Sovateltide

Strategic equity investment of $15 M to support completion of Pharmazz's pivotal Phase 3 study for Sovateltide to treat patients with acute cerebral ischemic strokeExpansion of the exclusive license agreement with Sun Pharma for marketing and distribution of Sovateltide in India to certain additional Emerging Market countries WILLOWBROOK, Ill., Aug. 21, 2024 (GLOBE NEWSWIRE) -- Pharmazz, Inc. (“Pharmazz” or the “Company”), a biopharmaceutical company focused on developing and commercializing novel therapeutics to treat patients in critical care, announced that it has entered into an agreement with Sun Pharmaceutical Industries Limited (Reuters: SUN.BO, Bloomberg: SUNP IN, NSE: SUNPHARMA, BSE: 524715, "Sun Pharma" and includes its subsidiaries and/or affiliated companies) to support development of Sovateltide and extend the scope of its strong working relationship to commercialize a first-in-class innovative drug, Sovateltide (Tyvalzi™). Developed by Pharmazz for potential global use, Sovateltide is indicated for treating acute cerebral ischemic stroke in markets where it is launched. Pursuant to the agreement, Sun Pharma will make a strategic equity investment of $15 M in two tranches, subject to certain conditions, to support the development of Pharmazz's lead compound, Sovateltide, through a pivotal Phase 3 trial in the U.S. to treat patients with acute cerebral ischemic stroke. As the world's leading specialty generic pharmaceutical company, Sun Pharma’s equity investment further validates the promising developmental pathway for Sovateltide. Previously, Pharmazz entered into a license agreement with Sun Pharma to commercialize Sovateltide in India under Sun Pharma owned brand name Tyvalzi™. This collaboration is now being expanded to drive the asset’s commercialization efforts in certain additional Emerging Market countries. Sun Pharma’s investment and collaboration will bring valuable operational expertise and strategic inputs to the Pharmazz management team. About Sovateltide Sovateltide is a first-of-its-kind drug to treat acute cerebral ischemic stroke that can be administered up to 24 hours after the onset of symptoms. Pharmazz has received agreement from the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the study design and statistical analysis plan of its Phase 3 clinical trial of Sovateltide for treating acute cerebral ischemic stroke patients. The protocol is titled, “A Multicentric, Randomized, Double-blind, Parallel, Placebo-controlled Phase III Study to Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke.” ClinicalTrials.gov ID: NCT05691244. Sovateltide is a first-in-class drug to treat acute cerebral ischemic stroke, a condition in which the loss of blood supply to the