Mary Hamby, PhD, Cognition Therapeutics Inc., Pittsburgh, PA, shares the findings of a cerebrospinal fluid (CSF) proteomic analysis looking the pharmacodynamic activity of CT1812, a small molecule sigma-2 receptor (S2R) modulator under investigation for the treatment of Alzheimer’s disease (AD). CT1812 is proposed to act via displacement of toxic amyloid-beta (Aβ) oligomers from neuronal synapses. This exploratory analysis assessed the proteomes of patients with mild-moderate AD, treated with CT1812 or placebo for 6 months as part of the randomized, controlled SPARC trial (NCT03493282). Following tandem-mass tag mass spectrometry, differential expression analyses identified several proteins that were significantly altered by CT1812, compared to placebo. Pathway analysis identified these proteins as being tied to synaptic function, amyloid biology, and inflammation. These data support the proposed mechanism of action of CT1812 and have identified several candidate biomarkers of target engagement/disease modification that could be used in future clinical trials. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.