povetacicept

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Ligands
povetacicept

GtoPdb Ligand ID: 14426

Synonyms: ALPN-303 | TACI vTD-Fc

Compound class: Peptide

Comment: Povetacicept (ALPN-303) is a Fc fusion protein that contains a variant TACI domain of the TNFRSF13B receptor for the peptide cytokines B cell activating factor (BAFF; TNFSF13B) and a proliferation-inducing ligand (APRIL; TNFSF13) [2]. It functionally antagonises the cellular signalling pathways of these ligands via TNFRSF13B on B cells.
In the peptide sequence provided the TACI domain is amino acids 1-43, with a short linker (GSGGGGS 44-50 ) and the remainder being the Fc domain. The functional peptide is a dimer, linked by inter-chain disulphide bridges.

References
1. Davies R, Peng SL, Lickliter J, McLendon K, Enstrom A, Chunyk AG, Blanchfield L, Wang N, Blair T, Thomas HM et al.. (2024) A first-in-human, randomized study of the safety, pharmacokinetics and pharmacodynamics of povetacicept, an enhanced dual BAFF/APRIL antagonist, in healthy adults. Clin Transl Sci, 17 (11): e70055. [PMID:39494621]
2. Evans LS, Lewis KE, DeMonte D, Bhandari JG, Garrett LB, Kuijper JL, Ardourel D, Wolfson MF, Debrot S, Mudri S et al.. (2023) Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases. Arthritis Rheumatol, 75 (7): 1187-1202. [PMID:36705554]
3. Rinaldi E, Puleo E, Consonni A, Miglietti M, Mantegazza R, Wang N, Peng SL, Lewis KE, Dillon SR, Baggi F. (2025) Povetacicept (ALPN-303; TACI vTD-Fc), an enhanced, potent dual inhibitor of BAFF and APRIL, ameliorates experimental autoimmune myasthenia gravis in C57BL/6N mice. Front Immunol, 16: 1533093. [PMID:40547042]
4. Sharma I, Panta R. (2025) Emerging Therapies in IgA Nephropathy: From A Proliferation-Inducing Ligand (APRIL) and B-cell Activating Factor (BAFF) Inhibitors to Precision Medicine. Cureus, 17 (12): e99870. [PMID:41573494]

References

1. Davies R, Peng SL, Lickliter J, McLendon K, Enstrom A, Chunyk AG, Blanchfield L, Wang N, Blair T, Thomas HM et al.. (2024)
A first-in-human, randomized study of the safety, pharmacokinetics and pharmacodynamics of povetacicept, an enhanced dual BAFF/APRIL antagonist, in healthy adults.
Clin Transl Sci, 17 (11): e70055. [PMID:39494621]

2. Evans LS, Lewis KE, DeMonte D, Bhandari JG, Garrett LB, Kuijper JL, Ardourel D, Wolfson MF, Debrot S, Mudri S et al.. (2023)
Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.
Arthritis Rheumatol, 75 (7): 1187-1202. [PMID:36705554]

3. Rinaldi E, Puleo E, Consonni A, Miglietti M, Mantegazza R, Wang N, Peng SL, Lewis KE, Dillon SR, Baggi F. (2025)
Povetacicept (ALPN-303; TACI vTD-Fc), an enhanced, potent dual inhibitor of BAFF and APRIL, ameliorates experimental autoimmune myasthenia gravis in C57BL/6N mice.
Front Immunol, 16: 1533093. [PMID:40547042]

4. Sharma I, Panta R. (2025)
Emerging Therapies in IgA Nephropathy: From A Proliferation-Inducing Ligand (APRIL) and B-cell Activating Factor (BAFF) Inhibitors to Precision Medicine.
Cureus, 17 (12): e99870. [PMID:41573494]