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Abstract: SA-PO878

Results of Single-Arm, Phase 1b Study of Anti-C1q Treatment (ANX009) Show that the Classical Pathway Is a Key Driver of Complement Activation and Consumption in Patients with Active Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Bao, Min, Annexon Biosciences, Brisbane, California, United States
  • Lichauco, Juan, Saint Luke's Medical Center, Quezon City, Philippines
  • Chen, Hsiang, Tri-Service General Hospital, Taipei, Taiwan
  • Gomez, Harold, Angeles University Foundation Medical Center, Angeles City, Central Luzon, Philippines
  • Tee, Michael Lucas, Medical Center Manila Inc, Manila, Manila, Philippines
  • Arroyo, Caroline, Iloilo Doctors Hospital, Iloilo City, Philippines
  • Lan, Joung-Liang, China Medical University Hospital, Taichung, Taiwan
  • Fang, Yao-Fan, Chang Gung Memorial Hospital Linkou, Taoyuan, Taiwan
  • Chang, Edmund, Annexon Biosciences, Brisbane, California, United States
  • Yousefpour, Noosha, Annexon Biosciences, Brisbane, California, United States
  • Low, Julian, Annexon Biosciences, Brisbane, California, United States
  • Chang, Qing, Annexon Biosciences, Brisbane, California, United States
  • Osterloh, Jeannette, Annexon Biosciences, Brisbane, California, United States
  • Manser, Paul, Annexon Biosciences, Brisbane, California, United States
  • Mongan, Ann, Annexon Biosciences, Brisbane, California, United States
  • Yednock, Ted, 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, San Francisco, California, United States
Background

Lupus nephritis (LN) is an autoantibody-mediated disease involving glomerular deposition of immune complexes containing pathogenic anti-C1q antibodies, leading to C1q binding and activation of the classical complement pathway. ANX009 is a subcutaneously administered antigen-binding fragment of a humanized antibody that inhibits C1q interaction with immune complexes. Plasma measures of classical complement activation (C4d/C4 ratio) strongly correlate with disease activity in LN patients, suggesting that these patients may benefit from anti-C1q therapy.

Methods

LN-01 is an ongoing, single-arm, phase 1b study evaluating safety and tolerability of ANX009 in patients (N≤8) with class III or IV LN, high plasma C4d/C4 ratio, and urine protein/creatinine ratio >0.5 g/g at study enrollment. Patients undergo an 8-week screening period, a 3-week treatment period, and an 11-week off-treatment follow-up period. Primary and secondary endpoints are the percentage of patients with treatment-emergent adverse events (TEAEs) and change in complement biomarkers, respectively.

Results

To date, 4 patients completed treatment, one patient discontinued treatment, and screening is ongoing. Among 3/5 patients, 29 TEAEs occurred. All AEs were non-serious, except fever of unknown diagnosis in one patient. Injection site reactions arose in 3/5 patients—mild, mostly erythema. C4d/C4 ratio decreased with treatment in all 5 patients and returned to baseline after treatment cessation. Inhibition of C1q also resulted in normalization of downstream complement markers of activation and consumption for the entire pathway.

Conclusion

In this interim analysis, ANX009 administered subcutaneously was well tolerated and demonstrated C1q target engagement and complement inhibition in 5/5 patients. Normalization of all downstream activation markers and primary components, notably C3 and C5b-9, suggests the classical pathway, not the alternative pathway, is a key driver of complement activation in these LN patients. These interim results support further study of anti-C1q therapy in LN patients.

Funding

  • Commercial Support – Annexon Biosciences