Neumora Therapeutics NMRA-511 Alzheimer's Study Shows Positive Results

Neumora Therapeutics announced results from its Phase 1b signal-seeking study of NMRA-511 in people with Alzheimer's disease agitation. NMRA-511, an oral, highly potent, brain-penetrant and selective antagonist of the vasopressin 1a receptor met the goal of the Phase 1b study, demonstrating a clinically meaningful effect size in people with AD agitation. In the study, NMRA-511 demonstrated a favorable tolerability and safety profile with no reports of somnolence or sedation. The Phase 1b study investigated NMRA-511 in healthy elderly adult participants as well as people with agitation associated with dementia due to AD. Part A was a randomized, double-blind, placebo-controlled cohort designed to evaluate the safety, tolerability and pharmacokinetics of NMRA-511 in eight healthy elderly participants. Part B was a multicenter, randomized, double-blind, placebo-controlled, parallel-group cohort designed to evaluate the safety, tolerability, and efficacy of NMRA-511 20 mg twice-daily in 80 people with AD agitation. The Phase 1b study was designed as a signal-seeking study to demonstrate a clinical effect and was not powered for statistical significance. Key findings from Part B of the Phase 1b study include: 71 patients were included in the efficacy analysis. 36 patients were included in the pre-specified sub-population of patients with elevated anxiety at baseline. In the MAS, patients treated with NMRA-511 demonstrated a -2.6 and -2.1 placebo-adjusted change from baseline on CMAI total score at Weeks 6 and 8 respectively, representing a Cohen's d effect size range of 0.20 - 0.23. In the elevated anxiety population, NMRA-511 demonstrated a -7.6 and -5.6 placebo-adjusted change from baseline on CMAI total score at Weeks 6 and 8 respectively, representing a Cohen's d effect size range of 0.51 - 0.64. NMRA-511 demonstrate a favorable tolerability and safety profile. Treatment emergent adverse events were typically mild to moderate in severity, and there were low treatment discontinuations due to TEAEs. The most common adverse effects in the study were nasopharyngitis, urinary tract infection, anemia, arthralgia, diarrhea, dizziness, headache, hyponatremia, myalgia, nausea, vomiting and abdominal pain. Neumora intends to advance the development of NMRA-511. The following next steps are planned for the program: Initiate a multiple ascending dose extension study investigating higher doses of NMRA-511 in 2026. Formulation development to enable once-daily dosing via an extended-release formulation of NMRA-511 in 2026. Initiate a Phase 2/3 dose ranging study with NMRA-511.