Boehringer Ingelheim and the Lower Franconian company EMFRET Analytics want to advance an active substance for the treatment of strokes. Its roots lie in the Würzburg University Medicine.
Professor Bernhard Nieswandt and his team at the Institute of Experimental Biomedicine at the University Hospital of Würzburg (UKW) can proudly look back on many years of development: a discovery made by the platelet researcher 25 years ago has become a beacon of hope for the treatment of acute strokes.
This is the inhibitor EMA601, which blocks a signalling pathway of the blood platelets extremely effectively: It prevents thrombosis and thrombo-inflammatory disease processes without impairing vital blood clotting.
A recent agreement between the German pharmaceutical company Boehringer Ingelheim and the Lower Franconian company EMFRET Analytics GmbH & Co. KG, which Nieswandt co-founded, now brings this promising agent one step closer to a potential therapeutic application.
Cooperation and licence agreement
Boehringer Ingelheim has signed a cooperation and licence agreement with EMFRET with the aim of initially jointly developing the novel and promising active substance EMA601 further preclinically and thus laying the foundations for its clinical testing.
If successful, the antibody developed in Würzburg would result in a potential "first-in-class" active substance that could revolutionise anti-thrombotic and anti-inflammatory therapy.
"Boehringer Ingelheim has been shaping 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 in expanding the range of stroke treatments and reflects the partners' shared commitment to making significant progress for patients worldwide."
The burden of stroke will continue to rise
Stroke remains one of the leading causes of death and disability, with around 11.9 million new cases each year and 93.8 million people living with long-term consequences. Due to the ageing and growing population, the global burden of stroke will continue to increase.
"The figures emphasise the need for new therapeutic approaches that further improve treatment outcomes in acute care. I am therefore all the more pleased about this intra-German cooperation, which combines the excellent basic research on thrombo-inflammatory mechanisms at the University Medical Centre Würzburg, the innovative strength of a regional biotech start-up and the comprehensive expertise of Boehringer Ingelheim in clinical development and translation," says Professor Matthias Frosch. The Dean of the Faculty of Medicine in Würzburg congratulates all those involved on this important step in the development history of EMA601.
The story of the discovery
In 2001, Bernhard Nieswandt and his doctoral student Valerie Orth (née Schulte), then still at the University of Witten-Herdecke, were the first to describe the central role of the receptor GPVI, which is found exclusively on blood platelets (thrombocytes) and their precursor cells in the bone marrow.
GPVI binds to exposed collagen on injured vessel walls and thus triggers the activation and accumulation of platelets - an important step in haemostasis. However, excessive activation of GPVI can lead to the formation of dangerous blood clots and thus to vascular occlusion. In the study, the researchers neutralised GPVI in the mouse model using a monoclonal antibody so that the platelets could no longer react effectively to collagen. This led to protection against thrombosis without severely disrupting normal haemostasis.
A year later, Nieswandt set up the first working group at the then newly founded Rudolf Virchow Centre (RVZ) at the University of Würzburg as part of a Heisenberg Fellowship from the German Research Foundation (DFG). At the same time, together with Valerie Orth, Susanne Nieswandt and Ralph Ziehfreund, he founded the company EMFRET Analytics GmbH & Co KG in Würzburg, which commenced operations in 2002 in the Technology and Start-up Centre (TGZ) Würzburg.
In 2005, Valerie Orth took over as Chief Executive Officer (CEO) and Bernhard Nieswandt focussed on the scientific management of the company as Chief Scientific Officer (CSO). In 2006, the company relocated its headquarters to Eibelstadt in the district of Würzburg.
Founding team delighted with huge success
"We are a classic bootstrap company and have built up our programme on our own without external capital," reports Dr Valerie Orth. "This means that we developed and produced antibodies and reagents for research and distributed them worldwide."
This created the financial basis for long-term projects aimed at advancing antibody-based active substances for therapeutic use in humans.
"It is a huge success that the antibody EMA601 developed by us has attracted the strategic interest of Boehringer Ingelheim, one of the world's leading manufacturers of stroke drugs," says Valerie Orth.
GPVI blockade can provide therapeutic protection
In 2007, one year before Bernhard Nieswandt took over as Head of the Chair of Experimental Biomedicine I at the UKW, he discovered together with Guido Stoll, then Head of the Stroke and Neuroinflammation Working Group at the Neurological Clinic of the UKW, and other researchers that GPVI blockade is therapeutically effective in preclinical stroke models. The inhibition of the surface receptor significantly reduced the infarct size in the brain, improved the neurological outcome, but did not increase the risk of intracranial haemorrhage.
The scientists had thus laid the foundation for the development of GPVI inhibitors.
EMA601 is a highly effective GPVI inhibitor
"Our GPVI inhibitor EMA601, which was developed in Würzburg, shows clear efficacy even at very low doses," says Bernhard Nieswandt. According to him, EMA601 is a very potent GPVI inhibitor and could therefore offer decisive clinical advantages and be widely used.
Nieswandt and his team of scientists from Emfret and the UKW proved this in November 2024 using a combination of biochemical tests, cell experiments and animal models in the European Heart Journal.
Nieswandt: "Firstly, we were able to show that EMA601 specifically inhibits the GPVI signalling pathway without paralysing coagulation. Secondly, GPVI blockade prevented the formation of pathological clots in the mouse model. And finally, GPVI blockade reduced not only thrombosis but also inflammation-driven tissue damage after ischaemia."
Thrombo-inflammation as a driving force of infarct growth
Despite considerable progress - from the introduction of intravenous lysis therapy in Europe in 1995 by Boehringer-Ingelheim, in which the blood clots are dissolved with medication, to endovascular thrombus removal by interventional neuroradiology around 20 years later - stroke therapy remains limited: In around half of successfully recanalised patients, the restoration of blood flow alone is not sufficient for a good functional outcome.
The problem is so-called thrombo-inflammation. This term was coined in Würzburg.
"We were able to show in animal studies that an inflammatory process, thrombo-inflammation, is set in motion as soon as the vascular occlusion begins in the downstream, poorly perfused areas of the brain in the vascular system, which remains active despite recanalisation and allows the infarcts to continue to grow," explains Professor Guido Stoll. "Against this background, EMA601 could be a promising add-on therapy to lysis or thrombectomy after it was able to inhibit further infarct growth after recanalisation in humanised GPVI mouse models."
A major advantage of EMA601 is the preclinically demonstrated low bleeding risk: in contrast to conventional antithrombotic agents, EMA601 does not appear to impair normal blood clotting, which is particularly important for use in acute stroke, as otherwise life-threatening cerebral haemorrhages could occur.
