Incyte Corporation (INCY) Earnings Call Transcript & Summary

[Audio Gap] Importantly, Dr. Pandya has dedicated his career to the treatment and care of patients with pigmentary disorders, including vitiligo patients. He's also the principal investigator for our povorcitinib vitiligo Phase II study, which was presented earlier today. Before we start, just wanted to mention one housekeeping item. This is our safe harbor statement. Just to remind everyone that safe harbor rules govern our remarks, and we ask that you review our latest SEC filings for a summary of the risk factors associated with our business. Why are we here? We are very excited to have shared or have had 3 oral presentations today at the late-breaking session at the American Academy of Dermatology Meeting. In addition to those 3 late-breaking oral presentations, we also presented or had 11 additional -- or excuse me, 8 additional abstracts for a total of 11 presentations and abstracts. What we'd like to do is focus today on the oral presentations that were made earlier. So we've made significant progress in our pipeline for vitiligo. And the slide shows, obviously, Opzelura, the first and only product approved for repigmentation for vitiligo patients. But that's the first of additional products that we are trying to develop for vitiligo patients. We have JAK1 specific oral molecule, povorcitinib, which Dr. Pandya will present and talk about later in the presentation, as well as our newest development product, auremolimab, which is an IL-15 receptor beta monoclonal antibody that targets skin-resident memory T cells and has the potential to provide a very durable and long-lasting response for patients. So we're obviously very excited by our vitiligo pipeline and very excited to be making history in vitiligo. Here is the agenda. I'll start the presentation with the rehash of the presentations by Dr. John Harris, Chair at University of Massachusetts, who talked about the relapse and maintenance in patients rerandomized to ruxolitinib number of vehicle in our long-term extension study. Then I'll also share the presentation done by Dr. David Rosmarin, Chair at the University of Indiana, who talked about the continued treatment with ruxolitinib cream in patients from our TRuE-V study to look at the safety and efficacy of continued treatment. Then I'll turn it over to Dr. Pandya, who will talk about the povorcitinib Phase IIb results that he shared earlier today. And also, he will provide some perspective about the patient treatment -- the patients that he treats with vitiligo as well as Opzelura's role in his clinical practice. And then in the last half hour of the presentation, we'll be joined by Dr. Steven Stein, Incyte's Chief Medical Officer, to answer some questions about our pipeline. So let me start by presenting the data from our long-term extension from our TRuE-V studies done and completed earlier this year and published in the New England Journal of Medicine. This is a schematic just to remind folks of the study design. So in the TRuE-V studies, we randomized about 670 patients, adolescents and adults, 2:1 with either ruxolitinib or vehicle cream. So at week 52, we've shared that data. And at week 52, the patients who had basically an almost complete response, defined as achieving a facial VASI score of 90 or greater, were rerandomized in a blinded fashion to either receive or continue to receive ruxolitinib cream twice a day or vehicle cream. And this is important because to look at randomized withdrawal, to look at durability, you really need to incorporate this blinded rerandomization design feature. For the patients who did not achieve or were not able to achieve a complete response or almost a complete response by week 52, they continued in an open-label fashion with ruxolitinib cream twice daily for an additional 52 weeks. So in terms of the objectives of the 2 cohorts within the study, in cohort A, we wanted to look at the relapse rate. And we define the relapse rate as basically losing the baseline facial VASI75 that they achieved in the earlier study. And then we also want to see the durability or the duration of response of patients randomized to either vehicle or ruxolitinib cream. And in the cohort B, we know that there are some patients who take a little bit longer to repigment their skin. And so we wanted to see what happens with continued therapy. Can -- those patients who were not able to achieve a complete response or almost a complete response, were they able to see improvement with continued therapy? And I think a very -- another very important objective of this long-term extension study was to really look at the safety with basically 2 years of continuous ruxolitinib treatment, rux cream treatment. And just a reminder, in terms of the 2 patient populations that were randomized in the long-term extension portion, if you take a look at the week 52, in the pink, that's the patients or those are the patients that were able to achieve a facial VASI90 or greater, and it's about 30% of the patients. All of the other patients, as you can see, many of them did very well. Many of them achieved a facial VASI75 or greater, facial VASI50 and even a facial VASI25, all of those patients continue to receive ruxolitinib cream in an open-label fashion. So this is just a summary of some of the important data that was presented by Dr. Harris earlier today. This figure, this slide summarizes the maintenance, as defined as patients -- the percent of patients who were able to keep a facial VASI90 response through this long-term treatment period. And in the blue line are patients that continued, and again in a blinded, randomized fashion, ruxolitinib cream twice daily. And in the green line, you see the patients who are rerandomized to vehicle cream, essentially withdrawn from active treatment. And you can see the vast majority of patients who continued with ruxolitinib cream were able to maintain the facial VASI90 response for basically another year. And so that was very encouraging. And surprisingly, 21% of the patients, so you withdraw active treatment, but 21% of the patients or more than 21% of the patients were able to maintain their facial VASI90 response through a whole year. And so this is very exciting. I think there are patients that can really have a durable response to treatment. But how about the patients who -- when the patients do lose the response, how long does it take? And in this slide, summarizes the time to relapse. And again, just a reminder, relapse was defined as when patients' response drop below VASI75. And again, in the blue line, you see patients who were rerandomized to ruxolitinib cream, you see the vast majority of them are able to keep a facial VASI75 response or higher. And then in the green, you see the patients rerandomized to vehicle. And the time to relapse in the vehicle arm, we see that 29% of the patients who were withdrawn for rux cream relapsed. And again, just pointing to the durability response in this patient population that was able to achieve either a complete or almost complete response in pigmentation. So very exciting data. I think great news for patients who stopped treatment for one reason or another, many of them are able to maintain their pigmentation for a very long period of time. And then for the patients who did lose their response or pigmentation over time, an important question is, well, what happens if they basically restart treatment? And in this slide, you see the time to regain at least the facial VASI75 over time as well as time to regain a facial VASI90 response over time. And the one thing I need to point out, though, is many of these patients lost a response later in the year of treatment. And so many of them didn't have a lot of time to gain back the repigmentation. But for the patients that lost response were basically restarted on ruxolitinib cream, we see that 75% of those patients basically were able to regain the facial VASI75, and the median time it took was about 12 weeks. And again, very, very exciting that majority of them, almost 70% of those patients, were able to achieve a facial VASI90 response. And the median time to retreatment or median time to reachieve that response was 15 weeks. So it's really great news for patients. So we have many patients who have a durable response. And for the patients who do lose their response, they can basically reachieve the high clinical response that they achieve with treatment. They get it back if they restart ruxolitinib cream. So just turning to cohort B. The cohort B again was the patients who weren't able to achieve a facial VASI90 response by week 52. And if you take a look at them and follow them over time, so in the left, you see the facial VASI75. Again, that was the primary efficacy variable in our pivotal study. So if you track those 2 groups of patients, in the blue are the patients who were initially randomized to active drug, so ruxolitinib cream 1.5% twice a day. And in the green were patients who were initially randomized to placebo or a vehicle cream for 6 months or 24 weeks and then crossed over to active treatment at week 24. So there's going to be a lag in terms of getting treatment suppressing the immune response and therefore, seeing the pigmentation, allowing the melanocytes to come back and lay down new pigment into the skin. So for the patients who started off in ruxolitinib cream and weren't able to achieve a facial VASI90 response at week 52, you see that the continued treatment leads to continued improvement. And the same goes for the patients initially randomized to vehicle cream. Again, over time, their response to the number of patients who have a better response, who were able to achieve a facial VASI75 improves with continued treatment. And the same goes for the percentage of patients, the proportion of patients who were able to achieve a facial VASI90. And again, this is really important because the facial VASI90 really is almost a clear or almost a full repigmentation response. And so we see that patients who are a little bit slower in response with continued therapy can really achieve an outstanding outcome clinically. So really, really encouraging data from that second cohort because we know that some patients will take a little bit longer. And I think physicians can really, if they understand this, can reassure them that with continued therapy, they will continue or most of them will continue to get a better outcome, better repigmentation over time. In terms of safety, and I think this is really, really critical, and so you have many patients, in fact, most of the patients who were treated continuously for almost 2 years or for 2 years with ruxolitinib cream. So -- and what we saw from both cohorts is that there was no change in the safety profile with an additional year of continuous therapy in these patients. And so very reassuring from a safety perspective. Again, we -- in the earlier part of the study, the most common side effect that we saw was acne, application site acne as well as a little bit of application site itching. And we saw a little less of that in the second year of treatment. But we didn't really see anything that changed the safety, overall safety profile of ruxolitinib cream. So I think this is very reassuring for patients as well as for treating physicians that 2 years of therapy, you continue to see a continued improvement in terms of repigmentation, but really don't see any change in terms of the overall safety. So in terms of what we see from this long-term study, from the 2 cohorts in the study, we see that with continued therapy, most patients will see continued repigmentation. And so that's a very important message to -- for physicians to tell their patients to provide that level of reassurance. And then other, obviously, critical aspect is for patients who are able to achieve response, and then for some reason, they either stop therapy because they want to take a break or for other reasons, we know that -- or we see that there is a very durable response. Many of these patients will essentially keep their pigmentation for an extended period of time. And when they do lose their pigmentation, when they restart ruxolitinib cream, we see that most of them are able to regain their pigmentation. So again, very reassuring from a long-term treatment perspective. And again, the last thing is that safety is we don't see any additional liabilities with an additional year of treatment, and so very well-tolerated. This is what we saw in the first year, and we continue to see that safety pattern in the second year. And so as I mentioned, Opzelura, this is great data, but we're not done there yet. We have lots of other clinical studies. I just wanted to point out one in particular that is somewhat relevant to this data set, and it is a Phase II study that essentially combines ruxolitinib cream with phototherapy. Especially for those patients who are a little bit slower in response, if they want to speed up the repigmentation, we're going to see if phototherapy can boost the melanocyte activity. We know that ruxolitinib cream takes care of the inflammation and the immune response against melanocytes, but what it doesn't do is boost the melanocytes that are perhaps senescent or have not been active for many years. And so we know that phototherapy can boost that response. And so we're studying the combination therapy and should have that data, hopefully, sometime either at the end of this year or early next year. So with that, I would like to turn the podium over to Dr. Pandya.

