BACKGROUNDThere is no clear information on the regulation of liver blood flow by the autonomic nervous system. We conducted this study to investigate whether quiescent hepatic stellate cells (qHSCs) regulate liver blood flow in response to the sympathetic neurotransmitter norepinephrine (NE).METHODSqHSCs isolated from mice were cultured in Dulbecco's modified Eagle medium without fetal bovine serum for 1 day on collagen gel. NE-induced qHSC contraction was evaluated using the quantitative single-cell contraction measurement method that we had developed previously. For the measurement of liver perfusion pressure in situ, a buffer solution was perfused from the portal vein in mice.RESULTSNE-induced a reversible contraction of qHSCs. This contraction was suppressed by the nonmuscle myosin II inhibitor blebbistatin, the myosin light chain kinase inhibitor ML-9, the Rho kinase inhibitor H-1152, the calmodulin inhibitor W-7, the store-operated calcium channel inhibitor YM-58483, and the IP₃ receptor inhibitor xestospongin C. In contrast, the transient receptor potential C channel inhibitor SKF96365 did not affect the NE-induced contraction.CONCLUSIONThese results suggest that qHSCs contract in response to NE.NEW & NOTEWORTHYThe present study provides direct evidence for the first time that norepinephrine (NE) induces a reversible contraction of isolated single quiescent hepatic stellate cells (qHSCs) and further suggests that the NE-mediated qHSC contraction participates in the regulation of liver blood flow in vivo.

2024-07-30·Biological and Pharmaceutical Bulletin

Difference in Contractile Mechanisms between the Early and Sustained Components of Ionomycin-Induced Contraction in Rat Caudal Arterial Smooth Muscle

Article

作者: Aida, Kazuki ; Ishii-Nozawa, Reiko ; Mita, Mitsuo

We previously reported that the sustained component of contraction induced by depolarizing stimulation by high K⁺ concentration in rat caudal arterial smooth muscle involves a Ca²⁺-induced Ca²⁺ sensitization mechanism whereby Ca²⁺ entry through voltage-gated Ca²⁺ channels activates proline-rich tyrosine kinase 2 (Pyk2), leading to activation of RhoA/Rho-associated kinase (ROCK). In the present study, we investigated a potential role for Pyk2-mediated RhoA/ROCK activation in contraction mediated by elevation of cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) induced by a Ca²⁺ ionophore, ionomycin, rather than by depolarizing stimulation. Ionomycin (60 µM) induced slow and sustained contraction of rat caudal arterial smooth muscle due to influx of Ca²⁺. Pre-treatment with a myosin light chain kinase (MLCK) inhibitor, ML-9 (30 µM), inhibited both the early phase (4 min) and the sustained phase (30 min) of ionomycin-induced contraction. On the other hand, a ROCK inhibitor, HA-1077 (3 µM), and Pyk2 inhibitors, sodium salicylate (10 mM) and PF-431396 (3 µM), suppressed only the sustained phase of ionomycin-induced contraction. A calmodulin (CaM) inhibitor, W-7 (150 µM), but not W-5 (150 µM), suppressed the early phase of contraction. Early or sustained increase of ionomycin-induced 20 kDa light chain of myosin (LC₂₀) phosphorylation was inhibited by each inhibitor in a manner similar to the attenuation of contraction. These results indicate that the early phase of ionomycin-induced contraction is mediated by MLCK activation by [Ca²⁺]_i elevation, whereas the sustained phase of ionomycin-induced contraction involves RhoA/ROCK activation and inhibition of myosin light chain phosphatase (MLCP) through CaM-independent Pyk2 activation by [Ca²⁺]_i elevation.

2024-02-01·Journal of Biological Chemistry

Myosin 9 and N-glycans jointly regulate human papillomavirus entry

Article

作者: Hao, Cui ; Liu, Yan-Jun ; Zhang, Yang ; Jiang, Hao ; Wang, Wei ; Liu, Wei ; He, Fujie

Persistent high-risk HPV infection is closely associated with cervical cancer development, and there is no drug targeting HPV on the market at present, so it is particularly important to understand the interaction mechanism between HPV and the host which may provide the novel strategies for treating HPV diseases. HPV can hijack cell surface heparan sulfate proteoglycans (HSPGs) as primary receptors. However, the secondary entry receptors for HPV remain elusive. We identify myosin-9 (NMHC-IIA) as a host factor that interacts with HPV L1 protein and mediates HPV internalization. Efficient HPV entry required myosin-9 redistribution to the cell surface regulated by HPV-hijacked MEK-MLCK signaling. Myosin-9 maldistribution by ML-7 or ML-9 significantly inhibited HPV pseudoviruses infection in vitro and in vivo. Meanwhile, N-glycans, especially the galactose chains, may act as the decoy receptors for HPV, which can block the interaction of HPV to myosin-9 and influence the way of HPV infection. Taken together, we identify myosin-9 as a novel functional entry receptor for high-risk HPV both in vitro and in vivo, and unravel the new roles of myosin-9 and N-glycans in HPV entry, which provides the possibilities for host targets of antiviral drugs.

