dazodalibep

Home
Ligands
dazodalibep

GtoPdb Ligand ID: 13453

Synonyms: MEDI-4920 | MEDI4920 | VIB 4920 | VIB-4920 | VIB4920

Comment: Dazodalibep (VIB4920, formerly MEDI4920) is a fusion protein that is designed to bind to and neutralise the biological actions of the CD40 ligand (CD40L) [1-2]. Structurally dazodalibep contains two tandem human Tn3 tenascin C modules (that bind CD40L [3]) linked to human serum albumin. Previous studies have demonstrated that anti-CD40L antibodies can cause thromboembolic adverse events that arise through antibody Fc-mediated cross-linking between FcγRIIa and CD40L on platelets. The dazodalibep Fc negative fusion protein approach was initiated to mitigate these platelet-related safety issues.

References
1. Karnell JL, Albulescu M, Drabic S, Wang L, Moate R, Baca M, Oganesyan V, Gunsior M, Thisted T, Yan L et al.. (2019) A CD40L-targeting protein reduces autoantibodies and improves disease activity in patients with autoimmunity. Sci Transl Med, 11 (489). [PMID:31019027]
2. Nicholson SM, Casey KA, Gunsior M, Drabic S, Iverson W, Cook H, Scott S, O'Day T, Karanth S, Dixit R et al.. (2020) The enhanced immunopharmacology of VIB4920, a novel Tn3 fusion protein and CD40L antagonist, and assessment of its safety profile in cynomolgus monkeys. Br J Pharmacol, 177 (5): 1061-1076. [PMID:31648370]
3. Oganesyan V, Ferguson A, Grinberg L, Wang L, Phipps S, Chacko B, Drabic S, Thisted T, Baca M. (2013) Fibronectin type III domains engineered to bind CD40L: cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of two complexes. Acta Crystallogr Sect F Struct Biol Cryst Commun, 69 (Pt 9): 1045-8. [PMID:23989160]
4. St Clair EW, Baer AN, Ng WF, Noaiseh G, Baldini C, Tarrant TK, Papas A, Devauchelle-Pensec V, Wang L, Xu W et al.. (2024) CD40 ligand antagonist dazodalibep in Sjögren's disease: a randomized, double-blinded, placebo-controlled, phase 2 trial. Nat Med, 30 (6): 1583-1592. [PMID:38839899]

References

1. Karnell JL, Albulescu M, Drabic S, Wang L, Moate R, Baca M, Oganesyan V, Gunsior M, Thisted T, Yan L et al.. (2019)
A CD40L-targeting protein reduces autoantibodies and improves disease activity in patients with autoimmunity.
Sci Transl Med, 11 (489). [PMID:31019027]

2. Nicholson SM, Casey KA, Gunsior M, Drabic S, Iverson W, Cook H, Scott S, O'Day T, Karanth S, Dixit R et al.. (2020)
The enhanced immunopharmacology of VIB4920, a novel Tn3 fusion protein and CD40L antagonist, and assessment of its safety profile in cynomolgus monkeys.
Br J Pharmacol, 177 (5): 1061-1076. [PMID:31648370]

3. Oganesyan V, Ferguson A, Grinberg L, Wang L, Phipps S, Chacko B, Drabic S, Thisted T, Baca M. (2013)
Fibronectin type III domains engineered to bind CD40L: cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of two complexes.
Acta Crystallogr Sect F Struct Biol Cryst Commun, 69 (Pt 9): 1045-8. [PMID:23989160]

4. St Clair EW, Baer AN, Ng WF, Noaiseh G, Baldini C, Tarrant TK, Papas A, Devauchelle-Pensec V, Wang L, Xu W et al.. (2024)
CD40 ligand antagonist dazodalibep in Sjögren's disease: a randomized, double-blinded, placebo-controlled, phase 2 trial.
Nat Med, 30 (6): 1583-1592. [PMID:38839899]