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Abstract: SA-PO931

Classical Complement Activation in Lupus Nephritis Correlates with Disease Biomarkers: Results from Two Observational Studies

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Chang, Edmund, Annexon Biosciences, Brisbane, California, United States
  • Low, Julian, Annexon Biosciences, Brisbane, California, United States
  • Yousefpour, Noosha, Annexon Biosciences, Brisbane, California, United States
  • Bao, Min, Annexon Biosciences, Brisbane, California, United States
  • Osterloh, Jeannette, Annexon Biosciences, Brisbane, California, United States
  • Chang, Qing, Annexon Biosciences, Brisbane, California, United States
  • Artis, Dean R., Annexon Biosciences, Brisbane, California, United States
  • Kroon, Henk-Andre, Annexon Biosciences, Brisbane, California, United States
  • Andrews-Zwilling, Yaisa, Annexon Biosciences, Brisbane, California, United States
  • Dall'Era, Maria, University of California San Francisco Department of Medicine, San Francisco, California, United States
  • Yednock, Ted, Annexon Biosciences, Brisbane, California, United States
  • Mongan, Ann, Annexon Biosciences, Brisbane, California, United States
Background

Lupus nephritis (LN) is an autoantibody-mediated disease that can activate C1q and the classical complement pathway. Pathogenic anti-C1q antibodies (PACAs) are often present, amplifying classical pathway inflammation and contributing to progressive kidney damage. Elevated C4d and reduced C4 are markers of classical complement activation and consumption, respectively. For LN patients in the CLUES/UCSF Study, C4d/C4 ratio positively correlated with PACAs and urine protein-creatinine ratio (UPCR). To validate this correlation, the Sanguine Bio study was conducted.

Methods

Samples were collected from 40 LN patients (plus 20 healthy controls) from the CLUES/UCSF Study and 24 LN patients (plus 10 healthy controls) from Sanguine Bio. Complement activation and consumption (C4d, C4), exploratory biomarkers in plasma and urine, and UPCR were evaluated.

Results

Sanguine Bio samples from a subset of LN patients demonstrated elevated C4d/C4 compared to healthy controls indicating classical complement pathway activation (Figure). Urinary biomarkers of LN correlated with C4d/C4 ratio in these patients.

Conclusion

In these LN patients, C4d/C4 ratios were elevated and correlated with LN biomarkers in blood and urine, supporting classical complement activity. These data support an ongoing, phase 1b study of ANX009 with the goal of assessing safety, tolerability, and pharmacodynamics of repeat-doses of subcutaneous ANX009 with standard of care in adults with LN. ANX009 is an anti-C1q antigen binding fragment targeting LN patients with evidence of classical complement activity (elevated C4d/C4).

Figure. A Subset of Patients with LN Demonstrated Elevated C4d/C4 Over Healthy Controls

Funding

  • Commercial Support – Annexon Biosciences