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Boehringer Ingelheim and the Lower Franconian biotech company EMFRET Analytics have signed a cooperation and license agreement for the preclinical development program of the GPVI blocking antibody EMA601. University Hospital Würzburg has supported the development of this novel compound from the outset. EMA601 specifically targets the platelet surface receptor glycoprotein VI (GPVI). Studies conducted in Würzburg showed that EMA601 very effectively blocks the GPVI signaling pathway, thereby preventing thrombosis and thrombo inflammatory disease processes without impairing essential blood coagulation. This makes EMA601 interesting for use in acute stroke.
Würzburg. Professor Bernhard Nieswandt and his team look back with pride on a long development journey: What began as a discovery by the platelet researcher 25 years ago has become a promising candidate for stroke treatment. A recent agreement between the German pharmaceutical company Boehringer Ingelheim and the Lower Franconian company EMFRET Analytics GmbH & Co. KG now brings this promising candidate one step closer to potential therapeutic application.
Surface receptor GPVI plays a central role in the development of thrombosis and infarction, but is not required for normal blood coagulation
In 2001, Bernhard Nieswandt and his then doctoral student Valerie Orth (née Schulte) were the first to describe the central role of the receptor GPVI, which is found exclusively on thrombocytes (blood platelets) and their precursor cells in the bone marrow, while working at Witten/Herdecke University (https://doi.org/10.1084/jem.193.4.459). GPVI binds to exposed collagen on injured vessel walls, triggering platelet activation and aggregation – an essential step in hemostasis, or the stopping of bleeding. Excessive GPVI activation, however, can lead to the formation of dangerous thrombi (blood clots) and subsequent vessel occlusion.
In their study, the researchers neutralized GPVI in a mouse model using a monoclonal antibody, preventing platelets from responding effectively to collagen. In these pre-clinical studies this resulted in protection against thrombosis without significantly disturbing normal hemostasis.
One year later, as part of a Heisenberg Fellowship from the German Research Foundation (DFG), Nieswandt established the first research group at the newly founded Rudolf Virchow Center (RVZ) of the University of Würzburg. At the same time, together with Valerie Orth, Susanne Nieswandt, and Ralph Ziehfreund, he founded EMFRET Analytics GmbH & Co. KG in Würzburg, which began operations in 2002 at the Würzburg Technology and Startup Center (TGZ). In 2005, Valerie Orth assumed the role of Chief Executive Officer, while Bernhard Nieswandt focused on scientific leadership as Chief Scientific Officer. In 2006, the company relocated its headquarters to Eibelstadt near Würzburg.
GPVI inhibitor EMA601 attracts the interest of a leading pharma company
“We are a classic bootstrapped company and built our program independently without external capital,” reports Dr. Valerie Orth. “We developed, produced, and distributed antibodies and reagents for research worldwide.” This created the financial foundation for long term projects aimed at developing antibody based therapeutics for use in humans. “It is a major success that the antibody EMA601 we developed has attracted the strategic interest of Boehringer Ingelheim, one of the world’s leading manufacturers of stroke medications,” says Orth.
A 2007 study already showed therapeutic protection through GPVI blockade in a preclinical stroke model
In 2007—one year before Bernhard Nieswandt assumed the Chair of Experimental Biomedicine I at University Hospital Würzburg (UKW) – he and Guido Stoll (then head of the Stroke and Neuroinflammation research group at the Department of Neurology) and other researchers discovered that GPVI blockade is therapeutically effective in a preclinical stroke model (https://doi.org/10.1161/CIRCULATIONAHA.107.691279). Inhibiting the surface receptor significantly reduced infarct size in the brain, improved neurological outcomes, and did not increase the risk of intracranial bleeding.
These findings laid the foundation for the development of the GPVI inhibitor EMA601.
EMA601 is a very potent GPVI inhibitor
“Our GPVI inhibitor EMA601, discovered in Würzburg, shows significant efficacy,” says Bernhard Nieswandt. According to him, EMA601 is a very potent GPVI inhibitor and has therefore the potential to offer clinical advantages.
In November 2024, Nieswandt and his team – together with scientists from EMFRET and University Hospital Würzburg – demonstrated this through a combination of biochemical tests, cell based assays, and animal models, published in the European Heart Journal (https://doi.org/10.1093/eurheartj/ehae482). “We were able to show, first, that EMA601 selectively inhibits GPVI signaling without shutting down the coagulation system. Second, GPVI blockade prevented the formation of pathological clots in a mouse model. And finally, GPVI blockade reduced not only thrombosis but also inflammation driven tissue damage following ischemia.”
Thrombo inflammation: a driving force of infarct growth even after successful recanalization of large vessel occlusions
Despite significant advances – from the introduction of intravenous thrombolysis in Europe in 1995 by Boehringer Ingelheim, which dissolves blood clots pharmacologically, to endovascular clot removal by interventional neuroradiology around 20 years later – stroke therapy remains limited. In approximately half of successfully recanalized patients, restoring blood flow alone is not sufficient to achieve good functional outcomes. The underlying problem is so called thrombo inflammation, a term that was largely coined in Würzburg. “In animal studies, we were able to show that an inflammatory process – thrombo inflammation – is triggered in the downstream hypoperfused brain areas as soon as vessel occlusion begins. This process remains active despite recanalization and allows infarcts to continue growing,” explains Professor Guido Stoll.
