Neumora Restructures Phase III Depression Trials Following Setback

Neumora Therapeutics, a biopharmaceutical company focused on neuroscience, has announced significant changes to its clinical trial program for navacaprant, a promising drug candidate for major depressive disorder (MDD). This restructuring comes in the wake of disappointing results from a recent Phase III study.

KOASTAL Program Adjustments

After failing to meet the primary endpoint in the KOASTAL-1 trial earlier this year, Neumora has temporarily halted two ongoing Phase III trials, KOASTAL-2 and KOASTAL-3, to implement strategic modifications. The company aims to strengthen the study design and improve the likelihood of success for navacaprant, a kappa opioid receptor (KOR) antagonist designed to modulate dopamine and reward processing pathways.

Key changes to the KOASTAL program include:

• Reducing the number of clinical trial sites
• Implementing enhanced medical monitoring through the Massachusetts General Hospital Trials network
• Introducing a new screening tool to prevent participant overlap across multiple clinical trials

These adjustments are expected to delay the availability of topline data, with results now anticipated in the first half of 2026. Neumora's CEO expressed confidence in the revised approach, stating, "We believe these changes strengthen the studies and look forward to delivering topline data in 2026."

Pipeline Reprioritization

In conjunction with the KOASTAL program restructuring, Neumora has made strategic decisions regarding other pipeline assets:

1. The company has discontinued a Phase II trial of navacaprant for bipolar depression, choosing to concentrate resources on the core MDD indication.

2. Development continues for NMRA-511, a vasopressin 1a receptor (V1aR) antagonist targeting Alzheimer's disease agitation. A Phase Ib study is ongoing, with data expected by the end of 2025.

3. Progress on NMRA-266, a schizophrenia candidate, has been impacted by an FDA clinical hold imposed in April 2024 due to safety concerns observed in preclinical studies.

Market and Analyst Perspectives

Despite the setbacks, market analysts remain cautiously optimistic about Neumora's prospects. William Blair analysts noted that the company's decision to optimize site selection and enhance medical monitoring for the KOASTAL trials is based on thorough analyses of the KOASTAL-1 results.

The restructuring of Neumora's clinical programs highlights the challenges and adaptability required in neuroscience drug development, as the company works to address the significant unmet need in major depressive disorder treatment.