PORTEFEUILLE

The immune system is the natural defense system against infections and faulty cells. In autoimmune disorders, this system loses tolerance for certain self-structures and starts to attack the own body. In patents, this self-attack can destroy various cell types and organs. Harmful autoantibodies play a crucial role in the development and progression of many autoimmune disorders. If these disease-causing autoantibodies could be selectively removed, then many patients could be efficiently treated for the first time.

However, up to date patients are still treated with unselective immunosuppression using mostly anti-cancer drugs. The unselective suppression comes at a high price - it can cause severe side effects and the health condition of patients can be significantly impaired under treatment. This situation clearly indicates the unmet medical need for more accurate and safer treatments.

Our Antibody-catch™ technology platform provides a promising base for highly accurate and safe treatments. It enables the rational and straightforward design of drugs that eliminate disease-causing autoantibodies with an unprecedented level of efficacy and selectivity; and this without any adverse immunosuppression. The platform focus is on autoimmune diseases that involve pathogenic anti-glycan autoantibodies. These anti-glycan antibodies are crucial in the pathogenesis of many autoimmune disorders of the nervous system including peripheral neuropathies such as anti-MAG neuropathy, multifocal motor neuropathy, Guillain-Barré syndrome, and they also play a role in subtypes of multiple sclerosis, Parkinson’s and Alzheimer’s disease.

In this project we aim to substantiate the Antibody-catch™ platform by preparing a library of drug candidates for autoimmune disorders of the nervous system and by validating a selection of these compound in vitro and in vivo. Furthermore, we will impel the preclinical development of one drug candidate towards first clinical trials to prepare the validation of the platform in a clinical context.

The development of more effective and safer treatments for autoimmune disorders is imperative. This projects aims to support the development of a radically new therapeutic approach for these devastating disorders. Compared to immunosuppressive drugs that are currently used in therapy the compounds derived from the Antibody-catch™ platform are highly selective, biodegradable scavengers for disease-causing autoantibodies. They bind and neutralize disease-causing antibodies without non-specific suppression of the immune system. These scavengers have the potential to introduce a new level of efficacy and safety in autoimmune disease treatments. A further advantage of the technology platform is its versatility and broad applicability to a multitude of conceivable disorders involving pathogenic autoantibodies against carbohydrate structures.

We have successfully generated a library of glycopolymers, with potential therapeutic relevance in different autoimmune conditions. We could show that specific pathogenic anti-glycan autoantibodies can be neutralized in vitro in an antigen-specific manner. We furthermore could provide a proof of principle for in vivo removal of pathogenic anti-MAG antibodies in an immunological model for anti-MAG neuropathy. Treatment results in this model are promising and were published in the renowned scientific journal PNAS. We have successfully manufactured a non-GMP batch of our most advanced glycopolymer and initiated preclinical safety and toxicity studies. Furthermore, we have received the orphan drug designation from the EMA for the treatment of anti-MAG neuropathy with the aforementioned glycopolymer.

A series of glycopolymers was designed for the treatment of multifocal motor neuropathy and was successfully validated in vitro with set of neuropathy sera. This same compound could potentially also be used to treat subtypes of the devastating Guillain-Barré syndrome. As the platform potential is broad, we have started to evaluate uses of platform-derived glycopolymers in various indications besides autoimmune neuropathies.

Selective in vivo removal of pathogenic anti-MAG autoantibodies, an antigen-specific treatment option for anti-MAG neuropathy. Herrendorff R, Hänggi P, Pfister H, Yang F, Demeestere D, Hunziker F, Frey S, Schaeren-Wiemers N, Steck AJ and Ernst B. PNAS (2017), 114(18): E3689-E3698. doi: 10.1073/pnas.1619386114;
Carbohydrate ligands that bind to antibodies against glycoepitopes of glycosphingolipids. Herrendorff R, Ernst B, Pfister H, Steck AJ. Patent PCT/EP 2016/071711 (2016);
Carbohydrate ligands that bind to IgM antibodies against myelin-associated glycoprotein. Herrendorff R, Yang F, Steck AJ, Ernst B. Patent PCT/EP 2015/055140 (2015);
Anti-MAG Neuropathy - a Carbohydrate Polymer Effectively Blocks Pathogenic Anti-MAG Antibodies. Herrendorff R, Yang F, Schaeren-Wiemers N, Steck AJ, Ernst B. Journal of Neuromuscular Diseases 1, Supplement 1, 292 (2014), Abstract PS3-329/#110.

Synthetischer Zucker gegen Autoimmunkrankheit, Universität Basel News, 18. April 2017
Closing of Polyneuron’s seed financing round
Brain Forum 2016 Innovation Award
Top100 Startups Award 2016
«Erfolgreiche Spin-offs der Universität Basel», uniintern Magazin für die Mitarbeitenden der Universität Basel, Ausgabe 01/2016;
«Antibody-Catching Glycopolymers Keep Peripheral Nerves Going», Lifescence plus Magazin, Ausgabe 02/2016, Seiten 10-12.