University of Antwerp

尿失禁是一种极为普遍的疾病，严重影响着全球数百万人。并且，大多数患者并没有得到有效治疗。国际尿控协会（ICS）的数据显示，中国女性尿失禁发生率为 30.9%——接近三分之一。 尿失禁可以发生于任何年龄，但在女性和老年人群中更常见，约30%的老年女性和15%的老年男性患病。由于尿失禁在很大程度上不被认知和报道，许多患者在就医过程中并不会向医生陈述该病，许多医生也不会特别问及患者的尿失禁问题。 作为一种隐秘、难以启齿的疾病，尿失禁可能带来皮肤感染、尿路感染、孤独抑郁等多种问题，导致患者生活质量大大下降。 Amber Therapeutics是一家牛津大学孵化的创业公司，总部位于英国伦敦，成立于2021年，致力于开发新一代智能生物电疗法，旨在为神经系统功能性疾病患者开发智能、创新性的神经调控疗法。目前，Amber Therapeutics正专注于开发能够治疗女性混合性尿失禁的适应性神经调节疗法——Amber-UI，旨在帮助尿失禁女性恢复正常生理功能。 实现个性化自适应阴部神经调节 据估计，美国有 680 万患者适合接受现有的骶神经调节疗法，但该疗法的普及程度很低，每年植入约 50,000 例，并且仅用于治疗急迫性尿失禁。混合性尿失禁的发病率是急迫性尿失禁的三倍多，但到目前为止，市场上几乎还没有出现相关的单一疗法可供患者使用。 Amber Therapeutics称，Amber-UI是首个针对尿失禁进行临床开发的完全植入式闭环生物电疗法，它能够通过微创外科手术进入并靶向直接控制尿失禁的神经——阴部神经，并进行刺激和生理反应监测。 Amber-UI利用其新一代神经调节平台 Picostim DyNeuMo 的智能功能来创建“合成反射弧”，该反射弧可以感知、解释和响应患者的个体信号，即能够模拟人体的自然反射机制，通过收集和分析患者的生理数据来识别问题，并根据这些信息调整刺激参数和治疗策略，从而帮助患者恢复正常的生理功能。Amber-UI可以根据个体需求进行定制，并能够根据不同事件进行动态响应，在不同操作模式之间进行调整，实现个性化自适应阴部神经调节。 这一优势源于公司在2023年的一次收购活动。2023年9月5日，Amber Therapeutics宣布收购 Bioinduction及其Picostim DyNeuMo神经调控治疗平台，并将该平台用于Amber-UI的闭环疗法。 Picostim DyNeuMo 系统最初是作为颅内植入物开发的，用于对帕金森病患者进行深部脑刺激治疗。该系统与牛津大学牵头的学术合作联盟合作，进一步完善了闭环自适应疗法，目前正在进行多项首次人体治疗试验。Amber Therapeutics则将新一代 Picostim DyNeuMo 平台用于提供 Amber-UI 疗法的植入式系统。该硬件由先进的集成数据科学工具包提供支持，用于快速构建自适应治疗算法模型。 此外，此次收购还为公司带来了一支技术精湛的团队，在开发和生产用于治疗尿失禁的神经调控设备方面拥有丰富经验，迄今为止已通过 Bioinduction 的子公司 Finetech Medical 植入了4000多台设备。本次收购将加速 Amber-UI 疗法引入美国的关键试验，并最终在全球实现终端市场商业化。 将成为首个能够解决急迫性和压力性尿失禁的单一疗法 现有的治疗方法主要集中于急迫性尿失禁（突然强烈地需要排空膀胱）或压力性尿失禁（因跳跃或咳嗽等活动引起的尿液泄漏），而Amber-UI 则代表了突破性的进步，成为首个能够解决混合性（急迫性和压力性）尿失禁的单一疗法，将在这个25年来几乎没有真正创新的领域迈出重要一步。 凭借其在闭环神经调节领域的专业积累，Amber-UI的多模式疗法既能直接调节膀胱的排尿冲动，又能增强对咳嗽或上举等活动引起的尿液渗漏的抵抗力，从而恢复正常的膀胱功能。Amber-UI 的急性刺激显示出对屏障肌肉功能（括约肌和盆底收缩及肌电图测量）和抑制逼尿肌过度活动的明显效果，导致平均膀胱容量增加，从而降低混合性尿失禁患者的尿失禁发生频率。 并且，目前大多数治疗尿失禁的植入疗法都是静态的，或者只能间接影响膀胱（如骶神经或胫神经刺激）。而 Amber-UI 可以刺激阴部神经，这是控制尿失禁的自然途径，并能在需要时加强现有的生理反射。Amber-UI 集成传感器的患者控制自适应算法可以对相关的盆腔神经肌肉活动的生理生物标志物在体内进行实时检测和分类，执行完全自适应（闭环）刺激的控制策略。 2024年2月27日，Amber Therapeutics宣布 Amber-UI的首次人体试验取得了积极的初步结果，该研究的初步数据已在泌尿动力学、女性盆腔医学和泌尿生殖重建学会 (SUFU) 年会（2024 年 2 月）上公布。 AURA-2 试验招募了13名患有严重难治性尿急性尿路感染或混合性尿路感染的女性。本次试验实现了其主要目标，即证明 Amber 的新手术程序的安全性和可行性，验证了一种可扩展的方法，可以准确地将两个电极导线植入阴部神经。 同时，该疗法显示出了初步疗效的有力证据，尤其是对患有混合性尿失禁的女性，其中五分之四的研究完成者在六个月的随访中完全解决了尿失禁发作。在混合性和难治性急迫性尿失禁患者中，症状相关的生活质量均得到了临床显著改善。 完成欧洲医疗技术公司有史以来规模最大的A轮融资之一 作为一家成立于2021 年的初创企业，Amber Therapeutics在尿失禁领域取得的突破性创新离不开背后专业的核心团队支持。 联合创始人兼首席执行官Aidan Crawley 于 2021 年在牛津科学企业担任驻地企业家时创立了这家公司。Aidan 在创办和管理早期科技公司方面拥有丰富的经验。他是 Addepar 在美国的首位业务招聘人员，并担任业务发展主管，帮助公司从零收入增长到 5000 万美元，并实现了超过 10 亿美元的估值。 首席工程师Tim Denison和首席科学家Stefan De Wachter则在神经系统疾病治疗、算法技术、疗法创新等方面为Amber Therapeutics提供了强有力的专业支持。 Amber Therapeutics联合创始人兼首席工程师Tim Denison负责领导公司的技术开发和工程工作。此外，他还在牛津大学工程科学和临床神经科学系联合任职，在研究生理闭环系统的基本原理方面经验颇丰。值得注意的是，在此之前，Tim 是美敦力的技术研究员和恢复性治疗集团研究与核心技术副总裁，领导监督用于治疗慢性神经系统疾病的新一代神经接口和算法技术的设计，为基于脑和脊髓的商业化疗法开发关键传感器和算法。 联合创始人兼首席科学家Stefan De Wachter负责疗法设计和临床创新。Stefan 兼任比利时安特卫普大学医院泌尿外科主任和安特卫普大学泌尿外科教授，主要研究方向是膀胱和尿道神经生理学，尤其侧重于使用神经调节方法对排尿功能障碍进行新型诊断和治疗，曾发表了 200 多篇经同行评审的论文。作为世界公认的盆腔健康领域的创新者，在过去 20 年中，他为几乎所有与推进新疗法相关的重大关键试验做出了重要贡献，并于 2012 年获得欧洲泌尿外科委员会研究员资格。 2024 年6月10日，Amber Therapeutics宣布成功完成 A 轮融资，该笔融资是欧洲医疗技术公司有史以来规模最大的 A 轮融资之一，由 New Enterprise Associates (NEA) 领投，新投资者 F-Prime Capital、Lightstone Ventures 和 Intuitive Ventures 以及现有投资者 Oxford Science nterprises (OSE) 和 8VC 共同参与投资，融资总额达1 亿美元（约合人民币7.25亿元）。此次融资所得将用于推动Amber-UI 的开发，通过试点和关键研究获得美国监管部门的批准。 在A轮融资结束之际，NEA的首席Tiffany Le、Lightstone Ventures的合伙人Caroline Gaynor和F-Prime的首席Kevin Chu加入了Amber Therapeutics的董事会。此外，OSE 负责人 Liliane Chamas也是董事会成员之一。 在与监管机构进行初步讨论后，Amber-UI 在欧洲的试点研究和在美国的关键性试验计划已经启动，预计2024年下半年将公布全部入组研究的结果。 Amber Therapeutics的技术平台用途广泛，公司计划将其用于探索骨盆和更广泛神经系统的其他新型治疗应用。未来，Amber Therapeutics将继续专注于智能生物电疗法的开发，彻底改变患有混合性尿失禁的女性的生活质量，并将继续进行创新和技术开发，以满足全球范围内未满足的临床需求。 近 期 推 荐 声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。 动脉网，未来医疗服务平台

