Neumora Therapeutics (NMRA) Stifel 2024 Healthcare Conference summary

Pipeline overview and clinical updates

• Seven programs in the pipeline, all targeting novel mechanisms for brain diseases.

• Lead asset navacaprant is in three parallel phase III trials for MDD, with top-line data from KOASTAL I expected around year-end 2024 and KOASTAL II/III in the first half of 2025.

• Navacaprant is also in phase II for bipolar depression, with data expected in the second half of 2025.

• NMRA-511, a V1a receptor antagonist for Alzheimer's agitation, is in phase 1b with data expected in the second half of 2025.

• Early pipeline includes neurodegenerative targets like NLRP3, GCase, and CK1 delta.

Study design and execution strategies

• KOASTAL studies powered at 90% to detect a 3.2-point placebo-adjusted change on MADRS at week six.

• Phase III design changes include switching primary endpoint from HAM-D17 to MADRS and shortening the primary endpoint to six weeks to reduce placebo response.

• Enhanced site selection, use of central raters, and digital compliance monitoring (AiCure app) implemented.

• Placebo-controlled reminder scripts used to minimize expectation bias.

• Flexibility to increase sample size by 20-25% built into protocols.

Competitive landscape and differentiation

• Navacaprant is 300-fold selective for kappa over mu opioid receptors, potentially reducing side effects like pruritus compared to less selective competitors.

• Aticaprant's recent randomized withdrawal study seen as a bullish signal for the class.

• Navacaprant's lack of itch signal at clinical doses attributed to its selectivity.