Thank you, Jim. It's a pleasure for me to be here to really speak about these exciting studies. I've been in practice for 30 years, and this is the most exciting time I've ever seen for vitiligo and the vitiligo community. I was a professor at UT Southwestern for 30 years, internal medicine background, then went into dermatology. After running our cutaneous lymphoma clinic and autoimmune blistering disease clinic, I decided to focus all my time to pigmentary disorders. So for the last 13 years, I have been laser-focused only on pigmentary disorders, including hypopigmentation, which is what you're seeing here, and hyperpigmentation. My practice is in Sunnyvale, California, and I only see pigmentary patients by referral. And so I see quite a few patients. And I can talk later about the numbers, et cetera. I'm also the President of the Global Vitiligo Foundation and really working with the entire vitiligo community in trying to improve awareness and research for vitiligo. Well, I have the pleasure of being the PI for this -- for the povorcitinib Phase IIb study. And you can see some of my other co-authors here. And from the beginning, really consulting with Incyte on the design of the study, and now we're seeing the results of the study. In this study design, we enrolled adults 18 to 75 years of age with nonsegmental vitiligo. They had to have over 8% total body surface area and the face had to have more than 0.5%. Now what does that mean? Well, if you look at the Opzelura study, the criteria were over 3%. Most vitiligo studies that have been done by industry have been more like 3% or more and then the F-VASI is 0.5%. So we already are looking for more difficult-to-treat patients. When you look at the study design, you'll see there were 4 arms. There was the povorcitinib 45 milligram, 75, 15, and placebo. After 6 months, the primary endpoint was read, then the patients were transitioned to either continuing with 45 if they were on 45 initially or continuing on 75. The 15-milligram group was then transitioned to 75, and the placebo was also transitioned to 75 milligrams. The primary efficacy was the improvement in the T-VASI in this study. Patient demographics, these are really important numbers to look at because this is the first time somebody has tried to look at total VASI improvement in vitiligo. Why is this important? Because improvement in vitiligo is a 2-step process. First, you have to remove the inflammatory T cells, and then you have to stimulate the melanocytes to repigment. Or you can do that on the face because patients are exposed to sunlight. But when you're looking at T-VASI, the vast majority of the lesions are covered by clothing. And so this was a much higher bar that we had to reach. The age of the patients was older than the previous industry-sponsored studies. It was 50. Vitiligo usually starts in the 20s -- between 20 and 30. So these were older patients, and older patients tend to be harder to treat. Also, you can see the majority were white, but I was really happy this study enrolled a lot of Hispanics, 19% Hispanics, which is equivalent to the United States population of Hispanics. I was also happy to see that 33% were skin types 4 through 6. And this is a chronic problem in dermatologic studies is that we don't have patients with darker skin types that enroll. But this was a robust number of patients with skin types 4 through 6. The baseline F-VASI was the highest we've ever seen in any industry-sponsored study for vitiligo. It was 1.3. Just to give you an idea of what that means, the entire phase is 3 or 3.5. So 1.3 means 1/3 of your face is white compared to your normal skin. And that's a lot. That is quite noticeable compared to, let's say, 0.25 or 0.5. The T-VASI was huge, 25%. The average T-VASI of patients coming into my clinic is 3%. These patients had severe vitiligo involving a large part of their body, and so again, a high bar to try to repigment that. Not only do they have a high T-VASI, but these lesions are going to be large and melanocytes have to migrate, they migrate slowly. So larger lesions take longer to repigment than smaller lesions. The duration of the disease was 19 years. Again, the longest duration of any study that's been done, and long duration of disease is harder to treat. These patients have white hairs. The vitiligo not only destroys the melanocytes in the epidermis, but it destroys the melanocytes at the base of the black hairs, which makes repigmentation harder. So the longer you have the disease, the harder it is to treat these patients. The duration -- I'm sorry, the family history was also high. You can see 28.7. And there's some feeling, although the data is not that strong, that patients with family history of vitiligo may have more severe disease than those who don't have a family history. You can see 27% had thyroid disease. And previous therapy, topical corticosteroids, 50%; calcineurin inhibitors, 37%; and 45% had, had some type of phototherapy. So these were naive patients when it comes to treatment. Here we have the T-VASI results at the outcome measure. Now I normally like to talk to my patients about how -- what percent improvement they're going to have. Like you're going to have 30% improvement in your lesions over a period of 6 months, for example, or 60%. But the T-VASI is a high bar because we're asking 50% of the color to come back over the entire body on average. Again, that is a very high bar. And you can see the results here with the 3 bars that there was a difference between placebo and the numbers there at 24 weeks. When you look at the transition, you'll see that the group that was on 15 milligrams and then transition to 75 milligrams rose up when they go up to 36 weeks. And in the other 2 groups in the green bar and the blue bar did go up as well. Now there is some variation. When I looked at this, I wondered why the green bars were higher than the blue bars even though the blue was 75 milligrams. And some of this may have to do with the fact that it's possible that these were not evenly distributed patients. It may turn out that the patients in the blue bar, the 75-milligram group, had more involvement of the body, also had signs of activity, and signs of activity can make your treatment more difficult. So we need to look at this data and get a little bit more granular to find out why there's a difference here. And also in terms of the crosshatched red group as they revved up at 75 milligrams, we're again going to have to look at those patients carefully to see what exactly was the baseline value of their VASI scores and then how much activity they had. But you can see that there was clearly a difference compared to placebo, and they continue to improve through week 36 of treatment. When we look at the F-VASI50, or 50% of your color is back on the average over your entire body by 6 months, you can see in the green, and I'm having trouble reading that number exactly, but you can see it's around 40-something percent. And then it continued to improve through week 36 of treatment, where you can see it is quite highest in both the 75-milligram group and the 45-milligram group. The F-VASI75 is -- seems to be one of the more commonly looked at outcome measures now. Studies have shown that patients believe that 75% to 80% repigmentation is what they consider clinically relevant on their face. We haven't asked patients for the body in larger studies, and we're working on that in the Global Vitiligo Foundation to find out what's relevant for them in terms of clinical improvement for the body. But suffice it to say, F-VASI75 seems to be a good goal to try to get to. And you can see that there was a significant number compared to placebo that did achieve that F-VASI75. This is a slow process. These patients who are not being treated with phototherapy, they were getting just regular sunlight. They were not asked to sunbathe, as they are in other countries that the way vitiligo is treated. And yet, we did see that improvement, and that continued on through week 36 of treatment. Here are some patient photographs. You can see the patient on the left, she had 44% improvement in her F-VASI at 24 weeks, and then she was switched to the 75 milligrams, she was on 15 milligrams. And now at 75 milligrams at week 36, 12 weeks later, she zoomed up to 85% improvement in her F-VASI. And then on the extremity, you see the patient on the right, she improved by 31.8% and then she zoomed up to 64.8%. In these pictures, you can see the perifollicular repigmentation. This patient was fortunate that she had hair follicles with black hairs. And around those black hairs, the melanocytes migrated up the lateral root sheet and then filled in the skin, and you can see the hundreds of dots on her skin as a result of those melanocytes migrating out of those follicles. That takes time. That takes months and months and months of time. Even if all the T cells are removed from the skin, it requires time for those melanocytes to respond, and they will do so more with light exposure and she was just us getting incidental sun exposure to extremity. It was generally well tolerated. No serious adverse events were considered related to treatment. No new safety signals were observed. I'll just point out acne. Acne is something that we see in JAK inhibitors, and you can see the 75-milligram at 14% acne, 7% -- I'm sorry, yes, 75, 14%. And then 45 milligrams was 7%. So there was a difference there in those numbers. That seemed to be the most important. You can see the fatigue was in 14% in the 75-milligram group and 7% in the 45-milligram group. So this was the first report of povorcitinib in patients with extensive, and I just want to underline extensive severe vitiligo. It was associated with substantial repigmentation with -- in patients with this extensive vitiligo after 24 weeks. And we saw continued improvement through 36 weeks, and I'm looking forward to seeing the follow-up data, the 52-week data, to see how these patients improve. And it was generally well tolerated with a good safety profile and a few great -- greater than 3 of serious adverse events. All right. So I'm going to go on and give you kind of a general overview of vitiligo and kind of the big picture and give you a little bit of information about my practice and how I treat these patients and what I see. Again, I have this clinic in California, specialty in vitiligo and pigmentary disorders. I see about 80 vitiligo patients per month. And of those 80 patients, about 20 are new and 60 are follow-ups. You can see the Palo Alto Medical Foundation, where we have the pigmentary disorder clinic. At least 50% have facial vitiligo. Almost all have visible lesions, that's why they come to see me. Very few come for vitiligo that's exclusively in areas covered with clothing. And 100% of my patients receive treatment, at least some type of treatment. I'm very active in the vitiligo community. Again, President of the GVF. Also organized the Vitiligo International Symposium. Vitiligo is bad enough in the United States, but it's a disaster in other country. When you look at quality of life studies that compare Saudi Arabia, the Middle East, India, have the highest effects on quality of life. A lot of that has to do with culture. A lot of that has to do with the fact that this was thought to be a curse. Going back thousands of years, it's in the Ebers Papyrus in Egypt. It's in the Rig Veda in the Hindu writings, and it's in Leviticus Chapter 13. Vitiligo goes back a long way, and there is a stigma to it. And so that's why our international symposium is well-attended by doctors from around the world. We just had it in Bangalore. Our next one will be in Cairo. I'm also an editor for MyVitiligoTeam, which has 10,000 followers online, on social media, that learn about vitiligo, and our Board of Directors supplies this information. So I'm quite a bit involved in the area of vitiligo. I have a very busy practice. We have right now about a 5-month waiting list, if you want to see me as a new patient with vitiligo. And that's very distressing to patients because, as you can see, in 3 months, you can have relapses, you can have worsening of your vitiligo. And so many of them have told me, "Doctor, 5 months ago when I made my appointment, I just had a little bit, but look at me now, it's gotten the worse on my face because it took that long to get in to see you." So there is a problem with not having enough doctors that understand vitiligo and actually have seen a patient from 0 to 12 months and watch that patient get better with serial photographs. That motivates a doctor. That motivates the patient. Most dermatologists do not do that. And that's something that I hope Incyte can partner with us so that we can teach doctors how to properly take care of vitiligo so that we can have more positive results. Unfortunately, because of my time constraints, I just can't see any more than I'm seeing right now. Well, you know what vitiligo is, and you know that -- what it does to people. What you see is on the surface, but it really affects the patient's psychologically quite a bit. You can see anxiety, depression, suicidal ideation. There's a famous young man named David, who the vitiligo -- all of us who are vitiligo specialists have heard of him because he's been presented in various meetings. And he had vitiligo on his face. He was African-American, and he took his life