A Phase 1, multicenter study evaluated safety, tolerability, pharmacokinetics, and early biomarker effects of nimacimab, a peripherally restricted CB1 receptor antibody, in 83 adults with metabolic-associated fatty liver disease (MAFLD). Findings from this Phase 1 trial of nimacimab in MAFLD were presented at EASD 2025, highlighting its favorable safety profile and early biomarker effects.

Participants received weekly IV doses of 0.6, 1.2, or 2.5 mg/kg nimacimab, or placebo, for 4 weeks, with follow-up through Day 67. Nimacimab was well tolerated at all doses, with no deaths, serious adverse events, or discontinuations. Most treatment-emergent adverse events were mild, including dizziness, headache, and gastrointestinal complaints. Only two participants developed persistent anti-drug antibodies, which minimally affected drug exposure. Pharmacokinetics showed a half-life of 18–22 days, consistent with other IgG therapeutics.

Exploratory biomarker analyses revealed promising trends: dose-dependent reductions in LDL cholesterol, hyaluronic acid (adipose tissue fibrosis marker), ALT, and ELF scores. Participants receiving nimacimab also experienced modest weight loss without dietary intervention.

These results indicate that nimacimab has a favorable safety profile and may beneficially modulate metabolic and fibrosis-related biomarkers in MAFLD. Ongoing Phase 2 trials are exploring its potential for weight loss and broader metabolic disease management.