TFR2

TU7710 has the potential to be a highly effective and long-acting treatment for bleeding episodes as well as for preventing bleeding during surgery or invasive procedures in hemophilia patients with inhibitors Interim results from an ongoing Phase 1a study in healthy male volunteers will be presented at International Society on Thrombosis and Haemostasis (ISTH) 2024 Congress BOSTON and SEONGNAM, South Korea, March 26, 2024 /PRNewswire/ -- TiumBio Co., Ltd. (Kosdaq: 321550), a clinical-stage biopharmaceutical company focused on discovering and developing innovative therapeutics for patients with rare and incurable diseases, has announced the filing of a Clinical Trial Application (CTA) with the Italian Medicines Agency (AIFA) and the Spanish Agency of Medicines and Medical Products (AEMPS) to initiate a Phase 1b study of TU7710, a novel recombinant activated factor VII (rFVIIa) for hemophilia patients with inhibitors. The Phase 1b clinical trial is an open-label, single and multiple-dose escalation study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of TU7710, aiming to determine the recommended Phase 2 dose. The trial will enroll up to 18 hemophilia A or B patients with inhibitors and will be conducted in Italy and Spain. TU7710 is a long-acting rFVIIa with a half-life 6-7 times longer than NovoSeven, a rFVIIa widely accepted as a standard treatment, which is achieved through TiumBio's transferrin fusion protein technology. Thus, it will substantially reduce both burdens of treatment costs and frequent dosing of NovoSeven for patients. TiumBio is currently conducting a Phase 1a study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TU7710 in healthy adult male volunteers. Interim results from the study will be present at the ISTH 2024. "We believe that TU7710 will become a highly effective medication that can manage bleeding episodes and prevent bleeding during surgical operations with its longer half-life compared to NovoSeven," said Hun-taek Kim, Ph.D., MBA, Founder and CEO of TiumBio. "Our team has been developing TU7710 as an innovative hemophilia treatment option, which is strengthened by our experience with Afstyla, an FDA-approved recombinant Factor VIII originally discovered by our R&D team members at SK Chemicals," he added. Hemophilia is a congenital bleeding disorder caused by the absence of deficiency of blood clotting factors. Blood coagulation factor VIII deficiency is classified as hemophilia type A, and blood coagulation factor IX deficiency is classified as hemophilia type B. rFVIIa is a bypassing agent therapy for patients with hemophilia A or B who develop neutralizing antibodies, but there are currently only limited treatment options available on the market, including the leading drug NovoSeven, a product by Novo Nordisk. About TiumBio Co., Ltd. TiumBio (Kosdaq: 321550) is a clinical-stage biopharmaceutical company focused on the discovery and development of innovative therapeutics for patients with rare and incurable diseases. Its mission is to expand the hope and happiness of mankind through our science. TiumBio boasts three leading pipeline assets: merigolix (code name: TU2670), TU2218, and TU7710, all in various stages of clinical development. Merigolix is a once-daily, oral GnRH receptor antagonist being developed for the treatment of endometriosis and uterine fibroids and is undergoing in global Phase 2 clinical trials. TU2218 is a first-in-class oral immune-oncology therapy targeting TGF-β and VEGF pathways to promote response rates in cancer patients when used in combination with immune checkpoint inhibitors. TU7710 is a novel rFVIIa designed to extend its half-life in order to provide more clinical benefits to hemophilia patients with inhibitors. With its expertise in drug development, TiumBio is committed to the discovery and development of innovative treatments to ease the burden of debilitating diseases. For further information, visit our website at and connect with us on LinkedIn. Contacts: Junseok Jang, Head of Corporate Communications & Investor Relations [email protected] Suna Cho, Manager, Corporate Communications & Investor Relations [email protected] Da-ye Song, Manager, Corporate Communications & Investor Relations [email protected] SOURCE TiumBio

