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Steven B. Binder announces planned retirement and is appointed Executive Vice President, Special Projects, effective April 22, 2024, through December 31, 2024 Christopher Prentiss appointed Chief Financial Officer, effective April 22, 2024 DANBURY, Conn. and WESTLAKE VILLAGE, Calif., March 26, 2024 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD), a company focused on the development and commercialization of inhaled therapeutic products and devices for patients with endocrine and orphan lung diseases, announced today that Steven B. Binder will retire from his position as Chief Financial Officer, effective April 22, 2024. Mr. Binder plans to remain at MannKind through the end of the year as Executive Vice President, Special Projects. Christopher Prentiss has been appointed as Chief Financial Officer, effective April 22, 2024. Mr. Prentiss will be a member of MannKind’s executive leadership team and will report to Michael Castagna, Chief Executive Officer. “We are excited to have Chris join us at such a pivotal time as our new CFO,” said Michael Castagna, PharmD., Chief Executive Officer for MannKind Corporation. “Chris will be responsible for ensuring we maintain our fiscal discipline as we continue to deleverage the balance sheet and invest behind our growth opportunities in the coming years.” “At the same time, we are deeply grateful for the vision, dedication, and leadership Steve has provided our company during his tenure at MannKind,” continued Castagna. “Steve’s fiscal stewardship has guided our recapitalization, helped us record nearly $200 million total revenue last year, helped us achieve profitability in recent quarters and bolstered the balance sheet with over $300 million in cash and investments at the end of 2023. We are pleased that Steve will remain with MannKind for the rest of 2024, allowing for an optimal transition with Chris.” “I look forward to working with Chris and remain totally committed to MannKind’s continued success,” said Steve Binder, Chief Financial Officer. “Together, we plan to help the leadership team deliver on our 2024 milestones, build shareholder value and achieve our MannKind mission.” Chris has over 20 years of experience serving in financial leadership positions within the biopharma industry in both private and public companies. Since September 2022, Mr. Prentiss has served as Chief Financial Officer of ADARx Pharmaceuticals, Inc., a privately held clinical-stage biotechnology company, where he helped to raise nearly $250 million in funding. Between April 2015 and November 2021, he held a series of finance positions of increasing responsibility at the commercial-stage biotech company Adamas Pharmaceuticals, Inc., culminating in Chief Financial Officer. His responsibilities at Adamas included finance, accounting, investor relations, information technology and facilities. During his tenure, the company launched GOCOVRI® (in 2018) as well as acquired OSMOLEX® ER. At the time Adamas was acquired by Supernus Pharmaceuticals, Inc. in 2021, it had an annual revenue run rate of approximately $100 million. His earlier career also included senior financial roles at InterMune, Inc., Dynavax Technologies Corporation and MannKind. Mr. Prentiss began his career in the assurance practice at KPMG LLP. A licensed CPA (inactive) in California, he earned his Bachelor of Science degree in Accounting