Neumora Therapeutics (NMRA) H.C. Wainwright 27th Annual Global Investment Conference summary

NLRP3 inhibitor program in obesity

• NLRP3 mechanism targets CNS-mediated pathways, aiming to suppress appetite by acting on the hypothalamus, offering a novel approach distinct from gut-hormone-based therapies.

• The oral small molecule is designed for high brain penetration, affordability, and ease of use, potentially providing a more convenient alternative to injectables.

• Preclinical DIO mouse model data expected later this year will inform clinical development, with plans to initiate first-in-human trials in Q1 2026.

• Three clinical paradigms are planned: monotherapy, combination with GLP-1s to reduce side effects, and maintenance therapy post-GLP-1 induction.

• The molecule may offer benefits such as reduced GI side effects and lean muscle mass sparing, addressing key limitations of current incretin therapies.

Broader metabolic and comorbidity potential

• NLRP3 inhibitors may provide additional benefits in cardioprotection, osteoarthritis, and other comorbidities beyond obesity.

• The therapy could improve patient experience by reducing GI adverse events and potentially sparing lean muscle mass.

• Dose flexibility may allow tailored weight loss rates for diverse patient needs, including those with NASH.

• Key opinion leaders are interested in exploring NASH as a future indication, with potential for IND-enabled and phase 4 studies.

M4 PAM franchise development

• Two new M4 positive allosteric modulators (PAMs), 861 (in phase 1) and 898 (to enter clinic by year-end), have been developed with improved safety and brain penetration.

• The franchise approach aims to address multiple neuropsychiatric and neurodegenerative indications, starting with schizophrenia and potentially expanding to dementia-related psychosis and bipolar disorder.

• Phase 1 studies in stable schizophrenia patients will focus on dose tolerance, PK, and side effect profiles, with prioritization of the lead asset for proof-of-concept studies.