INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease.

Background: Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears to have relatively little binding to amyloid plaque.

Objectives: To assess safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment and mild dementia due to AD).

ACU193, a Monoclonal Antibody that Selectively Binds Soluble Aß Oligomers: Development Rationale, Phase 1 Trial Design, and Clinical Development Plan.

Background: Alzheimer's disease is a large and growing unmet medical need. Clinical trial designs need to assess disease-related outcomes earlier to accelerate the development of better treatments for Alzheimer's disease. ACU193 is a monoclonal antibody that selectively targets amyloid β oligomers, thought to be the most toxic species of Aβ that accumulates early in AD and contributes to downstream pathological effects.

ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disease that affects 50 million people worldwide, with 10 million new cases occurring each year. The emotional and economic impacts of AD on patients and families are devastating. Approved treatments confer modest improvement in symptoms, and recently one treatment obtained accelerated approval from the United States Food and Drug Administration (FDA) and may have modest disease modifying benefit.

An acute functional screen identifies an effective antibody targeting amyloid-β oligomers based on calcium imaging.

Soluble amyloid β oligomers (AβOs) are widely recognized neurotoxins that trigger aberrant signaling in specific subsets of neurons, leading to accumulated neuronal damage and memory disorders in Alzheimer's disease (AD). One of the profound downstream consequences of AβO-triggered events is dysregulation of cytosolic calcium concentration ([Ca]), which has been implicated in synaptic failure, cytoskeletal abnormalities, and eventually neuronal death. We have developed an in vitro/in vivo drug screening assay to evaluate putative AβO-blocking candidates by measuring AβO-induced real-time changes in [Ca].