from Loyola Marymount University and an MBA from Indiana University’s Kelley School of Business. About MannKind MannKind Corporation (Nasdaq: MNKD) focuses on the development and commercialization of innovative therapeutic products and devices to address serious unmet medical needs for those living with endocrine and orphan lung diseases. We are committed to using our formulation capabilities and device engineering prowess to lessen the burden of diseases such as diabetes, pulmonary arterial hypertension (PAH) and nontuberculous mycobacterial (NTM) lung disease. Our signature technologies – dry-powder formulations and inhalation devices – offer rapid and convenient delivery of medicines to the deep lung where they can exert an effect locally or enter the systemic circulation. With a passionate team of Mannitarians collaborating nationwide, we are on a mission to give people control of their health and the freedom to live life. Please visit mannkindcorp.com to learn more, and follow us on LinkedIn, Facebook, Twitter or Instagram. Forward-Looking Statements This press release contains forward-looking statements about the expected tenure of executives, maintaining financial discipline, deleveraging MannKind’s balance sheet, investing in growth opportunities, delivering on milestones, building shareholder value and achieving MannKind’s mission that involve risks and uncertainties. Words such as “believes”, “anticipates”, “plans”, “expects”, “intends”, “will”, “goal”, “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon MannKind’s current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, the risks that our results of operations will fluctuate for the foreseeable future and that we may incur losses and may not generate positive cash flow from operations in the future, risks related to the “at will” relationship between us and our current and future employees, risks of a loss of continuity and accumulated knowledge and of inefficiency during a transitional period, and other risks detailed in MannKind’s filings with the Securities and Exchange Commission, including under the “Risk Factors” heading of its Annual Report on Form 10-K for the year ended December 31, 2023. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and MannKind undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release. GOCOVRI and OSMOLEX ER are registered trademarks of Supernus Pharmaceuticals, Inc. MANNKIND is a registered trademark of MannKind Corporation. For MannKind: Christie Iacangelo, Corporate Communications (818) 292-3500 Email: media@mannkindcorp.com Rose Alinaya, Investor Relations (818) 661-5000 Email: ir@mannkindcorp.com

作者｜糯米丁 一说到帕金森，很多人的第一反应就是：抖！手抖！但帕金森只是单纯的手抖吗？这种常见的老年性疾病，如何诊断？又有什么治疗方案呢？  01  帕金森氏症的简介帕金森氏症（图1）是一种慢性神经系统疾病， 国际帕金森和运动障碍协会（IPMDS）将帕金森氏症定义为：“伴有黑质致密神经变性和突触核蛋白沉积的核心临床运动综合征”。帕金森氏症引起的运动障碍包括：动作迟缓、震颤麻痹、不自主运动、僵硬、行走困难、失衡；非运动障碍症状包括：认知功能受损、痴呆、睡眠障碍、疼痛和感觉障碍。 图1 帕金森氏症 图片源自必应  02  帕金森氏症的诊断帕金森氏症最初的诊断是基于帕金森氏症的运动障碍，而没有生理生化检测指标可以进行替代诊断，最近的研究表明，α-突触核蛋白种子扩增测定可以准确区分帕金森患者与健康对照，或能确定疾病的分期。α-突触核蛋白种子扩增测定可以在疾病早期甚至症状出现之前识别帕金森病患者，通过脊髓穿刺可以检测脊髓液中是否存在α-突触核蛋白团块，α-突触核蛋白是在路易体中发现的一种蛋白质，是帕金森病的微观标志物。目前，这项帕金森病检测目前仅在临床前试验阶段，患者出现依从性较差的现象，未来还希望开发新的生物标志物定义帕金森氏症，或使用血样代替脊髓液进行检测，以在生物学基础上为诊帕金森氏症提供诊断依据。  03  帕金森氏症的遗传学和发病机制IPMDS在帕金森氏症的遗传学研究中提出，携带部分基因突变的个体更有可能患帕金森氏症。目前有7个基因被指定为单基因诱因，其中4个导致晚发常染色体显性遗传疾病（LRRK2、CHCHD2、VPS35和SNCA），3个导致早发常染色体隐性遗传疾病（PARKIN、DJ1和PINK1）。此外，基因GBA突变被定义为是帕金森病最常见的遗传风险因素，外显率高达30%。