The Janssen Pharmaceutical Companies of Johnson & Johnson announced on Wednesday the first results of the in vitro MODIF-Y studies, supporting a hypothesis that may differentiate the mechanism of first-in-class TREMFYA(R) (guselkumab) from risankizumab due to the ability of TREMFYA to bind to CD64 positive (CD64+) cells in addition to interleukin (IL)-23 - both of which are key components of the immune system.

These findings, which are being presented at the Society for Investigative Dermatology (SID) annual meeting 18-21 May 2022 in Portland, Oregon, demonstrate TREMFYA binds simultaneously to CD64 via its native fragment crystallisable (Fc) region and to IL-23 via its antigen-binding region, suggesting the potential to neutralise IL-23 right at the site where it is secreted. Further studies will be conducted in vitro and in vivo to generate additional evidence supporting this hypothesis.

IL-23, a cytokine secreted by activated monocyte/macrophage and dendritic cells, is known to be a driver of inflammatory diseases, including plaque psoriasis (PsO), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). CD64 is a receptor that binds the Fc region of immunoglobulin G and is highly expressed on the surface of certain immune cells that are major producers of IL-23.

The MODIF-Y studies explored mechanisms potentially underpinning therapeutic profile differences between TREMFYA, a fully human monoclonal antibody specific for the p19 subunit of IL-23 with a native Fc region, and risankizumab, a humanised anti-IL-23 monoclonal antibody with a mutated Fc region.