{"id":38407,"date":"2025-12-06T09:00:00","date_gmt":"2025-12-06T08:00:00","guid":{"rendered":"https:\/\/www.etap-lab.com\/?post_type=ressource&#038;p=38407"},"modified":"2026-10-14T15:19:58","modified_gmt":"2026-10-14T13:19:58","slug":"oral-novel-vwf-targeting-thrombolytic-tgd001-as-a-universal-thrombolytic","status":"publish","type":"ressource","link":"https:\/\/www.etap-lab.com\/en\/ressource\/oral-novel-vwf-targeting-thrombolytic-tgd001-as-a-universal-thrombolytic\/","title":{"rendered":"Oral session: Novel von Willebrand Factor Targeting Thrombolytic TGD001 is Effective in Diverse Thrombotic Models, Demonstrating Its Potential as a Universal Thrombolytic"},"content":{"rendered":"\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-7387b849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Discover the oral presentation abstract on <strong>Novel von Willebrand Factor Targeting Thrombolytic TGD001 is Effective in Diverse Thrombotic Models, Demonstrating Its Potential as a Universal Thrombolytic, <\/strong>presented during the 2025 ASH Annual Meeting (Orlando, Florida, USA) by TargED, in which findings presented were implemented by STROK@LLIANCE team on our <em>in vivo<\/em> models of thrombosis, including <a href=\"https:\/\/www.etap-lab.com\/en\/cro-services\/neurovascular-stroke\/in-vivo-models\/#subcat-184\">Acute Ischemic Stroke<\/a> and <a href=\"https:\/\/www.etap-lab.com\/en\/cro-services\/neurovascular-stroke\/in-vivo-models\/#subcat-190\">pulmonary embolism<\/a>. Published in <strong><em>Blood<\/em> (2025) 146 (Supplement 1): 203.<\/strong> <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Significant milestones since the publication:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The first patients have been successfully dosed in Phase 1b\/2a proof-of-concept clinical study evaluating<a href=\"https:\/\/targedbiopharmaceuticals.com\/news\/first-patients-successfully-dosed-in-tgd001-acute-ischemic-stroke-study\/\" target=\"_blank\" rel=\"noreferrer noopener\"> TGD001 as a potential treatment for acute ischemic stroke <\/a>(July 16, 2026).<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Read the full article here:\u00a0<\/strong>DOI: <a href=\"https:\/\/doi.org\/10.1182\/blood-2025-203\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1182\/blood-2025-203<\/a><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><mark style=\"background-color:rgba(0, 0, 0, 0)\" class=\"has-inline-color has-blue-light-color\"><em><strong>Keywords:<\/strong><\/em> Vascular Biology, Thrombosis, and Thrombotic Microangiopathies; New mechanisms ; new therapies; animal model, fibrinolytic agents, thrombus, von willebrand factor, fibrin, alteplase, thrombolytic therapy, embolism, plasmin.<\/mark><\/p>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<div class=\"wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex\">\n<div class=\"wp-block-button is-style-primary\"><a class=\"wp-block-button__link wp-element-button\" href=\"https:\/\/www.etap-lab.com\/en\/contact\/\">CONTACT AN EXPERT NOW<\/a><\/div>\n<\/div>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Authors<\/strong>: Volker Laux 1, Claudia Tersteeg 2, Sarah Vandelanotte 3, Sarah Mc Fie 1, Danielle Versluis 1, Filio Petsini 1, Anne-Sophie Delmote 2, Kristof Vercruysse 1, Simon de Meyer 3, Karen Vanhoorelbeke 2, Steven de Maat 1<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Affiliated<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>1. TargED Biopharmaceuticals, Utrecht, Netherlands<\/li>\n\n\n\n<li>2. KU Leuven Campus Kulak, Kortrijk, Belgium<\/li>\n\n\n\n<li>3. KU Leuven, Laboratory for Thrombosis Research, Kortrijk, Belgium<\/li>\n<\/ul>\n\n\n\n<div style=\"height:40px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><mark style=\"background-color:rgba(0, 0, 0, 0)\" class=\"has-inline-color has-black-color\">ABSTRACT:<\/mark><\/strong><\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\">TGD001: A Novel Universal Thrombolytic Targeting von Willebrand Factor and Fibrin<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Thrombi have heterogeneous compositions, limiting the efficacy of standard-of-care (SoC) thrombolytic treatments. While fibrin has been the main target for current thrombolytics (&#8220;fibrinolytics&#8221;), such as tissue plasminogen activator (tPA), the presence and accessibility of fibrin in thrombi is highly variable. Other thrombus constituents, like von Willebrand factor (VWF), have been shown to reduce tPA&#8217;s efficacy. Therefore, targeting both VWF and fibrin could increase the efficacy of thrombolytic treatments. Hereto, TGD001 was created for VWF-targeted plasmin-mediated thrombolysis. In contrast to SoC fibrinolytics, TGD001&#8217;s thrombolytic activity utilizes the ubiquitous presence of VWF in all thrombi, resulting in thrombolysis that is independent of fibrin, making TGD001 a more universal and potentially more effective thrombolytic.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\">Mechanism of Action: How TGD001 Promotes Targeted Thrombolysis<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">TGD001 is comprised of an antibody fragment with a high affinity to VWF, joined to the catalytic domain of human urokinase-type plasminogen activator. Upon binding to VWF, the catalytic domain of TGD001 is brought near plasminogen, resulting in its activation to plasmin at the site of the thrombus. The formed plasmin can then degrade both VWF and fibrin, resulting in effective thrombolysis of large vessel occlusions, as in <a href=\"https:\/\/www.etap-lab.com\/en\/cro-services\/neurovascular-stroke\/in-vivo-models\/#subcat-184\">acute ischemic stroke (AIS)<\/a> or myocardial infarction, as well as thrombolysis of the many small vessel occlusions seen in thrombotic microangiopathies (TMAs), such as thrombotic thrombocytopenic purpura (TTP). To demonstrate efficacy, TGD001 was assessed in several in vivo preclinical models of thrombosis, including AIS, <a href=\"https:\/\/www.etap-lab.com\/en\/cro-services\/neurovascular-stroke\/in-vivo-models\/#subcat-190\">pulmonary embolism<\/a>, and TTP.