TargED Biopharmaceuticals has commenced clinical development of TGD001, a novel thrombolytic agent, with the dosing of the first participant in a Phase 1 clinical trial. This first-in-class 'fusion protein' drug is designed to address a wide range of thrombotic disorders, including acute ischemic stroke (AIS) and immune-mediated thrombotic thrombocytopenic purpura (iTTP). The Phase 1 study, conducted at a clinic in Germany, is a randomized, double-blind, placebo-controlled, single-ascending dose study evaluating the safety, tolerability, and pharmacokinetics of TGD001 in healthy volunteers.
Addressing Unmet Needs in Thrombotic Disorders
Thrombotic disorders, such as AIS and iTTP, pose significant challenges in healthcare. Acute ischemic stroke, a leading cause of preventable death and disability, often has limited treatment options, with up to 80% of patients ineligible for currently available thrombolytics like intravenous alteplase (tPA). iTTP, a rare and life-threatening micro-thrombotic disorder, also presents challenges, with a 15% mortality rate despite recent treatment advances and long-term health impairment in half of the survivors.
TGD001: A Novel Approach to Thrombolysis
TGD001 is engineered to break down clots of all sizes and compositions, from the large clots causing AIS to the micro-clots associated with iTTP. Its unique two-step mechanism of action involves targeting clots via an antibody fragment that binds to a non-functional domain of von Willebrand Factor (VWF), a protein present in all thrombi. Subsequently, in the immediate vicinity of the thrombus, TGD001 activates the endogenous enzyme system that degrades both VWF and fibrin, two key components forming the structural bond in the thrombus. This targeted approach aims to enable rapid and effective thrombolysis without systemic activation of the lysis cascade, potentially reducing the risk of bleeding.
Clinical Development Plans
The first safety read-out from the Phase 1 study is anticipated by mid-2025. Following this, TargED intends to initiate two proof-of-concept trials in the second half of 2025: a Phase 2a trial in AIS patients and a Phase 1b trial in iTTP patients. The European Commission granted TGD001 Orphan Drug Designation for iTTP in July 2024.
Expert Commentary
Kristof Vercruysse, CEO and co-founder of TargED, stated, "The dosing of the first participant with our lead compound TGD001 marks a watershed in the treatment of thrombotic disorders. Today’s thrombolytics show efficacy, but their significant drawbacks greatly limit their safety and effectiveness, and result in restricted utility. TGD001 is specifically designed to address these shortcomings."
Steven de Maat, CSO and co-founder of TargED, added, "Up to 80% of AIS patients cannot be treated with currently available thrombolytics such as intravenous alteplase (tPA). Meanwhile, there is significant room for improvement in the treatment of iTTP... TGD001 has the potential to greatly improve outcomes in both these indications and, we believe, in other thrombotic indications as well."
