AC Immune SA (Nasdaq: ACIU) reported that its oral NLRP3 inflammasome inhibitor ACI-19764 was safe and well-tolerated across single and multiple ascending dose cohorts in a first-in-human Phase I study, with cerebrospinal fluid penetration confirmed — a finding that supports the molecule's intended use in neurological disease.
ACI-19764 is being developed as a brain-penetrant NLRP3 inhibitor for potential use across neurodegenerative diseases including Alzheimer's and Parkinson's disease, rather than for a single indication at this stage. The cardiovascular-risk Phase Ib cohort provides an earlier opportunity to establish whether NLRP3 inhibition produces measurable anti-inflammatory effects in patients before the program advances into neurological efficacy studies.
The Phase I/Ib trial (NCT07463196) is a single-center, double-blind, randomized, placebo-controlled study enrolling up to 78 healthy participants in Europe, with primary endpoints of safety, tolerability, pharmacokinetics (PK), and pharmacodynamics. Preliminary data showed no serious adverse events and no treatment withdrawals across doses up to 20 mg per day in the single ascending dose cohorts. Serum half-life exceeded 30 hours, and daily doses of 10 mg or below achieved plasma concentrations above the IC90. A blinded review of whole blood assay data indicated dose-dependent inhibition of IL-1β release, consistent with on-target NLRP3 engagement, though causal attribution to treatment cannot be drawn from blinded data.
The Lausanne, Switzerland-based company said CSF penetration was confirmed, a prerequisite for any central nervous system application. Based on the PK profile, AC Immune said it expects the therapeutic dose to be 10 mg or below once daily. The trial has now expanded into a Phase Ib cohort enrolling patients with cardiovascular disease risk, defined by elevated high-sensitivity C-reactive protein (hsCRP) combined with type 2 diabetes and/or obesity. Initial hsCRP data from this cohort — intended to provide early evidence of anti-inflammatory activity in a disease-relevant population — are expected before the end of 2026, with full Phase I/Ib results anticipated in H1 2027.