Neumora Therapeutics (NMRA) Status Update summary

Program overview and unmet need

• Brain diseases affect over 1.5 billion people globally and are a leading cause of disability, with major depressive disorder (MDD) impacting more than 280 million people worldwide.

• Current MDD treatments often fail to address core symptoms like anhedonia, with up to 85% of patients not achieving remission or discontinuing due to side effects.

• Navacaprant, a highly selective kappa-opioid receptor antagonist, is being developed as a once-daily oral monotherapy for MDD and other neuropsychiatric disorders.

Clinical data and differentiation

• Phase II studies showed navacaprant significantly improved depressive symptoms and anhedonia, with a favorable safety profile and no weight gain or sexual dysfunction.

• Navacaprant demonstrated robust efficacy on multiple depression scales (HAM-D17, SHAPS, HAM-D6), with higher response and remission rates compared to placebo.

• The drug's 300-fold selectivity for kappa over mu-opioid receptors may allow higher dosing and fewer side effects than other KOR antagonists.

Phase III COASTAL Program design

• The COASTAL Program includes three replicate phase III, randomized, double-blind, placebo-controlled studies (COASTAL-1, -2, -3) and a long-term safety extension (COASTAL-LT).

• Primary endpoint is change in MADRS score at week six; key secondary endpoint is change in SHAPS score, targeting both depressive symptoms and anhedonia.

• Studies are powered at 90% for the primary outcome and incorporate advanced placebo mitigation and real-time data oversight to ensure trial integrity.