Complex study provided insight into immunological pathways

‘In the course of 2025, we evaluated the results of a study on a first-in-class compound from our client Sanofi. Thanks to our immune challenge models, we were able to demonstrate in healthy study participants the added value of this drug,’ says Clinical Scientist Anouk Meijs. The compound is a monoclonal antibody that targets IL-1R3, also known as IL-1RAP. This is a central co-receptor which plays a crucial role in the pro-inflammatory signalling mediated by three key IL-1 family pathways (IL-1, IL-33, IL-36). ‘The compound was developed to inhibit those three cytokine pathways’, says Meijs.

‘In consultation with our sponsor, we opted for an in-depth mechanistic study in healthy participants. We used two of our immune challenge models on the skin and compared the investigational compound with two drugs that are already on the market,’ says Meijs. The challenge models Meijs and her colleagues used addressed two of the three interleukin pathways mentioned above: intradermal lipopolysaccharide (LPS), activating the IL-1 pathway, and imiquimod, which acts primarily via the IL-36 pathway. The investigational compound was compared with placebo and with the two active comparators: the IL-1 inhibitor canakinumab and the IL-36 inhibitor spesolimab.

The local skin reaction induced by LPS and imiquimod was evaluated using techniques from the Dermatoolbox®: erythema with the Antera 3D camera and skin blood perfusion with the laser speckle camera. In addition, fluid was collected from suction blisters and skin biopsies were taken, in which the researchers looked for cytokines using Olink technology and gene expression with RNA sequencing. Meijs: 'The initial results from the visual measurements were already favourable. And that first impression was confirmed by the analysis of the blister fluid and the biopsies. The compound does indeed inhibit inflammation generated along both pathways, while with the other compounds we only saw the expected effect on the pathways that the drug inhibits. The inhibitory effect of the new drug was shown to be comparable and potentially superior to its comparators'.

Meijs and her team presented the results together with researchers from Sanofi at the annual congress of the European Academy of Dermatology and Venereology in Paris in September 2025. Research Director R&D lab and Immunology Dr Matthijs Moerland explains how the study and its results also provided scientific value: ‘Because we were able to compare this special compound with two other agents in two of our challenge models, we learned even more about the immunological pathways involved in our challenge models. This adds to the value of these models we use to contribute to the development of new immunomodulatory compounds.’