项与 ML-009 相关的新闻（医药）

2023-11-02

·药明康德

12家创新药公司完成新一轮融资！

▎药明康德内容团队编辑根据药明康德内容部数据统计，今年10月，全球生物医药行业共有224起融资事件。其中，有12起涉及5000万美元以上的大额融资，已公开的融资总额达到了42亿美元，主要发生在C轮或更早的融资阶段。总体来看，全球的生物技术公司都在积极地寻求融资，并得到了许多投资机构的青睐，这无疑展现了该领域的巨大潜力和吸引力。本文将重点介绍其中部分完成大额融资的公司。▲长按识别上方二维码，获取《2023年10月全球5000万以上融资事件盘点》MapLight Therapeutics：中枢神经系统疾病新药研发公司10月30日，MapLight Therapeutics完成超额认购的2.25亿美元C轮融资，以继续推进其对神经精神疾病和神经疾病的变革性疗法开发。此次融资得到了新投资者Novo Holdings、5AM Ventures、Cowen Healthcare Investments的支持。MapLight Therapeutics是一家临床阶段的生物医药公司，致力于开发靶向性的新型疗法，以改善脑部疾病患者的生活。本轮融资将推动该公司旗下新型M1/M4毒蕈碱激动剂ML-007C-MA与外周毒蕈碱拮抗剂构成组合疗法的开发进程，以期于2024年进入治疗精神分裂症和阿尔茨海默病相关精神病的2期临床试验，并使公司的其他管线项目继续取得进展。除了ML-007C-MA之外，MapLight公司目前还有两种产品处于临床开发阶段：ML-007是一种毒蕈碱受体激动剂，用于靶向M1和M4毒蕈碱受体亚型，正在研究用于治疗运动障碍；ML-004是一种5HT-1b激动剂，目前正处于治疗自闭症谱系障碍患者社会交流障碍的2期临床试验中。此外，MapLight的临床前产品还包括ML-016和ML-009，前者是一种GPR-6拮抗剂，正在研究用于治疗帕金森病和抑郁症，后者正在开发用于治疗多动症和冲动行为。▲MapLight Therapeutics产品管线MapLight公司成立于2019年，自成立以来，该公司已完成多轮融资，并成功将3款产品推进至临床开发阶段。公司的创始人兼首席执行官是Christopher Kroeger博士，他拥有超过20年在医药和医疗器械公司的领导及提供咨询的经验。在此之前，他还曾在多家生物医药公司中担任重要职务。Triveni Bio：抗体药物研发公司10月26日，Triveni Bio宣布完成9200万美元A轮融资。据悉，本轮融资资金将用于推动Triveni Bio先导抗体项目（TRIV-509）从临床前开发到2a期临床试验的进展，并助力新型抗体的研发。此次融资由Atlas Venture和Cormorant Asset Management共同领投，奥博资本（OrbiMed）、Viking Global Investors的私募股权业务、Invus、Polaris Partners、Alexandria Venture Investments和其他投资者参投。Triveni Bio是一家生物技术公司，通过融合人类遗传学、同类最佳抗体设计和精准医学方法，Triveni Bio致力于功能性抗体药物的研发。公司先导抗体项目（TRIV-509）能靶向激肽释放酶5和7（KLK5/7），从而治疗特应性皮炎、哮喘、其他免疫学及炎症（I&I）适应症。公司的现任首席执行官是Vishal Patel博士，他曾担任Flagship Pioneering公司的投资组合战略与联盟主管，拥有与创业科学家和运营领导团队合作、指导科学和业务战略的丰富经验。Aiolos Bio：单克隆抗体研发公司10月24日，Aiolos Bio成立并完成了2.45亿美元A轮超额认购。公司将继续推进其主要候选药物AIO-001在中重度哮喘患者中的2期临床试验，同时积极评估其他开发机会。Aiolos Bio是一家临床阶段生物医药公司，旨在满足罹患呼吸系统疾病和炎症性疾病患者的未竟医疗需求。该公司团队具有丰富临床经验，已参与超过30项FDA药物批准。此次超额认购的A轮融资由Atlas Venture、Bain Capital Life Sciences、Forbion和Sofinnova Investments共同领投，RA Capital Management追加了投资。AIO-001是一种抗胸腺基质淋巴细胞生成素（TSLP）单克隆抗体，由于其药效具差异性、半衰期长，每年只需给药两次。TSLP抑制剂在解决严重哮喘症状方面的作用已得到证实，目前正在针对其他免疫疾病（如慢性阻塞性肺病和慢性自发性荨麻疹）进行研究。2023年8月，Aiolos Bio从恒瑞医药获得了该药物在大中华地区以外的全球开发和商业化独家权益。在多项临床研究中，AIO-001在健康志愿者和哮喘患者身上表现出令人鼓舞的安全性、耐受性、药代动力学和生物活性，并且免疫原性较低。Aiolos Bio的共同创始人兼首席执行官Khurem Farooq先生拥有超过25年的药物开发和运营领导经验。在加入Aiolos Bio之前，他曾在多家生物医药公司担任过高级管理职务。Rampart Bioscience：基因疗法研发公司10月24日，Rampart Bioscience宣布完成8500万美元的A轮融资，用于开发旨在减轻患者疾病和治疗负担的药物。新一轮融资以奥博资本提供的4000万美元种子投资为基础，合计共筹得1.25亿美元。此次A轮融资由Forbion领投，奥博资本、RA Capital Management和HealthCap参投。Rampart公司所拥有专有、基于DNA的药物平台HALO，旨在克服病毒和早期非病毒基因疗法的主要局限性和安全性问题，生产高效、持久、可重复给药的基因疗法。公司的多学科团队正在开发基于DNA的新型药物，其效力和持久性可带来变革性的持久临床疗效。公司最初专注于累及肝脏的遗传疾病，其首个项目旨在治疗一种罕见的遗传疾病——低磷酸脂酶症，这是一种罕见且可能致命的遗传病，会阻碍骨矿化。除此之外，Rampart公司还有其他项目正在开发中。Louis Breton先生是Rampart公司的首席执行官和共同创始人。Breton先生拥有超过25年的生物技术行业领导经验。在其职业生涯中，他创建了三家生命科学公司，为20多项产品的上市以及众多许可交易和监管谈判做出了贡献。他还被PharmaVOICE杂志评为生命科学行业最励志和非凡的100位领袖之一。