Phase I Study Finds Sustained AGT Suppression With ART101

Angiotensinogen (AGT) is a precursor in the renin-angiotensin-aldosterone system. This phase I study, conducted at a Beijing hospital from January 2025 to April 2026, evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of ART101, a GalNAc-conjugated siRNA targeting hepatic AGT. In a double-blind, placebo-controlled study, 40 healthy adults received a single dose of 25–600 mg or placebo; a separate open-label group included 8 patients with hypertension who received 600 mg. Follow-up lasted 24 weeks.

Treatment-emergent adverse events occurred in 23 of 30 active-treatment participants (76.7%) and 7 of 10 placebo recipients (70.0%); 6 of 8 patients in the hypertension group reported events. All were mild to moderate. No serious adverse events, injection-site reactions or hyperkalemia were observed. At 600 mg, mean maximum serum AGT reductions were 93% in healthy volunteers and 90% in patients with hypertension. At 24 weeks, placebo-corrected 24-hour ambulatory systolic blood pressure was 12.9 mm Hg lower in healthy participants.

These early findings support further study but do not establish blood pressure efficacy or long-term safety in people with hypertension. The hypertension group was small and open-label, and blood pressure findings were exploratory. The study was registered as CTR20250041 and CTR20253973.