Cognition Therapeutics is making strides in the development of CT1812, an orally delivered small molecule, as a potential treatment for Alzheimer's disease and dementia with Lewy bodies (DLB). Recent data from Phase 2 trials, the SHINE study in Alzheimer's and the SHIMMER study in DLB, indicate promising therapeutic benefits. These findings suggest CT1812 could address critical unmet needs in neurodegenerative disorders.
CT1812 Slows Cognitive Decline in Alzheimer's Patients
At the Clinical Trials on Alzheimer's Disease (CTAD) conference, Cognition Therapeutics presented data from its Phase 2 SHINE study, revealing that CT1812 significantly slowed cognitive decline in patients with mild-to-moderate Alzheimer's disease who had lower levels of plasma p-tau217, a key biomarker of Alzheimer's pathology. Specifically, patients with below-median baseline levels of plasma p-tau217 experienced a 95% slowing in cognitive decline as measured by the ADAS-Cog 11 scale and a 108% slowing as measured by the MMSE scale, compared to placebo patients.
Dr. Michael Woodward, who presented the analysis, suggested that plasma p-tau217 could serve as a predictive biomarker for treatment effectiveness. Dr. Anthony Caggiano, CMO and head of R&D at Cognition, noted that the treatment effect size appeared to increase over time, with plans to confirm these effects in a longer study. The SHINE study was a double-blind, placebo-controlled trial involving 153 adults, supported by approximately $30 million in grants from the National Institute on Aging of the National Institutes of Health (NIH).
Positive Results in Phase 2 SHIMMER Study for Dementia with Lewy Bodies
Cognition Therapeutics also announced topline results from its Phase 2 SHIMMER study, which evaluated CT1812 in patients with mild-to-moderate DLB. The study met its primary endpoint of safety and tolerability. DLB patients treated with CT1812 for six months experienced improvement in behavioral, functional, cognitive and movement measures compared to placebo.
According to the press release, there was an 82% slowing in the total neuropsychiatric inventory (NPI) with particularly strong reduction in anxiety, hallucinations, and delusions in the CT1812 treated arms. In addition, there was a marked reduction in caregiver distress, which suggests a positive impact on the day-to-day lives of those receiving the drug. Participants treated with CT1812 experienced a slowing of decline across all three cognitive measures compared to placebo, including fluctuations in attention which declined by 91%.
Mechanism of Action and Future Plans
CT1812 is an orally delivered small molecule that targets the sigma-2 receptor complex, potentially displacing toxic Aβ oligomers linked to Alzheimer's disease progression and alpha-synuclein oligomers linked to DLB. Cognition Therapeutics is also evaluating CT1812 in clinical programs for other degenerative conditions, including dry age-related macular degeneration.
The company is preparing for a Phase 3 trial discussion with the FDA following an end-of-Phase 2 meeting. These results reinforce zervimesine's potential to address the complex and debilitating symptoms of DLB. Detailed data from the SHIMMER trial will be presented at the International Lewy Body Dementia Conference in January 2025.
