Supportive Evidence for CT1812 as Treatment for Alzheimer Disease: Anthony Caggiano, MD, PhD

WATCH TIME: 5 minutes

"It (CT1812) was a ligand for what’s known as the sigma-2 receptor, and then subsequent research has shown that the sigma-2 receptor interacts directly with the amyloid-ß oligomer receptor, and when bound to drug, the affinity of oligomers for the receptor is reduced. Essentially, more oligomers are coming off and fewer are coming on, and we believe that’s how we’re protecting neurons."

Over the years, it has been difficult to develop disease-modifying therapeutics for patients with Alzheimer disease (AD), the largest growing neurodegenerative disorder in the world. Although amyloid-ß has been the main key target for drug development, anti-amyloid-ß monoclonal antibodies have limited selectivity for amyloid-ß oligomers, and their use is associated with adverse events including amyloid-related imaging abnormalities.

One therapeutic in development, CT1812 (Cognition Therapeutics), is a novel brain penetrant molecule that interferes with the binding of amyloid-ß oligomers to neurons, preventing synaptotoxicity. More specifically, CT1812 binds to the sigma-2 receptor and allosterically displaces amyloid-ß oligomers that are bound to neurons. CT1812 was evaluated in a phase 2 proof-of-concept study, dubbed SHINE (NCT03507790), that included 153 adults with mild-to-moderate AD.

Presented at the 2024 Alzheimer’s Association International Conference (AAIC), held July 28-August 1 in Philadelphia, Pennsylvania, results showed that the therapy met its primary objective and demonstrated a favorable safety and tolerability profile, consistent with previous clinical experience. In the study, patients were assigned to either placebo or 1 of 2 does of CT1812 (100 mg or 300 mg) for a 6-month treatment period. Overall, the therapy did not achieve statistical significance on the first of the ordered secondary efficacy end points in the pooled dosed groups; however, it did demonstrate an effect on several cerebrospinal fluid biomarkers.

During the meeting, Anthony Caggiano, MD, PhD, chief medical officer and head of Research & Development at Cognition Therapeutics, sat down with NeurologyLive® to provide an overview of the clinical data presented, and some of the topline findings. In addition, he described the unique mechanism of action of CT1812, targeting sigma-2 receptor, and how it may be beneficial in treating AD. Furthermore, he provided context as to how this agent differs from other previously approved novel treatments.

Click here for more coverage of AAIC 2024.

REFERENCE
1. Cognition Therapeutics’ Proof-of-Concept Phase 2 SHINE Trial Demonstrates Consistent Improvement in Cognitive Outcomes with Once-Daily Oral CT1812 in Mild-to-Moderate Alzheimer’s Patients. News release. Cognition Therapeutics. July 29, 2024. Accessed August 1, 2024. https://ir.cogrx.com/news-releases/news-release-details/cognition-therapeutics-proof-concept-phase-2-shine-trial