NBI-1065844 (TAK-831) is an investigational treatment for schizophrenia that targets glutamate, an abundant neurotransmitter in the brain. In schizophrenia, N-methyl D-aspartate (NMDA) receptor dysfunction on GABA interneurons results in disinhibition of cortical or hippocampal glutamate neurons projecting to the basal ganglia. NBI-1065844 is a potential first-in-class, oral, selective and inhibitor with a high binding affinity to d-amino acid oxidase (DAAO). Inhibition of DAAO, which is a co-agonist of the NMDA receptor, increases D-serine levels, which may reverse NMDA hypofunction.
NBI-1065844 is currently being evaluated in Phase II studies, including the Phase II INTERACT proof-of-concept study in treating/managing negative symptoms of schizophrenia. These symptoms include blunted affect, alogia (reduction in quantity of words spoken), avolition (reduced goal-directed activity due to decreased motivation), asociality, and anhedonia (reduced experience of pleasure).
NBI-1065844 is being developed by Neurocrine Biosciences and Takeda Pharmaceutical Company Limited as part of a strategic collaboration announced in June 2020.