Abivax：小分子靶向新药研发公司10月20日，Abivax公布其首次公开发行价格并公开发行股票，预计总毛收益约为2.36亿美元。Abivax是一家处于临床阶段的生物技术公司，致力于开发利用人体自然调节机制调节慢性炎症患者免疫反应的疗法。其主要候选药物obefazimod（ABX464）是一款用于治疗溃疡性结肠炎（UC）的小分子药物，它能够通过上调一种独特的RNA剪接产物和抗炎因子miR-124的表达，进而抑制许多炎症反应介导物的生产，并在临床试验中显示出使UC患者缓解和“治愈”炎症病变的能力。该药物目前正处于治疗中度至重度活动性溃疡性结肠炎的3期临床试验阶段。公司的现任首席执行官是Marc de Garidel先生，他在医药和生物技术领域拥有40多年的经验，在过去12年中一直担任首席执行官职务。新元素医药：炎症和代谢疾病新药研发公司10月16日，新元素医药宣布完成由凯泰资本领投约8300万美元（约合6亿元人民币）的D轮融资，用于完成治疗慢性痛风的口服尿酸转运蛋白1（URAT1）抑制剂ABP-671的全球关键性临床试验。这笔资金还将用于推动公司治疗炎症和代谢性疾病的创新药物进入临床阶段。本轮融资由新老投资者共同参与，由凯泰资本岭头，其他投资者包括达晨财智、华金投资、乾道集团和新毅投资。本轮融资后，新元素医药总共筹集了近1.65亿美元。新元素医药成立于2012年，专注于代谢和炎症领域疾病的创新药研发。目前，该公司已有多个不同产品处于临床前及临床阶段。其中一款为URAT1抑制剂ABP-671，已在治疗痛风或高尿酸血症患者的中国2a期临床试验中取得积极结果，证实其可显著且安全地降低尿酸水平。公司的创始人、董事长兼CEO为史东方博士，他拥有创新药研发的丰富经验，发表过多篇研究论文，并拥有40余种专利授权。MinervaX：B族链球菌疫苗研发公司10月11日，MinervaX宣布完成5400万欧元的扩展融资。此次融资包括新投资者EQT Life Sciences和奥博资本的投资，以及现有投资者Novo Holdings、Pureos Ventures、赛诺菲风投（Sanofi Ventures）、Trill Impact Ventures、Adjuvant Capital、Wellington Partners、Industrifonden、Sunstone Life Science Ventures和LF Invest的参与。根据该公司新闻稿，这笔融资将使MinervaX能够在2024年将其新型B族链球菌（GBS）疫苗推向3期临床试验。MinervaX是一家B族链球菌疫苗研发公司，该疫苗的细菌抗原来源于B族链球菌的α-类表面蛋白家族，由两种融合蛋白组成，一种是AlpCN和RibN（GBS-NN），另一种是Alp1N和Alp2/3N（GBS-NN2），使用AlOH佐剂配制。目前，MinervaX正在多国470名孕妇中进行两项2期临床试验，证明该疫苗具有可接受的安全性特征、高度免疫原性，并产生具有功能活性的抗体。此外，MinervaX还在老年人中进行其新型GBS疫苗的1期临床试验。据悉，此次融资将使MinervaX能够在2024年将其GBS疫苗推进到3期临床试验。自成立以来，MinervaX颇受资本市场的青睐，已完成了多次融资。除了此次最新的融资，公司还在2022年12月完成了7200万欧元的融资，并在2020年12月完成了4740万欧元的B轮融资。公司的现任首席执行官是Per Fischer博士，他在生物技术和医药行业的产品开发和业务拓展方面拥有25年的经验。他曾创办并经营过多家生物技术公司。Agomab Therapeutics：纤维化疾病药物研发公司10月11日，Agomab Therapeutics宣布完成由Fidelity Management & Research领投的1亿美元C轮融资。获得资金将用于支持其主打候选疗法AGMB-129的2a期临床试验，用于治疗纤维化狭窄性克罗恩病（Fibrostenosing Crohn’s Disease，FSCD）。参加本轮融资的投资机构还包括新投资者EQT Life Sciences，Canaan和Dawn Biopharma（由KKR控制的投资平台），以及现有投资者。Agomab致力于通过靶向与纤维化相关的重要生长因子TGFβ和HGF的信号通路，治疗多种纤维化疾病。该公司曾入选2022年度生物技术猛公司（Fierce 15），并与辉瑞达成合作共同研发AGMB-129。AGMB-129是一款肠道限制型ALK5小分子抑制剂，已经获得美国FDA授予的快速通道资格。本次融资获得的资金还将用于推进和扩展Agomab的研发管线，包括AGMB-447，一种肺限制的ALK5小分子抑制剂，治疗特发性肺纤维化。以及AGMB-101和AGMB-102，用于治疗纤维化和退行性疾病的cMET激动性抗体。Agomab公司在此次C轮融资之外，还有其他财务亮点。该公司在2022年7月完成了4050万美元的B轮扩展融资，并在2021年3月完成了7400万美元的融资。Agomab公司的现任首席执行官是Tim Knotnerus先生，自2019年加入Agomab以来，他与团队一起筹集了2.4亿美元的资金，并开发了广泛的产品线。在加入Agomab之前，他积累了丰富的投资及业务拓展经验。他曾入选知名行业媒体Endpoints News发布的生物医药40岁以下新一代领导者榜单（Endpoints 20 under 40）。靖因药业：小核酸药物研发公司10月16日，靖因药业（Sirius Therapeutics）完成6000万美元的B轮融资，以推进其siRNA新型疗法产品管线的临床开发和新一代核酸分子递送技术的迭代创新。本轮融资由汉康资本领投，康禧全球投资基金参与跟投，原有投资方奥博资本和泓元资本持续追加投资。截至目前，靖因药业已累计获得近亿美元融资。公开资料显示，靖因药业成立于2021年，聚焦新一代核酸创新疗法在心血管疾病领域的开发，致力成为颠覆慢病防治的领军者。该公司拥有小核酸药物研发的核心技术平台，并具有其自主知识产权。目前，靖因药业已建立了多个具有“first-in-class”和“best-in-class”潜力的差异化的产品管线。该公司的研发管线包含多款产品，其中2款产品SRSD107和SRSD101正处于IND申报阶段。AstronauTx：神经退行性疾病治疗药物研发公司10月9日，AstronauTx公司宣布完成4800万英镑（约6100万美元）的A轮融资。