EDP167, an ANGPTL3-target siRNA, showed favorable safety and lipid-lowering potential in Chinese healthy adult volunteers and subjects with mild dyslipidemia
J Wang, B Jiang, S L Zhong, H Wang, J LiuAbstract
Background
Angiopoietin-like 3 protein (ANGPTL3) is a key regulator of lipid metabolism. Clinical studies have shown that inhibition of ANGPTL3 could exert lipid-lowering effects in patients with dyslipidemia. EDP167 is a novel GalNAc-conjugated small interfering RNA (siRNA) therapeutic that selectively silences hepatic ANGPTL3 mRNA expression, offering a promising strategy for lipid lowering.
Purpose
The primary objective was to evaluate the safety and tolerability of a single dose of EDP167 in healthy adult volunteers and subjects with mild dyslipidemia (defined as 1.13 mmol/L≤TG<5.6 mmol/L and 1.8 mmol/L≤LDL-C<4.9 mmol/L). The secondary objectives included pharmacokinetic (PK) profile and pharmacodynamic (PD) effects (ANGPTL3, LDL-C, TG, and other lipid parameters) following a single subcutaneous injection of EDP167.
Methods
This was a phase 1, randomized, double-blind, placebo-controlled, single ascending dose (SAD) study. Subjects were sequentially enrolled into five cohorts (35, 100, 200, 300 or 400 mg). Each cohort consisted of six subjects receiving EDP167 and two receiving matching placebos.
Results
Between July 2025 and December 2025, a total of 40 subjects were enrolled and completed the 85-day follow-up. EDP167 was well tolerated across single doses ranging from 35 mg to 400 mg. All adverse events (AEs) were mild or moderate in severity, mostly transient and resolved spontaneously without intervention. There were no serious AE, death, or reports of injection site reactions. Exposure (Cmax and AUC) increased in a linear dose dependent manner over the 35 mg to 400 mg dose range. A single dose of EDP167 resulted in a dose-dependent reduction in serum ANGPTL3, with maximum mean reductions ranging from -69.03% to -87.52%, and these reductions persisted through the end of the study (Day 85, mean reductions -30.78% to -75.58%). EDP167 also led to substantial reductions in lipid parameters, especially within the 100 mg to 400 mg dose range, with maximum mean reductions in TG (-54.47% to -60.66%), LDL-C (-28.12% to -43.42%), non-HDL-C (-30.08% to -43.75%), ApoB (-20.95% to -31.33%) and remnant-C (-31.60% to -78.08%). No anti-drug antibody (ADA) was detected within the 35 mg to 300 mg dose range.
Conclusion
In healthy volunteers and subjects with mild dyslipidemia, single subcutaneous doses of EDP167 (35 mg to 400 mg) demonstrated a favorable safety and tolerability profile. A dose-dependent reduction in ANGPTL3 and substantial reductions in TG, LDL-C, non-HDL-C, ApoB and remnant-C were observed. As an early-phase clinical study, these results suggest potential clinical efficacy and lay a critical foundation for further development of EDP167 as a novel lipid-lowering agent.PD effects after a single dose of EDP167