Neumora Sees 20-Point CMAI Reduction for NMRA-511, Targets Higher Doses in 2026
In a phase 1b Alzheimer’s agitation trial, NMRA-511 produced a 20.1-point CMAI total score reduction at week eight (Cohen’s d 0.51–0.64) and a 0.82 aggression effect size, with no major CNS tolerability issues. Neumora plans a higher-dose multiple-ascending-dose cohort in 2026 and has cash to fund operations through Q3 2027.
1. Phase 1b Agitation Signal
NMRA-511 generated effect sizes of 0.46 on elevated-anxiety NPI agitation at week eight and 0.78 at week six and 0.38 at week eight on CGI-S in the prespecified elevated-anxiety subgroup. The drug also achieved a 20.1-point reduction on the CMAI total score (Cohen’s d 0.51–0.64) and a 0.82 effect on the CMAI aggression subscale.
2. Safety and Tolerability
The phase 1b study reported a favorable safety and tolerability profile, with no increased incidence of typical CNS adverse events such as headaches. A single serious adverse event of hyponatremia was observed but was attributed to confounding factors and not viewed as mechanistic.
3. Upcoming NMRA-511 Development Plans
Neumora plans to initiate a higher-dose multiple-ascending-dose cohort for NMRA-511 in 2026 and transition from a twice-daily to a once-daily extended-release formulation for pivotal studies in 2027, extending composition-of-matter exclusivity to 2046. Modeling suggests ~98% receptor occupancy at 40 mg doses, and future trials will stratify baseline anxiety for balanced cohorts.
4. Broader Pipeline and Cash Runway
The company expects a mid-2026 update on its M4 PAM program, a combined KOASTAL 2 & 3 readout in Q2 2026, and Q3 2026 biomarker data for NLRP3 inhibitor NMRA-215 targeting weight loss. Cash on hand is projected to fund operations into Q3 2027, covering these catalysts.