Safety Profile of CT1812 and Its Effect on Proteomic Biomarkers of Alzheimer Disease: Mary Hamby, PhD

WATCH TIME: 3 minutes

"We identified key pharmacodynamic biomarkers of CT1812 that correlate with reduced neurodegeneration and improved cognitive outcomes. This builds out our biomarker program, helping us understand the biological impact of CT1812 on patients with Alzheimer disease and providing a foundation for Phase 3 planning with a dose that demonstrates efficacy and excellent tolerability."

There are several emerging therapeutics in the Alzheimer disease (AD) pipeline, including CT1812 (Cognition Therapeutics), a brain-penetrant small molecule modulator of the sigma-2 receptor (SR2). The randomized, double-blind, placebo-controlled phase 2 trial (NCT03507790) dubbed SHINE assessed the safety and tolerability, exploratory cognitive and functional outcome measures, and exploratory biomarker effects of 2 CT1812 doses (100 mg, 300 mg; oral, once daily) in patients with mild-to-moderate AD.

Several analyses from SHINE were presented at the recently concluded 2025 AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases, held April 1-5 in Vienna, Austria. Among them included a post-hoc proteomic biomarker analysis of 45 participants using a tandem-mass tag mass spectrometry. Here, differentially abundant proteins (113 total) were mapped to 44 previously established protein co-expression network modules built from samples from healthy individuals, asymptomatic patients with AD, and those with AD. All told, the analysis corroborated previously identified pharmacodynamic biomarkers of CT1812 pathway engagement and disease modification as well as facilitated identification of novel biomarkers.

During the meeting, NeurologyLive^® sat down with Mary Hamby, PhD, vice president of research at Cognition, to better understand the findings and how they support the development of CT1812. Hamby spoke about how key biomarkers correlated with reductions in neurofilament light, a marker of neurodegeneration, as well as improvements in cognitive outcomes measure by the Alzheimer’s Disease Assessment Cognitive subscale 11. Additionally, she spoke on the safety profile of the drug, noting no adverse events reported in the 100 mg dose cohort, providing a clear path forward for phase 3 trials.

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REFERENCE
1. Lizama BN, Pandey K, Duong D, et al. CSF proteomic biomarker analysis from phase 2 study SHINE identified effects of S2R modulator Ct1812 in Alzheimer’s Disease. Presented at: 2025 AD/PD conference; April 1-5; Vienna, Austria. ABSTRACT 02-172