Neumora Therapeutics killed navacaprant Monday after Phase 3 trials KOASTAL-2 and KOASTAL-3 both missed the primary endpoint and every key secondary in major depressive disorder. It’s the company’s third consecutive Phase 3 strike for the kappa opioid receptor (KOR) antagonist.
In KOASTAL-2, navacaprant matched placebo on the Montgomery-Åsberg Depression Rating Scale at six weeks across more than 400 patients. In KOASTAL-3, it scored numerically below placebo across 400-plus patients. KOASTAL-1 had already failed in January 2025, prompting Neumora to pause and redesign those two replicate studies.
The stock dropped nearly 50% in premarket trading. Neumora is cutting 35% of its 96-person workforce, more than 30 employees, with reductions in Q2 and Q3 2026, saving roughly $10 million annually.
KOR antagonism in MDD has been losing ground for years. Johnson & Johnson also discontinued its KOR antagonist aticaprant after failing to show efficacy in MDD, and Neumora’s three-trial sweep now confirms the class hasn’t cracked the biology. The KOASTAL-3 result, where navacaprant scored numerically below placebo, suggests the problem isn’t dosing or patient selection: it’s the mechanism.
The company now pivots to three earlier-stage programs: NMRA-511 for Alzheimer’s disease agitation (Phase 1 data expected Q4 2026, Phase 2b launch by end of 2026), NMRA-898 for schizophrenia (data readout second half 2026), and NMRA-215 for obesity. Per the company’s 8-K filed Monday, cash runway extends into Q3 2027.
Sarah Chen