brain prevents brain tissue from receiving oxygen and nutrients, resulting in potential brain damage, neurological deficits, or death. Sovateltide promotes neurovascular remodeling by forming new neurons (neurogenesis) and blood vessels (angiogenesis). Sovateltide also protects neural mitochondria and enhances their biogenesis. It can be given to patients along with thrombolytic, and about 30,000 acute cerebral ischemic patients have been treated in India. About Pharmazz, Inc. Pharmazz is a privately held company developing novel products in critical care medicine. Pharmazz obtained marketing authorization for two of its first-in-class drug molecules, Centhaquine and Sovateltide, for hypovolemic shock and acute cerebral ischemic stroke, respectively, in India. In addition, the U.S. Food and Drug Administration (FDA) has approved two phase III INDs for Centhaquine as an agent for hypovolemic shock and Sovateltide for acute cerebral ischemic stroke. Additional information may be found on the Company’s website, www.pharmazz.com, and follow us on LinkedIn & X (Formerly Twitter). About Sun Pharmaceutical Industries Limited (CIN - L24230GJ1993PLC019050): Sun Pharma is the world’s leading specialty generics company with a presence in specialty, generics and consumer healthcare products. It is the largest pharmaceutical company in India and is a leading generic company in the U.S. as well as global emerging markets. Sun Pharma’s high-growth global specialty portfolio spans innovative products in dermatology, ophthalmology, and onco-dermatology and accounts for over 18% of company sales. The company’s vertically integrated operations deliver high quality medicines, trusted by physicians and consumers in over 100 countries. Its manufacturing facilities are spread across six continents. Sun Pharma is proud of its multicultural workforce drawn from over 50 nations. For further information, please visit www.sunpharma.com and follow us on LinkedIn & X (Formerly Twitter). Disclaimer: Statements in this “Document” describing the Company’s objectives, projections, estimates, expectations, plans or predictions, or industry conditions or events may be “forward-looking statements” within the meaning of applicable securities laws and regulations. Actual results, performance, or achievements could differ materially from those expressed or implied. The Company undertakes no obligation to update or revise forward-looking statements to reflect developments or circumstances that arise or to reflect the occurrence of unanticipated developments/circumstances after the date hereof. Contacts: Pharmazz, Inc. Investors Media David Costello Shruti Gulati Tel+1 630 780 6087Tel+1 630 780 6087E maildavid.costello@pharmazz.comE mailshruti.gulati@pharmazz.com

