AC Immune has announced encouraging preliminary findings from its phase 1 first‑in‑human study of ACI‑19764, an orally administered small molecule inhibitor of the NLRP3 inflammasome.
The trial is assessing safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers in Europe. Early data show ACI‑19764 was safe and well tolerated across single ascending dose and multiple ascending dose cohorts, including doses up to 20mg per day, with a serum half‑life greater than 30 hours. Clear cerebrospinal fluid penetration was confirmed and daily doses ≤10mg achieved PK concentrations above the IC90. Blinded review of whole blood assay data indicated dose dependent inhibition of IL‑1beta release.
Recruitment has now begun for a phase 1b cohort involving patients with cardiovascular disease risk, defined by elevated high‑sensitivity C‑reactive protein and the presence of type 2 diabetes and/or obesity. Initial results from this group are expected before year end.
Martin Zügel, interim CEO of AC Immune SA, commented: “These first‑in‑human data for ACI‑19764 are encouraging, and represent not only an important milestone for this program, but also the wider clinical momentum of our wholly‑owned programs. Based on these preliminary results, and previous preclinical studies, we are now poised to deliver key clinical evidence of anti‑inflammatory activity (hsCRP inhibition) in the coming months. We believe ACI‑19764 has the potential to be a powerful NLRP3 inhibitor, and we look forward to further exploring its therapeutic potential.”
Francesca Capotosti, Senior Vice President, Research at AC Immune SA, explained: “Chronic inflammation causes or exacerbates many different conditions, including CNS diseases, and with ACI‑19764 we are able to precisely target the intracellular NLRP3 complex to inhibit the production of potentially harmful downstream pro‑inflammatory factors.”
Kirsten Scott, Clinical Lead at AC Immune SA, added: “NLRP3 inhibitors are a growing modality, and with such a wide range of potential therapeutic applications in neurodegenerative diseases and beyond, we are optimistic that ACI‑19764 can represent a transformational treatment option for patients with unmet medical needs.”
ACI‑19764 targets the NLRP3 inflammasome to reduce chronic inflammation associated with multiple inflammatory, metabolic and neurological disorders. Further results from the ongoing phase 1/1b study are expected in H1 2027.