because he just could not live with this stain and this depigmentation and everybody is staring at him and having to explain it to hundreds of people. Just when he walks down the street, everybody is asking him about it and looking at him, et cetera, et cetera. So we have had suicides from that, certainly a high incidence of anxiety and depression, body dysmorphic disorder. It does impact careers, those who are seeking jobs. We have shut-ins, a lot of shut-ins who will not go out because of their vitiligo. And some of our individuals in the vitiligo community will visit people's houses to talk to people with vitiligo to help them try to get more confidence in getting out of their house. The economic burden is definitely significant, the multiple doctor visits. These patients are coming into my office 3 times a week for a whole year. If I'm lucky enough to get them a home unit, then they can be treated at home, but they still have to see me every 3 months. The medication cost is definitely there, lost time at work that they have to explain coming into my office this economic burden, and also lost time at school for the kids that I see with vitiligo. We did a study in which we looked at the psychosocial comorbidities, and we found many items, and these were hundreds and hundreds of patients that we did look at in this publication. And you can see the depressive disorder, behavioral impairment, emotional impairment, suicidality, anxiety-related disorders and just many different disorders that have been associated with vitiligo in multiple studies with its effect on quality of life. So the problem is that vitiligo is undertreated. The standard story I get is, "Doctor, I got this 10 years ago. I went in to see my dermatologist, they said, 'Oh, you have vitiligo. There's not much you can do for it. Here's a cream. It's probably not going to work, but you can try it.' I used it for 2 weeks, I stopped and my vitiligo get worse." I have heard that exact scenario hundreds of times, that story. Patients -- few patients are being treated correctly. There's lack of approved therapies. Now we finally have our first FDA-approved treatment and even clinical data. We don't have as robust clinical data as what Jim just showed for corticosteroids or tacrolimus, even though these have been around for decades, just these studies were never done. Vitiligo was underfunded. It's just not -- it's underresearched. The lack of compliance with treatment, and that's a big problem, and that makes me wonder about the slides that Jim showed. If you ask -- if you have a person who's already repigmented 90% of their face, and you tell them, keep putting this cream on twice a day for 365 more days, you know your compliance is potentially going to be lost. And so I think that we should be looking at maintenance treatments, for example, perhaps twice a week or 3x a week to see if they can maintain their treatment because compliance is a big problem with topicals. I'm looking forward, povorcitinib, once-a-day pill, which patients really do prefer over having to put something on twice a day. The burden with cost that we've already talked about, and then I've already talked about the fact that health care practitioners are really not that familiar with it. When we think about how many people have vitiligo, there's about 2 million to 3 million people about -- we think about 0.8% of the population and less than 200,000 are being treated. In fact, we are about to publish a study that shows that 40% of people with vitiligo are not even diagnosed. And the way we figured that out is we sent out an online survey, and we asked people to answer some questions, and they sent in some pictures. And we were able to diagnose vitiligo by pictures in patients who had never seen a doctor for those white spots, 40%, especially in the Latino and the African-American community who undergo the greatest health care disparities in this country. So there is a large number of people out there who are underserved and are not utilizing the -- utilizing health care. So I think that Opzelura can actually change this lack of treatment because I have had patients just this last week, 2 of them came in and I said, "Okay, can you tell me why you came in today?" They go, "Oh, I saw something on TV about this new cream, or I heard about something -- my relative. And I heard about Opzelura, and I'm here because I want to get on that. And I'd like to hear more about that because I've never heard of any FDA treatment for vitiligo." And so I think that's going to change the paradigm. It's going to bring thousands of patients into dermatology office because they're hearing about Opzelura, and they have this desire to treat. And I think that doctors will be more willing to treat because doctors are skeptical about tacrolimus. They're kind of fearful of corticosteroids. They don't think that low-potency corticosteroids work, especially on the face and -- I'm sorry, especially on the body. And on the face, they are reluctant to use high-potency corticosteroids. I personally don't think tacrolimus works from the neck down. I did a study in which we treated half the body with vaseline, half the body with tacrolimus. And after 12 weeks, we saw the same improvement with phototherapy. So we don't have robust data with those. And now we have with Opzelura this good robust data that actually went past the bar of -- the rigorous FDA standards of what's needed to get a medication approved. Now each patient is unique. We -- there are different drivers of patients seeking treatment. What will cause a patient to seek treatment? So here's the story I've heard many, many times. "Doctor, I got this on my knees when I was young. I just learned to wear Capri pants, I just learned to hide it. And it's been like that for 25 years. but I got this new job, I got a lot of stress. And look, now it's on my chin and my forehead. And I am scared to death that it's now going to be on my face. It's never been on my face. Now I want some treatment." I have heard that countless times. So it's the location and also the extent. "It was just on my fingers, Doctor. Now it's in the back of my hands, and now people can see it. I was able to hide it on my fingertips, but now people can see it." So extent is definitely an issue and location of the lesions. The number of years with vitiligo. When you look at the actual quality of life, you find that people who got it when they were 5 years old have a better quality of life as adults than people who got it as adults. They tend to have a higher stress from the vitiligo and lower quality of life. Access to a vitiligo treatment center is a big problem. Right now, we only have maybe 9 treatment centers of people who publish on this and see a lot of vitiligo patients, and we need a lot more. And one of our goals with the Global Vitiligo Foundation, in conjunction with support from Incyte, is to have more webinars and more educational events around the country for dermatologists, so they can learn state-of-the-art treatment of vitiligo. And insurance coverage, of course, is also an issue. These patients have difficulty getting phototherapy coverage, excimer light coverage. And Opzelura, surprisingly, we've been able to get good insurance coverage with -- for Opzelura in the majority of our carriers and especially now that Incyte has given us a very easy way to get prior authorizations authorized. So the majority of my patients are able to get it. I would say about 75% of my patients are able to get Opzelura. 25% are not able to get it, and most of them are the Medicare patients. So insurance coverage is also ways -- it's a factor in terms of those who come in for treatment. In terms of what percentage of patients have success with treatment and adhere to treatment, it really depends on the areas that are being treated. If they have vitiligo on their face, and they still have black hairs in the areas of vitiligo, 90-plus percent of those patients are going to respond to treatment. The hands don't respond as well. The feet don't respond as well. So I think that the vast majority are going to have a response, and Opzelura would be perfect for those patients. All right. In terms of the treatment plan, factors to think about, do they have stable vitiligo? Do we need to stabilize the vitiligo? So the patients you see there on the hand, you noticed that there's light brown areas as well as normal colored areas and then there are white areas. That's called trichrome vitiligo or 3-color vitiligo. If I biopsy those areas with light brown skin, I would see hundreds of T cells in the skin killing melanocytes. This is active disease. This patient has an infiltrate of T cells as opposed to someone who has white spots that have not changed for many years. So if they have unstable disease, I'm going to treat with oral steroids. I hope I can get something like povorcitinib in the future, something that's more aggressive. And -- but right now, I'll treat with oral steroids, topical Opzelura and phototherapy. I will pull out all the stops and treat this patient with all of that right now. So unstable vitiligo. And then also in terms of what their goals are, every patient is unique with their own hopes and fears and goals, and that's how I customize my treatment. If a patient says, "If I can't get 100% back, Doctor, then I don't want treatment," then we just stop right there. We have that conversation. But hardly anyone says that. They say, "If I can just get some back, I can feel like I'm more confident and I can -- if I can see the color coming back, then I will stick to continuing my treatment, and I want to go until I plateau." That's what the majority of patients will say. Some of them have had bad past experiences with treatments, and that's something I have to kind of overcome. But the nice thing about Opzelura is that even if they've had bad experience with dermatologists, when they see that commercial on TV, they say, "Oh, there's something new." And then they'll go online. They'll Google vitiligo specialists. They'll find me, and then they'll come in for that. They also need to know percentages. Every single patient I say, "Look, if you follow this treatment plan, -- you are -- over your entire body, you're going to be 25% better in 3 months, 50% better in 6 months and 75% better in 9 months." And those are real numbers from multiple studies as well as my experience. So it will be higher on the face, less on the hands. And when I explain that to patients, then they comply, and then they understand that they shouldn't call my office in 6 weeks wondering why they're not much better. It's a slow process. You really need to set those expectations. And then the logistics and the cost, where do you live? Do you live close to my office? I'm the Phototherapy Director for the entire Bay Area for Sutter Health. And so we have 8 centers where they can get phototherapy around the Bay Area. So that's one thing. The other thing is, can you afford a home unit? I have 600 patients with home units. So can we get you a home unit? So lots of things when it comes to logistics and how they're going to get phototherapy combined with their treatment. And of course, their ability to afford their treatment. Their age, some of my elderly patients think that it's too much hassle to do all this, and they just want to treat their face and they don't want to treat their body. They just want to maintain their treatment. But some of my younger patients want to keep -- going full board until they get maximum improvement. Cultural background is huge. I work in the heart of Silicon Valley. I've got Apple to my right in Cupertino. I got Google to my left in Mountain View. So we have a huge number of Asian patients in my practice who are all into -- in the IT field. When you come from an Asian background, you have much higher stakes when it comes to marriage, for example. If you have vitiligo and your parents are talking to the parents of the potential mate, they will -- they might call off the wedding because you have vitiligo, and they don't want vitiligo in the family. No longer do Indians and people from all Asia feel that vitiligo is leprosy. They understand that vitiligo and leprosy are different, although in ancient times, it was not there. In fact, the name for Vitiligo was [Foreign Language], which means white leprosy in Sanskrit. But we know now and all people in South Asia know it's not leprosy. However, they know it's genetic. And so if their family does not have vitiligo, they will not bring a bride or groom into their family with vitiligo. And this causes a tremendous amount of stress to the family. Not only that, but the 14-year-old brother of the woman who is looking to get married, if he has vitiligo, she won't get married because once they find out her brother has vitiligo, they're afraid those genes will come into their family. And so that 14-year-old young man has a tremendous amount of stress because of the sadness he's brought to his family. These are the stories I hear. These are the stories that a lot of dermatologists don't know when they see this desperate person coming with one single spot of vitiligo on each hand, wondering why is this person making such a big deal about their vitiligo. They don't understand what's going on in India, what's going on with marriage, what's going on with parents. You have to really scratch the surface