The first abstract demonstrates that the improvements of MACK-3, a diagnostic test for metabolic dysfunction-associated steatohepatitis, parallel the histological response to lanifibranor therapy in patients with MASH/NASH, in the NATIVE Phase IIb clinical trial.The second abstract brings additional evidence supporting the role of intrahepatic vascular alterations in the development of MASLD-related portal hypertension and the progression to MASH and highlights the potential of lanifibranor in addressing the different components of MASH disease including vascular alterations. Daix (France), Long Island City (New York, United States), May 22, 2024 – Inventiva (Euronext Paris and Nasdaq: IVA), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of metabolic dysfunction-associated steatohepatitis (“MASH”), also known as non-alcoholic steatohepatitis (“NASH”), and other diseases with significant unmet medical needs, today announced that two scientific abstracts have been selected for poster presentation at the upcoming International Liver Congress™ 2024 hosted by the European Association for the Study of the Liver (EASL) on June 5-8, 2024 in Milan, Italy. The first abstract evaluates the correlation of the response of the biomarker algorithm MACK-3 with the improvement of liver histology as well as markers of cardiometabolic health with lanifibranor treatment. MACK-3 is composed of HOMA-IR, AST and CK-18 and has been validated against histology as a diagnostic marker for active MASH/NASH with fibrosis. The authors demonstrated that the decrease in MACK-3 value at the end of a 24 week-treatment period was significantly higher among the patients treated with lanifibranor which were qualified as responders for the histological endpoints of “MASH/NASH resolution and fibrosis improvement”, “Fibrosis improvement without worsening of MASH/NASH” and “MASH/NASH resolution without fibrosis worsening, compared to patients treated with lanifibranor but qualified as non-responders for the endpoints. Similar results were observed for improvement of NAS, SAF, and individual liver lesions: steatosis, lobular inflammation, and ballooning. MACK-3 improvement correlated as well as with increase of adiponectin levels and decrease of Pro-C3, a circulating marker of fibrogenesis, following therapy with lanifibranor. These results warrant additional study to evaluate MACK-3 as a potential marker for the evaluation of a treatment response to lanifibranor. The second abstract evaluates the effect of the pan-PPAR agonist, lanifibranor, on the improvement of liver histology as well as vascular alterations in a model of early MASLD. An increase in intrahepatic vascular resistance related to endothelial dysfunction in MASLD can be a potential driver of disease progression. The authors demonstrated that in a model of early MASLD, lanifibranor improved steatosis, normalized the mean arterial blood pressure, strongly decreased the portal pressure in-vivo and normalized the transhepatic pressure gradient ex-vivo. Furthermore, lanifibranor also decreased the reactivity to the vasoconstrictor methoxamine and normalized the hyporeactivity to vasodilator acetylcholine. The results from the collaboration between the University of Antwerp and Inventiva support the role of intrahepatic vascular alterations in the development of MASLD-related portal hypertension as well as in the progression to MASH and highlight the potential of lanifibranor in addressing all the components of MASH disease. The details of the presentations are as follows: Abstracts : Abstract #1 title: "Improvements in MACK-3, a diagnostic test for active metabolic dysfunction-associated steatohepatitis, parallel response to lanifibranor therapy" Poster identifier: SAT-206 Presentation type: Poster presentation Authors: Michael P Cooreman, Sven Francque, Philippe Huot-Marchant, Lucile Dzen, Martine Baudin, Jean-Louis Junien, Pierre Broqua, Manal F Abdelmalek, Jérôme Boursier Date: Saturday June 8, 2024 – 8:30-17:00 (CEST) Abstract #2 title: "Altered liver vascular biology occurring in early stages of metabolic dysfunction-associated steatotic liver disease is significantly improved by the pan-peroxisome proliferator-activated receptor agonist lanifibranor, associating with improved liver histology" Poster identifier: THU-258-YI Presentation type: Poster presentation Authors: Shivani Chotkoe, Guillaume Wettstein, Jean-Louis