NMRA-898

NMRA-898 is a highly potent and selective M4 positive allosteric modulator (PAM) being developed by Neumora Therapeutics for the treatment of schizophrenia and potentially other neuropsychiatric disorders. It is structurally distinct from other M4 PAMs in Neumora's pipeline, including NMRA-266 and NMRA-861. The compound was developed following the unexpected convulsions observed with NMRA-266 in rabbit studies. NMRA-898 has been extensively tested in preclinical safety studies, including in rabbits, where it achieved exposures exceeding those that caused convulsions with NMRA-266, with no evidence of convulsions. The selective M4 PAM approach aims to modulate dopamine release in specific brain regions, potentially addressing both positive symptoms and cognitive deficits in schizophrenia with fewer metabolic and motor side effects compared to traditional antipsychotics. The compound is expected to enter clinical trials in 2025.