POS1531 GUSELKUMAB, AN IL-23P19 SUBUNIT–SPECIFIC MONOCLONAL ANTIBODY, BINDS CD64+ MYELOID CELLS AND POTENTLY NEUTRALISES IL-23 PRODUCED FROM THE SAME CELLS

Background Monoclonal antibodies targeting the interleukin (IL)-23p19 subunit are effective in treatment of psoriatic disease but have different molecular attributes that may translate to differences clinical efficacy. Within this class, guselkumab (GUS) is a fully human IgG1 monoclonal antibody with native Fc region, while risankizumab (RIS) humanised mutated region. Binding these therapeutic Fcγ receptor (FcγR) I, also known as CD64, interest, CD64 + IL-23-producing myeloid cells increased within inflamed tissue patients [1] . Furthermore, incidence and prevalence arthritis increases severity psoriasis [2] , joint activity positively correlated frequency peripheral monocytes [3] Objectives Functional characteristics antigen-binding regions GUS RIS were compared. Methods IL-23 binding affinity was evaluated vitro using kinetic exclusion assay (KinExA) surface plasmon resonance. In cellular potency measured by impact on IL-23-induced signal transducer activator transcription 3 (STAT3) phosphorylation blood mononuclear cells. FcγRs assessed transfected individual FcγRs. Primary “inflammatory” differentiated granulocyte-macrophage colony-stimulating factor interferon-γ (IFN-γ) induced produce via toll-like stimulation used assess potential capture endogenously secreted flow cytometry. The for IFN-γ primed trigger activation 41-plex cytokine bead assay. Results displayed comparable picomolar equivalent high inhibiting STAT3 phosphorylation. showed strongest compared other FcγRs, whereas had negligible any FcγR. GUS, not RIS, dose-dependent Fc-mediated primary monocytes. Moreover, CD64-bound able simultaneously from same ( Figure 1 ). did induce production. Conclusion binds its region neutralises potency. Our data suggest mechanistic benefit through enrichment disease, where increased, such potently at source These findings contribute clinical-therapeutic profiles between antibodies. References [1]Mehta, H. et al. J Invest Dermatol 2021;141:1707-1718. [2]Merola, J. Am Acad 2022;86:748-757. [3]Matt, P. Scand Rheumatol 2015;44:464-73. Acknowledgements: NIL. Disclosure Interests Dennis McGonagle Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB, Grant/research support from: Raja Atreya Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Celltrion Healthcare, Dr. Falk Pharma, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, InDex Kliniksa Merk Sharp & Dohme, Roche, Samsung Bioepsis, Stelic, Sterna Biologicals, Takeda, Tillotts, Maria Abreu Prometheus Bioscience, Focus Medical Communications, Imedex, Cornerstone Health, Landos Biophama, Cosmo James Krueger Aclaris, Allergan, Almirall, Arena, Aristea, Asana, Aurigene, Escalier, MoonLake Immunotherapeutics, Nimbus Lackshmi, Sanofi, Sienna Biopharmaceuticals, Sun Target-Derm, Valeant, Ventyx, Akros, Avillion, Exicure Incyte, Innovaderm, Kyowa Kirin, Novan, Parexel, Regeneron, Vitae Kilian Eyerich Hexal, LEO Kacey Sachen Shareholder Johnson Johnson, Employee Carrie Greving Deepa Hammaker Phuc Bao Eilyn Lacy Indra Sarabia Janise Deming Merle Elloso Christopher T. Ritchlin Iain McInnes Compugen, Evelo, Causeway Therapeutics, AstraZeneca, Cabaletta, Sanofi; Board member for: National Health Service Greater Glasgow Clyde; Trustee Versus Arthritis, Matthieu Allez Speakers bureau: Celltrion, IQVIA, Genentech/Roche, Anne Fourie Janssen.