zigakibart

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zigakibart

GtoPdb Ligand ID: 12101

Synonyms: BION-1301 | BION1301 | clone 14_1G.15

Comment: Zigakibart is an anti-TNFSF13 (APRIL) monoclonal antibody that has been designed for anti-inflammatory potential. Amino acid sequences for zigakibart's heavy and light chains (obtained from INN documentation) match the sequences for clone 14_1G.15 as claimed in patent US9969808B2 (Aduro Biotech) [1]. Aduro Biotech merged into Chinook Therapeutics in mid-2020, with this new entity holding the humanized IgG4 anti-APRIL mAb BION-1301 in its development portfolio. We predict that zigakibart is the INN for BION-1301. BION-1301 is described as blocking APRIL binding to both the BCMA and TACI receptors, to down-modulate B cell functions.

Immunopharmacology Comments
The disease-modifying potential of BION-1301 is mediated by blocking APRIL binding to its two main receptors, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA). Elevated APRIL levels are associated with the pathogenesis of IgA nephropathy. Hence, mAb-mediated neutralisation of APRIL to reduce receptor activation is a promising mechanism for the treament of IgA nephropathy. BION-1301 does not bind BAFF (required for normal B cell maintenance), which is in contrast to the approved APRIL antagonist atacicept which binds APRIL and BAFF.

Immunopharmacology Comments

The disease-modifying potential of BION-1301 is mediated by blocking APRIL binding to its two main receptors, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA). Elevated APRIL levels are associated with the pathogenesis of IgA nephropathy. Hence, mAb-mediated neutralisation of APRIL to reduce receptor activation is a promising mechanism for the treament of IgA nephropathy. BION-1301 does not bind BAFF (required for normal B cell maintenance), which is in contrast to the approved APRIL antagonist atacicept which binds APRIL and BAFF.