Neumora Overhauls Depression Drug Trials Following Phase 3 Setback

Neumora Therapeutics has announced significant changes to its clinical trial program for navacaprant, its oral kappa opioid receptor antagonist for major depressive disorder (MDD), following a recent phase 3 failure. The biotech is implementing a series of measures to optimize patient selection and trial management, while also making strategic decisions about resource allocation.

KOASTAL Program Revamp

The company's KOASTAL-1 study, which reported results in January, showed no difference in depression rating scale changes between navacaprant and placebo after six weeks of treatment. In response, Neumora has conducted extensive analyses to identify contributing factors to this outcome.

As a result, the biotech has paused its KOASTAL-2 and KOASTAL-3 trials while implementing several changes:

1. Limiting trial sites to those with the highest expertise in conducting MDD studies
2. Enhancing medical monitoring efforts
3. Strengthening patient screening processes, including the addition of the Verified Clinical Trial screening database

These amendments aim to ensure only appropriate patients are enrolled in future trials. Neumora expects to resume KOASTAL-2 and KOASTAL-3 later this month, with new projected readout timelines in Q2 2026 and Q1 2026, respectively.

Strategic Prioritization and Leadership Changes

In a move to focus resources, Neumora has discontinued its phase 2 trial of navacaprant in bipolar depression. The company stated it still believes the drug may benefit bipolar depression patients and will evaluate future opportunities in this indication.

The restructuring extends to the executive level, with Robert Lenz, M.D., Ph.D., Neumora's head of R&D, departing to pursue other interests. Lenz will continue in an advisory role. This follows last month's CEO transition, where Paul Berns, co-founder and executive board chair, replaced Henry Gosebruch.

Financial Outlook

Despite the trial delays, Neumora reports that both KOASTAL-2 and KOASTAL-3 readouts should still be covered by its current cash reserves of $307.6 million. This financial cushion allows the company to implement its revised strategy without immediate funding concerns.