱动神经变性的神经炎症成分方面的直接作用是有希望的，并且需要将其临床转化为其他临床前模型，并最终转化为患者。公司预计将在同行评审环境中呈现和/或发布这些数据。。

About Parkinson’s Disease

关于帕金森氏病

Parkinson’s disease (PD) is the most common movement disorder and the second most common neurodegenerative disease, affecting approximately 1% of individuals over the age of 60. Its prevalence increases significantly with age, and as the global population continues to age, the incidence of PD is expected to rise further.

帕金森氏病（PD）是最常见的运动障碍，也是第二常见的神经退行性疾病，约有1%的60岁以上人群受到影响。随着年龄的增长，其患病率显着增加，随着全球人口的不断老龄化，PD的发病率预计将进一步上升。

The hallmark of PD is the progressive degeneration of dopaminergic neurons, particularly in the substantia nigra, a region of the brain integral to the nigrostriatal pathway, which plays a crucial role in coordinating motor control. This neuronal loss leads to the characteristic motor symptoms of PD, such as bradykinesia, rigidity, and tremors, while patients also exhibit non-motor manifestations, such as cognitive decline, mood disturbances, and sleep disorders..

PD的标志是多巴胺能神经元的进行性变性，特别是在黑质中，黑质是大脑黑质纹状体通路不可或缺的区域，在协调运动控制中起着至关重要的作用。这种神经元丢失导致PD的特征性运动症状，例如运动迟缓，僵硬和震颤，而患者也表现出非运动表现，例如认知能力下降，情绪障碍和睡眠障碍。。

While the exact cause of the dopaminergic neuron loss is not fully understood, growing evidence highlights chronic neuroinflammation and immune dysfunction as central drivers of PD pathogenesis and progression. A key aspect of PD pathophysiology is neuroinflammation in the nigrostriatal pathway, including the presence of reactive astrocytes.

虽然多巴胺能神经元丢失的确切原因尚不完全清楚，但越来越多的证据表明慢性神经炎症和免疫功能障碍是PD发病机制和进展的主要驱动因素。PD病理生理学的一个关键方面是黑质纹状体途径中的神经炎症，包括反应性星形胶质细胞的存在。

This neuroinflammation has long been considered a downstream response to the death of dopaminergic neurons. However, increased evidence suggests that astrocytes have an initiating role in PD pathophysiology. Regulatory T cells (Tregs), a subset of T cells responsible for maintaining immune homeostasis and preventing excessive immune responses, are decreased and impaired in PD patients and preclinical models.

。然而，越来越多的证据表明星形胶质细胞在PD病理生理学中具有起始作用。调节性T细胞（Tregs）是负责维持免疫稳态和防止过度免疫反应的T细胞亚群，在PD患者和临床前模型中减少和受损。

Subsequently, chronic pro-inflammatory immune cell activation, oxidative stress, and mitochondrial dysfunction all contribute to neuronal damage. The combination of targeting the chronic, proinflammatory activation and enhancing the Treg immunosuppressive function offers promising therapeutic potential for a disease-modifying therapy that could effectively alter the course of the disease, reduce neuronal loss, and improve patient outcomes..

随后，慢性促炎性免疫细胞活化，氧化应激和线粒体功能障碍都会导致神经元损伤。靶向慢性促炎激活和增强Treg免疫抑制功能的组合为疾病缓解疗法提供了有希望的治疗潜力，该疗法可以有效改变疾病进程，减少神经元丢失并改善患者预后。。

References

参考文献

1. Kouli, Torsney, and Kuanl. Chapter 1 - Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis; Parkinson’s Disease: Pathogenesis and Clinical Aspects, Codon Publications, 2018

1.Kouli、Torsney和Kuanl。第1章-帕金森病：病因，神经病理学和发病机制；帕金森氏病：发病机制和临床方面，密码子出版物，2018年

2. Booth, Hirst, and Wade-Martins. The Role of Astrocyte Dysfunction in Parkinson’s Disease Pathogenesis; Trends in Neuroscience, 2017 June, 40(6): 358-370

布斯、赫斯特和韦德·马丁斯。星形胶质细胞功能障碍在帕金森病发病机制中的作用；神经科学趋势，2017年6月，40（6）：358-370

About COYA 302

关于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 fusion protein and is being developed for subcutaneous administration for the treatment of patients with ALS, AD, FTD, and PD.

