Ametefgene parvec

1. 引言：帕金森病概述与研究背景 帕金森病（Parkinson's Disease, PD）是全球第二大神经退行性疾病，我国患病人数预计2050年将达1050万，居全球首位。其核心临床表现为静止性震颤、运动迟缓等运动症状，及嗅觉减退、认知障碍等非运动症状，随病情进展导致患者丧失自理能力，给家庭与社会带来沉重负担。 传统治疗依赖左旋多巴等药物控制症状，但长期使用易引发运动并发症且无法阻断疾病进展。近十年，在遗传因素、神经炎症、蛋白质错误折叠等领域的研究突破，为开发新型疗法提供了契机。2025年我国科学家在《Science》发现PD全新治疗靶点FAM171A2，成为该领域里程碑事件。本报告系统梳理2015—2025年PD研究核心进展，为多领域相关人员提供参考。2.帕金森病病理机制研究进展2.1 遗传因素研究突破 迄今已发现17个家族性PD相关单基因（Park1~18），其中12个致病基因被克隆，LRRK2、GBA、SNCA为核心基因。LRRK2是最常见常染色体显性遗传致病基因，2025年研究确认其p.L1795F变异通过增强激酶活性致病，G2019S突变则增加患者认知障碍风险2-3倍。 GBA基因突变是重要风险因素，其p.N409S变异在PD患者中携带率达10%—15%，通过损害溶酶体功能导致α-突触核蛋白清除障碍。SNCA基因编码的α-突触核蛋白是路易小体核心成分，其突变或多拷贝引发早发性PD，2025年FAM171A2受体研究揭示其介导病理性α-突触核蛋白细胞内摄取的新机制。 全基因组关联研究（GWAS）成果显著，2024年多祖先荟萃分析确定78个全基因组显著性位点，我国研究发现rs61204179等新风险位点，多基因风险评分（PRS）最高五分位数个体发病风险是最低者的2.56倍，为精准风险评估奠定基础。2.2 神经炎症机制核心发现 神经炎症是PD发病关键环节，活化的小胶质细胞与星形胶质细胞释放TNF-α、IL-1β等促炎因子，形成神经元损伤的恶性循环。小胶质细胞兼具促炎与神经保护双重作用，其cGAS-STING通路过度激活会引发I型干扰素介导的炎症级联反应。 α-突触核蛋白与小胶质细胞的相互作用是研究热点：其聚集形式可激活NLRP3炎症小体，同时损害小胶质细胞吞噬功能与自噬通路，形成病理蛋白积累的正反馈。2024年研究证实CXCR4过表达通过刺激小胶质细胞促炎因子释放，触发多巴胺能神经元凋亡，为抗感染治疗提供新靶点。 神经炎症与α-突触核蛋白传播密切相关，病理蛋白可通过外泌体、隧道纳米管等途径扩散，小胶质细胞在此过程中既是受害者也是传播载体，这一发现为阻断病理进展提供了新思路。2.3 蛋白质错误折叠机制新认知 α-突触核蛋白错误折叠与聚集是PD核心病理特征。生理状态下其为无序蛋白，参与突触囊泡循环；病理状态下转变为富含β－折叠的异常结构，经寡聚体、原纤维阶段形成路易小体，其中寡聚体具有强神经毒性。 2025年复旦大学郁金泰团队的突破性研究发现，神经元膜受体FAM171A2可选择性结合病理性α-突触核蛋白并介导其内化，诱导细胞内单体蛋白错误折叠，这一机制被《Science》审稿人称为领域“圣杯”。该蛋白的发现为开发阻断病理传播药物提供了精准靶点。 α-突触核蛋白与线粒体功能障碍密切相关，其可通过VDAC转运至线粒体内膜，抑制离子交换与能量代谢，诱发活性氧（ROS）过量产生。液－液相分离（LLPS）是近年发现的新聚集机制，不同剪接异构体通过该途径组装成淀粉样聚集体，成为聚集早期干预的关键靶点。 蛋白质质量控制系统障碍加剧病理进程：GBA基因突变导致溶酶体功能受损，泛素-蛋白酶体与自噬－溶酶体系统异常共同促进α-突触核蛋白积累。此外，α-突触核蛋白构象多样性决定其毒性差异，Mini-P纤维因结构特性具有更强的神经元播种活性。2.4 其他关键病理机制 线粒体功能障碍是PD重要病理基础，PINK1和Parkin基因突变直接证实线粒体质量控制的关键作用。α-突触核蛋白病理可导致多巴胺能神经元线粒体基因表达下调、ATP生成障碍，激活凋亡通路。 氧化应激与铁代谢异常形成协同损伤：多巴胺氧化产生大量自由基，而PD患者抗氧化系统功能下降；黑质铁沉积增加可通过催化自由基生成加剧氧化损伤，7T MRI已能清晰显示黑质铁沉积变化。 兴奋性毒性与血脑屏障障碍也参与疾病进展：谷氨酸释放增加过度激活NMDA受体引发钙超载；长期左旋多巴代谢产生的醌类毒素可诱导小胶质细胞释放炎性因子，破坏血脑屏障导致外周免疫细胞浸润。自噬－溶酶体系统功能异常则影响病理蛋白清除与线粒体质量控制，成为疾病进展的核心环节。3. 帕金森病治疗方法发展3.1 传统药物治疗优化进展 传统药物仍是PD治疗基石，近年在剂型创新、给药优化与联合策略方面取得显著进展。《中国帕金森病治疗指南（第四版）》明确“不刻意推迟左旋多巴使用”理念，强调早期干预的重要性。 左旋多巴制剂呈现多剂型发展：标准片起效快适用于症状波动者，缓释片延长作用时间改善剂末现象，口腔速溶片便于吞咽困难患者，肠道凝胶通过持续泵入适用于晚期患者。2024年美国FDA对24小时皮下输注的ND0612进行重新审查，预计2025年底完成审批。 多巴胺受体激动剂以非麦角类为主，2024年7月注射用罗替高汀微球在我国获批，每周注射一次显著减少用药频率与浓度波动；透皮贴片则提升了吞咽困难或认知障碍患者的依从性。MAO-B抑制剂方面，沙芬酰胺作为双重作用药物，兼具多巴胺能与抗谷氨酸作用，2025年5月已在我国正式临床应用。 COMT抑制剂领域，奥匹卡朋于2024年11月在我国提交上市申请，与左旋多巴联用可显著延长“开”期时间。针对左旋多巴诱导的异动症（LID），金刚烷胺缓释制剂与伊曲茶碱（腺苷A2A受体拮抗剂）成为有效治疗选择。联合用药策略日益精细化，指南推荐根据患者年龄、症状特点制定个性化方案。3.2 基因治疗临床试验进展 基因治疗通过AAV载体等工具递送治疗性基因，成为PD治疗前沿方向。AskBio公司的AB-1005（AAV2-GDNF）获FDA再生医学先进疗法认定，2025年2月启动欧洲Ⅱ期试验，其递送的GDNF可促进多巴胺能神经元存活与功能恢复，I期试验显示良好安全性与初步疗效。 AAV-GAD基因治疗通过向苍白球内侧核递送谷氨酸脱羧酶基因，调节基底节环路功能，是唯一完成两项阳性结果假手术对照试验的中枢神经基因治疗。多巴胺合成相关基因治疗中，VY-AADC01通过AAV递送AADC基因，提升左旋多巴转化效率，显著减少“关”期时间。 RNA干扰技术靶向SNCA基因降低α-突触核蛋白表达，CRISPR/Cas9技术则可直接编辑LRRK2、PARK2等致病基因突变，虽目前多处于临床前阶段，但展现出根治遗传性PD的潜力。我国在该领域成果显著：瑞宏迪医药RGL-193注射液完成8例患者入组，天泽云泰VGN-R09b通过双基因递送实现神经保护与功能改善，均显示良好前景。