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Abstract: PO1843

Results of a Phase 1 Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BION-1301 in Healthy Volunteers

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Lo, Jeannette, Aduro BioTech Inc, Berkeley, California, United States
  • Yavrom, Sharon, Aduro BioTech Inc, Berkeley, California, United States
  • Fan, Jessy, Aduro BioTech Inc, Berkeley, California, United States
  • Endsley, Aaron N., Certara LP, Princeton, New Jersey, United States
  • Schroeder, Tamara, Aduro BioTech Inc, Berkeley, California, United States
  • Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
  • Essayan, David M., ONCORD, Inc., Westlake Village, California, United States
Background

IgA nephropathy (IgAN) is an autoimmune disease with no approved treatments1. Key steps in IgAN pathogenesis are the production of galactose-deficient IgA1 (Gd-IgA1), the generation of anti-Gd-IgA1 autoantibodies and the formation of immune complexes resulting in kidney inflammation and damage2. Patients with IgAN have elevated levels of A proliferation-inducing ligand (APRIL) which regulates B cell differentiation and proliferation3. In a study of patients with IgAN, those with high plasma APRIL levels had elevated levels of Gd-IgA1 and proteinuria and lower eGFR3. BION-1301, a first-in-class humanized anti-APRIL antibody, was well-tolerated with no dose-limiting toxicities in a Phase 1/2 first-in-human study in multiple myeloma4. This 3-part Phase 1 trial characterizes the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of BION-1301 in healthy volunteers (HV) and patients with IgAN.

Methods

(NCT03945318) Parts 1 and 2 are double-blind, randomized, placebo-controlled single and multiple ascending dose studies, respectively. Part 1 enrolled 36 HV in 5 dose cohorts, randomized in a 3:1 ratio to receive a single dose of BION-1301 or placebo delivered by IV infusion. Part 2 enrolled 27 HV in 3 dose cohorts, randomized in a 2:1 ratio to receive 3 doses of BION-1301 or placebo delivered by IV infusion every two weeks. Part 3 assesses a multiple dose regimen in patients with IgAN and is currently enrolling.

Results

BION-1301 was well-tolerated with low incidence of non-neutralizing ADAs in HVs. The PK profile was well behaved with a half-life supporting monthly dosing. Durable target engagement, suppression of IgA and IgM, and to a lesser extent IgG were observed following BION-1301 administration. IgG values remained in normal ranges with no increase of infections post-treatment. Updated data will be presented including B cell immunophenotyping of HVs and results from patients with IgAN, if available.

Conclusion

BION-1301, an anti-APRIL antibody, offers a pharmacodynamic window to exploit IgA suppression while tempering impact to IgG. BION-1301 may provide a novel approach to address the pathophysiology of IgAN.

Funding

  • Commercial Support –