Results show statistically significant decreases in stroke volume, edema, and necrotic area versus controls SAN DIEGO, Feb. 12, 2024 /PRNewswire/ -- VST Bio Corp. a leader in the development of innovative biologics to treat acute and chronic cardiovascular disease, presented data from a recent large animal study performed by VST Bio and Yale University demonstrating that a single iv bolus of VST-002 led to meaningful reduction in brain damage and improved function in an advanced model of ischemic stroke. Dr. Federico Corti, from the Cardiovascular Research Center of Yale University, presented data which showed that a single bolus of humanized anti-Syndecan 2 antibody (VST-002), administered either 3 hours or 6 hours after ischemia led to ~60% reduction of stroke damage as visualized by magnetic resonance imaging, with all measures being statistically significant over control animals. Histological analysis at 72 hours post-stroke confirmed a significant reduction of edema and area of necrosis in both early and delayed therapy groups. These findings indicate that anti-Sdc2 mAb promotes neuroprotection and suggest that this therapy could be used both in patients undergoing early reperfusion as well as outside the current reperfusion window guidelines. Furthermore, the treatment was safe with no observed toxicities. The study was performed by an independent CRO, blinded to treatment assignment. VST Bio Chief Executive Officer Krisztina Zsebo, PhD, said, "VST-002 human antibody therapy is being initially developed to treat ischemic stroke patients. The current standard-of-care is either thrombolytic therapy when given within the first 4.5 hours of stroke, or thrombectomy given within 24 hours. However, many hospitals don't offer thrombectomy because it requires specialist doctors, leaving the majority of patients ineligible for conventional treatment. VST-002 may offer an additional path to preserve brain function and improve recovery after ischemic stroke". Prof. Dr. Michael Simons of Yale University, chair of the Scientific Advisory Committee, commented: "The humanized anti-Syndecan 2 monoclonal antibody therapy has shown consistent efficacy in normalizing vascular patency in various preclinical assays and models while preserving normal vasculature1,2. A normalization of vascular permeability in acute stroke results in reduced local and systemic inflammation as well as decreased edema formation. As a result, there is a significant reduction of stroke size, even when VST-002 antibody therapy is initiated late after the onset of stroke. Reducing edema, inflammation, and secondary injury after stroke could have a meaningful benefit for stroke patient outcomes." About VST Bio VST Bio Corp., headquartered in San Diego, California, is developing vascular biologic therapies to treat acute cardiovascular disease. VST-002 antibody therapies are one of the Company's biotherapeutic product candidates in clinical development. For more information, visit . References: F Corti, E Ristori, F Rivera-Molina, D Toomre, J Zhang, J Mihailovic, ZW Zhuang, M Simons, "Syndecan-2 selectively regulates VEGF-induced vascular permeability.", Nat Cardiovasc Res. 2022 May; 1(5): pg 518-528 F Corti F and M Simons. "Modulation of VEGF receptor 2 signaling by protein phosphatases.", Pharmacol Res. 2017 Jan; 115: pg 107-123. Media Contact: Rebecque Laba (858) 663-8641 [email protected] Investor Contact: Krisztina Zsebo, Ph.D., Chief Executive Officer 619-889-5199 [email protected] Logo -

▎Armstrong2023年1月3日，迈威生物9MW3011的临床试验申请获得NMPA受理，用于治疗真性红细胞增多症和β-地中海贫血铁过载。根据迈威生物官方信息，9MW3011由其美国子公司自主研发，是一款针对全新靶点的单抗新药。作用机制上，9MW3011通过结合肝细胞表面表达的靶点蛋白，上调肝细胞表达铁调素的水平，抑制铁的吸收和释放，从而达到调节体内铁稳态的作用。铁是自然界中存量第二多的金属，仅次于铝，也是所有生命体的必需元素。在DNA复制、修复、翻译过程中的许多酶都依赖于铁的存在，往往通过Fe-S簇的方式来发挥正常的酶功能。人体每天从食物中吸收1-2mg的铁，食物中的铁通过十二指肠上皮细胞铁转运蛋白（ferroportin，FPN）进入血液中，并以与转铁蛋白（Transferrin）结合的形式存在。红细胞是利用铁的最主要位置，过量的铁则被储存在肝脏等器官中。衰老死亡的红细胞，其中的铁会通过巨噬细胞吞噬红细胞被再次利用。铁含量同时受到铁调素（Hepcidin）的严密调控，铁调素编码基因HAMP的表达反过来受到铁和红细胞的调控，从而形成一个精密的反馈控制系统。正常条件下，铁代谢调控系统可以维持体内正常的铁平衡，但在一些疾病状态，如β-地中海贫血、真性红细胞增多症等与铁稳态相关的疾病中，都会出现铁稳态的失衡。在β-地中海贫血（下图左）中，由于基因突变导致血红蛋白合成产生障碍，从而导致铁过载。在真性红细胞增多症（下图右）中，髓系细胞过度增殖，包括红细胞、粒细胞等。红细胞不受控的不断增殖生成伴随铁调素的抑制，后者又会进一步导致血浆中铁的上调。这些情况下就需要通过临床干预来调整铁稳态。在肝细胞内，有多个参与铁代谢的通路蛋白，BMP6结合到BMP6受体，并在HJV存在的情况下，激活SMAD1/5/8进而活化SMAD4，从而促进铁调素（Hepcidin）的表达。转铁蛋白受体2（TFR2）的下游信号通路与BMP受体类似。红细胞则通过分泌ERFE来抑制肝脏铁调素的表达，从而获得更多的铁元素。针对铁代谢的药物开发可能针对不同环节，涉及不同靶点，但通常铁调素都是其中的关键。以上调铁调素的药物开发为例，可以通过铁调素类似物放大其功能，也可以靶向TMPRSS6、FPN等来上调铁调素等。总结截至目前，β-地中海贫血、真性红细胞增多症等相关适应症领域尚无成熟有效的大分子治疗药物。9MW3011有望在未来获得孤儿药资格，并有望成为全球范围内首个调节体内铁稳态的大分子药物，期待其临床进展，并贡献中国原始创新力量。----------------------感兴趣的读者可以加入“医药笔记”知识星球。Armstrong技术全梳理系列GPRC5D靶点全梳理；CD40靶点全梳理；CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向；Claudin 6靶点全梳理；Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇；CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理；Ambrx技术全梳理；Vir Biotech技术全梳理；Immune-Onc技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理；Momenta技术全梳理；NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。