P1552: A PHASE 2, OPEN-LABEL STUDY TO ASSESS SAFETY, TOLERABILITY, AND CLINICAL EFFECT OF ANX005 IN PATIENTS WITH WARM AUTOIMMUNE HEMOLYTIC ANEMIA AND EVIDENCE OF COMPLEMENT ACTIVATION

Abstract

Background: Autoimmune hemolytic anemia (AIHA) is caused by autoantibody destruction of red blood cells (RBCs) and is divided into warm autoimmune hemolytic anemia (wAIHA) and cold agglutinin disease. In wAIHA, which accounts for 60-70% of AIHA cases, polyclonal immunoglobulin G (IgG) antibodies cause hemolysis of RBCs at core body temperatures. However, approximately 50% of wAIHA cases are not caused by pathogenic IgG alone. The correlation between autoimmune hemolysis and presence of complement on RBCs in wAIHA patients suggests a role for the complement system in the pathogenesis of wAIHA, which can be triggered by C1q binding to autoantibodies bound to RBCs. ANX005 is a humanized IgG4 monoclonal antibody that selectively binds and inhibits C1q, blocking activation of the classical complement pathway, with the potential to inhibit complement-mediated hemolysis in wAIHA. Aims: The goal of this clinical study is to evaluate two once-weekly IV infusions of ANX005 in patients with wAIHA having evidence of complement pathway activation to understand the effect of C1q inhibition on pathway markers and objective disease parameters. Methods: This is an open-label, repeat-dose, Phase 2 study (NCT04691570) of ANX005 in patients with wAIHA and evidence of classical complement pathway activation. Up to 12 patients will be enrolled in this study and undergo a screening period of up to six weeks prior to Day 1. Patients will receive two doses of ANX005 on Days 1 and 8. Safety and pharmacokinetic (PK)/pharmacodynamic (PD) evaluations will be completed on Days 4, 15, 22, 29, 36, 43, 50, 57, and 71. Individual study duration will be up to 16 weeks, and patients will complete study participation on Day 71. The primary objective is to evaluate the safety and tolerability of ANX005. Secondary objectives include evaluating the PK and PD profile of ANX005, examining markers of classical pathway activation, and determining the impact of classical complement inhibition on hemoglobin levels and biomarkers of hemolysis through Day 71 in this subset of patients. Results: Results from the Phase 2 trial are expected by the end of 2022. Image:Summary/Conclusion: In this Phase 2 study of ANX005 in patients with wAIHA and evidence of classical complement pathway activation, patients will receive two IV doses of ANX005 one week apart with the goal of evaluating its safety, tolerability, PK/PD, and clinical effect to further understand the role of classical complement in this heterogeneous disease as a target for effective therapy.