此次融资由诺华风险投资基金（Novartis Venture Fund）领投，并同时吸引了数家全球领先的风险投资机构，包括Brandon capital、百时美施贵宝（Bristol Myers Squibb）、EQT Life Sciences投资和MPM capital，现有投资者痴呆症发现基金（Dementia Discovery Fund）也参与了融资。AstronauTx是一家致力于开发阿尔茨海默病和其他神经退行性疾病创新疗法的公司，由痴呆症发现基金于2019年创建，额外的种子阶段资金来自UCL技术基金和英国未来基金，目标是开发创新药物来纠正大脑被破坏的生理机能，包括改善大脑中最丰富的细胞类型——星形胶质细胞的支持功能。2023年7月，AstronauTx宣布与丹麦生物技术公司Saniona合作，通过调节一个未公开的创新离子通道靶标来发现新治疗方法，扩大公司的研发管线。2023年9月，AstronauTx获得了Innovate UK的资助，用于资助其一个项目的临床前工作。本次A轮融资获得的资金将用于推进该公司的小分子药物组合，包括主打项目在阿尔茨海默病患者中进行的临床研究。预期治疗可提供症状改善并改变疾病进程。AstronauTx由Ruth McKernan博士和David Reynolds博士联合创建。McKernan博士在医药行业耕耘27年，曾经是位于英国哈洛（Harlow）的默沙东神经科学研究中心负责人和位于马萨诸塞州剑桥的辉瑞发现技术中心负责人。作为一名神经科学家，她在离子通道和再生医学领域发表超过120篇论文。Reynolds博士是一位有丰富医药研发经验的领导者，在默沙东、Lundbeck和辉瑞工作接近20年。Iambic Therapeutics：人工智能药物发现平台10月3日，Iambic Therapeutics宣布完成1亿美元B轮融资。本轮融资将用于推进公司候选药物的临床开发，扩大药物管线，并继续建设其人工智能药物发现平台。此次融资由Ascenta Capital和Abingworth共同领投，新投资者包括英伟达（NVIDIA）、Illumina Ventures、Gradiant Corporation和独立董事会成员Bill Rastetter。现有投资者也参与其中，包括 Nexus Ventures、Catalio Capital Management、Coatue、FreeFlow、奥博资本和红杉资本（Sequoia Capital）。Iambic Therapeutics致力于利用人工智能（AI）药物发现平台开发新疗法。通过将物理学和人工智能相结合，该平台可识别具有差异化药物特征的候选治疗药物。公司现有两种可进入临床的候选药物，高选择性和脑渗透性HER2抑制剂（IAM-H1）和选择性双CDK2/4抑制剂（IAM-C1），可解决细胞周期驱动癌症在治疗方面未满足的需求。此外，公司还创建了NeuralPLexer和OrbNet等方法来驱动其发现平台。公司的现任首席执行官是Thomas Miller博士，他在学术界有深厚造诣，他于2008年加入加州理工学院，2013年晋升为正教授，先后发表了130多篇经同行评审的文章和专利，并获得了众多研究奖项。阿诺医药：肿瘤免疫疗法研发公司10月3日，阿诺医药在美国纳斯达克市场上市。根据新闻稿公开信息，该公司预计从公开发售中获得总收益5750万美元并从同时进行的私募中获得总收益4000万美元。阿诺医药是一家临床阶段的专注于创新型肿瘤药物开发的全球性生物制药公司，在中美两地均设有研发及临床运营中心。根据公司介绍，该公司产品管线目前涵盖10余抗肿瘤候选药物，有4款药物处于临床阶段，其中，AN2025（buparlisib）已获得FDA的快速通道资格，有望可成为治疗复发性或转移性头颈鳞癌的潜在“first-in-class”药物，正在开展全球多中心的3期临床试验；AN1004（pelareorep）也已获得FDA的快速通道资格，是一款处于注册性试验阶段的、用于治疗转移性乳腺癌的可静脉注射的溶瘤病毒疗法。阿诺医药的创始人、董事长兼首席执行官是路杨先生，拥有逾20年的药物开发及商业运营管理经验，在公司战略规划、产品布局、市场开拓、人才引进、资本运作等方面具有丰富经验。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] MapLight Therapeutics Closes $225 Million Series C Funding Round to Advance Pipeline of Central Nervous System Therapeutics，Retrieved November 1, 2023 from https://www.prnewswire.com/news-releases/maplight-therapeutics-closes-225-million-series-c-funding-round-to-advance-pipeline-of-central-nervous-system-therapeutics-301970884.html[2] Triveni Bio Launches with $92 Million Series A Financing to Advance Genetics-Informed Precision Medicines for the Treatment of Immunological and Inflammatory (I&I) Disorders，Retrieved November 1, 2023 from https://www.prnewswire.com/news-releases/triveni-bio-launches-with-92-million-series-a-financing-to-advance-genetics-informed-precision-medicines-for-the-treatment-of-immunological-and-inflammatory-ii-disorders-301967602.html[3] Aiolos Bio Launches with $245 Million Series A Investment to Advance Development of Novel, Phase 2-Ready TSLP Antibody，Retrieved November 1, 2023 from