and understand that. So culture, ethnicity, those things are super important. I'm amazed at how much support there is in the African-American culture. African-Americans can handle vitiligo in such a noble way with so much support that I have just been blown away how they go through life with vitiligo and able to get support from their community. So when it comes to vitiligo, there are 3 pillars for effective treatment. And if you pay attention to these 3 pillars, you can get effective treatment. Again, there is a nuance in vitiligo treatment. And I hope that all 15,000 dermatologists can learn this now that we have these medications. First, you have to reduce the triggers. So we avoid trauma, and we also give antioxidants to reduce the triggers. We reduce the immune attack on the skin. We give tacrolimus, pimecrolimus, topical steroids, but now Opzelura is my go-to cream. If it's covered by insurance and the patients can get it, there's just no downside to Opzelura. It's well-tolerated, patients like it. It goes on well. It's not an ointment like tacrolimus. You can put it on your eyelids. You can put it on your -- around your mouth. You could put it on the genitals. It's just an easy medication to use. And then phototherapy comes in after 3 months. It takes about 10 to 12 weeks for phototherapy to remove those T cells in the skin. So I also, in the beginning, at least, certainly for the first 3 months have to give phototherapy, and that stimulates melanocytes and melanin production. Afamelanotide, is another drug that can be used, but it's not available in the United States. And sometimes we do skin grafting and cellular grafting. So these 3 pillars of therapy are important in all of my patients, and I actually go through all 3 pillars with every single patient that I see. So now with Opzelura, we have this first FDA treatment. It's got this impressive efficacy when you looked at the TRuE studies. And I use it as my #1 choice now. And 90% of my patients, I think, qualify for Opzelura. I don't use it in small children. It's not approved for children less than the age of 12, and I see many children with vitiligo. I don't use it for patients with extensive vitiligo because it's only approved for more than 10% -- up to 10% of body surface area. So I tend to avoid it in those individuals. But otherwise, I tend to use it in all my patients, and it's working well for me. So setting those expectations is important, the repigmentation takes time. And this is a great patient for me to illustrate that. This is my patient. She was in the Phase II study, and trust is super important. How do you see a patient every month in a clinical trial, and they're not getting better, and she continues to apply a cream twice a day? That's hard, and it requires trust between her and me. And she trusted me. I knew her. I knew her husband. I developed a relationship with them. And she came in month after month after month and did not get better. In fact, if you look at that second picture, she's actually a little bit worse. I didn't know she was on placebo. She didn't know she was on placebo, but this is how trials are done. And so I was promising her at month 4, month 5, that, "Don't worry at month 6, I know you're going to get the active drug. Don't worry, we know -- I don't know if you're on the active drug right now. It takes time for T cells to get cleared out. It takes time for melanocytes. I don't know if you're on." Look what happened here 6 months later. She repigmented dramatically, you can see like 90-plus percent. She was absolutely delighted, and so was her husband to see that repigmentation. And she understood about the slow migration of melanocytes. Fortunately, she went on. Incyte was able to provide phototherapy for these patients at home, and she got a home unit. She 100% repigmented her face and her neck. She came to our celebration of World Vitiligo Day. The day I saw her on the dance floor was one of my wonderful days, and I got to celebrate with her as she was so happy, so happy that she got her color back because she said, "Doctor, I'm black, and this is part of me. This color is actually how I define myself." It was very important for her own sense of self. So I just wanted to tell you that story because she was one of my memorable patients. Again, the speed of repigmentation depends on the area of the body, age, length of diagnosis and if they have black hairs. When I first saw her, I pulled out my dermatoscope and I noticed all her tiny hairs on her forehead, her temples, her cheeks, even her chin were black. And we have thousands of tiny hairs called vellus hairs on the face. So I knew she had the potential of improving. If all of them were white, I would still treat her exactly the same, but I wouldn't expect 90% repigmentation. It would be a lot less. So we have to look at these things before we start. So the percent of repigmentation definitely varies, and compliance is important. I explain this to patients who are complaining about applying it twice a day. "Doctor, I'm only putting it on once a day." I said, "Well, in the Phase II study, the once a day did improve, but the twice a day improved more. And if you want to have that delta, you want to have that 12% to 14% improvement, you should do it twice a day." The majority of patients are likely to respond to Opzelura. You can see the F-VASI responses after 52 weeks. You can see the F-VASI90, 75, 50 and the 25. And then Jim has already talked about that they continue to improve. I always talk about a plateau with phototherapy because after about 9 months of phototherapy, one plateaus, but it's very exciting for me to see there is no plateau. We have not hit the plateau quite yet with Opzelura. So I'm looking forward to seeing what happens to patients who are treated even longer. So they can respond to longer treatment. And if -- so the F-VASI is not reached and what they want, F-VASI90, we just keep going. Now what happens if F-VASI25 is not reached at week 24, you could add phototherapy to provide a boost. But actually, I would do that at week 12. If a patient insists that they do not want to do phototherapy and they just want to just get their sunlight from walking outside and at week 12, we don't have even an F-VASI25, 25% improvement, I am going to insist that they figure out a way to do phototherapy. And one way or the other, we'll try to figure out a way to do it, to get that phototherapy. In terms of follow-up. I see them at baseline, and I see them every 3 months. And my nurse takes a picture of their vitiligo lesions. And when they come back, I pull up the lesion on the screen with them, and I show them and I look to see if there's 25% improvement. The only way you're going to be able to detect 25% improvement is with photographs. Here you see more pictures, continued improvement at 104 weeks. So if a patient comes in at week 52, he's going to be happy, but many times, he's forgotten what he looked like initially. And I can't tell you how many times that I'll see a patient like in week 52 and he'll be looking at the glass as half empty. He'll say, "Look, Doctor, I still have this." And I said, "You know what, let's pull up your baseline picture." And when I pull up their baseline picture, they said, "Did I look like that?" I said, "Yes." "Because I forgot how bad I was. I'm glad I'm better." And that motivates him to continue. And you can see at week 104, he continued to improve with 83% improvement in this picture. And then so you have multiple possibilities for maintenance once the F-VASI90 is achieved. What would I do if F-VASI90 is achieved? Well, I have a conversation with my patient at that point. I'll say there's a possibility you could get F-VASI100 if you are willing to put this on twice a day. And so I'll say, "Look, you have a choice." Some patients say, "No, this is enough. I'm tired of putting this on twice a day. So I'm just going to stop." In that situation. You have about, as Jim said, about a 30% chance of losing a substantial amount of your color after 1 year. If you don't want to do that, you should stay on the Opzelura. The other option is something that hasn't been studied yet, and that's twice a week Opzelura. The reason I say that is because there was a study in which they used tacrolimus twice a week, and they found that if you use tacrolimus twice a week after you had repigmented, you only have a 10% chance of relapse, whereas if you don't use anything, you have a 40% chance of relapse. So I tell my patients on Monday and Friday, apply the cream, and they're willing to do that twice a week. That's something that they like. I will be excited to see if Opzelura will be able to match tacrolimus. I see no reason why it would not. So that's kind of what I do in terms of whether we're going to stay on Opzelura continuously, stop it or give it twice a week. The other good thing about the study that Jim talked about is that I tell my patients, if you do have a relapse, don't worry, it will -- we can repigment you. I say that with my photo -- even currently with my phototherapy patients that you can repigment. I will -- I tell them I will never let you get back to the way you were when you first saw me. That is -- that statement right there is such a relief to my patients when I tell them that. I'm going to work with you, and I'll never let you get back to the way you were when you first saw me. So how has it changed my clinical practice? Well, like I said, there's a lot of patient excitement. People are coming in. I actually am very happy that Incyte is putting these commercials, the one with Morgan Freeman, the one with Pearl Grimes on TV and these announcements because a lot of people really didn't even know about vitiligo or they thought there was no treatment. And for me to know there's 40% people out there who are not even coming to see a dermatologist, I want them in my office. I want them in dermatology offices, and this is what Incyte has helped us do. So they're excited. Motivation is high. They are proactively scheduling appointments to ask about Opzelura. Like I said, just this week, I had 2 say that. That's why they came to see me. I got this 4- to 5-month backlog. And so what does this mean for physicians? They need to provide patients this education like I've just told you. The way I've described it to you, I think if every dermatologist does it that way, we would have better compliance, we would have better results. And physicians, dermatologists would be more motivated. They can now offer this FDA-approved therapy backed by strong clinical data. And most patients should be able to access Opzelura through their insurance plan. I am very fortunate in that I have a wonderful Incyte representative in my practice in Sunnyvale. When Opzelura came out, she came in and told us exactly what to do. And my colleagues, many of them are still trying to figure it out, and so I really asked them to talk to their representative. She told us how to find a pharmacy that will do our prior authorizations. When I have a patient, my MA who is very good, she just copies my note, sends it to them. That pharmacy does the prior authorizations, they get it through insurance. If they can't, they go through the patient assistance program, everything is automatic. And like I said, 75% of my patients are able to get it paid for, and they only have a $10 or $20 co-pay, which is just fantastic. Every dermatologist should have that type of service, and I hope they do. So for me, it tends to be fairly easy, but I'm very fortunate in the support that I received from Incyte as well as my staff. The most difficult patients are the ones with Medicare. And I hope that Incyte and the Global Vitiligo Foundation can work on it so our Medicare patients can get a better deal and get access to this medication. So I think it's a game changer. Accutane was a game changer with acne, prolonged remission and for deep painful acne cysts. When you look at patients with psoriasis, the biologics that have been available have been a game changer. Dupixent is unbelievable. It just -- I just cannot believe what Dupixent does to atopic dermatitis patients that I've seen for 30 years, how it can clear patients. But now at Opzelura, we have some of these amazing results, and it's FDA approved, and we have really good robust data that it works. So I think this is going to be a real breakthrough and a game changer for us for vitiligo. So in terms of other exciting developments, I can't wait to see the results of the light therapy at Opzelura. Two of these patients are mine. So they're getting their light box this week. They did not have 25% improvement at week 12, so they qualify to get the light box. They're getting the light box, a panel at their house this week and then we'll be starting phototherapy. And I expect them to repigment very well with that combination. And then so the povorcitinib and other oral JAK inhibitors targets that inflammation, and that's going to be great for these patients with extensive vitiligo more than 10%, which are a lot of individuals. And then the IL-15 receptor antibody, which targets that, the auremolimab, I can barely say that, but to eliminate these cells to give us durable remission, I'm also excited about that because vitiligo does indeed come back in the same place that it was in the beginning. And if this antibody will remove that, then I'm excited about that, too.

