#4337 UPDATED INTERIM RESULTS OF A PHASE 1/2 STUDY OF BION-1301 IN PATIENTS 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. Approximately 30-45% of IgAN patients progress to end-stage kidney disease over a period of 20-25 years and proteinuria is the strongest predictor of disease progression [1]. BION-1301 is a novel humanized monoclonal antibody that blocks a proliferation-inducing ligand (APRIL), a cytokine that is elevated in patients with IgAN. APRIL promotes the production of pathogenic galactose-deficient IgA1 (Gd-IgA1), leading to immune complex deposition and subsequent kidney injury. Blocking APRIL with BION-1301 is a potential disease-modifying approach to directly target the pathogenesis of IgAN. In a Phase 1/2 study (NCT 03945318) in healthy volunteers and patients with IgAN, BION-1301 was well-tolerated with no serious adverse events (SAEs) and durably reduced free APRIL, IgA, Gd-IgA1, IgM and to a lesser extent, IgG [2]. Method For the ongoing phase 1/2 open-label, multicohort trial, eligibility criteria include adults with biopsy-proven IgAN, eGFR ≥30 mL/min per 1.73 m2, baseline urine protein excretion ≥0.5 g/24 hrs or UPCR ≥0.5 g/g, and on stable/optimized RASi (or intolerant). Cohort 1 received 450 mg of BION-1301 administered IV every 2 weeks, transitioning to SC at 600 mg every 2 weeks after at least 24 weeks. Cohort 2 receives 600 mg of BION-1301 SC every 2 weeks. Results In both Cohorts 1 and 2, BION-1301 was generally well-tolerated, with no SAEs or terminations due to AEs as of the last reported interim analysis (November 2022) [2]. Durable reductions in serum levels of free APRIL and immunoglobulins were observed in both cohorts. No anti-drug antibodies have been observed in patients with IgAN to date. In Cohort 1, clinically meaningful reductions in proteinuria were seen as early as 12 weeks (30.4% geometric mean UPCR reduction, n = 7), and were sustained through 24 weeks (48.8% geometric mean UPCR reduction, n = 8) and 52 weeks (66.9% geometric mean UPCR reduction, n = 8). Reductions in proteinuria were consistent in Cohort 2 (53.8% geometric mean UPCR reduction, n = 9) at 24 weeks. Significant and durable reductions in serum Gd-IgA1 concentrations were observed and were consistent across both cohorts. Updated data will be reported at the time of presentation. Conclusion BION-1301 offers disease-modifying potential by directly targeting the initiating pathogenesis of IgAN. Interim biomarker and clinical activity responses support advancement of BION-1301 into later-stage development for patients with IgAN.