https://www.businesswire.com/news/home/20231024577944/en/Aiolos-Bio-Launches-with-245-Million-Series-A-Investment-to-Advance-Development-of-Novel-Phase-2-Ready-TSLP-Antibody[4] Rampart Bioscience Announces $85M Series A Financing to Develop Novel DNA-Based Medicines with Veteran Team，Retrieved November 1, 2023 from https://www.businesswire.com/news/home/20231024873160/en/Rampart-Bioscience-Announces-85M-Series-A-Financing-to-Develop-Novel-DNA-Based-Medicines-with-Veteran-Team[5] Abivax Announces the Pricing of its Initial Public Offering on the Nasdaq Global Market，Retrieved November 1, 2023 from https://www.biospace.com/article/releases/abivax-announces-the-pricing-of-its-initial-public-offering-on-the-nasdaq-global-market-/[6] Atom Bioscience Raises $83M in a D-Round Financing to Support Global Pivotal Clinical Trials of ABP-671, a New Treatment for Chronic Gout，Retrieved November 1, 2023 from https://atombp.us/2023/10/16/atom-bioscience-raises-83m-in-a-d-round-financing-to-support-global-pivotal-clinical-trials-of-abp-671-a-new-treatment-for-chronic-gout/[7] MinervaX Raises EUR 54M in Upsized Financing to Advance the Development of its Maternal Vaccine Against Group B Streptococcus，Retrieved November 1, 2023 from https://www.prnewswire.com/news-releases/minervax-raises-eur-54m-in-upsized-financing-to-advance-the-development-of-its-maternal-vaccine-against-group-b-streptococcus-301952361.html[8] Agomab Raises $100 Million Series C to Advance Fibrosis-focused Pipeline. Retrieved November 1, 2023, from https://www.agomab.com/wp-content/uploads/2023/10/20231011_Agomab-Series-C_FINAL.pdf#new_tab[9] 靖因药业成功完成近亿美元融资，加速推进多款创新小核酸产品的临床开发，Retrieved November 1, 2023, from https://www.siriusrna.com/cn/html/companynews/52.html[10] AstronauTx closes £48 million ($61 million) Series A financing to create new treatments for Alzheimer's disease. Retrieved October 9, 2023, from https://www.prnewswire.com/news-releases/astronautx-closes-48-million-61-million-series-a-financing-to-create-new-treatments-for-alzheimers-disease-301949897.html[11] Iambic Therapeutics Announces Close of Oversubscribed $100 Million Series B Financing to Advance AI-Discovered Therapeutics into Clinical Development and Enters Collaboration with NVIDIA，Retrieved November 1, 2023, from https://www.businesswire.com/news/home/20231003865353/en/Iambic-Therapeutics-Announces-Close-of-Oversubscribed-100-Million-Series-B-Financing-to-Advance-AI-Discovered-Therapeutics-into-Clinical-Development-and-Enters-Collaboration-with-NVIDIA[12] Adlai Nortye Ltd. Announces Closing of Initial Public Offering，Retrieved November 1, 2023, from https://www.globenewswire.com/news-release/2023/10/03/2753988/0/en/Adlai-Nortye-Ltd-Announces-Closing-of-Initial-Public-Offering.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床2期临床1期