Junien, Luisa Vonghia, Denise van der Graaff, Joris De Man, Benedicte De Winter, Wilhelmus J. Kwanten, Sven Francque Date: Thursday 6, 2024 – 8:30-17:00 (CEST) Inventiva will also be present with a booth, and we are inviting you to visit us from Wednesday, June 5th until Saturday, June 8th at booth #N4 located in the exhibition hall 3 of the conference center. About Inventiva Inventiva is a clinical-stage biopharmaceutical company focused on the research and development of oral small molecule therapies for the treatment of patients with MASH/NASH and other diseases with significant unmet medical need. The Company benefits from a strong expertise and experience in the domain of compounds targeting nuclear receptors, transcription factors and epigenetic modulation. Inventiva is currently advancing one clinical candidate, has a pipeline of two preclinical programs and continues to explore other development opportunities to add to its pipeline. Inventiva’s lead product candidate, lanifibranor, is currently in a pivotal Phase III clinical trial, NATiV3, for the treatment of adult patients with MASH/NASH, a common and progressive chronic liver disease for which there are currently no approved therapies. Inventiva’s pipeline also includes odiparcil, a drug candidate for the treatment of adult MPS VI patients. As part of Inventiva’s decision to focus clinical efforts on the development of lanifibranor, it suspended its clinical efforts relating to odiparcil and is reviewing available options with respect to its potential further development. Inventiva is also in the process of selecting a candidate for its Hippo signaling pathway program. The Company has a scientific team of approximately 90 people with deep expertise in the fields of biology, medicinal and computational chemistry, pharmacokinetics and pharmacology, and clinical development. It owns an extensive library of approximately 240,000 pharmacologically relevant molecules, approximately 60% of which are proprietary, as well as a wholly-owned research and development facility. Inventiva is a public company listed on compartment B of the regulated market of Euronext Paris (ticker: IVA, ISIN: FR0013233012) and on the Nasdaq Global Market in the United States (ticker: IVA). www.inventivapharma.com Contacts InventivaPascaline ClercEVP, Strategy and Corporate Affairsmedia@inventivapharma.com +1 240 620 9175Brunswick GroupTristan Roquet Montegon /Aude Lepreux /Matthieu BenoistMedia relationsinventiva@brunswickgroup.com +33 1 53 96 83 83Westwicke, an ICR CompanyPatricia L. BankInvestor relationspatti.bank@westwicke.com +1 415 513-1284 Important Notice This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, forecasts and estimates with respect to Inventiva’s pre-clinical programs and clinical trials, including design, duration, timing, recruitment costs, screening and enrollment for those trials, including the ongoing NATiV3 Phase III clinical trial with lanifibranor in MASH/NASH, clinical trial data releases and publications, the information, insights and impacts that may be gathered from clinical trials, the potential therapeutic benefits of Inventiva’s product candidates, including lanifibranor, potential regulatory submissions, approvals and commercialization, Inventiva’s pipeline and preclinical and clinical development plans, the expected benefit of having received Breakthrough Therapy Designation, including its impact on the development and review timeline of Inventiva’s product candidates, the potential development of and regulatory pathway for odiparcil, and future activities, expectations, plans, growth and prospects of Inventiva and its partners. