Neumora Starts Phase 2 Study of Navacaprant for Bipolar Depression

Neumora Therapeutics, Inc., a biopharmaceutical company based in Watertown, Massachusetts, has announced the commencement of a Phase 2 clinical trial to assess the safety and efficacy of navacaprant for bipolar depression. Navacaprant is a novel kappa opioid receptor (KOR) antagonist, taken orally at an 80 mg dosage once per day. Previously, navacaprant has shown promise in improving symptoms of major depressive disorder (MDD) in a Phase 2 study and is currently being evaluated in a Phase 3 study for MDD.

This new Phase 2 study aims to address the unmet needs of patients with bipolar depression, particularly focusing on the symptoms of depressed mood and anhedonia, which are often inadequately managed by existing treatments. The trial will involve approximately 60 patients experiencing moderate-to-severe depressive episodes, as indicated by a Montgomery–Åsberg Depression Rating Scale (MADRS) score of 25 or higher. The primary endpoint will be the change in MADRS score after six weeks, with secondary endpoints assessing the impact on anhedonia and other related measures. The top-line results from this study are expected in the second half of 2025.

Robert Lenz, M.D., Ph.D., Executive Vice President and Head of Research and Development at Neumora, emphasized that navacaprant’s unique mechanism could benefit multiple neuropsychiatric disorders. He highlighted the significant unmet needs in treating bipolar depression, particularly due to the atypical symptomatology and resistance to current treatment options that many patients experience. Dan Iosifescu, M.D., a professor in the Department of Psychiatry at NYU Grossman School of Medicine, echoed these sentiments, noting the urgency for new treatment approaches. He pointed out that current therapies often require patients to try multiple medications, which impacts their quality of life and functional abilities. Research suggests that KOR antagonism could play a crucial role in alleviating depressive symptoms and anhedonia, reinforcing the potential of navacaprant.

Neumora Therapeutics, founded to tackle the global brain disease crisis, focuses on developing treatments for various neuropsychiatric and neurodegenerative diseases. Their pipeline includes seven clinical and preclinical programs targeting novel mechanisms of action. The company leverages a range of translational, clinical, and computational tools to support precision medicine approaches, aiming to redefine neuroscience drug development and improve outcomes for patients with brain diseases.

Navacaprant (NMRA-140) targets the KOR system, a well-characterized pathway known to mediate depressive-like states. By modulating this system, navacaprant aims to address mood, cognition, reward, and behavior, presenting a novel approach to treating MDD and bipolar depression. Bipolar disorder is characterized by extreme mood swings, including periods of mania and depression. Bipolar II disorder, in particular, involves depressive and hypomanic episodes without full manic episodes. Despite available treatments like mood stabilizers, antidepressants, and antipsychotics, many patients do not respond adequately, necessitating multiple lines of therapy. This often results in negative outcomes, underlining the need for new therapeutic options.

Neumora’s mission is to bring forward innovative therapies that enhance treatment outcomes and quality of life for patients suffering from brain diseases. Their integrated approach aims to generate insights that can enable precision medicine, offering hope for those with unmet needs in neuropsychiatric treatment.