# Depleting autoantibodies for the treatment of autoimmunity

> **NIH NIH R44** · ASTERO ERADO INC · 2024 · $1,019,427

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall goal of this project is to develop a novel therapeutic for the treatment of primary
(idiopathic) membranous nephropathy (MN). MN is a leading cause of nephrotic syndrome in
adults and has a variable clinical course. About one third of patients enter spontaneous remission,
whereas the remainder have persistent proteinuria that can lead to end stage renal disease and
even death. In 2009, the M-type phospholipase A2 receptor (PLA2R) that is present on podocytes
was identified as the target of autoantibodies in about 70-80% of MN patients. Such
autoantibodies are used as a diagnostic marker for MN, and patients with high PLA2R-specific
antibody levels typically have a poor prognosis.
 Although there are currently several therapies for MN, they can result in general
immunosuppression and other severe side effects. For example, cycles of high dose steroids and
alkylating agents can lead to cancer, osteoporosis and diabetes, and relapses occur in up to 30%
patients within five years following treatment. B cell-depleting antibodies such as rituximab are
also associated with increased risk of infection combined with a significant relapse rate. As a
result of the limitations of existing therapies for MN, there is an unmet need for the development
of improved, selective therapeutic approaches.
 This project seeks to address the need for new therapies for MN by developing engineered,
antibody-based reagents that specifically and rapidly deplete PLA2R-specific antibodies.
Importantly, these depleting agents do not affect the levels of other antibodies that have a
protective role against infection etc. This first-in-class, novel technology has been named Seldeg
technology (for selective degradation).
 The goal of the Phase I project was to provide a proof-of-concept by designing a Seldeg
molecule and showing its suitability for clinical development using in vitro assays. In this Phase II
application, we propose to move the Seldeg forward in the development process by carrying out
the necessary in vitro characterization and studies in animal models. The Specific aims are:
 1. To carry out drug development and testing of the PLA2R-Seldeg using in vitro analyses.
 2. To analyze the in vivo behavior of the PLA2R-Seldeg and targeted autoantibodies.
 The proposed approach could not only be transformative for the management of this
potentially devastating disease, but would also lay the foundations for analogous Seldeg-based
strategies to be taken in many other clinical settings where pathogenic antibodies lead to disease.

## Key facts

- **NIH application ID:** 10814322
- **Project number:** 5R44AI170180-03
- **Recipient organization:** ASTERO ERADO INC
- **Principal Investigator:** Sunil Kannanganat Sidharthan
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,019,427
- **Award type:** 5
- **Project period:** 2022-03-11 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10814322

## Citation

> US National Institutes of Health, RePORTER application 10814322, Depleting autoantibodies for the treatment of autoimmunity (5R44AI170180-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10814322. Licensed CC0.

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