Meeting on Abeta Oligomers in Alzheimer’s Disease (AD) and Other Misfolded Proteins in AD and Neurodegenerative Diseases

  • Increasing evidence points to Abeta oligomers as the toxic species in AD, and likely linked to Tau pathology and neuroinflammation.
  • Immunotherapies and small molecule anti-Tau therapeutics hold much promise in treating AD and neurodegenerative orphan indications.
  • Additional misfolded proteins, alpha-synuclein and TDP-43 exist alongside Beta-amyloid and Tau as concomitant pathologies, suggesting precision medicine approaches are required for treating AD and other neurodegenerative diseases.  

AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical-stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, shared top level insights from its Key Opinion Leader (KOL) luncheon meeting on Abeta oligomers and concomitant proteinopathies in AD and other neurodegenerative diseases, which took place on November 5, 2018, in New York City, United States.

The meeting featured presentations by Professor Michael W. Weiner, University of California San Francisco School of Medicine and Professor John Q. Trojanowski, Perelman School of Medicine, University of Pennsylvania.

Professor Weiner reviewed current understanding of the amyloid hypothesis of AD, emphasizing the key role Abeta oligomers as the most toxic species in the amyloid cascade, and which produce various downstream effects possibly involved in tau pathology and neuroinflammation. In regard to tau, Professor Weiner highlighted the excitement around antibody, vaccine and small molecule anti-tau therapeutics currently in clinical trials and development. Finally Professor Weiner explained the importance of diagnostics for early intervention in AD, and reviewed progress in brain PET imaging as well as molecular biomarkers in brain fluid and blood.

Alzheimer’s Disease can be thought of as an amyloid induced tauopathy, and therefore therapeutics targeting amyloid and tau hold much promise in finding a cure for this devastating disease. Imaging and biomarker diagnostics, particularly blood tests, will facilitate early treatment and improved clinical outcomes.’   Professor Weiner

Professor Trojanowski highlighted the existence of concomitant pathologies in a wide range of neurodegenerative diseases, emphasizing the importance of alpha-synuclein and TDP-43, in addition to Beta-amyloid and tau. These discoveries point to the future importance of precision medicine, involving therapeutics targeting the pathological proteins relevant to an individual patients and stage of disease.

Professor Trojanowski commented: “It is becoming clearer that clinical trial participants may be better defined by their various proteinopathies and that patient sub-classification may lead to improved clinical outcomes. The high prevalence of co-pathologies in neurodegenerative diseases, as well variation between individuals, indicates that diagnostics and combination therapy may be the ultimate requirement.”

Following the KOL presentations, Professor Andrea Pfeifer, CEO of AC Immune, gave an overview of the Company’s pipeline and strategy to be a leader in precision medicine in neurodegenerative diseases. The Company has nine products in various stages of clinical development and a sustainable pipeline of pre-clinical assets addressing key targets in AD and neurodegenerative diseases.

Professor Andrea Pfeifer commented: “We’re starting to see a clearer and more important need for precision medicine with the prevalence of co-pathology in AD, Parkinson’s and other neurodegenerative diseases. Our current therapeutic and diagnostic pipeline forms the basis of our forward strategy to become a leader in precision medicine as applied to AD and other neurodegenerative diseases.”

A replay of the event is available on the Investor page of AC Immune’s website.

KOL Biographies

Michael W. Weiner M.D.

Professor, Department of Radiology, University of California San Francisco School of Medicine

Dr. Weiner is Professor in Residence in Radiology and Biomedical Imaging, Medicine, Psychiatry, and Neurology at the University of California, San Francisco. He is Principle Investigator of the Alzheimer’s Disease Neuroimaging Initiative, which is the largest observational study in the world concerning Alzheimer’s Disease. He is the former Director of the Center for Imaging of Neurodegenerative Diseases (CIND) at the San Francisco Veterans Affairs Medical Center. During the past 25 years he has worked to develop and optimized the use of MRI, PET, and blood based biomarker methods to diagnose Alzheimer’s disease and other neurodegenerative disorders. Dr. Weiner’s research also focuses on monitoring effects of treatment to slow progressions in Alzheimer’s disease, and detecting Alzheimer’s disease early in patients who are not demented, but risk subsequent development of dementia.

John Q. Trojanowski M.D., Ph.D.

Co-Director Center for Neurodegenerative Research, Perelman School of Medicine, University of Pennsylvania

Dr. Trojanowski obtained his MD/PhD in 1976 from Tufts University, did his internal medicine internship at Mt. Auburn Hospital, his pathology and neuropathology at Massachusetts General Hospital and the University of Pennsylvania Perelman School of Medicine where he joined the faculty in 1981. He is Professor of Pathology and Laboratory Medicine, Director of the NIA Alzheimer’s Disease Center, the National Institute of Neurological Disorders (NINDS) Morris K. Udall Parkinson’s Disease Center, and the Institute on Aging. His research focuses on Alzheimer’s (AD) and Parkinson’s (PD) disease, amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD) which led to the discovery of the major disease proteins in these disorders.

About AC Immune

AC Immune is a clinical-stage Swiss-based biopharmaceutical company, listed on NASDAQ, which aims to become a global leader in precision medicine for neurodegenerative diseases. The Company designs, discovers and develops therapeutic as well as diagnostic products intended to prevent and modify diseases caused by misfolding proteins. AC Immune’s two proprietary technology platforms create antibodies, small molecules and vaccines designed to address a broad spectrum of neurodegenerative indications, such as Alzheimer’s disease (AD). The Company’s pipeline features nine therapeutic and three diagnostic product candidates – with five product candidates currently in clinical trials. The most advanced of these is crenezumab, a humanized anti-amyloid-ß monoclonal IgG4 antibody that targets monomeric and aggregated forms of amyloid-ß, with highest affinity for neurotoxic oligomers. Crenezumab is currently in two Phase 3 clinical studies for AD, under a global program conducted by the collaboration partner Roche/Genentech. Other collaborations include Biogen, Janssen Pharmaceuticals, Nestlé Institute of Health Sciences, Life Molecular Imaging (formerly Piramal Imaging) and Essex Bio-Technology.