Abstract: SA-PO0861
ADX-038, a Potent Complement Factor B siRNA, Provides Deep and Prolonged Inhibition of the Alternative Pathway
Session Information
- Glomerular Diseases: Management, Evolving Strategies, and Practice-Changing Advances
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Cheung, Chee Kay, University of Leicester, Leicester, England, United Kingdom
- Li, Zhen, ADARx Pharmaceuticals Inc, San Diego, California, United States
- MacLeod, Robert A., ADARx Pharmaceuticals Inc, San Diego, California, United States
- Patel, Aditya, ADARx Pharmaceuticals Inc, San Diego, California, United States
- Fong, Donald, ADARx Pharmaceuticals Inc, San Diego, California, United States
Background
IgA Nephropathy and Complement 3 Glomerulopathy are two, lifelong complement mediated nephropathies. Inhibition of C3 convertase formation and function has been shown to slow disease progression. Another approach for C3 convertase inhibition is through suppression of CFB, that is required to generate C3 convertase (C3bBb). Agazisiran (ADX-038) is a GalNAc-conjugated siRNA designed to suppress CFB levels and near complete inhibition of alternative pathway activity with subcutaneous injections every 3- or 6-months.
Methods
Preclinical evaluation of ADX-038 was conducted in rats, rabbits and non human primates (NHP). Pharmacodynamic analysis of CFB levels in cynomolgus monkeys following SC administration of ADX-038 was conducted as a part of the GLP, 40 week repeat dose toxicity study with a 13-week recovery period. Cynomolgus monkeys were administered subcutaneous doses of, 12, 32 or 96 mg/kg once every 2 months for 10 months. A Phase 1 study completed follow-up in March 2026. Healthy adults (41) were randomized and administered subcutaneous doses of 0.4mg/kg to 6.0 mg/kg (25 to 400 mg). Safety, as well as pharmacokinetic and pharmacodynamic measures were monitored.
Results
GLP toxicology studies demonstrate excellent safety and wide therapeutic index with the top dose defined as the NOAEL. In 40 week NHP studies, serum CFB protein levels post-treatment with agazisiran showed 94-98% reduction through day 281. At Day 372 , 13 weeks after the six bi-monthly doses, serum CFB levels remained decreased by 86% compared to predose levels on Day 1. In the Phase 1 trial, dose-dependent reductions in CFB protein levels and inhibition of AP activity were observed. A single 6mg/kg ADX-038 dose suppressed AP activity by 99% from baseline through 6 months. Treatment was well-tolerated. There was one SAE not related to treatment and TEAs were mild to moderate and did not result in discontinuation.
Conclusion
Unmet needs in the treatment of IgAN and C3G include improved efficacy and reduced treatment burden[RM1] . ADX-038 demonstrated excellent safety, potency and duration of effect in non-clinical studies. A Phase 1 study confirmed prolonged suppression of CFB up to 6 months. Based on these results, a Phase 2 study is ongoing and actively recruiting patients to assess the safety and efficacy in patients with complement mediated kidney diseases.
Funding
- Commercial Support – ADARx Pharmaceuticals