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Kidney Week

Abstract: SA-PO0806

Safety and Pharmacodynamics of SGB-9768, an siRNA Targeting Complement C3 in Healthy Volunteers

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Cross, Nicholas, New Zealand Clinical Research, Christchurch, New Zealand
  • Wu, Xiaojie, Huashan Hospital Fudan University, Shanghai, China
  • Sheng, Lili, Suzhou Sanegene Bio Inc., Suzhou, China
  • Yao, Xuekun, Suzhou Sanegene Bio Inc., Suzhou, China
  • He, Xiaolin, Suzhou Sanegene Bio Inc., Suzhou, China
  • Jin, Yuyan, Sanegene Bio USA Inc., Woburn, Massachusetts, United States
  • Zhang, Jing, Huashan Hospital Fudan University, Shanghai, China
Background

SGB-9768, a GalNAc-conjugated siRNA, inhibits hepatic complement C3 production in Heathy volunteers, warrants further investigation in its potential to treat complement-related kidney diseases.

Methods

Two phase 1, randomized, double-blind, placebo-controlled trials (SGB-9768-001, NZ; SGB-9768-002, China) evaluated the safety, pharmacokinetics, and pharmacodynamics of single subcutaneous doses of SGB-9768 in healthy volunteers.

Results

Study 001 enrolled 29 participants (mostly Caucasian) receiving 25–400 mg of SGB-9768 (4:2 active to placebo). Study 002 enrolled 37 participants (all Chinese) with doses of 50–600 mg (3:2 active to placebo at 50 mg, 6:2 at higher doses). All participants received vaccinations (meningococcal vaccine and pneumococcal vaccine) before dosing and prophylactic antibiotics throughout the study. SGB-9768 demonstrated a favorable safety and tolerability profile, with no significant infections, including no cases involving encapsulated organisms. There were no dose limiting toxicity or treatment-related serious adverse events (AE) or discontinuations due to AEs. Treatment-related AE reported in ≥10% of participants was injection site reaction.
PD data (Figure 1) showed dose-dependent serum C3 reductions of 52–85% (Study 001, 25–400mg) and 75–93% (Study 002, 50-600 mg) at 1 month, sustained at 52–84% and 69–92% at 3 months. Alternative pathway activity (Wieslab® AP) decreased by 43–99% (Study 001) and 66–100% (Study 002) at 1 month, sustained at 59–99% and 59–100% at 3 months. Classical pathway activity (Wieslab® CP) reductions ranged from 12–56% at 1 month.

Conclusion

SGB-9768 was safe, with sustained, dose-dependent reductions in C3 and complement activity, supporting development for kidney diseases like IgA nephropathy and C3 glomerulopathy.

Figure 1. Measures of serum complement C3 level (a), Wieslab® AP (b), Wieslab® CP (c) in healthy volunteers.

Funding

  • Commercial Support – Suzhou Sanegene Bio Inc.

Digital Object Identifier (DOI)