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beta-2 glycoprotein 1 autoantigen-drug conjugate
- Development stage
- Preclinical
- Lead developer
- Winnow Therapeutics
- Modality
- Peptide-Drug Conjugates → Peptide Conjugates → Peptides, Recombinant Proteins and Enzymes
01
Overview
Beta-2 glycoprotein 1 autoantigen-drug conjugate (β2GPI-AADC) is a preclinical-stage precision immunotherapy being developed by Johns Hopkins University and Winnow Therapeutics for the treatment of antiphospholipid syndrome (APS). The therapeutic is designed as an autoantigen-drug conjugate (AADC) consisting of a protein scaffold bivalently conjugated to the APS autoantigen beta-2 glycoprotein 1 (β2GPI domains I-V) and covalently linked to the cytotoxic payload monomethyl auristatin E (MMAE) via a cathepsin-cleavable valine-citrulline linker. β2GPI-AADC selectively binds to and crosslinks anti-β2GPI B-cell receptors (BCRs) on autoreactive B cells, triggering receptor-mediated endocytosis and lysosomal delivery. Intracellular cleavage of the linker releases MMAE, which inhibits tubulin polymerization and selectively eliminates pathogenic autoreactive B cells while sparing protective immunity.
- Other names
- beta-2 glycoprotein 1-AADCbeta2 glycoprotein 1-AADCbeta 2 glycoprotein 1-AADCβ2GPI-AADCβ2GPI-AADCs
02
Targets
CTSS (Cathepsin S)TUBB (Tubulin (alpha and beta subunits))B2GP1 (Beta-2-glycoprotein I)BCR (Immunoglobulin G B Cell Receptor)
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