Abatacept

This open-label Phase 1 study measures safety, peripheral and central inflammation, effects on Treg cell populations, and FTD progression; Five of the 8 planned FTD subjects have been enrolled to date; Results of study will inform Coya’s randomized, double-blinded Phase 2 trial of COYA 302 in patients with FTD 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 that five of eight patients have been enrolled in the investigator-initiated academic study of LD IL-2 + CTLA4-Ig combination in patients with Frontotemporal Dementia (FTD). The study is being conducted by Drs. Stanley Appel and Alireza Faridar at Houston Methodist Hospital. Topline results of the study will be leveraged to inform and finalize the planned trial design of a Company-sponsored, randomized, double-blinded Phase 2 trial of COYA 302 in patients with FTD. Coya has been awarded $5 million by the Alzheimer’s Drug Discovery Foundation (ADDF) to support the development of COYA 302 in FTD. The current investigator-initiated study is evaluating the effects of LD IL-2 + CTLA4-Ig on a variety of parameters in patients with FTD, including safety, tolerability, Treg cell populations, peripheral and central inflammation, and disease progression. COYA 302 is a proprietary formulation of this biologic combination therapy, comprised of low dose interleukin-2 (LD IL-2) and cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA4-Ig). Fred Grossman D.O., President and CMO of Coya, stated, “ We plan to submit an IND for FTD, and the data from the investigator-initiated study will inform some design features of this planned trial. COYA 302 has potential therapeutic application in a variety of neurodegenerative diseases, starting with ALS and FTD.” Tregs are dysfunctional and compromised in patients with FTD, skewing the immune system toward a proinflammatory status and potentially contributing to disease progression. The combination of LD IL-2 + CTLA4-Ig is believed to have additive and/or synergistic effects on enhancing Treg cell populations and lowering peripheral/central inflammation. Prior data presented by the investigators at the AD/PD 2024 Conference in March 2024 demonstrated that Treg suppressive function was significantly reduced in patients with FTD, compared to controls (p<0.01), demonstrating that Treg immunomodulatory function is negatively impacted in FTD and peripheral levels of inflammatory cytokines and chemokines are increased, supporting the critical role of the immune system in the pathophysiology of FTD. Treg dysfunction and increased levels of inflammatory cytokines and chemokines have been previously reported by Coya in other serious and progressive neurodegenerative diseases and support the multi-pathway combination approach of COYA 302 to target numerous components of the dysfunctional immune system. About Frontotemporal Dementia Frontotemporal dementia (FTD) is the result of damage to neurons in the frontal and temporal lobes of the brain. Many possible symptoms can result, including unusual behaviors, emotional problems, trouble