COYA 302是一种研究性和专有的生物联合疗法，具有双重免疫调节作用机制，旨在增强调节性T细胞（Tregs）的抗炎功能并抑制活化的单核细胞和巨噬细胞产生的炎症。COYA 302由专有的低剂量白细胞介素-2（LD IL-2）和CTLA4-Ig融合蛋白组成，正在开发用于皮下给药，用于治疗ALS，AD，FTD和PD患者。

These mechanisms may have additive or synergistic effects..

这些机制可能具有累加或协同效应。。

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 fusion protein 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..

这项研究是首次评估这种用于治疗ALS的双重机制免疫疗法。该研究中的患者连续48周接受研究性治疗，并通过ALSFRS-R量表评估其安全性和耐受性，Treg功能，氧化应激和炎症的血清生物标志物以及临床功能。。

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.

在48周的治疗期间，治疗耐受性良好。最常见的不良事件是轻微的注射部位反应。没有患者停止研究，也没有死亡或其他严重不良事件的报告。

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..

使用ALSFRS-R量表测量患者的疾病进展，ALSFRS-R量表是一种经过验证的评估工具，用于监测ALS患者的残疾进展。治疗开始后第24周（33.75±3.3）和第48周（32±7.8）的平均（±SD）ALSFRS-R评分与基线时的ALSFRS-R评分（33.5±5.9）相比无统计学差异，表明48周治疗期间疾病进展显着改善。。

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.

Treg抑制功能表示为促炎性T细胞增殖抑制的百分比，在治疗期间显示出统计学上显着的增加，并且在治疗后8周的清除期结束时显着降低。24周（79.9±9.6）和48周（89.5±4.1）的Treg抑制功能明显高于基线（62.1±8.1）（p＜0.01），表明治疗过程中Treg抑制功能增强且持久。

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)..

相比之下，与第48周治疗结束时相比，8周清除期结束时Treg抑制功能（平均值±SD）显着降低（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..

该研究还评估了炎症，氧化应激和脂质过氧化物的血清生物标志物。治疗开始后16周的可用数据表明这些生物标志物水平降低，这与观察到的Treg功能增强一致。正在对完整的生物标志物数据进行评估。。

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

COYA 302是一种尚未获得FDA或任何其他监管机构批准的研究产品。

About Coya Therapeutics, Inc.

关于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 Therapeutics，Inc.（纳斯达克股票代码：Coya）总部位于德克萨斯州休斯顿，是一家临床阶段生物技术公司，开发专有治疗方法，专注于调节性T细胞（“Tregs”）的生物学和潜在治疗优势，以靶向全身炎症和神经炎症。功能失调的Tregs是许多疾病的基础，包括神经退行性疾病，代谢性疾病和自身免疫性疾病，这种细胞功能障碍可能导致持续的炎症和氧化应激，导致免疫系统缺乏稳态。。

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的研究产品候选管道利用多种治疗方式，旨在恢复Tregs的抗炎和免疫调节功能。Coya的治疗平台包括Treg增强生物制剂，Treg衍生的外泌体和自体Treg细胞疗法。

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.

COYA 302是该公司领先的生物研究产品或“产品中的管道”，是COYA 301（COYA专有的LD IL-2）和CTLA4 Ig的专有组合，用于皮下给药，具有独特的双重作用机制，目前正在开发用于治疗肌萎缩侧索硬化症，额颞痴呆，帕金森病和阿尔茨海默病。

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..

。这种协同机制可能导致以持续和持久的方式重建免疫平衡和改善炎症，这可能是单独使用低剂量IL-2或CTLA4 Ig所无法实现的。。

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

有关Coya的更多信息，请访问www.coyatherapeutics.com

Forward-Looking Statements

前瞻性声明

This press release contains “forward-looking” statements that are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our current and future financial performance, business plans and objectives, current and future clinical and preclinical development activities, timing and success of our ongoing and planned clinical trials and related data, the timing of announcements, updates and results of our clinical trials and related data, our ability to obtain and maintain regulatory approval, the potential therapeutic benefits and economic value of our product candidates, competitive position, industry environment and potential market opportunities.