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\">Preclinical Evaluation in Acute Ischemic Stroke Models<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">TGD001 was evaluated in several rodent AIS models, each with distinct thrombotic triggers, resulting in different thrombus compositions. In the tPA-insensitive FeCl\u2083-induced AIS murine model, characterized by thrombi with low fibrin but high VWF and platelet levels, TGD001-treated mice had reduced lesion volumes at 24 hours compared to controls.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In a thrombin-induced AIS model using hyperglycemic mice, with fibrin-rich thrombi but insensitive to tPA treatment, TGD001 reduced lesion volumes at 24 hours compared to the control group.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Finally, in a tPA-sensitive embolic-induced AIS model in rats, characterized by fibrin-rich thrombi, tPA and TGD001 showed a reduction in neurological deficits at both 2 and 28 days after stroke onset.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Together, these data demonstrate TGD001&#8217;s efficacy for both VWF- and platelet-rich thrombi (FeCl\u2083-induced), as well as VWF-poor thrombi (thrombin and embolic-induced) in AIS models. Moreover, TGD001 demonstrated efficacy beyond that of tPA. Overall, TGD001 was well-tolerated and did not increase mortality or the risk of hemorrhagic transformation.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\">Human Thrombus Studies Confirm Broad Thrombolytic Activity<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">An in vitro thrombolysis experiment was conducted to assess TGD001&#8217;s ability to degrade thrombi of human origin extracted from patients with AIS during endovascular thrombectomy procedures. Incubation with TGD001 resulted in thrombolysis of all included thrombi. Histological analysis identified a significant correlation between higher VWF levels and enhanced thrombolysis by TGD001.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\">Efficacy in Pulmonary Embolism and Venous Thrombosis<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">To evaluate the efficacy of TGD001 in venous thrombosis, TGD001 was assessed in a rodent model of embolic pulmonary thrombosis. Treatment with TGD001 after induction of pulmonary embolism reduced the mean pulmonary arterial pressure to levels similar to sham-operated controls, indicating the effective removal of the thrombotic obstruction.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\">Therapeutic Potential in Thrombotic Thrombocytopenic Purpura (TTP)<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">TTP is a TMA hallmarked by deficient ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity, leading to the formation of widespread VWF and platelet-rich thrombi in the microvasculature during an episode. Despite the clinical success of the current SoC treatments, the initial thrombus burden at the time of diagnosis remains unresolved, leading to prolonged ischemic organ damage.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In both the congenital (Adamts13-\/-) and immune-mediated (anti-ADAMTS13 antibody) murine TTP models, TGD001 demonstrated efficacy, with rapidly attenuated thrombocytopenia and decreased tissue damage within 4 hours in the cTTP model.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><em>Conclusion<\/em><\/strong><\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\">TGD001 as a Universal Next-Generation Thrombolytic<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">In conclusion, findings from animal models representing diverse thrombotic and thromboembolic indications demonstrate the therapeutic potential of TGD001 for the treatment of thrombosis. Despite varying thrombi compositions, TGD001 effectively cleared the macro- and microvasculature, resulting in improved outcomes and collectively supporting TGD001 as a novel universal thrombolytic.<\/p>\n<\/div>\n<\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Discover the oral presentation abstract on Novel von Willebrand Factor Targeting Thrombolytic TGD001 is Effective in Diverse Thrombotic Models, Demonstrating Its Potential as a Universal Thrombolytic, presented during the 2025 ASH Annual Meeting (Orlando, Florida, USA) by TargED, in which findings presented were implemented by STROK@LLIANCE team on our in vivo models of thrombosis, including [&hellip;]<\/p>\n","protected":false},"featured_media":38433,"template":"","meta":{"_acf_changed":false},"categorie-de-ressource":[239],"marque-de-ressource":[242],"class_list":["post-38407","ressource","type-ressource","status-publish","has-post-thumbnail","hentry","categorie-de-ressource-oral-presentations","marque-de-ressource-strokalliance"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Oral session: Novel von Willebrand Factor Targeting Thrombolytic TGD001 is Effective in Diverse Thrombotic Models, Demonstrating Its Potential as a Universal Thrombolytic - ETAP-LAB<\/title>\n<meta name=\"description\" content=\"Oral session to present Novel von Willebrand Factor Targeting Thrombolytic TGD001 as Effective in Diverse Thrombotic Models. 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