communicating, difficulty with work, or difficulty with walking. FTD is rare and tends to occur at a younger age than other forms of dementia. About 60% of people with FTD are 45 to 64 years old. FTD is progressive, meaning symptoms get worse over time. In the early stages, people may have just one symptom. As the disease progresses, other symptoms appear as more parts of the brain are affected. It is difficult to predict how long someone with FTD will live. Some people live more than 10 years after diagnosis, while others live less than two years after they are diagnosed. There is no cure for FTD, and no treatments slow or stop the progression of the disease.1 References Atassi N, et al. The PRO-ACT database: design, initial analyses, and predictive features. Neurology, 2014;83:1719–1725. 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 cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA4-Ig) and is being developed for subcutaneous administration for the treatment of patients with ALS, FTD, and Parkinson’s Diseases (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 CTLA-4 Ig in a small cohort of patients with ALS conducted at the Houston Methodist Research Institute (Houston, Texas). 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 ALSFRS-R scores at week 24 and week 48 after initiation of treatment were not statistically different compared to the ALSFRS-R score at baseline, suggesting that disease progression was ameliorated 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. The study also evaluated serum biomarkers of inflammation, oxidative stress, and lipid peroxides. The available data up to 16 weeks after initiation of treatment suggested 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 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 therapy consisting 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 is designed to enhance the number and anti-inflammatory function of Tregs and simultaneously lower 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. Forward-Looking Statements 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. The words “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” and similar expressions are intended to identify forward-looking statements. 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 requirements and needs for additional financing. 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. 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. 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. 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. Investor Contact David Snyder, CFO david@coyatherapeutics.com CORE IR Bret Shapiro brets@coreir.com 561-479-8566 Media Contacts For Coya Therapeutics: Kati Waldenburg media@coyatherapeutics.com 212-655-0924

