Cellular Prion Protein Targeting Monoclonal Antibody Antagonist as a Therapy for Alzheimer's Disease

摘要/文摘

SUMMARY/ABSTRACT An estimated 5.6 million patients are currently living with Alzheimer’s disease and have no disease modifying therapies available. Without any major breakthroughs in identifying transformative treatments, the burden of patient care costs to the United States healthcare system is expected to skyrocket as our population ages. The clinical pipeline in Alzheimer’s disease has been met with high profile failures and setbacks, mostly with technologies that target removal or lowering of amyloid-β plaques. Novel methods for treating this disease are desperately needed, specifically those that target mechanisms independent of amyloid-β removal. Cellular prion protein has been identified as the primary receptor for toxic amyloid-β oligomers and is located at the synapses of neurons. This receptor has been validated as a key mediator of synapse loss in transgenic animal models of Alzheimer’s disease. Our product is a high affinity monoclonal antibody inhibitor of cellular prion protein. By blocking the activity of cellular prion protein, we aim to deliver a disease modifying therapeutic capable of preventing synapse loss and thereby preserving both cognitive and functional abilities for patients with Alzheimer’s disease. Preclinical evaluation of this antibody has been conducted with the murine version of the antibody product. Our goal for the Phase I segment of this award is to express, purify and characterize the activity of the human antibody form of the product to ensure drug-like properties in vitro. This will provide validation for large-scale production, pharmacokinetic and safety evaluation to be carried out during the Phase II segment. The overall goal of this SBIR is to provide preliminary toxicology data to predict that brain exposure reaches therapeutic levels at safe and feasible human doses. The commercial opportunity for a disease modifying therapeutic in Alzheimer’s disease is immense. Peak worldwide revenues for existing symptomatic Alzheimer’s treatments reached $4.3 B USD. A disease modifying therapy is expected to reach sales of >$10 B USD per year. Allyx Therapeutics will establish clinical proof-of-concept in a Phase II clinical trial before partnering with a large pharmaceutical partner for Phase III development and commercialization.