3.3 细胞治疗临床突破 细胞治疗通过移植功能性细胞替代受损神经元或提供神经保护，近年取得多项突破性进展。2025年《Cell》发表的研究显示，胚胎干细胞来源的A9-DPC细胞在I/IIa期试验中，实现运动症状改善且疗效呈剂量依赖性，安全性良好。 诱导多能干细胞（iPSCs）技术避免免疫排斥问题，BlueRock公司BRT-DA01作为全球首个PD干细胞疗法进入Ⅲ期试验，2025年启动exPDite-2试验并完成首例给药。我国在该领域处于国际领先地位：2025年11月中科大附一院施炯团队利用异体干细胞移植使6例患者恢复正常生活，其中37岁患者成为全球首例“治愈”的早发性PD患者；浙江完成首例自体iPSC衍生多巴胺前体细胞移植，症状改善显著。 神经干细胞与间充质干细胞治疗各具优势：北京协和医院通过鼻黏膜途径移植人源神经干细胞，改善中晚期患者症状；基因工程化间充质干细胞可稳定分泌多巴胺，实现神经保护与免疫调节双重作用。睿健医药NouvNeu001基于化学诱导技术，2025年4月启动Ⅱ期试验，其亚型NouvNeu003专门针对早发型患者。细胞治疗长期随访显示，经严格质量控制可有效规避肿瘤形成等风险。3.4 其他新兴治疗技术 神经调控技术实现智能化升级：自适应深部脑刺激（aDBS）通过AI算法实时监测脑活动，自动调整刺激参数，疗效优于传统DBS。磁共振引导聚焦超声（MRgFUS）作为无创技术，已在欧洲获批用于药物难治性震颤治疗。 免疫治疗聚焦α-突触核蛋白靶向：罗氏普拉西珠单抗虽IIb期试验未达主要终点，但在早期患者中显示潜在获益；主动免疫治疗UB-312与AFFITOPE® PD01A在I期试验中展现良好安全性与免疫原性，抗体应答者可获得显著获益。 线粒体靶向治疗与肠道菌群调节成为新方向：天玑济世TJ0113作为线粒体自噬诱导剂，Ⅱ期试验正在推进；研究证实肠道炎症加速α-突触核蛋白聚集，菌群调节策略进入临床试验。A2A受体拮抗剂VG081821AC完成Ⅱ期试验，通过非多巴胺能机制实现症状改善与潜在疾病修饰作用。4. 临床实践应用现状4.1 诊断技术革命性进步 生物标志物检测实现早期预警：2018—2023年种子扩增试验（SAA）以97%准确率检测脑脊液α-突触核蛋白，2025年徐评议教授团队研发的QSAA血液检测技术，仅需2-3毫升血液即可在一天内完成检测，准确率超90%，实现7—10年疾病预警。 神经影像技术精度显著提升：7T MRI空间分辨率达0.4毫米，通过SWI技术清晰显示黑质铁沉积；神经黑色素MRI联合QSM成像提高PD分期与认知评估效能；18F-FPCIT PET扫描早期即可发现纹状体多巴胺转运体不对称性摄取降低，敏感性达92.3%。 人工智能推动诊断革新：凝动医疗MODAS系统通过自然图像AI技术，实现毫米级震颤检测，评估效率提升4倍，准确率超95%；MultiParkNet深度学习框架整合五种异构数据源，测试准确率达96.74%。经颅超声作为经济无创手段，以黑质高回声为标志，敏感性达80%—90%，适合基层筛查。 多模态诊断策略成为主流，整合影像、电生理、运动功能等指标建立综合模型。嗅觉测试作为前驱期筛查手段被纳入指南，UPSIT评分≤15分成为重要诊断依据，显著提高早期识别率。4.2 治疗策略系统化升级 个体化治疗成为核心原则，指南推荐根据年龄分层用药：早发型患者（<65岁）优先选择非麦角类激动剂或MAO-B抑制剂，晚发型患者（≥65岁）首选左旋多巴。持续多巴胺能刺激（CDS）理念广泛应用，左旋多巴肠凝胶与皮下输注系统通过稳定血药浓度，显著改善晚期运动波动。 多学科团队（MDT）模式全面推广，2024年国家老年疾病临床医学研究中心分中心落地北大国际医院，整合神经内外科、康复科等资源提供一体化服务。中西医结合治疗规范化发展，《帕金森病中西医结合诊疗指南》发布，中药、针灸等手段有效改善非运动症状。 非药物治疗地位提升，太极拳、节律步态训练等运动疗法改善平衡与运动功能；康复治疗针对吞咽、语言障碍提供专业训练；心理干预缓解抑郁焦虑情绪。全程管理体系逐步建立，实现早期诊断、中期优化、晚期关怀的连续性服务。4.3 中国诊疗特色与发展 我国诊疗指南持续完善，第四版指南新增前驱期诊断标准，纳入嗅觉减退、REM睡眠行为障碍等核心指标。中西医结合成为独特优势，中国中医科学院西苑医院等机构的临床实践证实其在症状改善与病情延缓方面的效果。 专科诊疗体系日益成熟，北京宣武医院、上海瑞金医院等形成多学科协作优势，清华大学玉泉医院提出“病－脑－身”三维诊疗体系。药物可及性显著提升，罗替高汀微球、沙芬酰胺等新药陆续在华获批，奥匹卡朋上市申请已获受理。 基层诊疗能力逐步增强，《帕金森病基层诊疗指南2025》强调非运动症状的早期识别价值。科研创新成果丰硕，除FAM171A2发现外，基因与细胞治疗临床试验数量位居全球前列，展现我国在该领域的国际竞争力。医保政策持续优化，PD纳入慢性病管理，减轻患者经济负担。5. 社会影响与展望5.1 患者与家庭的多维负担 PD对患者身体功能造成渐进性损害，美国研究显示患者日常生活活动能力评分显著降低，我国约20%患者需长期护理，远超其他疾病的7%。非运动症状危害突出，半数患者伴有抑郁焦虑，15%—30%晚期出现认知障碍，显著增加护理难度。 经济负担沉重：美国PD患者3年增量成本达20,832美元，我国患者年均自付医疗费用6000-20,000元，晚期联合用药费用可增至5000-12,000元/年。家属照护压力巨大，每周平均提供31小时无偿照护，需承担三项以上生活护理，半数护理者周工作时长超100小时。 患者社会参与受限，逐渐退出社交活动导致孤独感加剧；心理问题双向传导，患者担心成为家庭负担，家属则面临照护与工作的双重压力，形成恶性循环，导致患者与家庭生活质量全面下降。5.2 未来趋势与挑战 精准医学成为发展核心，多组学技术推动PD分型精细化，PRS实现风险精准预测，基因指导的个体化治疗逐步落地。疾病修饰治疗有望突破，FAM171A2等新靶点为开发阻断病理传播药物提供可能，预计5-10年内将有1-2种疾病修饰药物获批。 人工智能深度赋能诊疗：可穿戴设备结合AI实时监测症状变化，手术导航系统提高DBS精准度，药物发现平台加速新药研发。联合治疗策略成为主流，药物与神经调控、基因与细胞治疗、中西医结合等模式实现疗效协同。 新型给药系统不断涌现，纳米递送、脑内植入装置等技术实现药物精准靶向。早期干预体系逐步建立，高危人群筛查与生活方式干预成为预防重点。 同时面临多重挑战：疾病异质性增加诊疗难度；药物研发转化率低，动物模型与临床存在差距；新技术成本高昂限制可及性；基因编辑等技术涉及伦理争议；基层专业人才短缺。国际合作与政策支持至关重要，需通过资源共享、技术转移、医保优化等措施推动全球PD防治进展。6. 结论与建议 2015—2025年PD研究取得里程碑式进展：病理机制方面，遗传因素、神经炎症、蛋白质错误折叠等领域的突破深化了疾病认知；治疗领域，传统药物优化与基因、细胞治疗的临床转化为患者带来新希望，我国在细胞治疗领域实现全球领先；临床实践中，早期诊断技术与个体化诊疗体系显著提升患者获益。 针对不同群体提出建议：科研工作者需加强基础与转化研究，推动多学科融合与国际合作；临床医生应更新知识体系，践行精准诊疗与MDT模式；政策制定者需加大科研投入，完善医保与长期照护制度，提升基层服务能力；患者与家属应积极配合治疗，参与康复训练与患者组织；社会各界需消除歧视，完善无障碍设施，支持公益事业。 展望未来，随着技术进步与社会协同，预计2035年实现疾病修饰治疗突破，2040年早期干预显著降低疾病影响，2050年PD成为可防可控的慢性疾病。通过全社会共同努力，将为PD患者点亮希望之光，最终实现疾病的有效控制与攻克。

