LBL-047

LBL-047 is a first-in-class, long-acting bispecific antibody fusion protein designed for the treatment of autoimmune diseases. It consists of a Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor (TACI) domain fused to an antibody targeting Blood Dendritic Cell Antigen 2 (BDCA2). The molecule is engineered with an afucosylated Fc region and incorporates the YTE mutation to extend its half-life in circulation, enabling less frequent dosing. Mechanistically, LBL-047 simultaneously inhibits B cell function by trapping BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), while also depleting interferon-secreting plasmacytoid dendritic cells (pDCs) via BDCA2 targeting. This dual action results in robust immunosuppression by reducing both B cell activity and type I interferon production from pDCs. Preclinical studies have demonstrated superior inhibition of B cell and plasma cell function compared to marketed TACI fusion proteins, significant depletion of pDCs, potent suppression of IFN-α release, excellent pharmacokinetic properties with prolonged reduction in immunoglobulin levels, and alleviation of disease symptoms in animal models relevant to multiple sclerosis. LBL-047 is being developed primarily for systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis (LN), Sjogren's syndrome, myasthenia gravis, and potentially other autoimmune disorders[1][5][6][7].