Neurimmune announced today that preclinical data relating to its human antibody NI203 targeting pathologic aggregates of the beta cell peptide hormone islet amyloid polypeptide (IAPP) have been published in the current issue of Nature Communications. The paper “A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models” describes a monoclonal antibody that binds selectively to IAPP oligomers and protects from IAPP toxicity.
NI203 was discovered by Neurimmune’s Reverse Translational MedicineTM (RTMTM ) technology through comprehensive analyses of memory B cell repertoires derived from healthy elderly subjects. The antibody efficiently neutralized IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro. NI203 treatment of transgenic or human islet-engrafted rodent type 2 diabetes models triggered the clearance of IAPP oligomers, resulting in beta cell protection and improved glucose control.
“We are excited about these results which provide the scientific basis for the development of NI203 as a potential disease-modifying treatment for patients with type 2 diabetes and progressive beta cell loss”, said Jan Grimm, CSO of Neurimmune. “Depleting pathologic IAPP oligomers from the pancreas is a novel therapeutic strategy anticipated to translate into durable control of beta cell health.”
Type 2 diabetes is a chronic metabolic disorder characterized by insulin resistance and progressive dysfunction and loss of insulin-producing pancreatic beta cells, resulting in insulin deficiency and elevated blood glucose. While the primary cause of beta cell failure in type 2 diabetes is unknown, the accumulation of aggregated forms of IAPP in pancreatic islets is a key contributor to decreased beta cell function and mass.
NI203 published in Nature Communications :
A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models
Fabian Wirth#1, Fabrice D Heitz#1, Christine Seeger1, Ioana Combaluzier1, Karin Breu1, Heather C Denroche2, Julien Thevenet3, Melania Osto4, Paolo Arosio5, Julie Kerr-Conte3, C Bruce Verchere2, François Pattou3, Thomas A Lutz4, Marc Y Donath6, Christoph Hock1,7, Roger M Nitsch1,7, Jan Grimm1
Nat Commun 2023 Oct 9;14(1):6294. doi: 10.1038/s41467-023-41986-0.
The authors’ affiliations are as follows: 1) Neurimmune AG, Wagistrasse 18, 8952, Schlieren, Switzerland. 2) BC Children's Hospital Research Institute and Centre for Molecular Medicine and Therapeutics, Departments of Surgery and Pathology & Laboratory Medicine, University of British Columbia, A4-151 950 W 28 Ave, Vancouver, BC, Canada. 3) Univ-Lille, Inserm, CHU Lille, U1190 - EGID, F-59000, Lille, France. 4) Institute of Veterinary Physiology, Vetsuisse Faculty of the University of Zürich, Winterthurerstrasse 260, 8057, Zürich, Switzerland. 5) Institute for Chemical and Bioengineering, ETH Zürich, Vladimir-Prelog-Weg 1-5/10, 8093, Zürich, Switzerland. 6) Clinic for Endocrinology, Diabetes & Metabolism, and Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031, Basel, Switzerland. 7) Institute for Regenerative Medicine-IREM, University of Zürich, Wagistrasse 12, 8952, Schlieren, Switzerland. 8Neurimmune AG, Wagistrasse 18, 8952, Schlieren, Switzerland. #Contributed equally.
About Neurimmune
Neurimmune is a biopharmaceutical company translating human immune memory into antibody therapeutics. Neurimmune develops drug candidates for CNS and related protein aggregation diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, dementia with Lewy bodies and ATTR cardiomyopathy. Neurimmune discovered aducanumab, a human monoclonal antibody that removes amyloid beta from brains of patients with Alzheimer’s disease, and licensed it to Biogen. With its Reverse Translational MedicineTM technology, Neurimmune also discovered the anti-miSOD1 antibody AP-101 for ALS and the anti-ATTR antibody NI006 for ATTR cardiomyopathy, programs being currently evaluated in clinical trials. Furthermore, Neurimmune has three antibody programs in preclinical development and additional research programs in the areas of CNS, inflammatory, viral and cardiometabolic diseases.
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