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Innovative, Nature-inspired Mechanism, Dissolving Blood Clots Without Inducing Bleeding, Shows Promises of Enhanced Safety and Efficacy CAMBRIDGE, MA, USA I September 24, 2024 I Thrombolytic Science, LLC (TSI), a private clinical-stage biotech company focused on developing clot-dissolving therapies for thrombotic diseases, announced today that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for mutant prourokinase, a recombinant fibrinolytic pro-enzyme. A U.S.-based clinical trial will further confirm the safety and tolerability of TSI’s novel mutant prourokinase (mproUK) in healthy volunteers. “We are thrilled to achieve this important milestone with the FDA clearance for our first U.S. clinical trial of mproUK,” said Alexis C. Wallace, MSc. Eng., MBA, CEO of TSI. “Our innovative approach to fibrinolytic therapy has the potential to transform the treatment landscape for life-threatening thrombotic conditions, offering patients a faster, safer, and more effective reperfusion option. Following promising Phase II results from the DUMAS trial in stroke patients in the Netherlands, we’re now advancing to a Phase II trial in the UK for myocardial infarction following MHRA approval. This IND clearance is a significant step toward expanding access to our low-dose fibrinolytic treatment for broader patient populations globally.” In the natural, physiological mechanism of clot lysis, while tissue plasminogen activator (tPA) initiates clot lysis, prourokinase completes the dissolution of the fibrin clot. “This difference is comparable to the starter of a car and its engine.  tPA is like the starter, whereas prourokinase is the engine”, explained Victor Gurewich, MD, TSI co-founder and discoverer of prourokinase. “Physiological fibrinolysis requires a mini bolus of r-tPA followed by an infusion of a low dose of mproUK. In recent clinical studies, this treatment has been shown to be free of bleeding risk and rethrombosis while having the potential to re-establish blood flow earlier and being more cost effective than in-hospital surgical solutions.” About mproUK TSI’s treatment is based on the natural, biological clot dissolving mechanism involving the sequence of tPA and prourokinase, the latter having been stabilized by a single site mutation. This mutation has significantly improved the safety of prourokinase without interfering with its biological clot lysing mechanism of action.  A successful proof of concept clinical trial using native prourokinase in heart attack patients, preceded by a mini dose of tPA was previously published, the PATENT trial. More recently, promising results were obtained with mutant proUK in ischemic stroke patients, the DUMAS trial. About Thrombolytic Science (TSI) Thrombolytic Science, LLC, is a privately held biotech company developing a new-generation clot-dissolving therapy for heart attack, ischemic stroke and other thrombotic diseases, based on the groundbreaking research on prourokinase by its scientific co-founders at BIDMC / Harvard Medical School SOURCE: Thrombolytic Science

Boehringer Ingelheim’s Metalyse (tenecteplase) has been recommended by the National Institute for Health and Care Excellence (NICE) as a treatment option for acute ischaemic stroke (AIS) in adults. The decision could help save the NHS millions of pounds due to Metalyse costing less than the current standard for treating this type of stroke, Actilyse (alteplase), which is also sold by Boehringer in the UK. Strokes are estimated to be responsible for around 100,000 hospital admissions in England every year. Representing around 85% of all stroke cases in the UK, AIS occurs when there is a blockage in a blood vessel, resulting in a restricted blood supply to the brain. Given during the early phases of a stroke, Metalyse is designed to activate the production of plasmin, an enzyme that breaks down blood clots, to help restore blood flow through the blocked artery. NICE’s decision was based on clinical evidence from the large ongoing UK trial, ATTEST-2, which has been investigating whether Metalyse is more effective and safer than Actilyse, along with published results from completed trials. Results demonstrated that Metalyse was as effective as Actilyse in breaking up blood clots or preventing new blood clots from forming after an AIS. Commenting on the recommendation, Helen Knight, director of medicines evaluation at NICE, said: “We know that… it is important that patients receive treatments that can help to reduce the effects of a stroke as quickly as possible. “[This] guidance means that not only will people who have had an AIS be able to access a new treatment option, but the NHS could save millions by switching to it, making it a very effective use of taxpayers’ money.” The recommendation comes after the Medicines and Healthcare products Regulatory Agency approved Metalyse in April to treat AIS within 4.5 hours of the first symptoms appearing, as well as suspected acute cases of myocardial infarction (heart attack) within six hours of symptoms. Most recently, Boehringer and Brainomix entered into a strategic partnership for a collaborative programme to improve the identification and access to treatment for people living with fibrosing lung disease in the US.

Ischaemic strokes, representing 85% of all stroke cases, occur when a clot interrupts the brain’s blood supply. Credit: NICE. The UK National Institute for Health and Care Excellence ( Nice ) has issued final guidance endorsing Boehringer Ingelheim ’s tenecteplase, marketed as Metalyse, as a treatment option for adult patients suffering from acute ischaemic stroke for National Health Service (NHS) use. This recommendation is poised to generate significant savings for the NHS due to the cost-effectiveness of the product compared to alteplase, another thrombolytic treatment. Clinical trials have demonstrated that tenecteplase is as effective as alteplase in dissolving blood clots and averting the formation of new ones following an acute ischaemic stroke. The cost advantage of tenecteplase could lead to substantial financial benefits for the NHS. Administered within four and a half hours of the onset of stroke symptoms, tenecteplase activates plasmin production, an enzyme crucial for clot breakdown. This process is vital for re-establishing blood flow through arteries blocked by clots. See Also: MHRA approves Pfizer-BioNTech’s Comirnaty JN.1 vaccine Pipeline power: Sionna’s AbbVie deal could redefine CF therapeutics Delivered intravenously, the asset received licensing in the UK for ischaemic stroke treatment in April 2024. Ischaemic strokes, representing 85% of all stroke cases, occur when a clot interrupts the brain’s blood supply. This deprivation of oxygen damages or kills brain cells, resulting in stroke symptoms. In England, 100,000 individuals are hospitalised due to stroke each year, with the vast majority experiencing an ischaemic stroke. One million people in the country live with the consequences of stroke. NICE medicines evaluation director Helen Knight stated: “We know that stroke is one of the biggest killers and causes of disability, therefore it is important that patients receive treatments that can help to reduce the effects of a stroke as quickly as possible. “The guidance means that not only will people who have had an ischaemic stroke be able to access a new treatment option, but the NHS could save £millions by switching to it, making it a very effective use of taxpayers’ money.”