Potential Therapy, CT1812, Seen as Safe and Able to Target Disease Markers, Cognition Reports
Cognition Therapeutics’ lead drug candidate for mild-to-moderate Alzheimer’s disease (AD), CT1812, was shown to be well-tolerated and to lower brain levels of proteins involved in the disease, the company reports.
These results, part of a Phase 1b/2a clinical trial, were given in an oral presentation at the recent 10th Clinical Trials on Alzheimer’s Disease (CTAD) meeting in Boston by Lon Schneider, MD, a professor at the USC Keck School of Medicine, and in a poster presentation by a company executive.
An abstract on the Schneider’s talk is titled “The Anti-Aβ Oligomer Drug CT1812 for Alzheimer’s: Phase 1b/2a Safety Trial Outcomes.”
CT1812 is a small molecule that has shown an ability to effectively penetrate into the brain. Once there, it works to displace the amyloid-beta (Aβ) oligomers from their binding sites (or receptors) on neuron cells in the brain, and dispel the oligomers from the cerebrospinal fluid (CSF). Aβ oligomers are thought to play a major role in Alzheimer’s disease pathology, and CT1812 has demonstrated an ability to stop memory loss in animal models of AD.
The clinical trial (NCT02907567) was conducted to determine the safety and pharmacokinetics (the drug’s behavior in the body) of CT1812. It enrolled 19 people with mild-to-moderate AD, and treated them with either placebo or one of three doses of CT1812 (90, 280 and 560 mg) for 28 days. Levels of AD protein biomarkers and cognitive outcomes of treatment were also measured as secondary, exploratory goals.
Results showed that CT1812 was well-tolerated at all doses, and adverse events reported in 16 of the 19 patients were mild or moderate. Pharmacokinetics were similar to those seen in prior studies.
Importantly, CT1812 achieved a greater than 80% concentration of “brain receptor occupancy” at all doses, as measured in the CSF. An 80% concentration, the company reports, was determined in preclinical studies to be the minimum level necessary for treatment effectiveness.
Levels of proteins involved in AD pathology were also measured in the CSF of patients. Results showed signficantly lower levels of a protein called neurogranin, which is high in AD patients as it is a marker of synaptic damage, in those treated with CT1812. Synaptic damage refers to damage to the signaling function of neurons, or nerve cells, which can lead to AD.
Other AD-related proteins were also seen at reduced levels in patients treated with CT1812, including synaptotagmin-1, another marker of synaptic damage.
Cognitive outcomes in the study, however, were similar between the two groups after 28 days.
“The changes observed in protein biomarker levels after treatment with CT1812 were consistent with a positive effect on synapses as well as CT1812’s mechanism of action,” Susan Catalano, Cognition’s chief scientific officer and founder, said in a press release. She also presented the poster reporting protein level findings at the meeting.
Cognition plans further studies of CT1812, including a Phase 2 trial of the treatment’s potential efficacy. It was placed on fast track development by the U.S. Food and Drug Administration in October as a potential Alzheimer’s treatment.