然而，基因检测不能作为帕金森氏症的诊断标准，但它有助于预测家庭成员的患病风险    近年来，对帕金森氏症发病机制的研究逐渐深入，研究表明NR4A2基因的突变与帕金森氏症的发病相关，NR4A2基因是一种转录因子，发生突变后会导致多巴胺能神经元的功能失调，进而引发帕金森氏症的症状。此外，线粒体DNA的缺失和LRRK2基因的突变也与帕金森氏症的发病机制有关，线粒体是细胞内能量产生的主要场所，其缺失会导致能量供应不足，进而损害多巴胺能神经元的功能。LRRK2基因突变则会导致蛋白质异常积聚，从而引发细胞毒性反应。这些发现都为揭示帕金森氏症的发病机制提供了重要线索。帕金森氏症的流行病学研究显示，地理和族群差异对其发病率有一定影响。白种人中帕金森氏症的患病率明显高于其他族群，且在美国东北部和中西部地区患病率较高。这一现象可能与遗传因素和环境的相互作用有关。此外，一些研究还发现，长期暴露于农药和重金属等环境污染物的人群患帕金森氏症的风险较高。这些流行病学数据为帕金森氏症的预防和控制提供了参考依据。  04  未来帕金森氏症治疗的展望帕金森氏症无法治愈，但可以使用药物、手术和康复治疗手段减轻症状。我国于2020年发布了《中国帕金森氏症治疗指南》（图2），帕金森氏症的治疗药物包括复方左旋多巴、多巴胺受体激动剂、抗胆碱能药和金刚烷胺等。尽管多巴胺替代疗法仍然是帕金森病治疗的金标准，但运动障碍对患者的生活影响预示着未来对新的治疗方法的需要。 图2 帕金森氏症的治疗流程 图片源自《中国帕金森氏症治疗指南》神经调控技术在帕金森氏症的康复应用广泛，非侵入性神经调控技术利用声音、光线、电流或磁场等物理和化学因素，对中枢神经系统和周围神经系统进行刺激，改善疾病症状。其中，重复经颅磁刺激（rTMS）和经颅直流电刺激（tDCS）是最常用的非侵入性神经调控技术。rTMS通过刺激脑部神经元来增强大脑皮层的兴奋性，或通过修复异常的神经可塑性来改善运动症状和非运动症状，如认知障碍、睡眠障碍和抑郁等。研究显示，rTMS可以增加帕金森氏症患者运动平衡训练的效果，并且改善患者的整体认知功能。此外，rTMS联合药物治疗可以显著提高帕金森氏症患者的临床疗效，能够改善运动症状和认知功能障碍。tDCS则是通过在特定脑区施加微弱电流来调节神经元的兴奋性。研究发现，在帕金森氏症患者中，tDCS可以辅助运动、改善平衡和步行能力，并且调节前额叶皮层的兴奋性，从而改善认知功能和步态障碍。此外，tDCS还可以结合计算机辅助认知康复训练，改善帕金森氏症患者的认知功能。近年来，机器人科学在医疗领域的应用也取得不错的成果。在康复医疗领域，机器人可以分为自理支持机器人、护理支持机器人、训练支持机器人和就业机器人四类。其中，训练支持机器人是一种将机器人穿戴后进行辅助或替代训练的技术，训练支持机器人在帕金森氏症的康复治疗中应用最广泛。例如，对HY 3级帕金森氏症患者进行了Gait Trainer GT1训练支持机器人的训练，结果显示相较于常规康复训练方法，机器人训练可以改善帕金森氏症患者的步行速度和平衡能力，但对于步态自动性没有显著差异。对HY 2级以上帕金森氏症患者进行了一个月的训练支持机器人训练，发现相较于常规康复方法，机器人训练对于存在冻结步态的帕金森氏症患者更有优势，这与之前的研究结果相似。另外，有研究报道了机器人训练在帕金森氏症患者上肢功能障碍方面的应用。例如，使用Bi-Mnu-Track机器人进行上肢训练，发现上肢的运动功能和灵活性得到了提高。进行了随机对照试验，对帕金森氏症住院患者进行了外骨骼半自主训练，结果发现机器人训练可以显著提高帕金森氏症患者的上肢灵活性、执行功能和整体生活质量。总的来说，机器人训练系统作为一种新的治疗技术，能够客观、精确地控制训练与运动参数，可以稳定、安全地进行重复训练，并提供实时反馈。 图3 患者使用康复机器人 图片源自bing  05  总结研究机构和医学专家正致力于帕金森氏症的研究和治疗，探索新的治疗方法、寻找更有效的药物、开发创新的康复和支持方案，并提高公众对帕金森氏症的认识和理解。未来的帕金森氏症治疗将继续探索多种治疗方式的综合应用，通过科学技术的不断进步和医疗模式的创新，为患者提供更有效的治疗和康复方案，以更好地应对帕金森氏症的全球挑战。 主要参考文献 Chaudhuri KR, Martinez-Martin P, Brown RG, et al. The metric properties of a novel non-motor symptoms scale for Parkinson's disease: Results from an international pilot study. Mov Disord. 2007;22(13):1901-1911.Aarsland D, Bronnick K, Larsen JP, Tysnes OB, Alves G. Cognitive impairment in incident, untreated Parkinson disease: the Norwegian ParkWest study. Neurology. 2009;72(13):1121-1126.Nuytemans K, Theuns J, Cruts M, Van Broeckhoven C. Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum Mutat. 2010;31(7):763-780.Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA. 2020;323(6):548-560. Chung-Hsin Tsai et al. "Mutations in NR4A2 associated with familial Parkinson disease." Nature Genetics 36, no. 3 (2004): 225-227.  Cortes-Canteli M et al. "High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease." Proceedings of the National Academy of Sciences 105, no. 34 (2008): 12961-12966. gSamantha J. West et al. "Kinase Activity of Mutant LRRK2 Mediates Neuronal Toxicity." Science 316, no. 5820 (2007): 439-442.  Thomas Gasser. "Genetics of Parkinson Disease: Paradigm Shifts and Future Prospects." Nature Reviews Neurology 7, no. 6 (2011): 306-318.Allison W. Willis et al. "Geographic And Ethnic Variation In Parkinson Disease: A Population-based Study Of US Medicare Beneficiaries." Archives of Neurology 64, no. 9 (2007): 1240-1245.   2024 BiG十周年   6月13-14日，十年一药，日出东方！BiG十周年  关键词：  源头创新与转化、创新技术平台（PROTAC/分子胶；双抗ADC；小核酸药物；AI+大分子）、临床研究&国际化开发策略（肿瘤/CNS/自免/代谢疾病领域）▼关于BiGBiomedical Innovation Group2014年2月，一个专业机构：BiG生物医药创新社（Biomedical Innovation Group）在充满药味的上海张江应运而生，伴随着中国新药的黄金十载，BiG以“开放、民主、平等“的精神为宗旨，旨在为中国生物医药行业的发展创造一个滋养原创的生态环境。共建Biomedical创新生态圈！如何加入BiG会员？