Cognition Therapeutics (CGTX) Study Update summary

Study design and objectives

• SHINE was a phase 2, six-month, randomized, double-blind, placebo-controlled trial in mild to moderate Alzheimer's disease, enrolling 153 participants across multiple countries.

• Participants were randomized to receive 100 mg, 300 mg of CT1812, or placebo daily; primary objectives included safety, tolerability, and efficacy on cognitive and functional endpoints.

• All participants had confirmed amyloid pathology and were stratified by baseline plasma p-tau217 above or below the median value of 1.0 pg/mL.

• Efficacy was assessed using ADAS-Cog 11/13, MMSE, ADCS-ADL, and CGIC.

• The study was supported by approximately $30 million in NIH grants.

Mechanism of action and rationale

• CT1812 is an orally delivered small molecule that antagonizes the sigma-2 receptor complex, displacing toxic Aβ oligomers from synapses and facilitating their clearance in CSF.

• The mechanism is distinct from anti-amyloid immunotherapies and is proposed to protect synapses and slow neuronal injury.

• Prior data suggest individuals with lower plasma p-tau217 respond better to amyloid-based therapies.

• Cognition Therapeutics focuses on small molecule therapeutics for neurodegenerative and retinal diseases, with CT1812 as its lead candidate.

Key efficacy and safety findings

• In the below-median p-tau217 subgroup, CT1812 preserved cognition with 95% slowing of decline on ADAS-Cog 11 (p=0.04) and 108% slowing on MMSE (p=0.02) versus placebo.

• CT1812-treated participants showed 39% less cognitive loss than placebo on ADAS-Cog 11 over six months in the overall population.

• Functional endpoints (ADCS-ADL, CGIC) favored CT1812 in the low p-tau217 group, with observed differences of 1.24 and 0.51 points, respectively.

• Safety profile was favorable, with most adverse events mild or moderate and similar rates between treatment and placebo; no discontinuations due to adverse events at 100 mg.

• Discontinuations and liver enzyme elevations were mainly in the 300 mg group; no deaths in CT1812 group, one death (cancer) in placebo.