STAT6

So this is IL-4 and 13 dupixent.

And we went with the target right downstream, STAT6.

We looked at IRAC5.

This is type 1 interferon, B-cell autoantibodies.

These diseases can be treated by one drug, one mechanism only, which is blocking type 2 inflammation through IL-4 and 13 signaling.

So Dupixent has shown it, but there is no drug that targets this pathway intracellularly.

With a degrader, we can go after this transcription factor, STAT6.

And now we're in these two global face-to-face studies, one in AD, one in asthma.

So maybe there's a direct depletion there, but I think there's more to come there.

But the bottom line is that when you inhibit type 2 inflammation, especially if you're blocking, say, a STAT6 pathway through IL-4 receptor alpha, you would expect that IL-C2s could indirectly be affected as well.

And so it's very hard to know, you know, without depleting IL-C2s directly, which I'm actually place and find a specific marker, but there's no way to tell where you are in the chain of events in terms of the effect on ILC2s.

And nearly all of these studies haven't looked at tissue ILC2s, which I'd be most interested in because those are the ones that are wrecking havoc basically in terms of organ disease in our patients.

Now, if that same naive CD-positive, CD4-positive T cell is is encountering high levels of interleukin or another modulatory cytokine.

The transcription factors will be swapped out and more GATA3 and then STAT6 will be generated.

Those two proteins, GATA3 being the transcription factor, that leads to then the phenotype, the differentiated phenotype of Th2.

Th2 will then secrete interleukin 4, 5, and 13.