Neumora Therapeutics (Neumora Therapeutics (NMRA)) had a rough Monday. The clinical-stage biopharma announced it is pulling the plug on its lead depression candidate, navacaprant, after two Phase 3 studies failed to show the drug worked better than a sugar pill. As a result, the company is slashing its workforce by 35% and pivoting to its remaining pipeline programs.
The two trials, KOASTAL-2 and KOASTAL-3, enrolled 430 and 422 adults with major depressive disorder (MDD), respectively. Patients received either 80 mg of navacaprant or a placebo, and the main goal was to measure changes in depression severity using the Montgomery-Åsberg Depression Rating Scale (MADRS) over six weeks. Spoiler: the drug didn't move the needle.
In KOASTAL-2, patients on navacaprant saw a change of -12.2 on the MADRS scale, while the placebo group saw -12.0. That tiny difference of 0.3 points came with a p-value of 0.813 — far from statistically significant. KOASTAL-3 was even worse: navacaprant patients improved by -10.1, while placebo patients improved by -10.8. The drug actually did worse than placebo, with a p-value of 0.480.
The company also looked at a subgroup of 426 patients enrolled after some study tweaks in early 2025. There, navacaprant and placebo produced identical changes of -12.1, with a p-value of 0.976. Ouch.
On the bright side, navacaprant was safe and well tolerated, with no new safety signals. But in the world of depression drugs, safety without efficacy doesn't pay the bills.
So what's next for Neumora? The company is shifting focus to three other programs. First up is NMRA-511, a V1a receptor antagonist for Alzheimer's disease agitation. Neumora expects to finish a multiple ascending dose study in the fourth quarter of 2026, which will help pick the dose for a Phase 2b trial planned before year-end.
Then there's NMRA-898, an M4 positive allosteric modulator for schizophrenia. Phase 1 data should drop in the second half of 2026. And for NMRA-215, an NLRP3 inhibitor for obesity, the company plans to complete a 13-week rat toxicology study by mid-2026, give an update in August, and start clinical studies before the end of the year.
To conserve cash, Neumora is cutting about 35% of its staff, which should save roughly $10 million per year. The company expects to take about $2 million in one-time restructuring charges. With its current cash and equivalents, Neumora says it can fund operations into the third quarter of 2027 and hit those clinical milestones.
Investors didn't stick around to see how this plays out. Shares of Neumora were down 44.86% at $0.98 at the time of publication, according to market data. It's a tough day for a company that just lost its lead asset, but at least the pipeline still has some shots on goal.
