Small Molecules, Big Decisions: Where Do TYK2 Inhibitors Fit in Psoriasis Treatment?

And we're gonna start our talk and our presentation today first by going over some of what are some of the gaps that still remain in clinical care for our patients with moderate to severe plaque psoriasis, and where might TYK2 inhibitors fit in that particular paradigm.

So I would say when we're thinking about our systemic therapies for moderate to severe plaque psoriasis, we have here in pink, for example, our available oral agents.

And we also, here on the right-hand side, uh, the blue squares represent all the biologic agents that we have.

If we focus on the oral therapies, we've had our traditional oral therapies for a while, including methotrexate, cyclosporine, and acitretin.

And we have also our newly approved i gotrokinra, which is a IL-23 receptor-targeted oral peptides that's newly approved.

But prior to that, we've had two advanced oral therapies, such as apremilast, which is a PDE4 inhibitor, and our deucravacitinib, which I will say is probably our first-generation TYK2 inhibitor, which has brought, uh, many of our patients, uh, much r- needed relief, uh, during that time.

However, we still see, uh, some significant limitations with regards to our oral therapies for patients with moderate to severe plaque psoriasis, uh, for example, and especially with conventional oral therapies, though I would have to say, Larry, we, we see fewer and fewer use of the conventional therapies due to our more advanced oral therapies these days.

Uh, but that being said, I will say up till now when we're looking at our sort of first-generation advanced th- therapies, we're still seeing that many would switch to a biologic within about a year or two when we look at the latest literature due to some of the efficacy gaps, for example, that we're seeing.

And also, those who stay on oral medications sometimes report a lower quality of life.

And I would say a lot of this is, uh, more due to some of the efficacy gaps that, that we may see in this particular area.

And thinking about other challenges that we've seen with just treatments in general for our moderate to severe plaque psoriasis patients, I would say one of the key thing is probably long-term maintenance of response.

We may have patients who respond well initially, but then over a period of time they may lose that response, and we are oftentimes saddled with the question, "What to go to next? Should we consider dose escalation, or should we consider, for example, switching to a whole different class of therapies or potentially another, uh, medication in the same class?" So these are some of the continual challenges for patients with moderate to severe plaque psoriasis.

Uh, but I would say overall, uh, we are fortunate to have a number of different choices, but we, with these choices sometimes can come with a little bit of confusion as well, what to select for which patient, and so forth.

Now, today's talk is about TYK2 inhibitors, and we just talked about, for example, deucravacitinib being our first-generation TYK2 inhibitors.

We're really thinking about now next-generation TYK2 inhibitors and how are they different.

And when we're really thinking about the next-generation TYK2 inhibitors is thinking about oral therapies for a pathway we know that's very well implicated in psoriasis pathogenesis, which Larry will talk about a little bit later.

But really in terms of can we be even more potent, but also can we be even more specific in our inhibition of TYK2, and can we do it in a way such that we can preserve the safety profile also of these medications such that, such that our patients Can take these medications, uh, feel that they tolerate these medications well, but not only just doing that, but also that, uh, their, uh, overall health, uh, is not affected, but, uh, rather, uh, improves significantly as a result of taking these medications.

Few other improvements, uh, and then updates that have occurred during the last few months.

I mentioned i gotrol kinra already.

That's FDA-approved.

In addition to that, for apremilast, we now have the extended release formulation in the US, which is important because now we can take a twice-daily medication to a once-daily medication.

So if you have patients already responding or on, uh, apremilast, consider switching them to a once-daily medication for convenience issues.

Okay, here's a reminder to please submit your questions for us to answer during the faculty Q&A, and Larry and I look forward to seeing those questions.