A Pilot Electroencephalography (EEG) Study to Evaluate the Effect of CT1812 Treatment on Synaptic Activity in Subjects with Mild to Moderate Alzheimerʼs Disease

摘要。认知治疗公司（cognitive Therapeutics, Inc., CogRx）正在开发一种疾病改善药物ElaytaTM （CT1812）

ABSTRACT. Cognition Therapeutics, Inc. (CogRx) is developing ElaytaTM (CT1812), a disease-modifying drug for Alzheimer’s disease (AD). CT1812 is the first highly brain penetrant selective sigma-2 receptor antagonist small molecule. This first-in-class drug candidate selectively displaces amyloid-β oligomers bound to neuronal receptors at synapses and protects synapses from toxic oligomer effects, clearing them from the brain into the cerebrospinal fluid (CSF). When administered once daily for 28 days to mild to moderate AD patients, CT1812 significantly reduces concentrations of synaptic degeneration markers in AD patient CSF. Based on our review of publicly-disclosed clinical trial data, no other therapeutic currently in development selectively targets the most toxic form of the Aβ protein – oligomers. No other AD drug candidate reduces synaptic damage markers as much, and as rapidly, as CT1812 in Alzheimer's patients. Our Aim in the proposed trial is to identify non-invasive measures to quantify the CNS impact of CT1812 demonstrated ability to reduce synaptic damage in AD patients. This pilot trial project proposes to evaluate the effect of one month of CT1812 treatment on quantitative EEG in a Phase 1b randomized double-blind, placebo-controlled, crossover clinical trial in AD patients. We hypothesize that the rapid reduction in synaptic damage CSF biomarkers seen in previous clinical trials will be accompanied by a reduction in global theta power and provide information on the suitability of this sensitive non-invasive qEEG method of measuring synaptic function for measuring patient response to drug treatment in future efficacy studies. Completion of this pilot study in AD patients will inform the design and methods of the subsequent Phase 2a proof of concept trials with CT1812.