。前瞻性陈述包括除本演示文稿中包含的历史事实陈述之外的所有陈述，包括有关我们当前和未来财务业绩、业务计划和目标、当前和未来临床和临床前开发活动、我们正在进行和计划中的临床试验和相关数据的时机和成功、我们临床试验和相关数据的发布时间、更新和结果、我们获得和维持监管批准的能力、我们候选产品的潜在治疗效益和经济价值、竞争地位、行业环境和潜在市场机会的信息。

The words “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” and similar expressions are intended to identify forward-looking statements..

“相信”、“可能”、“会”、“估计”、“继续”、“预期”、“打算”、“预期”等词语以及类似的表达旨在识别前瞻性陈述。。

Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors including, but not limited to, those related to risks associated with the impact of COVID-19; the success, cost and timing of our product candidate development activities and ongoing and planned clinical trials; our plans to develop and commercialize targeted therapeutics; the progress of patient enrollment and dosing in our preclinical or clinical trials; the ability of our product candidates to achieve applicable endpoints in the clinical trials; the safety profile of our product candidates; the potential for data from our clinical trials to support a marketing application, as well as the timing of these events; our ability to obtain funding for our operations; development and commercialization of our product candidates; the timing of and our ability to obtain and maintain regulatory approvals; the rate and degree of market acceptance and clinical utility of our product candidates; the size and growth potential of the markets for our product candidates, and our ability to serve those markets; our commercialization, marketing and manufacturing capabilities and strategy; future agreements with third parties in connection with the commercialization of our product candidates; our expectations regarding our ability to obtain and maintain intellectual property protection; our dependence on third party manufacturers; the success of competing therapies or products that are or may become available; our ability to attract and retain key scientific or management personnel; our ability to identify additional product candidates with significant commercial potential consistent with our commercial objectives; and our estimates regarding expenses, future revenue, capital re.

前瞻性陈述受到已知和未知风险、不确定性、假设和其他因素的影响，包括但不限于与新型冠状病毒影响相关的风险；我们的产品候选开发活动以及正在进行和计划进行的临床试验的成功，成本和时间安排；我们计划开发和商业化靶向治疗药物；我们的临床前或临床试验中患者登记和给药的进展；我们的候选产品在临床试验中达到适用终点的能力；我们候选产品的安全概况；我们的临床试验数据支持营销应用的潜力，以及这些事件的时间安排；我们获得运营资金的能力；我们候选产品的开发和商业化；；我们候选产品的市场接受率和程度以及临床实用性；我们候选产品的市场规模和增长潜力，以及我们服务这些市场的能力；我们的商业化、营销和制造能力和战略；与第三方就我们候选产品的商业化达成的未来协议；我们对获得和维持知识产权保护能力的期望；我们对第三方制造商的依赖；已经或可能获得的竞争疗法或产品的成功；我们吸引和留住关键科学或管理人员的能力；我们能够确定与我们的商业目标一致的具有重大商业潜力的其他候选产品；以及我们对费用、未来收入、资本重组的估计。

We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy, short-term and long-term business operations and objectives, and financial needs.

我们的这些前瞻性陈述主要基于我们目前对未来事件和趋势的预期和预测，我们认为这些事件和趋势可能会影响我们的财务状况、运营结果、业务战略、短期和长期业务运营和目标以及财务需求。

Moreover, we operate in a very competitive and rapidly changing environment, and new risks may emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make.

此外，我们的经营环境竞争激烈，变化迅速，新的风险可能会不时出现。我们的管理层不可能预测所有风险，也不可能评估所有因素对我们业务的影响，也不可能评估任何因素或因素组合可能导致实际结果与我们可能做出的任何前瞻性陈述中所包含的结果存在重大差异的程度。

In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed herein may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Although our management believes that the expectations reflected in our forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances described in the forward-looking statements will be achieved or occur.

鉴于这些风险、不确定性和假设，本文讨论的前瞻性事件和情况可能不会发生，实际结果可能与前瞻性声明中预期或暗示的结果存在重大不利差异。虽然我们的管理层认为我们的前瞻性声明中反映的期望是合理的，但我们不能保证前瞻性声明中描述的未来结果、活动水平、绩效或事件和情况能够实现或发生。

We undertake no obligation to publicly update any forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise..

我们没有义务公开更新任何前瞻性声明，无论是书面的还是口头的，无论是由于新信息、未来发展还是其他原因。。