Great. Thank you so much, Dr. Pandya. That was wonderful. I really appreciate the patient perspective, how you treat the patients. And it's a reminder to us at Incyte of how important it was for us to develop Opzelura, but also the commitment that we have to develop additional treatments for your vitiligo patients. So with that, that's the end of the presentation portion of our segment. I'd like to ask Dr. Steven Stein, Incyte's Chief Medical Officer, to join us on the stage. And while he does that, I just want to make sure that a microphone is available to the participants in the audience. And what we'll do is start with the participants in the audience with questions.

Rob Andrew here from William Blair, on for Matt Phipps' team. It's been highlighted a few times in the conference and here tonight as well that exposure to sunlight is pretty important here. I'm from the North of England. It's particularly warm. I see the sun outside, I'm probably not going outside. So I'm just kind of wondering given the lack of an obvious dose response for povorcitinib, is there any evidence that geographical differences or behavioral differences, seasonal differences in the clinical trials actually lead to a different response just given the impact that, that might have on sun exposure?

Maybe I can address that or at least try to tackle that. So we do have indirect evidence that sunlight makes a difference in terms of the responses that we saw in the clinical trials. And the reason for that is when you take a look at the delta, the difference between the facial VASI response and the total body response, we take a look at the body, the trunk, and those areas are definitely much slower to repigment than the face. So absolutely. So if there's a person who's not going outside, their facial VASI score is not going to improve as fast. And in fact, I remember Dr. Rosmarin telling us there was a patient -- one of his patients who had residual hypopigmentation on his forehead. And he just -- he reminded him, why don't you take your hat off. And he took his hat off and that area repigmented. So we know that whether it's natural or ambient light versus a phototherapy, that does impact the rate of repigmentation.

