NMRA-511 · program
NMRA-511 for Agitation in Alzheimer's disease
NMRA-511 for agitation associated with Alzheimer's disease dementia. Phase 1b signal-seeking study (NCT06546995) reported positive topline on 2026-01-05, meeting its goal with a clinically meaningful placebo-adjusted CMAI reduction (notably in an elevated-anxiety subgroup) and a favorable safety/tolerability profile with no somnolence or sedation. Neumora plans to report data from a multiple ascending dose (MAD) expansion cohort evaluating higher doses in 2H 2026 and to initiate a Phase 2 study in Alzheimer's disease agitation in Q1 2027; an extended-release once-daily formulation is in development. Phase remains phase_1 because Phase 2 has not yet started.
Development timeline
- UpcomingAnticipated initiation of a Phase 2 study of NMRA-511 in Alzheimer's disease agitation, planned for Q1 2027.↗
- UpcomingAnticipated readout from a multiple ascending dose (MAD) expansion cohort evaluating higher doses of NMRA-511, expected in 2H 2026.↗
- metNMRA-511 Phase 1b signal-seeking study in Alzheimer's disease agitation met its goal: clinically meaningful placebo-adjusted CMAI reductions (notably 7.6/5.6 points at weeks 6/8 in the elevated-anxiety subgroup), favorable safety, no somnolence/sedation.↗
- Phase 1b study NCT06546995 reached primary completion (per ClinicalTrials.gov), with overall status COMPLETED.
- Phase 1b signal-seeking study (NCT06546995) initiated; two-part design (Part A: ~8 healthy elderly safety/PK; Part B: AD agitation efficacy at NMRA-511 20 mg BID). A prior Phase 1a in 92 healthy adults (doses 5-40 mg, well tolerated, no SAEs) preceded it; no NCT located for the Phase 1a.↗
Readouts
- Q1 2027AnticipatedRegistry results
Anticipated initiation of a Phase 2 study of NMRA-511 in Alzheimer's disease agitation, planned for Q1 2027. ↗
- 2H 2026AnticipatedInterim analysis
Anticipated readout from a multiple ascending dose (MAD) expansion cohort evaluating higher doses of NMRA-511, expected in 2H 2026. ↗
- 2026-01-05ReportedTopline datametNCT06546995
NMRA-511 Phase 1b signal-seeking study in Alzheimer's disease agitation met its goal: clinically meaningful placebo-adjusted CMAI reductions (notably 7.6/5.6 points at weeks 6/8 in the elevated-anxiety subgroup), favorable safety, no somnolence/sedation. ↗
Clinical trials in Agitation in Alzheimer's disease
NCT06546995Phase 1Completedn=87
A Phase 1b, Randomized, Double-blind, Placebo-controlled Pilot Study to Evaluate the Effects of NMRA-323511 Among Healthy Elderly and Adults With Agitation Associated With Dementia Due to Alzheimer's Disease
metefficacyChange from baseline in Cohen-Mansfield Agitation Inventory (CMAI), modified analysis set (NMRA-511 20 mg BID vs placebo) — Placebo-adjusted CMAI reduction -2.6 at week 6 and -2.1 at week 8 (Cohen's d 0.20-0.23); n=71
In the modified analysis set (n=71), twice-daily NMRA-511 produced clinically meaningful placebo-adjusted CMAI reductions of 2.6 points at week 6 and 2.1 points at week 8. The study was signal-seeking and not powered for statistical significance, so no p-values were reported. The company characterized the study as having met its goal.
metsafetySafety and tolerability (TEAEs, discontinuations, somnolence/sedation) — Discontinuations due to TEAEs 2.5%; no somnolence or sedation reported
Favorable tolerability and safety profile: treatment-emergent adverse events generally mild to moderate; low discontinuation due to TEAEs (2.5%); notably no reports of somnolence or sedation. Common AEs (>5%) included nasopharyngitis, UTI, anemia, arthralgia, diarrhea, dizziness, headache, hyponatremia, myalgia, nausea, vomiting, and abdominal pain.
metefficacy_subgroupChange from baseline in CMAI, elevated-anxiety subpopulation (Rating Anxiety in Dementia score >=12) — Placebo-adjusted CMAI reduction -7.6 at week 6 and -5.6 at week 8 (Cohen's d 0.51-0.64); n=36
In the prespecified elevated-anxiety subgroup (n=36; Rating Anxiety in Dementia score >=12), NMRA-511 produced larger placebo-adjusted CMAI reductions of 7.6 points at week 6 and 5.6 points at week 8 (Cohen's d 0.51-0.64), supporting a precision-targeted, anxiety-driven agitation hypothesis. Signal-seeking study; no p-values reported.
Mechanism of action
Highly potent, selective, brain-penetrant antagonist of the vasopressin 1a receptor (V1aR / AVPR1A), a Gq-coupled GPCR implicated in regulation of aggression, affiliation, stress and anxiety/threat responses. Antagonism of V1aR is hypothesized to reduce agitation symptoms, including in anxiety-driven agitation in Alzheimer's disease. Reported preclinical selectivity: >3,000-fold over V1b (AVPR1B) and V2 (AVPR2) receptors and ~300-fold over the oxytocin receptor.
| Target | Action | Affinity |
|---|---|---|
| V1a receptorprimaryAVPR1A | Antagonist | —ⓘ |
← Full NMRA-511 compound page (identity, identifiers, all indications)
Sources
- A Phase 1b, Randomized, Double-blind, Placebo-controlled Pilot Study to Evaluate the Effects of NMRA-323511 Among Healthy Elderly and Adults With Agitation Associated With Dementia Due to Alzheimer's Disease — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06546995 - NMRA-323511 in healthy elderly and adults with agitation due to Alzheimer's disease (study record) — ClinicalTrials.gov (U.S. National Library of Medicine)
- Neumora Therapeutics Announces Initiation of Phase 1b Study of NMRA-511 for Treatment of Alzheimer's Disease Agitation — Neumora Therapeutics, Inc. (Investor Relations)
- Neumora Therapeutics Announces Positive Results from NMRA-511 Phase 1b Signal-Seeking Study in Alzheimer's Disease Agitation — Neumora Therapeutics, Inc. (Investor Relations)
- Neumora Therapeutics Announces Positive Results from NMRA-511 Phase 1b Signal-Seeking Study in Alzheimer's Disease Agitation — Neumora Therapeutics, Inc. (via GlobeNewswire)
- NMRA-511 drug profile and latest updates (MAD expansion 2H 2026; Phase 2 Q1 2027 guidance) — Synapse (PatSnap)