AC Immune reported positive Phase I first-in-human data for oral ACI-19764: the drug was safe and well tolerated at doses up to 20 mg/day in healthy volunteers and showed cerebrospinal fluid exposure, confirming blood–brain barrier penetration. Early pharmacodynamic signals demonstrated dose-dependent modulation of IL-1β, consistent with NLRP3 inflammasome inhibition. Patient dosing has begun in individuals with type 2 diabetes and/or obesity at elevated cardiovascular risk, and full Phase I/Ib results are expected in H1 2027.
AC Immune’s ACI-19764 Shows CNS Penetration and Strong Phase I Safety Signals; Patient Dosing Underway
AC Immune is now dosing patients in the study following positive results in a cohort of healthy volunteers. Credit: SergioVas / Shutterstock.com.
Swiss biopharmaceutical company AC Immune has reported positive first-in-human Phase I results for its oral anti-inflammatory candidate ACI-19764, and has begun dosing the first patient cohorts as it advances into Phase I/Ib testing.
Phase I Healthy Volunteer Readout
In the European first-in-human study (NCT07463196), investigators evaluated pharmacokinetics (PK), safety, tolerability and pharmacodynamics (PD) of single and multiple ascending doses of ACI-19764 in healthy volunteers. Preliminary data show the drug was well tolerated at doses up to 20 mg per day, with no severe adverse events attributed to the compound and no discontinuations for safety reasons to date.
CNS Exposure And Target Engagement
Importantly, ACI-19764 was detected in cerebrospinal fluid (CSF), demonstrating penetration of the blood–brain barrier — a key requirement for potential neurodegenerative indications. Early pharmacodynamic signals also indicated dose-dependent modulation of IL-1β release, a pro-inflammatory cytokine downstream of the NLRP3 inflammasome that ACI-19764 is designed to inhibit.
Translational Rationale And Next Steps
By inhibiting NLRP3-driven inflammation, AC Immune believes ACI-19764 could have applications across inflammation-driven conditions, including metabolic and neurological diseases. Following the favourable healthy volunteer data, the company has started dosing patients with type 2 diabetes and/or obesity who are at elevated cardiovascular risk as defined by high levels of an inflammation-associated protein.
Jefferies analysts described the early Phase I readout as offering "encouraging validation" of ACI-19764’s activity, citing CNS penetration, initial target engagement and the potential for efficacy at a low once-daily dose while noting that the programme remains at an early stage and comparative positioning is still unclear.
AC Immune expects to present full Phase I/Ib results in the first half of 2027. Observers will be watching the forthcoming patient data to better understand the drug's potential efficacy, dose optimization and competitive positioning in the inflammation and neurodegeneration landscape.
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