Berlin, Germany, and Research Triangle Park, N.C., USA, Dec. 09, 2025 (GLOBE NEWSWIRE) -- Not intended for UK Media Product designation supports development of innovative investigational gene therapies for Parkinson’s disease (PD) and congestive heart failure (CHF) AskBio Inc., a gene therapy company wholly owned and independently operated as a subsidiary of Bayer AG, today announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted the Pioneering Regenerative Medical Product designation (SAKIGAKE) for two of AskBio’s investigational gene therapy programs: AB-1005, for the treatment of Parkinson’s disease (PD), and AB-1002, for the treatment of non-ischemic heart failure with reduced left ventricular ejection fraction and New York Heart Association (NYHA) Class III heart failure despite appropriate medical therapy. The designation reflects Japan’s commitment to expediting the development and review of breakthrough therapies and is awarded to products demonstrating innovativeness (a new mode of action), prominent efficacy or safety data, and the potential to address severe diseases, especially when submitted first or simultaneously with other countries. This recognition offers significant advantages, including priority consultations and accelerated review timelines, thereby facilitating earlier participant access to transformative treatments. “Having AB-1005 and AB-1002 receive the Pioneering Regenerative Medical Product designation in Japan highlights our dedication to advancing innovative gene therapies for participants facing serious diseases,” said Canwen Jiang, MD, PhD, Chief Development Officer and Chief Medical Officer, AskBio. “This recognition not only accelerates regulatory review but also reaffirms our commitment to delivering advanced treatments to those living with serious chronic diseases that lack therapies targeting root causes.” AB-1005, currently being evaluated in the Phase II REGENERATE-PD trial, is an investigational gene therapy with adeno-associated viral (AAV) vector-mediated delivery of the glial cell line-derived neurotrophic factor (GDNF) gene for participants with moderate-stage PD. The therapy aims to restore neuronal function and potentially slow disease progression for people with limited treatment options. AB-1005 previously received US Food and Drug Administration (FDA) Regenerative Medicine Advanced Therapy (RMAT), FDA Fast Track, and UK Medicines and Healthcare products Regulatory Agency (MHRA) Innovation Passport