Positive Ph1 results for AC Immune's NLRP3 inflammasome inhibitor

AC Immune SA, a clinical-stage biopharmaceutical company developing targeted therapeutics for neurodegenerative diseases, has announced positive interim results from a Phase 1 study of ACI-19764 – its wholly-owned NLRP3 inflammasome inhibitor targeting chronic inflammation across inflammatory, metabolic, and neurological diseases.

ACI-19764 is an orally available, brain penetrant, small molecule drug candidate that specifically inhibits the NLRP3 inflammasome. It has shown high potency in vitro as demonstrated by the downstream inhibition of IL-1β production by human macrophages and human whole blood with an IC50 in the range of 2-20.5nM.

ACI-19764 statistically significantly inhibited neuroinflammation in vivo through reduced activation of Iba1+ microglial cells and GFAP+ astrocytes in preclinical models (including experimental autoimmune encephalitis (EAE) and chronic LPS-mediated central nervous system (CNS) inflammation).

The Phase 1 study is investigating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ACI-19764 in healthy volunteers in Europe, and Part 1 showed ACI-19764 was safe and well tolerated across both single and multiple ascending does cohorts, including doses up to 20 mg per day (SAD), with a serum half-life greater than 30 hours. Clear evidence of brain penetration was observed based on cerebrospinal fluid (CSF) exposure.

The trial has now commenced dosing of first patients with cardiovascular disease risk, as determined by elevated serum levels of high-sensitivity C-reactive protein (hsCRP) and the presence of either type 2 diabetes and/or obesity. Recruitment of this Phase 1b cohort is ongoing and initial results are expected before year end.

ACI-19764 targets the NLRP3 inflammasome to inhibit the production of pro-inflammatory factors and reduce chronic inflammation thought to be associated with disease progression in multiple inflammatory disorders, metabolic diseases, and neurological diseases. Supported by a strong preclinical data package (including 3-month toxicology data), ACI-19764 continues to advance through its Phase 1/1b clinical study, with additional data expected in H1 2027.

Martin Zügel, interim CEO of AC Immune SA, commented: “This first-in-human data for ACI-19764 is encouraging, and represents not only an important milestone for this programme, but also the wider clinical momentum of our wholly-owned programmes.”

AC Immune has a growing focus on its wholly owned proprietary clinical-stage programmes, including: ACI-7104, an active immunotherapy targeting α-synuclein (α-syn) in Parkinson's disease; and ACI-19764, a small molecule inhibitor of the NLRP3 inflammasome.

In December 2025, AC Immune announced that its vaccine-like α-syn-targeted immunotherapy had shown promise in slowing down the progression of Parkinson's disease. The results of the phase 2 VacSYn trial of ACI-7104.056 in patients with early-stage Parkinson's showed that the immunotherapy can reduce disease-related biomarkers – namely alpha-synuclein levels in the cerebrospinal fluids (CSF) and neurofilament light (NfL) – that AC Immune said pointed to a "stabilisation" of the Parkinson's disease process.

Previous chief executive Dr Andrea Pfeifer – now chief scientific officer at Women’s Health Access Matters – said the new data held "the promise of a tremendous step forward for millions of patients."