Neumora Therapeutics discontinued navacaprant after two phase 3 flops in major depressive disorder, failing to meet primary and key secondary endpoints in KOASTAL-2 and KOASTAL-3. The company also announced layoffs covering 35% of its workforce, following a stock drop of nearly 50% in premarket trading. The late-stage results were reported as showing no statistically significant improvement versus placebo at six weeks, with KOASTAL-3 showing numerically worse symptom scores than placebo. Analysts linked the outcome to a broader pattern of skepticism around kappa opioid receptor antagonism in depression. The operational impact is immediate: Neumora said it will redirect focus toward a pipeline that includes Alzheimer’s agitation candidate NMRA-511, schizophrenia asset NMRA-898, and an obesity inhibitor NMRA-215, with earlier-stage timelines suggesting a strategy to preserve options while exiting the failed MDD thesis.