Abstract: SA-PO730
First-in-Class Antigen-Specific Extracellular Protein Degrader, BHV-1400 for IgA Nephropathy, Selectively Targets Galactose-Deficient IgA for Rapid and Efficient Endolysosomal Degradation in the Liver
Session Information
- Glomerular Diseases: Therapeutic Strategies
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Lee, Seong, Biohaven Ltd, New Haven, Connecticut, United States
- Spliid, Charlotte B., Biohaven Ltd, New Haven, Connecticut, United States
- Estrella, Ana, Biohaven Ltd, New Haven, Connecticut, United States
- Mcgrath, Kathleen, Biohaven Ltd, New Haven, Connecticut, United States
- Yousuf, Hanna, Biohaven Ltd, New Haven, Connecticut, United States
- Rossi, Ann Marie, Biohaven Ltd, New Haven, Connecticut, United States
- Rasile, Brett, Biohaven Ltd, New Haven, Connecticut, United States
- Conroy, Scott, Biohaven Ltd, New Haven, Connecticut, United States
- Spiegel, David, Yale University School of Medicine, New Haven, Connecticut, United States
- Dubowchik, Gene, Biohaven Ltd, New Haven, Connecticut, United States
- Pirman, David, Biohaven Ltd, New Haven, Connecticut, United States
- Car, Bruce D., Biohaven Ltd, New Haven, Connecticut, United States
- Marcin, Lawrence R., Biohaven Ltd, New Haven, Connecticut, United States
- Bunin, Anna, Biohaven Ltd, New Haven, Connecticut, United States
- Coric, Vlad, Biohaven Ltd, New Haven, Connecticut, United States
Background
IgA nephropathy (IgAN) is the most prevalent form of glomerulonephritis, affecting 2.5 of 100,000 people worldwide. The production of galactose-deficient IgA1 (Gd-IgA1), and the subsequent formation and deposition of Gd-IgA1-IgG immune complexes in the kidney mesangium drive the onset and progression of IgAN. Targeting pathogenic Gd-IgA1 in IgAN patients offers a promising strategy to decrease immune complex formation, potentially leading to a reduction in kidney inflammation and pathology.
Methods
Biohaven engineered a novel, bifunctional antibody-based, protein degrader, BHV-1400, that specifically targets extracellular Gd-IgA1 for degradation via the ASGPR-mediated endolysosomal pathway in the liver. Here, we present data illustrating the reactivity of BHV-1400 with IgAN patient samples.
Results
In in vitro assays, BHV-1400 mediates efficient specific cellular internalization and degradation of monomeric and multimeric deglycosylated IgA (dg-IgA). Pharmacological data indicates that BHV-1400 facilitates a rapid reduction of exogenous dg-IgA both in the bloodstream and tissues, most notably within kidney glomeruli.
Conclusion
Thus, Gd-IgA1 degradation with BHV-1400 offers significant promise as a novel and effective precision, disease-modifying approach for treating IgAN.
Funding
- Commercial Support – Biohaven Pharmaceuticals