MO207: A Phase 1/2, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BION-1301 in Healthy Volunteers and Adults with IGA Nephropathy

Abstract BACKGROUND AND AIMS Immunoglobulin A nephropathy (IgAN) is the leading cause of primary glomerulonephritis worldwide with limited treatment options, especially for high-risk patients [1]. BION-1301 is a novel humanized monoclonal antibody that blocks a proliferation-inducing ligand (APRIL), a soluble factor that has been shown to be elevated in patients with IgAN and is correlated with poorer outcomes, including increased proteinuria and decreased eGFR [2, 3]. APRIL promotes IgA class switching, the survival of IgA-secreting plasma cells and the excess production of a galactose-deficient variant form of IgA1 (Gd-IgA1), which is an initiating step in the multi-hit pathogenesis of IgAN. This leads to the generation of anti-Gd-IgA1 autoantibodies and the formation of nephritogenic immune complexes that deposit in the kidney, resulting in inflammation and damage [2–4]. Blocking APRIL with BION-1301 is a novel approach to address the underlying pathogenesis of IgAN by reducing circulating levels of Gd-IgA1 and preventing the formation of pathogenic immune complexes. The primary objective of this Phase 1/2 study is to assess the safety and tolerability of BION-1301 in healthy volunteers (HV) and patients with IgAN, and secondarily to assess the PK, PD, immunogenicity and preliminary clinical activity. METHOD The Phase 1/2 study (NCT03945318) is comprised of three parts. Parts 1 and 2 were blinded, placebo-controlled single and multiple ascending dose designs in HV and have been completed. Part 3 is a multicenter (USA, UK, South Korea), multicohort, open-label study in up to 40 patients with IgAN. Patients in Cohort 1 receive 450 mg of BION-1301 administered IV every 2 weeks for up to 1 year. After completing at least 24 weeks of IV dosing, patients in Cohort 1 transitioned from receiving 450 mg of BION-1301 IV to receiving 600 mg of BION-1301 SC every 2 weeks. Patients in Cohort 2 receive 600 mg of BION-1301 SC every 2 weeks for up to 1 year. Additional cohorts may be added to explore other doses and dosing schedules. Key eligibility criteria for Part 3 include: (1) biopsy-verified diagnosis of IgAN within 10 years, (2) baseline urine protein excretion ≥ 0.5 g/24 h or UPCR ≥ 0.5 g/g and (3) stable/optimized dose of ACE-I/ARB (or intolerant). RESULTS Final HV data from Parts 1 and 2 have been presented at earlier conferences [5]. Part 3 is on-going and updated interim data from patients with IgAN in Cohort 1 who received BION-1301 IV as well as patients