Roughly eighteen months after Neumora Therapeutics reported the first late-stage flop for navacaprant in major depressive disorder (MDD), the asset has now completed a clean sweep of trial misses in the indication.
Monday morning, Neumora reported that its Koastal-2 and Koastal-3 studies of navacaprant in MDD did not achieve statistical significance on their primary or key secondary endpoints. Following trial failures, Neumora is discontinuing development of the drug candidate and preparing to lay off 35% of its staffers, according to a June 15 press release.
In the studies, navacaprant, a kappa opioid receptor antagonist, did not significantly outperform placebo on the change in patients' Montgomery-Åsberg Depression Rating Scale (MADRS) scores by week 6. In fact, in the Koastal-3 study, patients actually fared better on placebo on the depression rating measure, Neumora said.
Back at the start of 2025, Neumora reported that the drug missed in the Koastal-1 study, sending its stock crashing 80% at the time. Early Monday, in the wake of the Koastal-2 and Koastal-3 flops, the stock was down 45% to 98 cents. Altogether, Neumora's stock is down roughly 95% from a peak in early 2025.
The company had little positive to say about navacaprant in its release. In a statement, chairman and CEO Paul L. Berns said Neumora remains "excited" about other near-term catalysts for the biotech's pipeline, namely trial readouts in Alzheimer’s disease agitation, schizophrenia and cardiometabolic disease.
With the Koastal trial's fail comes word of layoffs. To achieve annual savings of $10 million, Neumora plans to reduce its workforce by approximately 35%. It expects the reorganization to result in one-time costs of $2 million. With the changes, Neumora's cash runway should extend into the third quarter of 2027, the company said.
With navacaprant gone, the company's pipeline now includes the V1a receptor antagonist NMRA-511 as a potential treatment for Alzheimer’s disease agitation, the M4 positive allosteric modulator NMRA-898 as a schizophrenia prospect and its NLRP3 inhibitor NMRA-215 in obesity.
A brainchild of Arch Venture Partners, Neumora came onto the scene in October 2021 with $500 million in funding. The company launched with the belief that major advances in neuroscience would allow it to precisely target patients to de-risk trials and improve outcomes.