designations, underscoring its global significance and potential for participants.1 AB-1002 is an investigational AAV gene therapy being studied for the treatment of adults with NYHA Class III heart failure with non-ischemic etiology. It previously received FDA Fast Track designation, and is designed as a one-time gene therapy targeting protein phosphatase 1 inhibition, with the intention of improving cardiac function and addressing the substantial global burden of congestive heart failure.2 “Bayer and AskBio’s collaboration continues to drive progress in gene therapy with a robust pipeline targeting central nervous system, cardiovascular, and other disease indications,” said Christian Rommel, PhD and Global Head of Research and Development for Bayer's Pharmaceuticals Division. “Receiving the designation in Japan, which is a first for Bayer, marks an important milestone in expanding global access to pioneering therapies and reinforces our shared commitment to delivering breakthrough science to improve outcomes for patients worldwide.” FDA RMAT is a designation granted by the FDA to regenerative therapies, including gene therapies, being developed to treat, modify, reverse, or cure serious or life-threatening diseases or conditions.3 Investigational products receiving this designation must have produced preliminary clinical evidence indicating that they may have the potential to address unmet medical needs for such diseases or conditions.3 RMAT provides recipients with enhanced access to the FDA, which could include intensive guidance on efficient drug development, rolling Biologics License Application (BLA) review, and other actions to expedite review.3 The FDA Fast Track program is designed to facilitate the development and expedite the review of new therapeutics that are intended to treat serious conditions and address unmet medical needs.3 The purpose of the program is to get important new therapeutics to participants earlier.3 Therapeutics that receive this designation benefit from eligibility for more frequent meetings with the FDA to discuss the clinical development plan and, if relevant criteria are met, eligibility for Accelerated Approval and Priority Review.3 The UK MHRA Innovation Passport is the entry point to the Innovative Licensing and Access Pathway (ILAP), which aims to accelerate time to market, facilitating participants access to innovative medicines. This designation provides Innovation Passport holders with the opportunity to work with the UK MHRA and partners to create product-specific Target Development Profiles (TDP) for new therapies. The TDP will define key regulatory and development features, identify potential pitfalls, offer access to specialist toolkits, and create a roadmap for delivering early participants access.4,5 AB-1005 and AB-1002 are investigational gene therapies that have not been approved