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Refining Alzheimer Treatment Through Biomarker-Based Patient Selection: Michael Woodward, MD, FRACP; Anthony Caggiano, MD, PhD

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“Patients with low baseline plasma phospho-tau exhibited a more pronounced response to CT1812, suggesting a targeted approach may enhance therapeutic outcomes in Alzheimer disease.”

CT1812 (Cognition Therapeutics) is an oral investigational, small-molecule sigma-2 receptor modulator in development for the treatment of Alzheimer disease (AD) and dementia with Lewy bodies. The therapy aims to displace Aβ oligomers from receptors on neuronal synapses, and thereby potentially protecting synapses from their toxic effects. The phase 2 SHINE trial (NCT03507790) assessed safety, tolerability, and effects of CT1812 on cognitive function in patients with mild-to-moderate AD.

A new prespecified analysis of data from SHINE showed that those treated with CT1812 who had baseline plasma p-tau217 below the median experienced a 95% slowing of cognitive decline, as measured by the 11-item Alzheimer’s Disease Assessment Scale–Cognitive subscale. The company noted that these same participants showed a 108% slowing, when measured by Mini-Mental State Examination. Notably, patients in the placebo groups for both analyses reported cognitive decline. Researchers also noted that complete results from this trial are anticipated to offer evidence as to whether the therapy can modify the disease course in this patient population.

These results were presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, held October 29 to November 1, in Madrid, Spain, by lead author Michael Woodward, MD, FRACP, head of dementia research at Austin Health. Following the presentation, Woodward and Anthony Caggiano, MD, PhD, chief medical officer at Cognition Therapeutics, sat down with NeurologyLive® to further discuss the findings of the presentation at the meeting. The duo talked about how baseline plasma phospho-tau level influenced treatment response in patients with AD and the implications of targeting low phospho-tau subgroups for future AD clinical trials. In addition, the experts spoke about the ways that CT1812 affected exploratory end points across different tau level subgroups.

Click here for more coverage of CTAD 2024.

REFERENCES
1. Woodward M, et al. Results from COG0201: A Randomized, Placebo-Controlled, Double-Blind, International, Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in Adults with Mild-to-Moderate Alzheimer’s Disease. Presented at: 2024 CTAD; October 29-November 1; Madrid, Spain. OC05.
2. Cognition Therapeutics Announces Results of Pre-specified Analysis of SHINE Study Data Presented at CTAD. News Release. Cognition Therapeutics. Published October 29, 2024. Accessed October 30, 2024. https://ir.cogrx.com/press_releases/cognition-therapeutics-announces-results-of-pre-specified-analysis-of-shine-study-data-presented-at-ctad/
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