Edding Genor's EDP167 Clinical Trial Enters a Crowded Race to Silence ANGPTL3
Edding Genor Group Holdings Limited, the Hong Kong-listed specialty pharmaceutical company, has completed a first-in-human Phase I study of EDP167, a GalNAc-conjugated small interfering RNA designed to silence hepatic expression of angiopoietin-like protein 3. The EDP167 clinical trial (NCT07412080), conducted at two sites in China, enrolled 40 healthy adults and subjects with mild dyslipidemia across five ascending dose cohorts. According to the registry listing, the study reached its primary completion date in December 2025, and the company disclosed in a February 2026 Hong Kong Stock Exchange filing that it had already dosed the first patient in a Phase II trial of EDP167 in homozygous familial hypercholesterolemia. The speed of that transition — from completed single-ascending-dose study to Phase II initiation in a rare, severe lipid disorder — signals confidence in the early safety data, though no results from the Phase I study have been posted publicly.
The trial matters less for what it tells us about EDP167 specifically, since efficacy and safety data remain undisclosed, and more for what it reveals about the intensifying global competition around ANGPTL3 as a drug target and the expanding role of Chinese biotech companies in RNA therapeutics.
Why ANGPTL3 Attracts So Many Programs
ANGPTL3 is a liver-secreted glycoprotein that acts as a natural brake on two enzymes central to lipid clearance: lipoprotein lipase, which hydrolyzes triglyceride-rich lipoproteins, and endothelial lipase, which participates in HDL remodeling. Individuals carrying loss-of-function mutations in the ANGPTL3 gene have lower levels of LDL cholesterol, triglycerides, and VLDL cholesterol without apparent adverse health consequences — a human genetic validation that has driven substantial pharmaceutical investment.
The critical feature that distinguishes ANGPTL3 targeting therapy from the dominant lipid-lowering paradigm is its independence from the LDL receptor pathway. Statins, ezetimibe, and PCSK9 inhibitors all ultimately depend on upregulating or preserving LDL receptor activity to clear circulating LDL particles. In patients with homozygous familial hypercholesterolemia, where LDL receptor function is absent or severely impaired, these agents are partially or wholly ineffective. Regeneron's evinacumab, a monoclonal antibody against ANGPTL3 protein approved by the US FDA in 2021 for HoFH, demonstrated that blocking this target can reduce LDL-C by roughly 47% even in patients with null-null LDLR genotypes. That approval established clinical proof of concept for the pathway but also exposed practical limitations: evinacumab requires monthly intravenous infusions and carries a US list price exceeding $450,000 per year.
RNA interference offers a potential solution to both problems. A GalNAc siRNA targeting ANGPTL3 mRNA, delivered by subcutaneous injection at quarterly or semi-annual intervals, could replicate the lipid-lowering biology of evinacumab with a dosing schedule and route of administration closer to what patients and payers have come to expect from inclisiran, Novartis's twice-yearly PCSK9 siRNA.
Design of the Phase I Study
The NCT07412080 trial used a sequential, randomized, quadruple-masked, placebo-controlled design. Five dose cohorts — 35, 100, 200, 300, and 400 mg — each enrolled eight subjects, with six receiving a single subcutaneous injection of EDP167 and two receiving a matching volume of normal saline. Eligible participants were adults aged 18 to 60 with a body mass index between 18.0 and 35.0 kg/m², fasting triglycerides between 1.13 and 5.6 mmol/L, and fasting LDL-C between 1.8 and 4.9 mmol/L. These lipid thresholds ensured that most enrollees had at least mildly abnormal lipid profiles, providing a pharmacodynamic signal window while avoiding the ethical complexities of withholding treatment in patients with established cardiovascular disease.
The primary endpoint was safety and tolerability over 85 days, assessed by adverse events, laboratory abnormalities, ECG changes, and physical examination findings. Secondary endpoints covered a broad pharmacokinetic panel — Cmax, Tmax, AUC, half-life, clearance, and volume of distribution, all measured within the first 48 hours — alongside pharmacodynamic assessments of ANGPTL3 protein, LDL-C, triglycerides, total cholesterol, non-HDL-C, VLDL-C, HDL-C, ApoB, ApoA-I, and Lp(a) tracked over the full 85-day observation window. The trial also included immunogenicity testing for anti-drug antibodies and a concentration-QTc analysis, both standard for GalNAc siRNA programs at this stage.
The study was conducted at the Second Affiliated Hospital of Zhejiang University School of Medicine in Hangzhou and Guangdong Provincial People's Hospital in Guangzhou, with an independent data monitoring committee overseeing safety.
An ANGPTL3 siRNA Landscape That Has Matured Rapidly
EDP167 enters clinical development as the fourth or fifth GalNAc siRNA directed against ANGPTL3 mRNA to reach human studies, depending on how one counts programs that have been restructured or partnered. The competitive dynamics are worth examining in some detail.
Arrowhead Pharmaceuticals' zodasiran is the clear frontrunner. Phase II data from the GATEWAY trial showed triglyceride reductions of approximately 55–60% and LDL-C reductions of roughly 25% with quarterly subcutaneous dosing. Arrowhead has advanced zodasiran into the Phase III ARCHES-2 pivotal trial in mixed dyslipidemia and is pursuing additional Phase III studies in severe hypertriglyceridemia. If those trials read out positively, zodasiran could reach the market before EDP167 completes dose optimization.