by any regulatory health authority, and their efficacy and safety have not been established or fully evaluated. AskBio is also exploring AB-1005 beyond PD and is currently conducting the MSA-101 trial in the U.S. for participants diagnosed with multiple system atrophy of the parkinsonian subtype (MSA-P) in a Phase I trial to assess the preliminary safety, tolerability, and efficacy of GDNF gene therapy for this rapidly progressing condition for which no treatment options are currently available.6 About Parkinson’s disease Parkinson’s disease (PD) is a progressive neurodegenerative disease.7 It has a significant impact on a person’s daily life.7 In PD, the death of dopamine producing nerve cells in the brain leads to the continuous loss of motor function.8 Symptoms include tremors, muscle rigidity, and slowness of movement.9 Additionally, people with PD experience non-motor symptoms, including fatigue and lack of energy, cognitive issues, and depression.9 Symptoms typically intensify over time and make everyday tasks increasingly demanding.9 The prevalence of PD has doubled over the past 25 years.7 Today, more than 10 million people worldwide are estimated to be living with PD.10 This makes it the world’s second most prevalent neurodegenerative disease.11 It is also the most frequent movement disorder.7,12 At present there is no cure, and current treatment options lack the holistic management of symptoms, so there is an urgent need for new therapies.13 About AB-1005 AB-1005 is an investigational gene therapy based on an adeno-associated viral vector containing the human glial cell line-derived neurotrophic factor (GDNF) transgene, which allows for stable and continuous expression of GDNF in localized regions of the brain after direct neurosurgical injection with convection-enhanced delivery.14,15 In nonclinical studies, GDNF has been shown to promote the survival and morphological differentiation of dopaminergic neurons, which could aid in the preservation and restoration of dopaminergic neuronal circuitries normally lost in the disease.15,16 Recombinant GDNF has long been evaluated as a potential treatment for diseases, such as Parkinson’s disease (PD), marked by progressive degeneration of midbrain dopaminergic neurons.17 Through a combination of an investigational gene therapy and innovative neurosurgical delivery approach, the GDNF hypothesis in PD can now be tested by getting this neurotrophic factor to these degenerating nigrostriatal neurons in a potentially more clinically relevant fashion.17 About the AB-1005 Phase Ib trial In the AB-1005 Phase Ib, multicenter, open-label, uncontrolled trial, participants were administered AB-1005 to the putamen via one-time bilateral convection-enhanced delivery.18 Participants were enrolled into two cohorts, mild (6 participants) and moderate (5 participants), based upon the duration and