“Against this background, EMA601 may have promise as an adjunct therapy to thrombolysis or thrombectomy, as it was able to inhibit further infarct growth after recanalization in humanized GPVI mouse models,” comments Stoll.
A major advantage of EMA601 is the low bleeding risk shown in pre-clinical studies: EMA601 does not appear to impair normal blood coagulation, an especially critical consideration in acute stroke, where otherwise life threatening intracranial hemorrhages can occur.
Cooperation and license agreement for the preclinical development of a potential first in class compound
These potential advantages convinced Boehringer Ingelheim. The pharmaceutical company has signed a cooperation and license agreement with EMFRET with the goal of jointly advancing the further preclinical development of the novel compound EMA601 and thereby laying the foundation for its clinical testing. If successful, the antibody developed in Würzburg could become a first in class compound that has the potential to transform antithrombotic and anti inflammatory therapy.
“Boehringer Ingelheim has shaped acute stroke care for decades,” says Søren Tullin, Senior Vice President and Global Head of Cardiometabolic Diseases Research at Boehringer Ingelheim. “This collaboration represents an important step toward expanding the treatment spectrum for stroke and reflects the shared commitment of the partners to achieve meaningful advances for patients worldwide.”
Stroke remains one of the most common causes of death and disability: Approximately 11.9 million new cases occur each year, and 93.8 million people live with long term consequences. Due to aging and population growth, the global burden of stroke is expected to continue to rise.
“These figures underscore the need for new therapeutic approaches that further improve outcomes in acute care. I am therefore particularly pleased about this Germany based collaboration, which brings together the excellent basic research on thrombo inflammatory mechanisms at University Hospital Würzburg, the innovative strength of a regional biotech startup, and Boehringer Ingelheim’s extensive expertise in clinical development and translation,” says Professor Matthias Frosch. The Dean of the Faculty of Medicine at the University of Würzburg congratulates all those involved on this important milestone in the development of EMA601.
Boehringer Ingelheim
Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,300 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at www.boehringer-ingelheim.com.
Emfret Analytics
Emfret Analytics GmbH & Co. KG is a privately held German biotechnology company dedicated to the development of platelet receptor–targeting antibodies for research, diagnostic and therapeutic applications. Founded in 2002, the company maintains a close and long-standing collaboration with the University of Würzburg, an internationally leading center for basic and translational platelet research. This partnership provides the scientific foundation for the design of novel research tools and translating advanced platelet biology into innovative therapeutic strategies. Emfret focuses on areas of high unmet medical need, such as stroke, acute lung injury, and selected autoimmune disorders. The strategic partnership with Boehringer Ingelheim on the company’s first clinical development candidate underscores the potential of a novel class of antibody-based therapeutics designed to precisely modulate pathogenic platelet activity while preserving essential hemostatic function. Learn more at https://www.emfret.com
Prof. Bernhard Nieswandt Nieswandt_B@ukw.de
Bernhard Nieswandt, Valerie Schulte, Wolfgang Bergmeier, Rabée Mokhtari-Nejad, Kirsten Rackebrandt, Jean-Pierre Cazenave, Philippe Ohlmann, Christian Gachet, Hubert Zirngibl.Long-Term Antithrombotic Protection by in Vivo Depletion of Platelet Glycoprotein VI in Mice.J Exp Med (2001) 193 (4): 459–470. https://doi.org/10.1084/jem.193.4.459
Christoph Kleinschnitz, Miroslava Pozgajova, Mirko Pham, Martin Bendszus, Bernhard Nieswandt, and Guido Stoll. Targeting Platelets in Acute Experimental Stroke: Impact of Glycoprotein Ib, VI, and IIb/IIIa Blockade on Infarct Size, Functional Outcome, and Intracranial Bleeding. Circulation. Volume 115, Number 17. 2007. https://doi.org/10.1161/CIRCULATIONAHA.107.691279
Stefano Navarro, Ivan Talucci, Vanessa Göb, Stefanie Hartmann, Sarah Beck, Valerie Orth, Guido Stoll, Hans M Maric, David Stegner, Bernhard Nieswandt. The humanized platelet glycoprotein VI Fab inhibitor EMA601 protects from arterial thrombosis and ischaemic stroke in mice, European Heart Journal, Volume 45, Issue 43, 14 November 2024, Pages 4582–4597, https://doi.org/10.1093/eurheartj/ehae482
In 2001, Valerie Orth and Bernhard Nieswandt first described the central role of the GPVI receptor, ...
Quelle: Thomas Berberich
Copyright: EMFRET Analytics
On the left a humanized GP6 (hGP6^tg/tg^) control mouse in which a thrombus (green) completely occlu ...
Copyright: Experimental Biomedicine I / UKW
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In 2001, Valerie Orth and Bernhard Nieswandt first described the central role of the GPVI receptor, ...
Quelle: Thomas Berberich
Copyright: EMFRET Analytics
On the left a humanized GP6 (hGP6^tg/tg^) control mouse in which a thrombus (green) completely occlu ...
Copyright: Experimental Biomedicine I / UKW
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