Neumora plunges 49% after navacaprant fails all three Phase 3 trials

Neumora Therapeutics abandoned its lead depression candidate after navacaprant failed two Phase 3 trials, completing a clean sweep of late-stage misses that wiped out 49% of the company's market value.

"While any clinical miss is always disappointing, we view this as a clearing event for the stock as focus shifts toward the company's promising pipeline," William Blair analysts wrote Monday.

In KOASTAL-2, 430 patients on navacaprant showed a Montgomery-Asberg Depression Rating Scale change of -12.2 versus -12.0 for placebo, yielding a p-value of 0.813. KOASTAL-3, with 422 patients, produced an even starker result: navacaprant patients scored -10.1 versus -10.8 on placebo (p=0.480). A pre-specified analysis of 426 patients enrolled after study optimizations in early 2025 showed identical changes of -12.1 in both arms (p=0.976). The drug had already failed KOASTAL-1 in January 2025, sending shares down 80%.

The discontinuation removes Neumora's most advanced asset, leaving the company with a pipeline of early-stage programs and cash lasting only into the third quarter of 2027. The Massachusetts-based biotech plans to cut 35% of its 96-person workforce, saving $10 million annually with $2 million in one-time restructuring costs.

Navacaprant, a kappa opioid receptor antagonist, was designed to treat major depressive disorder through a mechanism distinct from standard SSRIs. Johnson & Johnson had previously discontinued its own KOR antagonist aticaprant after similar efficacy failures, Stifel analysts noted.

Neumora's remaining pipeline includes NMRA-511 for Alzheimer's disease agitation, with Phase 1 data expected in the fourth quarter and a Phase 2b dose-ranging trial planned by year-end. The schizophrenia candidate NMRA-898, an M4 positive allosteric modulator, is slated for Phase 1 data in the second half of 2026. The company also plans to share 13-week preclinical findings for its NLRP3 inhibitor NMRA-215 in obesity by August, with clinical studies targeted before year-end.

The biotech launched in October 2021 with $500 million from Arch Venture Partners, betting that precision neuroscience could de-risk central nervous system drug development. Chairman and Chief Executive Officer Paul L. Berns said the company remains "excited" about near-term catalysts across the pipeline.

RBC Capital Markets analysts called the obesity program "a potentially differentiated opportunity," while noting that navacaprant's failure "does remove some optionality around a large, late-stage opportunity." Neumora shares closed at $0.98 on Monday, down roughly 95% from a peak in early 2025.

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