Cognition Therapeutics Publishes EEG Results from Phase 2 SEQUEL Study of CT1812 in Mild-to-Moderate Alzheimer’s

Aug. 22, 2024 -- Cognition Therapeutics, Inc. (NASDAQ: CGTX), a company in the clinical stage of drug development for neurodegenerative disorders, has announced findings from the SEQUEL study of its leading candidate, CT1812, aimed at treating Alzheimer’s disease. The results were published in The Journal of Prevention of Alzheimer's Disease. The SEQUEL study was conducted at a single site and involved 16 adults with mild-to-moderate Alzheimer’s disease who were treated with CT1812 or a placebo over a period of 29 days. The study's primary focus was to observe changes in brain wave patterns.

Participants treated with CT1812 displayed consistent improvement trends across various electroencephalography (EEG) parameters. Several of these improvements were statistically significant, such as changes in relative theta power in the central brain region (p=0.006) and AEC-c (p=0.034), which measures brain region connectivity.

Dr. Anthony O. Caggiano, the chief medical officer and head of R&D at Cognition Therapeutics, explained that the hallmark of Alzheimer’s disease is the gradual slowing of brain wave patterns and impaired connectivity due to synapse loss. He noted that quantitative EEG (qEEG) is a sensitive method for measuring neuronal electrical activity in the brain. The observed changes in EEG parameters during the SEQUEL study suggest that CT1812 may help normalize brain wave patterns and improve communication between different brain regions. The drug appears to protect synapses through its mechanism as an Aβ oligomer antagonist.

The SEQUEL study found that once-daily oral administration of CT1812 reduced global relative theta power and theta power in various brain regions, including the frontal, temporal, parietal, occipital, and central regions. Increased prominence of theta frequencies (4-8 Hz) and decreased alpha frequencies (8-12 Hz) are associated with cognitive decline in Alzheimer's patients. The improvement in theta power was accompanied by an improvement in global alpha AEC-c, an indicator of connectivity between brain regions. This has been found to be predictive of cognitive function changes in Alzheimer’s disease. These findings support the hypothesis that CT1812's neuroprotective mechanism may help normalize synaptic function.

CT1812 was generally well tolerated among participants, with mild or moderate treatment-emergent adverse events (TEAEs) reported in 11 patients in the CT1812 group and 6 in the placebo group. The treatment-related adverse events included diarrhea, nausea, and vomiting with the placebo; and diarrhea, nausea, and hepatic enzyme elevation with CT1812. None of these adverse events led to discontinuation, and no severe or serious adverse events were reported among the CT1812-treated participants.

The full study details are available in the open-access article titled “A Pilot Electroencephalography Study of the Effect of CT1812 Treatment on Synaptic Activity in Patients with Mild to Moderate Alzheimer’s Disease” in The Journal of Prevention of Alzheimer's Disease.

The SEQUEL study included 16 adults with mild-to-moderate Alzheimer’s disease, 15 of whom completed the study. Participants were randomized to receive either 300mg of CT1812 or a placebo daily for 29 days, followed by a 14-day wash-out period before switching to the other treatment arm for another 29 days. Quantitative EEG evaluations were conducted periodically throughout the trial. The study aimed to assess the safety and efficacy of CT1812 and its impact on brain electrical activity, focusing on the theta band.

The National Institute of Aging (NIA) of the National Institutes of Health (NIH) supported SEQUEL with $5.3 million in grant awards.

CT1812 is an experimental oral small molecule that targets the sigma-2 (σ-2) receptor complex, designed to displace toxic Aβ oligomers. This displacement helps regulate key cellular processes such as membrane trafficking and autophagy, which are impaired by toxic interactions with Aβ oligomers and other stressors. The damage to synapses can lead to cognitive impairment and the progression of Alzheimer’s disease.

Cognition Therapeutics is also recruiting participants for other studies, including the START study for early Alzheimer’s disease and the MAGNIFY study for geographic atrophy secondary to dry age-related macular degeneration. Enrollment has been completed for the SHIMMER study in adults with dementia with Lewy bodies.

Cognition Therapeutics focuses on developing small molecule therapeutics for age-related degenerative disorders of the central nervous system and retina. Their lead candidate, CT1812, is being investigated in clinical programs for Alzheimer’s disease, dementia with Lewy bodies, and dry age-related macular degeneration.