First-in-class fusion proteins towards accelerated thrombolysis
TargED Biopharmaceuticals B.V. is a biotechnology company that develops first-in-class biological drugs to improve treatment of thrombosis. TargED stands for Targeted Enzyme Delivery. Our biological drugs are unique by using small antibodies (“nanobodies”) to deliver enzymes to sites of thrombosis, enabling ‘targeted’ thrombolysis. As a result, the blood flow is restored faster, and the risk for organ failure is reduced.
TargED is a UMC Utrecht spin-off and is officially founded in July 2020. Our lead compound is Microlyse, which is currently under development for thrombotic thrombocytopenic purpura (TTP) and Acute Ischemic Stroke (AIS). Our objective is to accelerate thrombolysis in all forms of thrombosis, irrespective of the thrombus composition.
Kristof Vercruysse has over 15 years of experience in bringing biopharmaceutical compounds from preclinical proof of concept towards market authorization. Kristof gained hands-on experience with the development of Caplacizumab for treatment of Thrombotic Thrombocytopenic Purpura at Ablynx between 2007 and 2013. Subsequently, he joined Sourcia, a full-service boutique CRO that delivers tailor-made clinical drug development for biotech companies. At TargED, Kristof’s objective is to lead MICROLYSE towards the market as an entrepreneur. Kristof holds a Masters in Biomedical Science from Vrije Universiteit Brussel.
Coen Maas is an expert in thrombosis and hemostasis and associate professor at University Medical Centre Utrecht. Coen studies multiple rare, hematological diseases and believes that these misunderstood conditions can often be directly extrapolated to more prevalent multifactorial diseases, including stroke, atherosclerosis, diabetes, and Alzheimer’s disease. Coen is (co)author of >80 scientific publications and has been invited for >45 scientific presentations. In addition, he is inventor of two patents, one of which that covers our lead compound. Coen holds a Masters in Medical Biology and received his PhD in 2008, both at University Medical Centre Utrecht.
Marc van Moorsel holds a Masters in Innovation Sciences from Vrije Universiteit Amsterdam and currently works as PhD candidate at University Medical Centre Utrecht, investigating blood vessel markers towards innovative diagnostics and therapeutics in cardiovascular disease. Marc aims to combine his scientific understanding of drug development gained during his PhD with his passion: establishing a biopharmaceutical start-up.
Our lead compound Microlyse is a thrombolytic fusion protein consisting of two subunits: a nanobody domain targeting Von Willebrand Factor (VWF) and the protease domain of the plasminogen activator urokinase. Microlyse has a unique mode of action: by targeting the protease domain towards VWF, it initiates the active degradation of both VWF and fibrin. Interestingly, VWF is present in any thrombotic disease, while fibrin (the target for conventional thrombolytic agents) is not. Therefore, Microlyse could be a one-stop solution for any thrombotic disease, irrespective of the thrombotic composition!
Recently, we generated preliminary proof-of-concept for Microlyse in preclinical models of Thrombotic Thrombocytopenic Purpura (TTP) and Acute Ischemic Stroke (AIS). Currently, TargED is continuing to upscale the manufacturing of Microlyse, to establish additional proof in preclinical models and to generate Microlyse’s toxicology profile. In addition, TargED is expanding its product portfolio under current IP by developing variations on the lead compound.
The human body controls rupturing of vessels by beneficial wound healing. Wound healing is initiated by the binding of platelets to unrolled Von Willebrand Factor (VWF), a multimeric blood protein. The developing molecular ‘band-aid’ can later be strengthened by the formation of fibrin. When this process is uncontrolled, obstructive blood clots can develop, known as ‘thrombosis’. These clots prevent sufficient blood supply to organs. Dependent on the affected organ, this can result in for example stroke, myocardial infarction or kidney failure. Interestingly, thrombi always contain platelets and VWF, but they do not always contain fibrin. We are currently developing Microlyse for the thrombotic indications TTP and acute ischemic stroke.
Thrombotic Thrombocytopenic Purpura (TTP)
TTP has an orphan EMA/FDA designation and it affects 2-10 patients per million per year. In physiology, the enzyme ADAMTS13 cleaves VWF and prevents progressing into pathological thrombosis. In TTP patients, ADAMTS13 activity is impaired. Consequently, TTP patients experience acute attacks during which they develop countless thrombi composed of ultra large VWF molecules (UL-VWF) and platelets. These thrombi generally affect the microvasculature of organs such as the kidneys, heart and brain, leading to tissue ischemia and multi-organ failure. TTP patients risk shortened life expectancy and long-term complications. When untreated, mortality is 90%.
Microlyse is revolutionary in inducing the active degradation of VWF strands. As a result, the duration of tissue ischemia can be reduced, resulting in less organ failure and lower mortality.
Acute ischemic stroke (AIS)
AIS is the largest thrombotic indication worldwide, affecting 17 million people per year. Since the late 90s, AIS patients are treated with recombinant tPA (tissue plasminogen activator) to recanalize the occluded blood vessel. tPA becomes less effective when administered later after symptom onset. Consequently, administration >4.5 hours after onset is avoided as efficacy is outweighed by the unavoidable bleeding risk that comes with tPA therapy.
The reasons for the limited efficacy of tPA are still largely unclear. However, tPA requires the availability of fibrin in order to degrade thrombi. In AIS, thrombi often originate from vessel damage elsewhere, after which thrombi-parts dislodge, embolize and occlude arteries in the brain. These thrombi always contain VWF, but the presence of fibrin is uncertain and varies between cases. We and others therefore suggest that degrading VWF in addition to fibrin forms an attractive strategy to treat thrombosis in stroke.
GRANTED - NWO Take Off II
December 2020 - TargED is awarded the @NWO Take Off II loan (€250.000) to further develop its clot-busting lead compound, Microlyse, which could ultimately help millions of patients around the globe. What a welcome reward to a remarkable year 2020!
INVESTMENT - €1.35m Seed round
November 2020 - TargED proudly announces the closing of its first investment round from Curie Capital, Utrecht Health Seed Fund (UHSF) and Fonds InvesteringsRijpe STarts (FIRST), supported by additional funding from Health Holland!
July 2020 - As of July 4th, we’ve been officially established with a brand-new name: TargED Biopharmaceuticals. Why changing names? Because TargED actually covers what we provide: Targeted Enzyme Delivery.
GRANTED – Young Investigator Award
July 2019 - The CONTRAST voucher allows us to investigate the applicability of our lead compound in acute ischemic stroke
Marc van Moorsel