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will”, “would”, “could”, “might”, “should”, “designed”, “hopefully”, “target”, “potential”, “opportunity”, “possible”, “aim”, and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management's beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance, or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva's control. There can be no guarantees with respect to pipeline product candidates that the clinical trial results will be available on their anticipated timeline, that future clinical trials will be initiated as anticipated, that product candidates will receive the necessary regulatory approvals, or that any of the anticipated milestones by Inventiva or its partners will be reached on their expected timeline, or at all. Future results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates, due to a number of factors, including that Inventiva cannot provide assurance on the impacts of the Suspected Unexpected Serious Adverse Reaction (SUSAR) on enrollment or the ultimate impact on the results or timing of the NATiV3 trial or regulatory matters with respect thereto, that Inventiva is a clinical-stage company with no approved products and no historical product revenues, Inventiva has incurred significant losses since inception, Inventiva has a limited operating history and has never generated any revenue from product sales, Inventiva will require additional capital to finance its operations, in the absence of which, Inventiva may be required to significantly curtail, delay or discontinue one or more of its research or development programs or be unable to expand its operations or otherwise capitalize on its business opportunities and may be unable to continue as a going concern, Inventiva’s ability to obtain financing and to enter into potential transactions, Inventiva's future success is dependent on the successful clinical development, regulatory approval and subsequent commercialization of current and any future product candidates, preclinical studies or earlier clinical trials are not necessarily predictive of future results and the results of Inventiva's and its partners’ clinical trials may not support Inventiva's and its partners’ product candidate claims, Inventiva's expectations with respect to its clinical trials may prove to be wrong and regulatory authorities may require holds and/or amendments to Inventiva’s clinical trials, Inventiva’s expectations with respect to the clinical development plan for lanifibranor for the treatment of MASH/NASH may not be realized and may not support the approval of a New Drug Application, Inventiva and its partners may encounter substantial delays beyond expectations in their clinical trials or fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities, the ability of Inventiva and its partners to recruit and retain patients in clinical studies, enrollment and retention of patients in clinical trials is an expensive and time-consuming process and could be made more difficult or rendered impossible by multiple factors outside Inventiva's and its partners’ control, Inventiva's product candidates may cause adverse drug reactions or have other properties that could delay or prevent their regulatory approval, or limit their commercial potential, Inventiva faces substantial competition and Inventiva’s and its partners' business, and preclinical studies and clinical development programs and timelines, its financial condition and results of operations could be materially and adversely affected by geopolitical events, such as the conflict between Russia and Ukraine and related sanctions, impacts and potential impacts on the initiation, enrollment and completion of Inventiva’s and its partners’ clinical trials on anticipated timelines and the state of war between Israel and Hamas and the related risk of a larger conflict, health epidemics, and macroeconomic conditions, including global inflation, rising interest rates, uncertain financial markets and disruptions in banking systems. Given these risks and uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts, and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements. Please refer to the Universal Registration Document for the year ended December 31, 2023, filed with the Autorité des Marchés Financiers on April 3, 2024, and the Annual Report on Form 20-F for the year ended December 31, 2023, filed with the Securities and Exchange Commission on April 3, 2024. Other risks and uncertainties of which Inventiva is not currently aware may also affect its forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. All information in this press release is as of the date of the release. Except as required by law, Inventiva has no intention and is under no obligation to update or review the forward-looking statements referred to above. Consequently, Inventiva accepts no liability for any consequences arising from the use of any of the above statements. Attachment Inventiva - PR - EASL Abstracts - EN - 05 22 2024

