EXIST research transfer for immunology start-up
Novel protein to prevent immune system from attacking its own body

Ulm University

Ulm entrepreneurs Dr Arthur Dopler and Matteo Mohr are receiving 1.2 million euros for two years from the EXIST Transfer of Research programme. The federal and EU funding programme supports start-up projects that entail high risk and development costs. This project deals with a new type of protein that is intended to correct dysregulations in the immune defence system. The focus is specifically on the complement system, a part of the innate immune system whose malfunction is associated with severe diseases.

When the immune system targets the body’s own cells rather than pathogens, the body has a problem. Serious organ and tissue damage is the result. The cause can often be found in genetic dysregulation, which triggers life-threatening diseases. To date, the majority of these diseases can only be treated inadequately, if at all. At the Ulm-based start-up company, which combines pharmacological and biomedical research, the focus is on a promising protein that is able to avert dysregulation in a part of the innate immune system – the complement system.

The start-up, which has already received funding through the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) GO-Bio Initial programme, is now receiving funding for a two-year period from the EXIST Transfer of Research programme run by the Federal Ministry for Economic Affairs and Climate Action (Bundesministerium für Wirtschaft und Klimaschutz, BMWK) and the European Union’s European Social Fund Plus (ESF Plus) in the amount of 1.2 million euros. This money will be used to produce the novel protein, characterise it biochemically and biophysically and prove its effectiveness in vivo.

“Our aim is to bring this molecule to clinical application, to make it possible to treat diseases of the complement system more effectively and at the same time more gently”, says Matteo Mohr, the project manager. The scientist who studied bio process engineering and management at the Technical University of Munich has been conducting research at the Ulm University Medical Centre’s Institute for Experimental and Clinical Pharmacology, Toxicology and Naturopathy since 2022. These rare, but serious diseases of the complement system include paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). The clinical presentation of such diseases includes, for example, the disintegration of red blood cells, an increased tendency to form blood clots and damage to kidney function or the inner walls of blood vessels.

Overreactions of the immune system lead to life-threatening diseases

The role of the complement system as a part of the innate immune system is to combat pathogens as well as eliminate old and damaged cells by detecting, marking and destroying them. The network of over 40 different proteins can be set in motion via different activation pathways, which then trigger highly complex reaction cascades. “This process is strictly regulated. Several mechanisms prevent the complement system from overreacting and destroying healthy cells. However, genetic mutations or transplants can lead to dysregulation, which can result in life-threatening diseases”, explains Dr Arthur Dopler. The immunobiologist from Ulm, who will take over the scientific management of the start-up company after its founding, wrote his doctoral thesis on the complement system.

The novel molecule is now intended to ensure that a dysregulated complement system returns to being properly regulated. It was developed in the course of many years of research by Professor Christoph Schmidt, who has been conducting research at the Institute for Experimental and Clinical Pharmacology, Toxicology and Naturopathy at Ulm University since 2011. Schmidt, who is also Dr Dopler’s doctoral advisor, filed an international patent application for the protein, in cooperation with the physicians Professor Markus Huber-Lang (Institute of Clinical and Experimental Trauma Immunology) and Professor Hubert Schrezenmeier (Institute of Transfusion Medicine). The newly developed regulator protein is based on naturally occurring proteins of the complement system and combines their properties in a unique molecule. This innovative regulator can deactivate a large number of target molecules without becoming “used up”, thanks to its enzyme-like mode of action. This is a major advantage over the therapies currently available, as it makes the novel molecule highly effective. It also enables the treatment of a wide range of diseases and is effective exactly where it is meant to be.

The EXIST funding will now be used to demonstrate the effectiveness of the regulator in vivo. The founders will also establish a production process that can be used to produce the novel molecule on a laboratory scale. In order to achieve these goals, two new members specialised in protein production and analysis will be joining the team of founders. Over the next two years,

the team will also be drawing up a business plan, developing the company, and organising follow-up funding. “After that, the project will have to face the demanding and long-term process of drug development”, say the start-up founders. Professor Holger Barth, the director of the Institute of Experimental and Clinical Pharmacology, Toxicology and Naturopathy, where the start-up team is based, will be providing support. The start-up project is also receiving support from the Entrepreneurs Campus, the Life Science Incubator and the Ulm University Technology Transfer Centre.

Further information:
Matteo Mohr, email: matteo.mohr(at)uni-ulm.de

 

Text and mediacontactt: Andrea Weber-Tuckermann

 

Matteo Mohr and Dr. Arthur Dopler
(From left) Matteo Mohr and Dr Arthur Dopler are receiving 1.2 million euros from the EXIST Transfer of Research programme (Photo: Melanie Kamrath)
crystalline structure
The company is centred around a novel protein, which is intended to prevent the immune system from attacking the body. The figure (Graphic: Prof Christoph Schmidt / Uni Ulm) shows the crystalline structure of a previous version of the novel molecule in virtually atomic resolution.
Logos der EXIST-Fördergeldgeber