Transcript
Dr. Neal Bhatia (06:59):
Yeah. And this is a good segue because we can put tapinarof into context. I mean, I remember being involved in the trials when GSK had it and then Dermavant, now belongs to Organon, but the pathway of tapinarof has been of, "Where do we put it into place?"
And we've gone also from thinking about steroid-sparing and steroid alternative to actually, "Well, how do we optimize the mechanism of this molecule and put it together?" So just again, think about where does tapinarof fit in your practice, and obviously indications aside, which we'll talk about, but where does it fit in your mindset?
Dr. Joshua Grosshandler (07:36):
Yeah, I mean, I think that's a really good question, and I think one of the beauties of it is it really has this ability to work on a lot of different conditions, right? Back into, how does it work? We know it impacts the barrier, it helps with the homeostasis of the barrier by working within gene expression of filaggrin and involucrin and loricrin and ceramide biosynthesis. We know it works both in the Th2 and the TH1T helper 17 pathway. So, it allows us to work within both psoriasis and atopic derm. Again, one of the medicines that we currently have and that we can use, tapinarof, is approved in both indications. And so I think for me, it's been really nice because it gives you that luxury in both.
As you mentioned, I think a lot of people are wanting to get away from steroids, and I think they're becoming more and more... These nonsteroidal alternatives are becoming a big part of what we're doing on a daily basis, short-term and long-term. And I think that that's where I've used a lot of these medications, is thinking more to the long-term, not only because again, most of these diseases are chronic, and we're continuing to treat them, and we're going to need things that we want to continue with over time and feel where they're safe. And again, I think there's great data showing that many of these medications are that way, and especially the aryl hydrocarbon receptor agonists fit within that. And so I'm using them all over the place.
In addition, too, we know that they're nice, because for instance, in atopic dermatitis, tapinarof is approved down to two years of age. So we can feel where, "Hey, we're safe in using it in that pediatric patient." And psoriasis is approved in adults, but it really, I think, gives us that flexibility, and that's where I've positioned it, just in these places where you want something that you can use over really long periods of time and really not have to be concerned about risk side effect like a steroid, potentially, where you have to use it.
Dr. Neal Bhatia (09:28):
And that's an important context for a lot of not only parents, but you think about someone who's been on steroids for decades, they had no other choice of the matter for some. But you think about the eyelids, intertriginous areas where atrophy was prime. But from that, and you brought up the mechanisms of epidermal integrity, and some of those important markers like, again, filaggrin and loricrin, where does that translate to a practical use?
I mean, you talk about, again, we can talk to patients about not having risk of atrophy and anything else that would be a downside, but is there another component of the barrier restoration? Are we actually thinking we could use this to restore epidermal barrier that's lost maybe in 3A or areas like that, or is that too much of a reach?
Dr. Joshua Grosshandler (10:15):
No, I mean I think that that's on point, in some senses, right? I mean, if we talk about a lot of these conditions that we just mentioned, atopic dermatitis and psoriasis, we know that there's this barrier impairment, right? We know that there's, if you use the brick wall analogy, that we've got holes in the wall in both of those, and we're allowing our diseases to be driven more with allergens and irritants. And so I think if you think about how this works and how it has the ability to turn on those genes to increase what we're missing, filaggrin, involucrin, loricrin, and that ceramide biosynthesis, I think it is something that can be helpful.
Now, if you go back traditionally and think about maybe some of our other medications or with any atopic dermatitis, for example, 4 and 13, when they're binding and they're creating atopic dermatitis, if you want to say it that way, they're actually also decreasing some of these things that we were just mentioning like filaggrin and such. And so it's this compounding. Interesting enough, it kind of does that actually through the aryl hydrocarbon receptor.
And so, again, I think we're used to using maybe some of these other medications that we're used to thinking about, "This is this mechanism," maybe a little bit too simplistically, but I think it is really helping, and we're showing that. There's been different studies done in mice and other things like that. If you knock out the aryl hydrocarbon receptor, can you induce atopic dermatitis or can you not improve somebody if you're using these different medications? And so I think they've really shown in some of these things how important it is. And so, I do think that it is helping us treat our condition in addition to how we may classically think that we're doing that.