Free Virtual Summit Hosted by Leading Neurologists Offers Hope and Empowerment for Parkinson's Community Key Takeaways: The Parkinson's Solutions Summit 2.0 is a premier virtual event that aims to equip patients and their caregivers with knowledge and tools to manage and combat the disease effectively. Gain insights into holistic management strategies and treatment options from renowned neurologists and dozens of experts. Open to everyone and free of charge, this summit makes vital knowledge accessible to everyone seeking real solutions to regain control of their lives. CARLSBAD, Calif., April 4, 2024 /PRNewswire/ -- DrTalks, a leading platform dedicated to advancing health, wellness, and medicine education, is set to launch The Parkinson's Solutions Summit 2.0. This groundbreaking virtual event, happening from November 5 to 11, 2024, offers participants insights into holistic management strategies and treatment options from renowned neurologists and dozens of experts in related fields. The Parkinson's Solutions Summit 2.0 will feature various topics, including advanced tests, optimal lifestyle changes, and other holistic strategies to prevent or manage the condition. It will be hosted by two of the most recognizable experts in neurology: Kenneth Sharlin, MD, and Barbara Pickut, MD, MPH. Dr. Sharlin is a beacon of hope in the area of neurology and functional medicine. His vast experience encompasses treating complex neurological conditions, including Parkinson's and Alzheimer's. He is also the founder of Sharlin Health and Neurology, where he's created a refuge that ranks among the top neuroscience centers in the country. He emphasizes treating the root causes of neurodegenerative diseases rather than just finding band-aid solutions for symptoms. Dr. Pickut is a neurologist and movement disorders specialist. She has a double board certification in neurology and neuro-rehabilitation at the University of Antwerp in Belgium. Dr. Pickut served as chief of neurology at the Mercy Health Saint Mary's Hospital, where she was the medical director and director of research for Parkinson's and Movement Disorders. She is also an expert in mindful meditation, having conducted research into the correlation between mindful meditation and the reduction of symptoms of Parkinson's. The Parkinson's Solutions Summit 2.0 serves as another springboard in their mission to give hope and support to people with this disease to enable them to take control of their lives. Participants will be given access to a wealth of free resources and have the opportunity to engage directly with leading experts to address their unique challenges. This summit is more than just an event. It's a community coming together to share, learn, and support each other in the journey to regaining control of their lives. Participation is free, ensuring that everyone has access to this life-changing information. For more information about this summit and to register for free, please visit . About DrTalks: DrTalks brings together some of the most sought-after leaders on the front lines of health, wellness, and medicine. Get on-demand access to talks, summits, and more—straight from the source. The goal of DrTalks.com is to empower one billion people to get educated on their serious health conditions, and The Parkinson's Solutions Summit 2.0 is a crucial step toward achieving that goal. To learn more about DrTalks, visit our newsroom at . Press Contact: Mila Grandes Head of Content +1 (825) 945 - 2667 [email protected] Calgary, Canada SOURCE DrTalks