Summary
Neumora Therapeutics reported that its two phase 3 trials of navacaprant - KOASTAL-2 and KOASTAL-3 - failed to meet primary and key secondary endpoints in major depressive disorder (MDD). The company said it will discontinue development of navacaprant. Shares of the company fell 46.6% on the news.
Trial results
In KOASTAL-2, patients receiving navacaprant 80 mg showed a change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) that was similar to placebo, with a least-squares mean difference of -0.3. In KOASTAL-3, navacaprant produced a numerically lower change from baseline than placebo, with a least-squares mean difference of 0.7. KOASTAL-2 enrolled 430 adult patients with major depressive disorder, and KOASTAL-3 enrolled 422 adult patients.
The company said navacaprant was demonstrated to be safe and generally well tolerated, and that its safety profile in the phase 3 studies was consistent with prior clinical studies.
Financial and operational response
Following the trial outcomes, Neumora announced a reduction in its workforce of approximately 35%. The company expects this headcount reduction to generate annualized cost savings of about $10 million, partially offset by one-time restructuring costs of approximately $2 million. Neumora stated that its current cash and cash equivalents are expected to provide a runway into the third quarter of 2027.
Pipeline focus and near-term milestones
With navacaprant discontinued, Neumora said it will focus on advancing its remaining clinical portfolio. The programs highlighted by the company include:
- NMRA-511 for agitation associated with Alzheimer’s disease - the company plans to complete a multiple ascending dose cohort in the fourth quarter of 2026.
- NMRA-898 for schizophrenia - Neumora expects to report data from the ongoing phase 1 study in the second half of 2026.
- NMRA-215 for cardiometabolic disease - listed among the company’s remaining clinical priorities.
The company did not disclose additional changes to timelines for these programs beyond the milestones described above.
Market reaction
Neumora shares declined 46.6% on the day of the announcement following the discontinuation of navacaprant development after both phase 3 trials failed to reach statistical significance on primary and key secondary endpoints.
Implications
The company will reallocate resources toward its other clinical-stage assets and implement cost-saving measures to extend its cash runway into the third quarter of 2027. Management emphasized the safety and tolerability profile of navacaprant despite the lack of efficacy in the phase 3 studies.