Neumora Discontinues Navacaprant Clinical Program in Depression and Cuts 35% of Staff Following Phase 3 Failures
Neumora Therapeutics has terminated the clinical development of its lead candidate, navacaprant, and announced a major restructuring that includes laying off approximately 35% of its workforce. The decision follows a definitive failure in the Phase 3 KOASTAL clinical program, where the drug failed to show efficacy in treating major depressive disorder (MDD).
Navacaprant, an oral kappa opioid receptor (KOR) antagonist, was the crown jewel of Neumora's pipeline. The company was launched in 2021 by Arch Venture Partners with $500 million in backing under the premise that advanced neuroscience and precision medicine could de-risk psychiatric drug development. However, navacaprant has now gone "0 for 3" in its late-stage trials. After a first Phase 3 flop in the KOASTAL-1 trial in early 2025, the latest readouts from KOASTAL-2 and KOASTAL-3 showed that the drug failed to outperform placebo on the standard Montgomery-Åsberg Depression Rating Scale (MADRS) at week 6. In the KOASTAL-3 trial, patients on placebo actually fared better than those on the active drug.
The restructuring and layoffs are expected to save Neumora $10 million annually, extending its cash runway into the third quarter of 2027. The company is pivoting its resources to other pipeline candidates, including NMRA-511 (V1a receptor antagonist) for Alzheimer's disease agitation, NMRA-898 (M4 positive allosteric modulator) for schizophrenia, and NMRA-215 (NLRP3 inhibitor) for obesity.
Trial Findings & Restructuring Details
- KOASTAL-2 and KOASTAL-3 Results: Neither trial achieved statistical significance on primary or key secondary endpoints. Navacaprant failed to significantly reduce MADRS scores compared to placebo after 6 weeks of treatment.
- Workforce Reduction: Neumora is cutting 35% of its staff to generate $10 million in annualized savings, incurring a one-time charge of $2 million.
- Financial Status: The company's cash runway is now projected to last into Q3 2027.