Great. And I would say that I treated my patients in Texas, and they were walking outside in Dallas and Austin and those areas, and as I was talking to my colleagues in Boston, just talking about the study, they were not seeing as great responses as I was in Texas because the amount of UV exposure, sunlight exposure is so much more.

Maybe just, Jim and Dr. Pandya, any comments on the second part of that question, the dose or seemingly lack of dose response in this Phase II study. Any thoughts on perhaps the biology behind that?

Maybe I can start with maybe more of a biological perspective. And that is, so we know the povorcitinib has very good tissue penetration, but what we don't know is how much of it is needed or needs to get into the skin to block the interferon gamma as well as IL-15. the And so it was -- it looks like 45 and 75 had similar responses from a VASI perspective. But because the numbers are modest, that could have been just due to random change. But what appears for us is that the 45 and 75 look like a similar dose in terms of the response that you're able to achieve. The 15, definitely, I think you see some separation. And we're going to share some translational data later this year that supports that 45 and 75 probably are strong enough to get the repigmentation and probably you need more than 15 milligrams per day.

And what I would say is the T-VASI and the F-VASI have error in terms of measuring by the investigator. It's not an exact science. It's more difficult, in my opinion, than doing the PASI or the ESI or the [ CAEL ] score. And I've done all of those. Reason being is that not only do you measure the body surface area, but you have to multiply it by the amount of -- deep amount of pigmentation within the lesion. And it's hard enough for me to do who've seen thousands of patients, but it's hard to teach that to an investigator. And so when we look at these bars, we think that there's sometimes quite a difference, but there's actually a range of error when it comes to doing that. It's called the smallest detectable change. Ideally, what we should have is we should have a camera that takes a picture of the whole human body and then just tells us how many centimeter square of vitiligo they have at baseline and at 24 weeks. But the FDA doesn't allow that. The FDA sees the VASI is kind of is the gold standard. And so we have to use that. But studies have shown that there is an error, a significant error between raters. Even the same rater looking at the patient over time or twice, for example, intra-rater reliability can be an issue.

This is Divya from TD Cowen, on for Marc. So just looking at the povorcitinib data, it looks very promising. And I guess if it's approved, do you anticipate you'll keep these patients on povorcitinib chronically or maybe just like a bridge and use Opzelura as more of -- for maintenance therapy for these patients?

