Human IL-36R Antibody - Imsidolimab Biosimilar

Imsidolimab and IL-36 background

Imsidolimab (ANB019) is a fully humanized IgG4 monoclonal antibody (mAb) designed to inhibit interleukin 36 (IL-36) signaling by blocking the IL-36 receptor (IL-36R) [1]. 

IL-36 belongs to the IL-1 superfamily. Three isoforms, IL-36α, IL-36β, and IL-36γ, mediate pro-inflammatory functions, while a fourth one, IL-36Ra, acts as an antagonist [2,3]. IL-36 signalization requires the formation of a complex comprised of two subunits, IL-1R6 (aka IL-36R) and IL-1R3 (aka IL-1RAcP, IL-1 receptor accessory protein). The binding of agonist ligands to the IL-36R allows the recruitment of IL-1RAcP and the production of pro-inflammatory cytokines and chemokines through the activation of NF-κB and AP-1 [2,3]. The IL-36Ra antagonist inhibits the signaling by binding to IL-36R and preventing the recruitment of IL-1RAcP [2,3]. IL-36-associated immune response mainly takes place in barrier tissues, such as the skin, lungs, and intestines. Dysregulation of IL-36 isoform expression and signaling has been associated with inflammatory diseases such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease [2,3].

The anti-IL-36R mAb Imsidolimab has been developed as a potential treatment for inflammatory diseases, particularly generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) [4]. It is still under clinical investigation: Imsidolimab has shown promising results, well-tolerated with no serious adverse events and a low incidence of infections (GEMINI-1). A follow-up study, the GEMINI-2 trial, is in phase 3 [5].

References:

1. Iznardo H, Puig L. 2021. Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease. Int J Mol Sci.;22(9):4344.
2. Buhl A-L. & Wenzel J.,  2019. Interleukin-36 in infectious and inflammatory skin diseases. Front. Immunol. 10(1162). doi: 10.3389/fimmu.2019.01162.
3. Zhou L, Todorovic V. 2021. Interleukin-36: Structure, Signaling and Function. Adv Exp Med Biol.21:191-210.
4. Warren RB, et al., 2023. Imsidolimab, an anti-interleukin-36 receptor monoclonal antibody, for the treatment of generalized pustular psoriasis: results from the phase II GALLOP trial. Br J Dermatol. 189(2):161-169. 
5. NCT05366855 : Long-Term Safety and Efficacy of Imsidolimab (ANB019) in Subjects With Generalized Pustular Psoriasis (GEMINI-2)