stage of their Parkinson’s disease (PD).18 The objective of this investigation was to evaluate the safety and potential clinical effect of AB-1005 delivered to the putamen in participants with either mild- or moderate-stage PD. The outcomes assessed at 36 months were incidence of treatment-emergent adverse events (TEAEs) as reported by the participants or assessed clinically by physical and neurological examinations, motor symptoms as reported via the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and PD Motor Diary self-assessments, non-motor symptoms of PD, and brain dopaminergic network integrity as measured by DaTSCAN.18 These assessments will continue for up to five years. For more information, visit clinicaltrials.gov (NCT04167540) or askbio.com. About REGENERATE-PD REGENERATE-PD is a Phase II, randomized, double-blind, surgery controlled trial of the efficacy and safety of intraputaminal AB-1005 in the treatment of adults (45–75 years) with moderate-stage Parkinson’s disease.19 The trial will include an estimated 87 participants with trial sites located in Germany, Poland, the United Kingdom, and the United States.19 For more information about the REGENERATE-PD clinical trial, visit clinicaltrials.gov (NCT06285643), or visit askbio.com. About Congestive Heart Failure Heart failure occurs when the heart cannot pump blood efficiently enough to meet the body’s needs, including providing sufficient oxygen to the organs.20 Congestive heart failure results in the slowing of the blood flow out of the heart, which causes the blood returning to the heart through the veins to back up.21 This causes congestion in the body’s tissues.22 Symptoms may include shortness of breath, swelling in the legs and ankles caused by fluid retention, and fatigue.22 More than 64 million people worldwide are estimated to be living with heart failure.23 About AB-1002 AB-1002 is an investigational one-time gene therapy based on an adeno-associated viral vector administered to the heart to promote production of a modified version of the therapeutic inhibitor 1 (I-1c) protein designed to block the action of protein phosphatase 1, which is linked to CHF.24,25 This investigational gene therapy has not been approved by any regulatory authority, and its efficacy and safety have not yet been established or fully evaluated. About the AB-1002 Phase I trial This non-randomized, sequential dose-escalation trial (NCT04179643) includes escalating dose cohorts to evaluate the safety and preliminary efficacy of investigational gene therapy AB-1002 in 11 participants with New York Heart Association (NYHA) Class III non-ischemic heart failure with reduced ejection fraction (HFrEF).2 No adverse events were deemed related to AB-1002 in this trial, and clinically meaningful improvements were recorded across several efficacy assessments.26 The data further support that AB-1002 