关注并星标CPHI制药在线内皮素（ET）是一类由21个氨基酸组成的内源性多肽激素，具有强烈而持久的缩血管效应。此外，ET还参与心血管细胞的凋亡、分化和表型转化等多种病理过程，是心血管活动的重要调节因子之一。       ET包括ET-1、 ET-2和ET-3三种亚型，其中ET-1主要由血管内皮细胞合成，ET-2由肠道和肾脏产生，ET-3由神经组织释放。ET-2和ET-3与ET-1在N末端的2个和5个残基上存在差异，这决定它们在受体结合和亲和力上的差异。       ET通过作用于内皮素受体（ETR）调节人体多种重要的生理和病理过程。ETR属于典型的A类G蛋白偶联受体，包括ETA和ETB两种类型，其中ETA受体与ET-1和ET-2的结合亲、和力高于与ET-3，ETB受体与这三种异肽的结合亲和力相当。在被ET-1激活后，ETA受体和ETB受体呈现相反的血管调节作用：ETA受体激活导致长时间的血管收缩效应，而ETB受体则介导血管扩张。       内皮素系统在维持血管稳态中发挥着重要作用，与多种器官系统的血管疾病密切相关，是治疗心血管系统疾病的重要靶标之一。ETR作为内皮素系统的关键组成部分，因此成为药企积极布局的热门靶点。全球已获批的ETR靶向药       据不完全统计，目前全球监管机构已批准7款ETR靶向药，这些药物主要针对ETA受体，被批准用于治疗肺动脉高压。辉瑞的ETA受体拮抗剂西他生坦（sitaxentan，Thelin）也曾获监管机构批准，但因可能引起不能预测的严重肝损伤撤市。值得一提的是，近几年获批的ETR靶向药适应症与此前获批的不同，除了心脑血管疾病，还涉及肾病。       具体品种来看，克拉佐生坦是Idorsia公司开发的一种强效、选择性 ETA 受体拮抗剂，2022年1月在日本被批准用于预防脑血管痉挛、血管痉挛相关的脑梗死以及动脉瘤性蛛网膜下腔出血（aSAH）术后脑缺血症状。       阿普昔腾坦是一款新型口服双重ETA/ETB拮抗剂，可有效抑制ET-1与ETA和ETB的结合，从而阻断ET-1的作用。该药是马昔腾坦的活性代谢产物，具有更长的半衰期（48 h vs. 14 h），可以1天1次使用，降低血压，是第一个用于高血压治疗的ET受体拮抗剂。2024年3月，该药被FDA批准用于治疗难治性高血压，成为30多年来高血压领域获批的全新机制药物。       Sparsentan是一种每日一次的口服小分子药物，选择性靶向ETA受体和血管紧张素II 1型受体（AT1R）。2023年2月，FDA加速批准Sparsentan用于降低有快速疾病进展风险的原发性IgAN成人的蛋白尿，通常尿蛋白/肌酐比(UPCR) ≥1.5g/g。这使Sparsentan成为首个获批治疗IgAN的非免疫抑制疗法。       不过Sparsentan上市后遭遇多重质疑，首先是收到了FDA肝毒性和胚胎/胎儿毒性的黑框警告，其次在跟厄贝沙坦（血管舒张素Ⅱ受体阻滞剂）的"头对头"较量中错过了III期研究的次要终点。       Sovateltide是一种高选择性ETB受体激动剂，可增加血流量，显示抗凋亡活性，保护神经线粒体，促进神经血管重塑。2023年5月，该药在日本被批准用于治疗高血压急性脑缺血性中风。ETR靶向药研究进展       此外，目前全球还有多款在研ETR靶向药，详见下表。在研ETR靶向药大多作用于ETA受体。在研ETB受体靶向药整体进展较ETA受体靶向药慢，且适应症涉及肿瘤。而且，在研ETR靶向药的药物类型也比较多样，除了小分子化药，还包括单抗、抗体偶联药物（ADC）。       Atrasentan进展较快，处于3期临床。该药是Chinook开发的ETA受体拮抗剂，可选择性阻断ETA受体，通过阻断肾小球系膜细胞活化，直接的抗炎和抗纤维化，降低球囊内压力和肾小球滤过屏障大分子通透性来减少免疫球蛋白A肾病(IgAN) 患者的尿蛋白。2023年6月，诺华通过收购Chinook将Atrasentan纳入囊中。2023年10月，atrasentan治疗高危进展型IgA肾病的关键3期临床试验ALIGN取得积极中期结果：研究达到主要疗效终点，IgAN患者中的蛋白尿具有统计学意义的显著减少。研究中Atrasentan的整体安全性及耐受性良好。       我国药企在ETR靶点也有布局。智康弘义的SC0062是针对慢性肾脏病的ETA受体小分子拮抗剂，其针对慢性肾脏病进行了全新的分子设计，具有独特的ETA高选择性，目标在保证疗效的同时进一步提升药物安全性。目前，SC0062正在开展针对IgA肾病和糖尿病肾脏病的2期临床研究。       临床前研究表明，SC0062具有良好的活性，能够有效改善急性肾损伤和慢性肾脏病模型的病理评分。在已完成的临床I期研究中，SC0062表现出良好的安全性和耐受性及药代动力学特征，同时未发现水钠潴留等副作用，有望成为潜在的Best-in-Class药物。       信立泰的SAL0120是其自主研发的小分子ETA受体拮抗剂，通过选择性拮抗ETA受体，在现有用药基础上达到进一步降低血压的目的，拟开发适应症包括轻、中度原发性高血压。       鸿运华宁开发了两款ETR靶向药。其中GMA131是其自主研发的一款ETA靶向单抗。临床前及临床研究显示：GMA131具有良好的安全性，且在高脂饲料联合STZ诱导的糖尿病肾病模型中表现出了优于小分子内皮素受体拮抗剂（ERA）的疗效。2022年11月，GMA131在美国获批临床，用于治疗糖尿病肾病。       ETB靶向药较少，其中DEDN6526A是一款ADC类候选药物，由人源化 IgG1 抗 ETB单克隆抗体MEDN6000A和一种强效抗有丝分裂剂(MMAE)通过蛋白酶抑制连接体马来酰亚胺基缬氨酸-瓜氨酸-对氨基苄氧羰基 (MC-VC-PAB) 连接而成。MEDN6000A 在与其配体结合位点不同的表位上对 ETB 具有选择性和高结合亲和力。总结       整体来看，ETR是个多面手，其靶向药除被批准治疗肺动脉高压、高血压等疾病，还被批准用于治疗原发性免疫球蛋白A肾病。虽然全球监管机构已批准了７款ETR靶向药，但国内外药企还在积极挖掘ETR靶向药市场，在研ETR靶向药大多作用于ETA受体，适应症也在不断扩张。尤其是ETB受体靶向药，被开发用于治疗恶性肿瘤。期待在药企的不懈努力下，ETR靶向药可以可以开启更多的可能。【企业推荐】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~