2023-10-30

·PRNewswire

MapLight Therapeutics Closes $225 Million Series C Funding Round to Advance Pipeline of Central Nervous System Therapeutics

Funding will support development of multiple clinical candidates to treat neurological and psychiatric disorders, including Phase 2 studies for ML-007C-MA in 2024 in schizophrenia and Alzheimer's disease psychosis Novo Holdings led a group of top-tier, new investors including Cowen Healthcare Investments, 5AM Ventures and others SAN FRANCISCO, Oct. 30, 2023 /PRNewswire/ -- MapLight Therapeutics, a clinical-stage biopharmaceutical company working to develop targeted, novel therapeutics to improve the lives of people with brain disorders, today announced the closing of an oversubscribed $225 million Series C financing to continue the advancement of MapLight's transformative treatments for neuropsychiatric and neurological conditions. New investors Novo Holdings, 5AM Ventures, Cowen Healthcare Investments, and others joined MapLight's existing syndicate in the financing. This round of funding will advance ML-007C-MA, a novel M1/M4 muscarinic agonist agent combined with a precision matched peripheral muscarinic antagonist, into Phase 2 trials for schizophrenia and Alzheimer's disease psychosis in 2024, and enable continued progress on the company's other pipeline programs. "MapLight has built a diverse pipeline of innovative neuroscience therapeutics targeting a spectrum of Central Nervous System (CNS) disorders where the challenges faced by patients and families are significant and the unmet need is high. This financing will fuel the important clinical development necessary to bring these innovative therapies to patients," said Christopher Kroeger, M.D., MBA, Chief Executive Officer, and Founder. "The enthusiasm and continued support of our existing investors, combined with the significant commitment from this new slate of top tier funds, provides validation for our circuit-based discovery platform approach, the quality of our clinical assets, and the strong capabilities of our team." In addition to ML-007C-MA, MapLight currently has two other products in clinical development: ML-007 is under study for dyskinesia, and ML-004, a 5HT-1b agonist is currently in Phase 2 for social communication deficits in patients with autism spectrum disorder. MapLight's pipeline preclinical assets include ML-016, a GPR-6 antagonist under study for both Parkinson's disease and depression, and ML-009, in development to treat hyperactivity and impulsivity. "MapLight is advancing what we believe will be the best-in-class muscarinic agent for difficult-to-treat disorders including schizophrenia and Alzheimer's disease psychosis. Schizophrenia alone affects around 3 million adults in the U.S. and 1 percent of the worldwide population," said Jim Trenkle, Ph.D., MBA, Partner in the Venture Investments group at Novo Holdings. "We are delighted to partner with a very strong group of existing and new investors to catalyze significant advancements in the fight against these important central nervous system disorders, and to support the talented, dedicated team at MapLight." In connection with the financing, Jim Trenkle, Ph.D., MBA, Partner in the Venture Investments group at Novo Holdings will join the MapLight Therapeutics Board of Directors. About ML-007 ML-007 is a muscarinic receptor agonist designed to target M1 and M4 muscarinic receptor subtypes with no direct activity on dopamine receptors. Deficits in M1 receptors are linked to schizophrenia, and M1 receptors directly regulate neural circuits known to be important in both psychosis and cognition. M4 receptors regulate a complementary neural circuit known to be important in psychosis. About ML-007C-MA ML-007C-MA is a combination muscarinic agent in clinical development for the treatment of neurologic and neuropsychiatric conditions. ML-007C-MA unlocks the full therapeutic potential of ML-007, an M1/ M4-preferring muscarinic agonist, by pairing it with a precision-matched muscarinic antagonist to block peripheral side effects. ML-007C-MA was specifically designed with the goal of delivering powerful muscarinic agonist activity to the brain while preventing side effects outside of the brain with a muscarinic antagonist. About ML-004 ML-004 is MapLight's 5HT-1b agonist currently in Phase 2 clinical trials. MapLight is developing ML-004 for the treatment of social communication deficits in patients with autism spectrum disorder. About Schizophrenia Schizophrenia is a serious, debilitating mental illness characterized by disturbances in perception, thinking, emotional reaction, and behavior. Schizophrenia can cause people to interpret reality abnormally and includes a combination of positive, negative, and cognitive symptoms. Approximately 60% of people with schizophrenia have no response or only a partial response to the available standard of care treatments, leaving a substantial portion of the population with urgent unmet needs. About Dyskinesias Dyskinesias are a category of movement disorders that are characterized by uncontrollable, abnormal, and repetitive muscle movements that can be disruptive to function and quality of life. Dyskinesia can be the result of an underlying condition or develop as a side effect of dopaminergic medications (drug-induced dyskinesia), commonly used to treat Parkinson's disease, depression, bipolar disorder, schizophrenia, and irritability in autism. About Alzheimer's Disease Psychosis Over 40% of people with Alzheimer's disease (AD) will experience delusions and hallucinations as part of the disease, a condition known as AD psychosis. The condition is often recurrent, severe, and is associated with an increased likelihood of nursing home placement and increased morbidity and mortality. There is no FDA approved medication for the treatment of AD psychosis. About MapLight Therapeutics MapLight is working to develop targeted, novel therapeutics to improve the lives of people with difficult-to-treat brain disorders. MapLight's unique discovery platform combines novel, proprietary technologies to uncover the individual circuits that misfire in brain disorders and target those circuits with effective, safe therapeutics. MapLight was founded in 2019 by a team of renowned neuroscientists who led the discovery of such groundbreaking technologies as optogenetics and STARmap. Learn more at . About Novo Holdings A/S Novo Holdings is a holding and investment company that is responsible for managing the assets and the wealth of the Novo Nordisk Foundation. The purpose of Novo Holdings is to improve people's health and the sustainability of society and the planet by generating attractive long-term returns on the assets of the Novo Nordisk Foundation. Wholly owned by the Novo Nordisk Foundation, Novo Holdings is the controlling shareholder of Novo Nordisk A/S and Novozymes A/S and manages an investment portfolio with a long-term return perspective. In addition to managing a broad portfolio of equities, bonds, real estate, infrastructure and private equity assets, Novo Holdings is a world-leading life sciences investor. Through its Seeds, Venture, Growth, and Principal Investments teams, Novo Holdings invests in life science companies at all stages of development. As of year-end 2022, Novo Holdings had total assets of EUR 108 billion. Media Contact MapLight Therapeutics Charmaine Lykins, Chief Commercial Officer, [email protected] Logo - SOURCE MapLight Therapeutics, Inc.