may be highly cardiotropic when administered as a single intracoronary injection. Full results were published in October 2025 in the prestigious peer-reviewed journal Nature Medicine and are available via open access.26 About GenePHIT GenePHIT is a Phase II adaptive, double-blinded, placebo-controlled, randomized, multi-center trial conducted to evaluate the safety and efficacy of the one-time administration of investigational gene therapy AB-1002, via antegrade intracoronary artery infusion, in males and females age >18 years with non-ischemic cardiomyopathy and New York Heart Association (NYHA) Class III heart failure symptoms.27 For more information, please visit euclinicaltrials.eu (EUCT#2024-510581-17-00), clinicaltrials.gov (NCT#05598333), or askbio.com. GenePHIT is being conducted at 46 locations across the United States, Austria, Germany, the Netherlands, Spain, and the United Kingdom. About AskBio AskBio Inc., a wholly owned and independently operated subsidiary of Bayer AG, is a fully integrated gene therapy company dedicated to steering gene therapy into a new era where it can transform the lives of a wider range of people living with rare and more common diseases. The company maintains a portfolio of clinical programs across a range of disease indications related to a single gene or multiple factors across cardiovascular, central nervous system, and neuromuscular conditions, with a clinical-stage pipeline that includes investigational therapeutics for congestive heart failure, limb-girdle muscular dystrophy, multiple system atrophy, Parkinson’s disease, and Pompe disease. AskBio’s end-to-end gene therapy platform includes our Pro10™ technology and Aava™ manufacturing platform, which make gene therapies more accessible by making research and commercial grade manufacturing more affordable. With global headquarters in Research Triangle Park, North Carolina, the company has generated hundreds of proprietary capsids and promoters, several of which have entered pre-clinical and clinical testing. An early innovator in the gene therapy field with over 900 employees in five countries, the company holds more than 600 patents and patent applications in areas such as AAV production and chimeric capsids. Learn more at www.askbio.com or follow us on LinkedIn. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2024, the Group employed around 93,000 people and had sales of 46.6 billion euros. R&D expenses amounted to 6.2 billion euros. For more information, go to www.bayer.com. Find more information at www.bayer.com. ime (2025-0209e) Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. Forward-Looking Statements AskBio This press release contains “forward-looking statements.” Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “will,” “intends,” “potential,” “possible,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding AskBio’s clinical trials. These forward-looking statements involve risks and uncertainties, many of which are beyond AskBio’s control. Known risks include, among others: AskBio may not be able to execute on its business plans and goals, including meeting its expected or planned clinical and regulatory milestones and timelines, its reliance on third-parties, clinical development plans, manufacturing processes and plans, and bringing its product candidates to market, due to a variety of reasons, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved in a timely manner, potential disagreements or other issues with our third-party collaborators and partners, and regulatory, court or agency feedback or decisions, such as feedback and decisions from the United States Food and Drug Administration or the United States Patent and Trademark Office. Any of the foregoing risks could materially and adversely affect AskBio’s business and results of operations. You should not place undue reliance on the forward-looking statements contained in this press release. AskBio does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof. References Askbio.com. AskBio receives FDA Fast Track and MHRA Innovation Passport designations for AB-1005 investigational GDNF gene therapy for Parkinson’s disease. Available at: https://www.askbio.com/askbio-receives-fda-fast-track-and-mhra-innovation-passport-designations-for-ab-1005-investigational-gdnf-gene-therapy-for-parkinsons-disease. Accessed: December 2025.Clinicaltrials.gov. AB-1002 in Patients With Class III Heart Failure (NAN-CS101). Available at: https://clinicaltrials.gov/study/NCT04179643. Accessed: November 2025.Food and Drug Administration. Expedited Programs for Regenerative Medicine Therapies for Serious Conditions. Available at: https://www.fda.gov/media/120267/download. Accessed: December 2025.UK Government. Innovative Licensing and Access Pathway. Available at: https://www.gov.uk/guidance/innovative-licensing-and-access-pathway. Accessed: December 2025.UK Government. First Innovation Passport awarded to help support development and access to cutting-edge medicines. Available at: https://www.gov.uk/government/news/first-innovation-passport-awarded-to-help-support-development-and-access-to-cutting-edge-medicines. Accessed: December 2025.ClinicalTrials.gov. GDNF Gene Therapy for Multiple System Atrophy. Available at: https://clinicaltrials.gov/study/NCT04680065. Accessed: December 2025.World Health Organization. Parkinson Disease. Available at: https://www.who.int/news-room/fact-sheets/detail/parkinson-disease. Accessed December 2025.Ramesh S & Arachchige A. Depletion of dopamine in Parkinson’s disease and relevant therapeutic options: A review of the literature. AIMS Neurosci. 2023 Aug 14;10(3):200-231.National Institutes of Health. Parkinson’s Disease. 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