Age-related Build-up of Toxic Proteins
Several neurodegenerative disorders are characterized by an age-related build-up of toxic proteins in the brain, which bind to neuronal receptors and disrupt key cellular processes.
Alzheimer’s disease in particular is caused by the age-related buildup of proteins including beta amyloid (Aβ). Under normal conditions, the cell removes these proteins from the brain before they are allowed to accumulate and aggregate into more toxic forms. However, in Alzheimer’s disease, the cellular damage response is disrupted, allowing the formation of toxic Aβ oligomers. These oligomeric forms of the Aβ protein bind to synapses where they cause a cascade of damage and eventual loss of neurons.
A Unique Approach to Treating Alzheimer's Disease
In Alzheimer’s disease, the preponderance of evidence suggests that Aβ oligomers are toxic when bound to neuronal synapses. The damage they inflict causes a cascade of damage and eventual loss of synapses. Synapses are the communication points between neurons, facilitating signal transmission throughout the brain. Loss of these structures is directly correlated with cognitive decline in Alzheimer’s disease.
Previous therapeutic approaches have attempted to a) reduce the production of Aβ by inhibiting the enzymes that generate Aβ: γ-secretase or β-secretase; or b) removing Aβ using targeted monoclonal antibodies. None of these compounds selectively targeted Aβ oligomers and to date they have demonstrated limited effect.
Learn about the causes of Alzheimer's disease and our proposed mechanism of treatment
Restoring Damaged Cellular Processes
Displaces oligomers from neurons (A) and from Alzheimer's patient neocortical tissue (B)
Development Status in Alzheimer's Disease
CT1812 has completed three Phase 1 trials and enrollment has concluded in two Phase 2 clinical trials with two additional physiology trials ongoing in patients with Alzheimer’s disease. Cognition has been awarded a $75.8M grant from the NIA to study CT1812 in a study of 540 Alzheimer’s disease patients. This study will be conducted collaboration with the distinguished Alzheimer’s Clinical Trial Consortium (ACTC) and is expected to commence in 2021.
Select Completed Studies
- CT1812 was generally safe and tolerated in patients with mild-to-moderate Alzheimer’s disease.
- All adverse events were mild or moderate; there were no serious adverse events.
- CT1812 achieved CSF concentrations greater than 80 percent estimated brain receptor occupancy, a level previously demonstrated in preclinical studies to be the minimum efficacious dose.
- Protein biomarkers associated with Alzheimer’s disease changed differentially in CT1812-treated vs. placebo patients.
- Assessing target engagement.
- Expect topline results by YE 2021.
- Assessing disease-modification as a measure of synapse density with PET imaging.
- Expect topline results by YE 2021.
- Double-blind, placebo-controlled study.
- Enrollment complete.
- Top-line results from Part A (n=24) showed positive trend in cognitive function in favor of CT1812.
- Treatment-emergent adverse events were well balanced across all treatment groups in Part A.
- Enrollment and treatment in Part B (n=38) continues.
- Assessing disease-modification as a function of synapse function as measured by qualitative EEG.
- Expect topline results in 2022.
- 540-person Phase 2 study in early Alzheimer’s disease in collaboration with the Alzheimer’s Clinical Trials Consortium (ACTC).
- Supported by a $75.8 million grant from the National Institute on Aging (NIA) of the National Institutes of Health (NIH).
- Expected to commence in 2021.