临床2期

2023-10-30

·PRNewswire

MapLight Therapeutics Closes $225 Million Series C Funding Round to Advance Pipeline of Central Nervous System Therapeutics

Funding will support development of multiple clinical candidates to treat neurological and psychiatric disorders, including Phase 2 studies for ML-007C-MA in 2024 in schizophrenia and Alzheimer's disease psychosis Novo Holdings led a group of top-tier, new investors including Cowen Healthcare Investments, 5AM Ventures and others SAN FRANCISCO, Oct. 30, 2023 /PRNewswire/ -- MapLight Therapeutics, a clinical-stage biopharmaceutical company working to develop targeted, novel therapeutics to improve the lives of people with brain disorders, today announced the closing of an oversubscribed $225 million Series C financing to continue the advancement of MapLight's transformative treatments for neuropsychiatric and neurological conditions. Continue Reading New investors Novo Holdings, 5AM Ventures, Cowen Healthcare Investments, and others joined MapLight's existing syndicate in the financing. This round of funding will advance ML-007C-MA, a novel M1/M4 muscarinic agonist agent combined with a precision matched peripheral muscarinic antagonist, into Phase 2 trials for schizophrenia and Alzheimer's disease psychosis in 2024, and enable continued progress on the company's other pipeline programs. "This financing will fuel the important clinical development necessary to bring these innovative therapies to patients," said Christopher Kroeger, M.D., MBA, Chief Executive Officer, and Founder Post this "MapLight has built a diverse pipeline of innovative neuroscience therapeutics targeting a spectrum of Central Nervous System (CNS) disorders where the challenges faced by patients and families are significant and the unmet need is high. This financing will fuel the important clinical development necessary to bring these innovative therapies to patients," said Christopher Kroeger, M.D., MBA, Chief Executive Officer, and Founder. "The enthusiasm and continued support of our existing investors, combined with the significant commitment from this new slate of top tier funds, provides validation for our circuit-based discovery platform approach, the quality of our clinical assets, and the strong capabilities of our team." In addition to ML-007C-MA, MapLight currently has two other products in clinical development: ML-007 is under study for dyskinesia, and ML-004, a 5HT-1b agonist is currently in Phase 2 for social communication deficits in patients with autism spectrum disorder. MapLight's pipeline preclinical assets include ML-016, a GPR-6 antagonist under study for both Parkinson's disease and depression, and ML-009, in development to treat hyperactivity and impulsivity. "MapLight is advancing what we believe will be the best-in-class muscarinic agent for difficult-to-treat disorders including schizophrenia and Alzheimer's disease psychosis. Schizophrenia alone affects around 3 million adults in the U.S. and 1 percent of the worldwide population," said Jim Trenkle, Ph.D., MBA, Partner in the Venture Investments group at Novo Holdings. "We are delighted to partner with a very strong group of existing and new investors to catalyze significant advancements in the fight against these important central nervous system disorders, and to support the talented, dedicated team at MapLight." In connection with the financing, Jim Trenkle, Ph.D., MBA, Partner in the Venture Investments group at Novo Holdings will join the MapLight Therapeutics Board of Directors. About ML-007 ML-007 is a muscarinic receptor agonist designed to target M1 and M4 muscarinic receptor subtypes with no direct activity on dopamine receptors. Deficits in M1 receptors are linked to schizophrenia, and M1 receptors directly regulate neural circuits known to be important in both psychosis and cognition. M4 receptors regulate a complementary