CLEC4C

The activation of innate and adaptive immune responses including toll-like receptor sensing pathways in plasmacytoid dendritic cells is central to the pathogenesis of CLE.

Litifiblimab is a monoclonal antibody targeting BDCA2, a receptor expressed on PCs, and is designed to inhibit downstream production of type I interferons and other pro-inflammatory mediators.

In the Phase 2 LILAC Part B study of patients with CLE, litifiblimab demonstrated significant improvements in skin disease activity compared with placebo.

However, not all patients responded equally, suggesting the possibility of underlying biological heterogeneity.

And I think there's still a lot to be worked out, I think, in terms of the mechanism for how they're functioning.

So that brings us to what is BDCA2 and what makes it an interesting target for treating CLA?

Yes, BDCA2 is a C-type lectin that's expressed on the surface of the plasmacytoid dendritic cell.

And, you know, in the natural state, it serves as a down regulator of signaling through TLR7 and 9, which are in the endosome of the PDC.

And it also acts in its natural state for antigen capture because we know that dendritic cells, of course, are very important in antigen presentation to initiate the adaptive immune response.

And, you know, so thus it's a very interesting target because in ligating BDCA2, as I just mentioned, you will see a down regulation and inhibition of signaling through TLR7 and 9, which are very important in nucleic acid sensing, both RNA and DNA.

which then lead to the production of type 1 interferon and a variety of other pro-inflammatory cytokines.

So by harnessing this natural kind of inhibitory mechanism through binding to BDCA2, the idea here is to basically inhibit signaling through these very important toll-like receptors 7 and 9.