Neumora Therapeutics (NMRA) investor relations material

Study background and objectives

• Agitation affects over 70% of Alzheimer's patients, with significant unmet need due to limited efficacy and tolerability of current treatments; prevalence is expected to rise as the population ages.

• Current treatments are limited, with the only approved therapy carrying a boxed warning for mortality in elderly dementia patients.

• NMRA-511 targets the V1a receptor, linked to anxiety and aggression, with preclinical and clinical evidence supporting its mechanism.

• Preclinical studies show V1aR antagonists reduce anxiety and aggression in animal models, and NMRA-511 reduced anxiety-related behaviors in marmosets without affecting locomotor activity or causing sedation.

Study design and patient population

• Phase 1b was a randomized, double-blind, placebo-controlled study with 40 Alzheimer's agitation patients on NMRA-511 and 40 on placebo for 8 weeks; Part A assessed safety in healthy elderly.

• Inclusion: adults 55–90 with mild-severe dementia and significant agitation; a pre-specified elevated anxiety subgroup was analyzed.

• Primary endpoint was change in CMAI total score from baseline to week eight; pre-specified analysis for patients with elevated anxiety (RAID ≥12).

• Baseline demographics were balanced, with slightly higher anxiety in the placebo group.

Efficacy results

• NMRA-511 showed a 15.7-point reduction in CMAI total score at week eight, with a Cohen's d of 0.2–0.23 in the total population, similar to Auvelity.

• In patients with elevated anxiety, a 20.1-point reduction was observed, with a Cohen's d of 0.51–0.64, surpassing previous benchmarks and outperforming comparators.

• Improvements were observed in both aggressive and non-aggressive agitation sub-scores, with significant reduction in aggression subscore.

• In the elevated anxiety subgroup, NMRA-511 achieved a placebo-adjusted CMAI reduction of -7.6 at week 6 and -5.6 at week 8, with effect sizes up to 0.64.