Optimization of a novel series of 3-(piperazinylmethyl)indolesas 5-hydroxytryptamine-6 receptor (5-HT6R) antagonists resulted in identification of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (SUVN-502) as a clinical candidate for potential use in the symptomatic treatment of Alzheimer’s disease. SUVN-502 is a pure 5-HT6R antagonist with &gt;100 fold selectivity against other closely related serotonin subtypes. It exhibited excellent ADME properties and robust preclinical efficacy. Co-treatment of SUVN-502 with standard of care memantine and donepezil (triple combination) produced synergistic effects in animal models. SUVN-502 showed excellent margin of safety in preclinical long-term safety studies. The clinical portions of the single and multiple ascending dose studies evaluating safety, tolerability and pharmacokinetics have been successfully completed allowing the initiation of a Phase-2 proof of concept study in USA. The efficacy and safety of SUVN-502 is currently being evaluated in moderate AD patients aged between 50 to 85 years currently treated with donepezil and memantine. Details of the preclinical data and Phase-2 study design will be presented.

SUVN-502, A novel, potent and pure 5-HT6 receptor antagonist - proof-of-concept study design in moderate Alzheimer’s disease patients

254th National Meeting (2017)

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