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

总结/摘要 据估计，目前有560万患者患有阿尔茨海默病，并且没有疾病修饰。 可用的治疗。如果在确定变革性治疗方面没有任何重大突破， 随着人口老龄化，美国医疗保健系统的病人护理费用预计将飙升。的 阿尔茨海默病的临床管道已经遇到了高调的失败和挫折，主要是 靶向去除或降低淀粉样蛋白-β斑块的技术。治疗这种疾病的新方法是 迫切需要的，特别是那些靶向机制独立于淀粉样蛋白-β去除。 细胞朊病毒蛋白已被鉴定为毒性淀粉样蛋白-β寡聚体的主要受体，位于 神经元的突触该受体已被证实是转基因小鼠中突触丢失的关键介质。 阿尔茨海默病的动物模型。我们的产品是一种高亲和力的单克隆抗体， 朊病毒蛋白通过阻断细胞朊病毒蛋白的活性，我们的目标是提供一种改善疾病的治疗方法， 能够防止突触丧失，从而保留患者的认知和功能能力， 患有老年痴呆症 已使用抗体产品的鼠版本进行了该抗体的临床前评价。我们 该奖项第一阶段的目标是表达，纯化和描述人类活动的特征 抗体形式的产品，以确保在体外的药物样特性。这将为大规模 在II期阶段进行生产、药代动力学和安全性评价。整体 本SBIR的目标是提供初步毒理学数据，以预测大脑暴露达到治疗水平 在安全和可行的人体剂量水平。 阿尔茨海默病的疾病改善治疗的商业机会是巨大的。峰值 现有的阿尔茨海默氏症对症治疗的全球收入达到43亿B美元。的疾病 改良疗法的年销售额有望达到100 B美元以上。Allyx Therapeutics将建立临床 在与大型制药合作伙伴合作进行III期临床试验之前，在II期临床试验中进行概念验证 开发和商业化。

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.