Neumora Therapeutics announced on June 15 that it will discontinue its oral drug candidate for major depressive disorder following failures in two late-stage studies. The Massachusetts-based biotechnology company also said it will lay off 35% of its workforce as a result.
The decision comes after navacaprant, Neumora’s kappa opioid receptor antagonist, failed to meet primary or key secondary endpoints in the Phase 3 KOASTAL-2 and KOASTAL-3 trials. At six weeks, the treatment did not show statistically significant improvement in depressive symptoms compared to placebo, based on the Montgomery-Asberg Depression Rating Scale. In KOASTAL-2, more than 400 participants taking navacaprant had similar symptom scores to those on placebo; in KOASTAL-3, over 400 patients actually had numerically lower scores than their placebo counterparts.
Following the announcement, Neumora’s stock dropped nearly 50% in premarket trading. Analysts wrote that while disappointing, the outcome was not wholly unexpected due to previous trial failures and broader skepticism about kappa opioid receptor antagonists for depression. In January 2025, Neumora had already reported failure of its KOASTAL-1 study and paused further development before reworking ongoing trials.
Analysts from William Blair said Monday that "the 50% premarket drop in share price is 'an overreaction to a very high risk event,'" adding, "While any clinical miss is always disappointing, we actually view this event as a clearing event for the stock as focus now shifts toward the company’s promising clinical pipeline." This pipeline includes NMRA-511 for Alzheimer’s disease agitation with Phase 1 data expected later this year and plans for a Phase 2b trial by year-end; NMRA-898 for schizophrenia with data anticipated in the second half of this year; and NMRA-215 targeting obesity.
RBC Capital Markets analysts wrote, "Discontinuation of navacaprant, while always viewed as a very high-risk program, does remove some optionality around a large, late-stage opportunity, though with promise remaining in the rest of the early-stage pipeline..."
To reduce costs following these developments, Neumora will implement layoffs affecting more than thirty employees out of ninety-six full-time staff reported at last year’s end. The reduction is expected during the second and third quarters and projected to save approximately $10 million annually.
