AC Immune has initiated a Phase 1 trial of its brain-penetrant NLRP3 inhibitor ACI-19764, with first results expected in the second half of 2026

AC Immune has dosed the first participant in a Phase 1 clinical trial of ACI-19764, an orally administered small molecule inhibitor of the NLRP3 inflammasome.

The study is evaluating safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers. It is being conducted in Europe and is structured in two parts: single ascending doses followed by multiple ascending doses.

Primary endpoints include safety and tolerability, alongside pharmacokinetics in plasma and cerebrospinal fluid. Secondary measures include assessment of target engagement through inhibition of IL-1β. Exploratory endpoints will examine the compound’s effect on immune-related fluid biomarkers.

Initial data are expected in the second half of 2026.

NLRP3 inhibitors are being investigated as a potential therapeutic class across a range of inflammatory, metabolic and neurodegenerative conditions. Chronic activation of the NLRP3 inflammasome has been linked to diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and frontotemporal dementia.

ACI-19764 is designed to penetrate the brain and selectively inhibit NLRP3 activity. In preclinical studies, the compound demonstrated high potency in human whole blood assays and showed brain exposure in animal models. The company also reported reductions in neuroinflammatory markers in vivo, including decreased activation of microglia and astrocytes.

Andrea Pfeifer, chief executive of AC Immune, said: “We are delighted to announce the dosing of the first participant in the Phase 1 trial in healthy volunteers of our lead NLRP3 inhibitor. This is another important milestone in demonstrating the power of AC Immune’s small molecule discovery capabilities for targeting key pathways that contribute to neurodegeneration and other diseases. Robust preclinical data have shown that ACI-19764 has best-in-class potential based on its potency and PK profile, as well as its ability to reduce neuroinflammation and limit neurodegeneration in vivo. This suggests ACI-19764 could have a disease-modifying effect relevant to neurodegenerative diseases, and we are looking forward to studying it further in the clinical setting.”

The programme expands AC Immune’s small molecule pipeline targeting neuroinflammation and related pathways in central nervous system disorders.