Well, I know that if I remove -- if I stop the medication that's suppressing the T cell from infiltrating the epidermis and killing melanocytes, I feel like they will slowly come back. I'm not removing these T cells from the bone marrow, from the spleen, from the lymph nodes. They're there. We don't have a medication that zaps them permanently. And so what will happen is eventually over time, perhaps through trauma, perhaps through sun exposure, whatever it stimulates interferon gamma, it will come back. And so I think that with povorcitinib, let's say that I do get 90% repigmentation or a substantial amount, and now they have a very small amount of vitiligo, then you could just switch to Opzelura absolutely. But the problem is that if they, for example, had 30% to begin with and now they only have 5%, if they apply Opzelura to that 5%, the rest is not being treated and the T cells tend to come back into the same places where they used to be before. But with the new IL-15 receptor antibody, if we can remove those resident memory T cells, then hopefully, we'll have a durable remission, so they won't get it back. So those are some of the thoughts that we have.

Any additional questions from the room? Could you use the microphone? Thank you.

Yes. You mentioned that about 25% of the patients get a rejection from the payers, and usually Medicare. Is that because Medicare does not cover it? Or is it -- what are the reasons for denial?

I wish I knew. Medicare just -- I guess Medicare Part D doesn't really cover it. I don't know if -- maybe folks at Incyte.

Yes. So Barry Flannelly is Head of the U.S. Commercial organization will respond.

Yes. So far, Medicare does not cover it for a variety of reasons. It's a little just -- for example, doesn't cover Dupixent either. It's just one of those things. We're definitely working on it, and we'll do it, particularly for vitiligo in the AD patient population, we don't have as many patients on Medicare that are using the drug, but for vitiligo even in the study -- in TRuE-V studies, I think it was about 10%. We're over 65. So it's something that we're working on, but it takes a little longer than the commercial payers.

Great. Okay. If there are no more questions in the room, operator, if you could open up the line for questions for folks who are on the line.

[Operator Instructions] Our first question comes from Kripa Devarakonda with Truist Securities.

Congrats on all the data. Jim, Steven, this is -- my first question is for you guys. So if there are patients in the withdrawal cohort that were then retreated. It looks like 75% of the patients who relapsed due to withdrawal were able to achieve F-VASI75 and about 69, I think, of those who achieved F-VASI90. Can you maybe talk about what might be happening with the patients that did not respond? And does this -- do you think this means that people -- patients are more likely to stay on treatment and would not want drug holidays? I know you can repigment. And Dr. Pandya a question for you. You mentioned that it's typically patients who have facial lesions that come for treatment. How many vitiligo patients do you think fall into that category? And with Opzelura and povorcitinib were to be approved, do you think that might change the way patients seek treatment?

Do you want me to take the first part? So thank you for the question. So what likely has happened is that Opzelura lost the response out in month 20 -- or 24 and then restart treatment. They really don't. We ended the study at year 2, so week 104. And so many of those patients will likely have been able to regain their facial VASI75 and even their facial VASI90 if we had kept the study going longer. So I think there's nothing to believe that we haven't seen anything where patients will develop tachyphylaxis. They don't respond to retreatment. Based on what we saw in the retreatment arm, I think that was just a factor of basically stopping the study at year 2.

Yes. I personally think that the vast majority of people who we think have tachyphylaxis are just noncompliant, and that's why they are not achieving the F-VASI90. And I'm sorry, could you repeat your second question?

I had a question for Dr. Pandya about patients. You said patients typically who have facial lesions are the ones who come for treatment, which you have Opzelura approved. And if povorcitinib will also going to be approved, like if they have options, would patients who don't have facial lesions also come in for treatment in the other parts of the body? And what percentage of patients are the ones who only have facial lesions?

Well, first of all, I think at least 50% of my patients have facial lesions. And in terms of what percent only have facial lesions, it's hard for me to kind of estimate it. Maybe 10% to 20%, something like that would have face and ear lesions only. Almost everybody has some lesion somewhere else when they have facial lesions. And so yes, they're coming in for facial lesions, and the Opzelura is perfect for them. If you're asking about povorcitinib and what I would do for that in the future, if they have more than 10% body surface area and especially if they're getting more active disease, and I'm afraid that they're going to go to 12%, 15%, 20%, and povorcitinib certainly makes sense for them in patients with active disease. And so you could even combine it where you perhaps even get an even better result if you use Opzelura on the face and povorcitinib so that you could treat both the body and the face. And there's lots of different options that we could have in the future. There aren't that many people who have no face lesions and the body lesions that want to get treated, except for those who have it on their hands. I have quite a few patients who have it on their hands and feet, especially in certain cultures where their feet are showing a lot in various social settings. Those who have them, they want to get treated on their hands and feet. Those will be the type of patients of Opzelura. Nothing actually works on the hands and feet as well as it works on the face. So in those patients, we will be treating aggressively with phototherapy from the beginning, along with topicals and then perhaps even grafting those patients later on.

Our next question comes from Jessica Fye with JPMorgan.

Starting on povorcitinib, following up on, I think, the first question, I just want to clarify, I'm sure you guys have gone back and looked at the baseline characteristics for the different dose arms in that trial and what might explain the unusual dose response on T-VASI50 or even F-VASI50, are you saying you think different light exposure explains that unusual dose response? Or are you just suggesting that's a possibility, but not something you've specifically established? That's the first question. Second, would the aim be to use F-VASI75 as an approvable endpoint for povorcitinib? Or is there a different approval endpoint you're considering? And then third question, switching to Opzelura. I'm curious what the message to physicians is going to be on the back of this long-term vitiligo data. Is the marketing message going to be keep patients on long term because if you don't, a reasonable proportion will lose their response. Or is it to say patients can try to come off drug after they've gotten a good response, and if they lose it, don't worry, the data shows they can get it back.

Great. Maybe I'll take the first 2 and ask Dr. Pandya to address the third question. So in terms of the povorcitinib Phase II study, the variability, and so we're going to share data obviously out to year 1 and actually longer. And so Dr. Pandya mentioned that repigmentation is a slower process. And I think what we see later is that the repigmentation accelerates over time. I think you saw that with the week 36 versus the week 24. And part of the challenge at week 24 was because of the slower repigmentation, especially in patients with more extensive disease, as well as the smaller cohort size, it probably led to some of the variability as well as what Dr. Pandya mentioned about the VASI assessment. So we -- the data is very good, and week 36 will clearly look better and the variability reduced as you go farther out as these patients are repigmenting more. As they repigment more, to Dr. Pandya's point, the VASI assessment, there's less intra-observer, inter-observer variability. So in terms of -- actually, I just forget the second question. I think it was...

What would you expect the approval endpoint to be for povorcitinib? Should we think of it as being F-VASI75 like for Opzelura? Or is there a different approval endpoint you'd be pursuing?

So we typically don't discuss the regulatory strategy, but -- so whenever you have a new drug approval and a new indication, you should look at the regulatory or the endpoints that were used for the approval. And that will give you an idea for what's going to be required for subsequent products. So it's likely going to be the facial VASI75 as the primary efficacy variable.

And in terms of the way that I would think about the long-term data, I think that the long-term data is exciting because it shows that people continue to improve, and I would say, continue to use it to the patients and also the dermatologists until you plateau, until the patient plateaus because we haven't quite seen a plateau even now after 2 years. So there's good reason for even those patients who have partial improvement to just to keep going until the plateau happens. In terms of stopping it and then having to restart, it was -- I feel like that's also something that's good news, although I would not really recommend stopping it until you do plateau. And then it's exciting to know that you can repigment when you do stop it and the patient does have a relapse. But I also think that -- I would tell dermatologists that in the long term, you may not need to use Opzelura every single day. In the long term, we need to do further studies to find out what a good maintenance would be. But we all feel like biologics are something that you use long term. We all know that if you stop the biologic, the psoriasis is going to come back. Dermatologists are used to that, of having patients on it for years and years and years because we know that the pathogenesis of the disease is just that way.

