Kidney Week

Abstract: PO1632

Pharmacodynamic and Clinical Responses to BION-1301 in Patients with IgA Nephropathy: Initial Results of a Ph1/2 Trial

Session Information

• Glomerular Diseases: Treatment and Outcomes
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom

Jonathan Barratt, MBChB, PhD

• Hour, Billy T., Amicis Research Center, Northridge, California, United States

Billy T. Hour,

• Schwartz, Brian S., Chinook Therapeutics Inc, Seattle, Washington, United States

Brian S. Schwartz,

• Sorensen, Bess, Chinook Therapeutics Inc, Seattle, Washington, United States

Bess Sorensen,

• Roy, Suzanne E., Chinook Therapeutics Inc, Seattle, Washington, United States

Suzanne E. Roy,

• Stromatt, Colleen L., Chinook Therapeutics Inc, Seattle, Washington, United States

Colleen L. Stromatt,

• MacDonald, Margaret, Chinook Therapeutics Inc, Seattle, Washington, United States

Margaret MacDonald,

• Endsley, Aaron N., Certara LP, Princeton, New Jersey, United States

Aaron N. Endsley,

• Lo, Jeannette, Chinook Therapeutics Inc, Seattle, Washington, United States

Jeannette Lo,

• Glicklich, Alan, Chinook Therapeutics Inc, Seattle, Washington, United States

Alan Glicklich,

• King, Andrew J., Chinook Therapeutics Inc, Seattle, Washington, United States

Andrew J. King,

Background

IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally, with up to 45% of patients at risk of progressing to ESKD. The initiating step in IgAN pathogenesis is the excess production of galactose-deficient IgA1 (Gd-IgA1), resulting in the formation of immune complexes that cause kidney inflammation and damage. A Proliferation-Inducing Ligand (APRIL) is elevated in IgAN patients and correlated with higher levels of Gd-IgA1 and proteinuria, and lower eGFR. BION-1301 is a novel monoclonal antibody targeting APRIL.

Here we present interim results from Part 3 of a Phase 1/2 study that characterizes the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary activity of BION-1301 delivered by IV administration in patients with IgAN.

Methods

Part 3 of this Phase 1/2 study (NCT03945318) is an ongoing multicenter, multicohort, open-label study in up to 40 IgAN patients. In Cohort 1, BION-1301 is dosed at 450mg IV every 2 weeks for up to 12 months. Key objectives of the study include safety and the characterization of PK, PD, immunogenicity and changes in proteinuria. Key eligibility criteria include: (1) urine protein ≥0.5 g/24h or baseline UPCR ≥0.5 g/g, (2) stable/optimized dose of ACE-I/ARB or ACE-I/ARB intolerant and (3) biopsy-verified diagnosis of IgAN within the past 10 years.

Results

Preliminary results from the first 5 patients show BION-1301 is well tolerated with no serious adverse events and no adverse events leading to discontinuation to date. BION-1301 drives durable reductions in serum free APRIL, Gd-IgA1, IgA and IgM, with a lesser reduction in IgG. A clinically meaningful reduction in 24-hour UPCR was observed within 3 months. Updated data in all IV treated patients, along with mechanistic response kinetics, will be presented at the meeting.

Conclusion

BION-1301 is a novel anti-APRIL monoclonal antibody being developed as a potential treatment for patients with IgAN. BION-1301 offers disease modifying potential by directly targeting the pathogenesis of IgAN. Promising early biomarker and clinical activity support the continued development of BION-1301 in IgAN.

Funding

• Commercial Support –