ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

ASN / Education & Meetings / Kidney Week /
Abstract: SA-PO733

Development of GE8820 for Selective and Rapid Removal of Pathogenic Autoantibodies in Primary Membranous Nephritis (PMN) and Other IgG4-Mediated Diseases

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Ganguly, Tanmoy C., Glycoera Inc, Newton, Massachusetts, United States
  • Back, Jonathan, Glycoera Inc, Newton, Massachusetts, United States
  • Hanes, Melinda, Glycoera Inc, Newton, Massachusetts, United States
  • Manni, Michela, Glycoera Inc, Newton, Massachusetts, United States
  • Hesler, Stephen, Glycoera Inc, Newton, Massachusetts, United States
  • Madala, Hanumantha Rao, Glycoera Inc, Newton, Massachusetts, United States
  • Billion, Oaklyne, Glycoera Inc, Newton, Massachusetts, United States
  • Oconnell, Courtney, Glycoera Inc, Newton, Massachusetts, United States
  • Cotter, Kellie, Glycoera Inc, Newton, Massachusetts, United States
  • Schelbert, Tina, Glycoera Inc, Newton, Massachusetts, United States
  • Mally, Manuela, Glycoera Inc, Newton, Massachusetts, United States
  • Sirena, Dominique Nicolas, Glycoera Inc, Newton, Massachusetts, United States
  • Hillson, Jan Leslie, Glycoera Inc, Newton, Massachusetts, United States
  • Kaundinya, Ganesh V., Glycoera Inc, Newton, Massachusetts, United States
Background

In PMN, anti-PLA2R autoantibodies are used as a diagnostic, levels are associated with disease activity, and most are of the IgG4 isotype. Disease can be transferred to models, and a mechanism of injury was demonstrated with the IgG4 fraction. GE8820 is a bifunctional biologic that selectively binds to human IgG4 and through a glycan mediated engagement of ASGPR on hepatocytes, targets it for liver degradation.

Methods

GE8820 a selective high affinity human IgG4 binder was expressed using the proprietary BiNDTM platform. Immuno-depletion experiments were performed in normal and PMN patient sera. In vivo experiments in rodents were performed by exogenously administering human IgG4 followed by GE8820 via iv route.

Results

Human IgG4 was selectively and completely depleted in both normal human sera and PMN sera. Depletion of IgG4 in pMN patient sera resulted in removal of PLA2R autoantibodies to levels below the threshold for serological positivity scores for pMN diagnosis. GE 8820 resulted in rapid (≤ 2hrs) and near complete (≥95%) depletion of IgG4 in a dose dependent manner.

Conclusion

Through selective depletion of the IgG4 subclass, GE8820 removed PLA2R autoantibodies from patient sera. GE8820 is being developed for the treatment of autoimmune diseases driven by pathologic IgG4 autoantibodies such as primary membranous nephropathy, muscle specific kinase driven myasthenia gravis and pemphigus vulgaris.

Immunodepletion of PLA2R autoantibodies in PMN patient sera

Rapid, deep and dose dependent depletion of human IgG4

Funding

  • Commercial Support – Glycoera Inc