neural circuit known to be important in psychosis. About ML-007C-MA ML-007C-MA is a combination muscarinic agent in clinical development for the treatment of neurologic and neuropsychiatric conditions. ML-007C-MA unlocks the full therapeutic potential of ML-007, an M1/ M4-preferring muscarinic agonist, by pairing it with a precision-matched muscarinic antagonist to block peripheral side effects. ML-007C-MA was specifically designed with the goal of delivering powerful muscarinic agonist activity to the brain while preventing side effects outside of the brain with a muscarinic antagonist. About ML-004 ML-004 is MapLight's 5HT-1b agonist currently in Phase 2 clinical trials. MapLight is developing ML-004 for the treatment of social communication deficits in patients with autism spectrum disorder. About Schizophrenia Schizophrenia is a serious, debilitating mental illness characterized by disturbances in perception, thinking, emotional reaction, and behavior. Schizophrenia can cause people to interpret reality abnormally and includes a combination of positive, negative, and cognitive symptoms. Approximately 60% of people with schizophrenia have no response or only a partial response to the available standard of care treatments, leaving a substantial portion of the population with urgent unmet needs. About Dyskinesias Dyskinesias are a category of movement disorders that are characterized by uncontrollable, abnormal, and repetitive muscle movements that can be disruptive to function and quality of life. Dyskinesia can be the result of an underlying condition or develop as a side effect of dopaminergic medications (drug-induced dyskinesia), commonly used to treat Parkinson's disease, depression, bipolar disorder, schizophrenia, and irritability in autism. About Alzheimer's Disease Psychosis Over 40% of people with Alzheimer's disease (AD) will experience delusions and hallucinations as part of the disease, a condition known as AD psychosis. The condition is often recurrent, severe, and is associated with an increased likelihood of nursing home placement and increased morbidity and mortality. There is no FDA approved medication for the treatment of AD psychosis. About MapLight Therapeutics MapLight is working to develop targeted, novel therapeutics to improve the lives of people with difficult-to-treat brain disorders. MapLight's unique discovery platform combines novel, proprietary technologies to uncover the individual circuits that misfire in brain disorders and target those circuits with effective, safe therapeutics. MapLight was founded in 2019 by a team of renowned neuroscientists who led the discovery of such groundbreaking technologies as optogenetics and STARmap. Learn more at . About Novo Holdings A/S Novo Holdings is a holding and investment company that is responsible for managing the assets and the wealth of the Novo Nordisk Foundation. The purpose of Novo Holdings is to improve people's health and the sustainability of society and the planet by generating attractive long-term returns on the assets of the Novo Nordisk Foundation. Wholly owned by the Novo Nordisk Foundation, Novo Holdings is the controlling shareholder of Novo Nordisk A/S and Novozymes A/S and manages an investment portfolio with a long-term return perspective. In addition to managing a broad portfolio of equities, bonds, real estate, infrastructure and private equity assets, Novo Holdings is a world-leading life sciences investor. Through its Seeds, Venture, Growth, and Principal Investments teams, Novo Holdings invests in life science companies at all stages of development. As of year-end 2022, Novo Holdings had total assets of EUR 108 billion. Media Contact MapLight Therapeutics Charmaine Lykins, Chief Commercial Officer, [email protected] SOURCE MapLight Therapeutics, Inc.

临床2期

100 项与 ML-009 相关的药物交易

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