导言 2024年6月，Janus激酶（JAK）抑制剂芦可替尼获中国国家药品监督管理局（NMPA）批准，用于治疗对糖皮质激素或其他系统治疗应答不充分的12岁及以上慢性移植物抗宿主病（cGVHD）患者，进一步拓宽芦可替尼受益人群。近日，该适应症正式列入国家医保目录，有望提高药物可及性，降低更多中国cGVHD患者负担。 专家寄语 张曦教授 陆军军医大学新桥医院 cGVHD是异基因造血干细胞移植（allo-HSCT）后常见并发症之一，严重影响患者的生存率和生活质量，亟需有效治疗方案以改善患者预后。今年6月，芦可替尼获批治疗激素难治性cGVHD（SR-cGVHD）患者，成为国内首个且目前唯一同时获批急性GVHD（aGVHD）和cGVHD的靶向药物，为GVHD全程管理发展注入新动力。近日，该适应症被纳入国家医保目录，有望提高治疗药物可及性和患者治疗依从性、改善患者生存和生活质量。期待随着芦可替尼的广泛应用，能够为更多患者带来治疗福祉，助力患者重获美好生活！ 机遇与挑战并存 cGVHD治疗仍存未尽之需 造血干细胞移植（HSCT）是治疗多种血液系统恶性肿瘤的有效手段。近年来，中国HSCT领域蓬勃发展，中国造血干细胞移植登记学组报告显示，2022-2023年间，中国移植中心共报告39918例HSCT，其中，allo-HSCT占比69%1，表明allo-HSCT已成为中国HSCT的主要形式。但不容忽视的是，cGVHD仍是患者移植后严重并发症及晚期非复发死亡主要原因，30%-70%患者会发生cGVHD2,3。cGVHD治疗尚存未尽之需：糖皮质激素作为cGVHD一线治疗标准方案疗效有限，约半数患者可进展为SR-cGVHD4，增加非复发死亡率5，而目前尚无标准的优选二线治疗方案；此外，cGVHD治疗周期较长，接受外周血干细胞移植的患者cGVHD中位治疗时间约3.5年6，使得cGVHD患者的器官功能和生活质量大幅下降7。因此，探索快速、高效治疗药物以助力患者实现更优生存。 共识与新药赋能 中国共识权威引领，芦可替尼提供cGVHD治疗新选择 随着新型靶向药物的出现及临床研究的不断推进，cGVHD在诊断、预防、治疗等方面取得了巨大进步，在此背景下，《慢性移植物抗宿主病诊断与治疗中国专家共识（2024年版）》重磅更新，并对cGVHD治疗策略进行优化规范，其中，针对cGVHD二线治疗，共识将芦可替尼作为一种主要的治疗选择，同时指出应根据患者靶器官实际受累情况，选择针对性治疗方法：对于皮肤受累、皮肤硬化型及肝脏受累患者推荐芦可替尼作为第一顺位选择，对于肺受累患者推荐选择阿巴西普、芦可替尼等药物治疗2。 作为选择性JAK1/2小分子抑制剂，芦可替尼可通过抑制JAK-STAT信号通路相关细胞和炎症因子，从而作用于cGVHD早期炎症、慢性炎症和器官纤维化的整个阶段8-11，全程抑制cGVHD发展。随机、开放标签、多中心III期REACH3研究显示，与接受最佳可及疗法（BAT，包括体外光分离置换疗法、小剂量甲氨蝶呤、霉酚酸酯、依维莫司/西罗莫司、英夫利昔单抗、利妥昔单抗、喷司他丁、伊马替尼和伊布替尼）治疗的SR-cGVHD患者相比，接受芦可替尼治疗的患者24周总体缓解率（ORR）更高，且任意时间的最佳总体缓解（BOR）更优（图1）12。同时，中国大型系统评价和荟萃分析还显示，接受芦可替尼治疗的SR-cGVHD患者常见受累器官均有良好获益，其中，皮肤、胃肠道和肝脏ORR分别可达84%、71%、70%13，证实芦可替尼在cGVHD患者中的获益。 图1.接受芦可替尼及BAT治疗的SR-cGVHD患者治疗结局（A：第24周ORR；B：BOR） 医保政策助力 医保纳入提高芦可替尼临床可及性，助力更多患者改善预后 2024年，共计162种药品进入国家医保谈判竞价环节，其中，芦可替尼cGVHD适应症纳入本次医保更新目录。该适应症的纳入对于cGVHD领域无疑是利好消息：对于患者而言，医保覆盖可减轻治疗经济负担、满足患者用药需求，促使更多患者能够及时获得治疗，延长生存并改善生活质量；对于领域发展而言，国家医保政策的更新可促进医疗资源合理分配、提高医疗服务的公平性和可及性、推动实现健康中国2030战略目标。 期待随着医保政策的逐步落实，更多cGVHD患者可从芦可替尼治疗中受益，提高治疗效果和生活质量，同时，也希望芦可替尼进一步开展研究探索，为更广泛患者带来健康与希望，共同迈向健康中国2030的美好未来。 专家简介 张曦 教授 主任医师、教授，博士（后）导师；长江学者特聘教授 陆军军医大学新桥医院血液病医学中心主任 中国人民解放军血液病中心主任 中华医学会血液学分会常务委员、造血干细胞应用学组副组长 中国抗癌协会血液肿瘤专委会副主任委员 中国医师协会血液科医师分会常务委员 中国血液病专科联盟副理事长 中国病理生理学会实验血液学专委会常务委员 Blood & Genomics杂志主编 主持国家、省部级课题46项；SCI论文143篇，主编专著3部，副主编3部；第一完成人获国家科技进步二等奖1项、中华医学科技一等奖1项、重庆市科技进步一等奖3项、二等奖1项，执笔行业指南12项，参编50项；获国家发明专利68项 获中国肿瘤青年科学家奖、陆军优秀科技人员标兵、重庆市首席专家工作室和重庆市创新群体领衔专家、重庆市首席医学专家、重庆市科技创新领军人才、天府学者特聘专家、全军拔尖人才、首批陆军科技英才；The Lancet，JCO，Blood，JHO，Leukemia，The Lancet Haematology，Science Bulletin，CMJ，Nat Cell Biol 等杂志编委和审稿专家 王筱淇 博士 医学博士，陆军军医大学新桥医院血液病医学中心 副主任医师 重庆市医师协会血液科医师分会委员，Blood&Genomics Associate Editor 从事造血干细胞移植并发症的相关机制研究，在J Clin  Invest.（2020、2023）、J Hematol Oncol. 、Haematologica、Leukemia、 Acta Biomater. 等杂志发表学术论文10余篇，影响因子＞10分 6篇，参编专著1部，主持国家自然科学基金、省部级及校级课题3项，作为课题骨干参与国家级省部级重点项目4项，执笔共识1部，参编行业指南3项，陆军军医大学“红医苗圃”，国防科技三等功，“四有”优秀文职人员，重庆市科技进步一等奖完成人之一。 参考文献： 1.Xu LP,et al.Bone Marrow Transplant.2024 Sep 25. 2.中华医学会血液学分会干细胞应用学组.中华血液学杂志.2024;45(8):713-726. 3.Miklos D,et al.Blood.2017;130(21):2243-2250. 4.Wu H, et al.JAMA Netw Open. 2021 Jan 4;4(1):e2034750. 5.Axt L, et al.Bone Marrow Transplant.2019;54:1805-14. 6.徐开林.中华血液学杂志.2018;(2):89-93. 7.王筱淇,等.临床血液学杂志.2024;37(9):597-601. 8.Schroeder MA,et al.Dis Model Mech.2011;4(3):318-333. 9.Zeiser R,et al.N Engl J Med.2017;377(26):2565-2579. 10.Schroeder MA,et al.Biol Blood Marrow。Transplant.2018;24(6):1125-1134. 11.张会,等.临床内科杂志.2021;38 (7):499-501. 12.Zeiser R, et al. N Engl J Med. 2021;385:228-238. 13.Xu Yang,et al.Blood (2022)140(Supplement 1):12888–12889. 审批码JAK0034683-79788，有效期为2024-11-26至2025-11-25，资料过期，视同作废