AC Immune Doses First Participant in Phase 1 Brain-Penetrant NLRP3 Trial
AC Immune has dosed the first participant in its Phase 1 trial of ACI-19764, an orally administered, highly brain-penetrant NLRP3 inhibitor, with healthy volunteer safety and pharmacokinetic data expected in H2 2026. Preclinical studies showed ACI-19764 achieved IC50s of 2-20.5nM, Kp,uu values of 0.71 in rat brain and 1 in dog CSF, and weight-control effects in diet-induced obesity models.
1. Phase 1 Trial Initiation
AC Immune has initiated a Phase 1 clinical trial of ACI-19764, dosing the first healthy volunteer in Europe. The study will assess safety, tolerability, pharmacokinetics and pharmacodynamics across single and multiple ascending dose cohorts, with cerebrospinal fluid sampling to evaluate target engagement.
2. Preclinical Profile of ACI-19764
ACI-19764 is an orally available small molecule designed to inhibit the NLRP3 inflammasome with high brain penetrance. Preclinical data demonstrate an IC50 range of 2–20.5nM, Kp,uu values of 0.71 in rat brain and 1 in dog CSF, robust reduction of neuroinflammation, and weight-control benefits in diet-induced obesity models.
3. Next Steps and Outlook
Initial Phase 1 data are slated for release in the second half of 2026, after which AC Immune plans to advance ACI-19764 into patient studies targeting neurodegenerative and metabolic inflammatory disorders. This trial represents a key milestone for the company’s small molecule pipeline expansion.