Human AME study of CT1812, a small molecule in phase 2 clinical trials for the treatment of Alzheimer's disease

PROJECT SUMMARY/ABSTRACT Alzheimerandapos;s disease (AD) afflicts nearly six million people in the United States (U.S), and this number is expected to double by 2050. Disease modifying medical therapies for AD continue to be an unmet need. The symptomatic treatments currently available regulate neurotransmitter levels, slowing cognitive decline for an average of only 6 months. Cognition Therapeutics (CogRx) is developing CT1812, the first brain penetrant small molecule that selectively clears toxic beta amyloid oligomers (AβOs) from the brain into cerebrospinal fluid (CSF). CT1812andapos;s mechanism of action has the potential to halt or slow cognitive decline, significantly alleviating AD progression. CT1812 is currently in Phase 2 trials in patients. Before CogRx can proceed to larger and longer studies that evaluate efficacy, a human Absorption, Metabolism, and Excretion (AME) study must be conducted per Food and Drug Administration expectations, to establish a robust and comprehensive knowledge of CT1812andapos;s pharmacokinetics (PK) and key metabolites. Approach. The overall research design will include (Aim 1) purifying and characterizing radiolabeled CT1812 in sufficient quantities with sufficient quality; (Aim 2) conducting an open-label AME clinical trial in which up to six healthy male volunteers are given oral [14C]-CT1812, followed by plasma, urine and feces collection for up to 14 days, and (Aim 3) analyzing samples to determine mass balance recovery, PK, and identification and quantification of the relative abundances of the metabolites. CogRxandapos;s long-term objective is to develop CT1812 as a potential disease-modifying therapeutic for AD treatment. Because no AD disease-modifying therapies exist currently, CT1812 would significantly advance AD treatment armamentarium. 1Project Narrative Cognition Therapeutics (CogRx) is developing CT1812, the first brain-penetrant small molecule that selectively clears toxic beta amyloid oligomers (AβOs) from the brain into cerebrospinal fluid (CSF), to treat Alzheimerandapos;s disease (AD) which afflicts nearly 6 million people in the U.S and is expected to double by 2050. A study of human absorption, metabolism, and excretion (AME) is required by the Food and Drug Administration (FDA), and its conduct has been explicitly requested for this program as a prerequisite to larger and longer studies. If successful, CT1812 will modify the disease, preserve memory, reduce immense healthcare costs and return quality of life to AD patients and their caregivers. 1