Interim Phase 1 Study Results of ADX-038: A Novel siRNA Against Complement Factor B, and Next Steps in IgAN and C3 Glomerulopathy (C3G)

Background: ADX-038 is a siRNA that targets complement factor B (CFB) mRNA, being developed for diseases with dysregulation of the complement system. The effects of ADX-038 on CFB protein levels and on the complement alternative pathway (AP) and classical pathway (CP) activity in healthy volunteers is reported with the discussion of the Phase 2 study in IgAN and C3G. Methods: As of 2/2025, 41 healthy adults were randomized and administered one subcutaneous dose of ADX-038 n=31 or placebo n=10. ADX-038 doses ranged from 0.4 to 6 mg/kg (actual doses 25 to 360 mg). Circulating CFB protein levels, and AP and CP activity were measured. Clinical safety was based on adverse events (AEs) and monitoring of clinical lab tests, physical exams (PE). Results: Dose-dependent reductions in CFB protein levels and inhibition of AP activity were observed, Figures 1 and 2. A single 4 mg/kg ADX-038 dose suppressed AP activity by 99% from baseline through 3M. As expected, CP activity was unchanged. Treatment was well-tolerated. The most common AE was upper respiratory tract infection, similar to placebo. There were no encapsulated bacterial infections nor clinically relevant changes in clinical lab tests, PE or vital signs. The Phase 2 study will dose IgAN and C3G patients Q3M with ADX-038. The primary objective of the study is to assess the tolerability of ADX-038, with the secondary objective of changes to proteinuria. Conclusion: A single dose of ADX-038 effectively silenced CFB gene expression, resulting in selective and near-complete suppression of complement AP activity. The durable on-target PD effects support its potential as an effective therapeutic agent for kidney diseases with a convenient (Q3M) subcutaneous dosing schedule. Based on these results, a Phase 2 study has been initiated to assess the safety and efficacy of ADX-038 in patients with complement mediated kidney diseases (eg. IgAN and C3G). Funding: Commercial Support - Adarx pharmaceuticals