One more thing just to add my 2 cents, I think the continued safety profile is really encouraging now out a further year with no other serious events and the same degree or less of acne or pruritus at the application site. That's very reassuring for us.

The next question comes from Salveen Richter with Goldman Sachs.

This is Matt on for Salveen. I had a few quick ones, if that's all right. I was wondering first, could you guys just specify -- I know 29% relapsed after stopping Opzelura in the patients that received -- that achieved a complete response. But what percent relapsed while continuing treatment? So what percent of those went below 75? And then I have a couple more.

Sure. What Dr. Harris presented, there was -- there were a few patients in the arm that was rerandomized to ruxolitinib cream. I think it was around 21%, 22% of those patients dropped below the facial VASI90. I think 14 maybe dropped below facial VASI75. And we think that most of that, to Dr. Pandya's point, was due to patient compliance with the continued treatment of medicine.

Got it. Got it. And then in terms of -- it sounds like -- I mean I know you haven't confirmed this because it's early, but it could be F-VASI75 for an approval endpoint. I mean, right now, I mean, just I guess the question for Incyte is, do you guys plan to advance this to a later-stage study? Are you still considering it? Or -- and do you need to see the longer-term data before you make a decision to advance? And then in terms of the comparability of the impact on facial scores versus Opzelura, it seems like -- it was a little -- at week 24, it was maybe a little bit less, 15% placebo adjusted versus around 23% for Opzelura. But then at week 36, it becomes -- it looks very comparable. I guess if you can get that, that's probably enough to get approved if F-VASI75 is the endpoint. But I'm also wondering, are you going to get patients just wanting to take the pill instead of putting on the cream, just given how kind of more convenient, better compliance-wise that is? I know safety is a consideration, but just interested to hear your thoughts there.

Sure. Let me address your second question, and Dr. Stein will address your first question. So in terms of the comparability, obviously, you need to always be careful comparing between studies, because it is a different patient population. Dr. Pandya pointed out, this was a much more severe patient population. So -- but if you take a look at the Opzelura data, we've got about 30% of the patients were able to achieve facial VASI75 at week 24. That bumps up to 52% or about 50% at week 52. So it is a little bit less than that. But again, you have to be very careful because you have 2 distinct different patient populations. And you had a pretty extensive facial involvement in the povorcitinib study. So -- but that being said, we're very excited about the data with povorcitinib. I think as we come out with the week 52 data, hopefully, everyone will see that with continued dosing, give people more time to repigment that povorcitinib will be a very good treatment option for vitiligo patients. So maybe I'll ask Steven Stein.

Yes, I'll lead off with a few editorial comments. I mean, I think Dr. Pandya said it well. You have been ignited the field in terms of vitiligo research, which is really great. So lots of other mechanisms being pursued, many other companies looking at it. In some way, in terms of the endpoint, it comes back to our own history in myelofibrosis. More than 12 years ago, the spleen volume response rate 35% or greater endpoint is really invented by Incyte, used in the initial COMFORT-I study and then became the de facto regulatory endpoint therein. And I think as Jim said it well, you have to look at precedents now. It's very likely that the FDA will look at facial VASI75 as the surrogate for clinical benefit going forward, that's what we expect. We haven't yet made the internal decision to go full steam ahead on a regulatory program, but this data is, in our minds, a really, really encouraging/outstanding. I think, again, Dr. Pandya said it well, one way to view this as a compliance play versus the cream. I think he made an outstanding point there, where people can take an oral pill a day and don't have to apply cream twice daily. So those will all factor into our decision, plus regulatory discussions coming up soon. The other flip side, maybe to make somewhat of a sort of fair balance comment is the view on JAKs in general at the FDA and class labeling. So with eyes wide open on the likelihood of future JAK inhibitors in inflammatory conditions, getting black box warnings, and that will play into the decision-making. But just to end, positively encouraged by the data. I love the view that this could be used for more severe patients, great compliance. Pending regulatory discussion, then we'll make the decision on whether or not to go full steam ahead. Thanks.

The next question comes from Mara Goldstein with Mizuho Securities.

This is Jerry Gong, on for Mara Goldstein. Congrats on the data. Two on Opzelura for me and then one on povorcitinib. So starting with Opzelura, I kind of want to follow up on the question on the kind of the relapsed patient rate in the withdrawal arm. So I think about 29% relapsed, and then I think in the presentation, around 40% maintained a response and some 20% discontinued treatment. Can you kind of share what happened to the remaining 10% of patients? Or am I thinking this the right way?

I'm sorry, there was some background noise. Could you repeat your question?

Sorry, yes. So in the withdrawal arm for Opzelura, about 29% of patients relapsed on treatment. And from the presentation itself, about 40% maintained a response and about 20% discontinued treatment. So kind of what happened to the remaining 10% of patients kind of not accounted for in those numbers?

Yes. I think. I'm sorry, there's...

We're in New Orleans, and then there's jazz band playing on the street outside.

There's a [ trumpeter ] playing right outside of the room. So I think I heard that what happens to those patients in the long-term follow-up when they lost the facial VASI90 or facial VASI75?

We hear the trumpet as well. But my question is more about like the patients that weren't accounted for in the relapse and response kind of maintained group in the withdrawal arm.

Jim, if I understand, I think if you focus on the 29% that relapsed, if you can just talk about that group further. That's the best I understood.

In the vehicle arm or in the active arm? In the vehicle arm? The vehicle arm. Yes. So...

Is it safe to think about like the other patients responding to treatment? How should we think about that?

You said something about other studies? Are you asking us to compare [ studies ]?

No, no, sorry. So 29% relapsed, right? So what kind of happened to the other 71% of patients? Did most of those maintain a response? Yes.

What happened to what?

The other remaining 71% of patients...

What happened to the other systems? Maybe a little slowly. What happened to the other systems? Is that what you asked?

The other remaining 71% of patients.

The other remaining 71% of patients in that particular -- okay. Thank you. Sorry about that. We have a Mardi Gras band outside our...

No. No. So that was the vehicle arm. And so when patients relapse, obviously, they restarted. Many of them didn't need -- didn't relapse and didn't need additional treatment, especially the ones -- as long as they maintain the facial VASI75, and it was a very large number of them, right? And so -- and the ones that did relapse. And then the other patients -- some of the patients we had some dropouts in that arm. We started with 110 and ended up with 90. And so -- so all of the patients were accounted for, but most of them actually did not drop below facial VASI75. So they did not basically go back on active treatment.

And this is what I -- in practice, when I have patients on -- I haven't used Opzelura for over a year, but other -- when I see that success and then the patient stops treatment, there are many who maintain that improvement for a year. But slowly but surely, the patients who had significant vitiligo to begin with, it creeps back at year 2, at year 3, at year 4. So I think that those -- that 71% of patients will -- that number will slowly go down over time when you go past the year.

Got it. And keeping with Opzelura, so we saw some benefit of some patients that relapsed and then restarted treatment in the vehicle arm. How are you thinking about the length of drug holiday and how it might affect the time it takes to regain a response?

Maybe I can ask Dr. Pandya to talk about the length of drug holiday based on his experience, extensive experience with vitiligo patients.

Yes, I think you can take a drug holiday usually for up to 3 months without really relapse. After about 3 months, then that's when I start seeing relapses, no matter whether you're taking a holiday from phototherapy or topicals. So I think that would be kind of a reasonable period of time where you can expect not to have a relapse is for about 3 months.

So if a patient in your practice comes back at month 6, and they've -- or started to depigment, that's when you would start the patient back on treatment.

Back on treatment. And some of them will say, "I need to take 3 months off this summer, and I can't do phototherapy. I can't do topicals or whatever," then I'll say, okay, you probably will be okay. I would recommend you get a little bit of sunlight and get a little bit of sunlight, but you'll probably be okay. But if you go beyond 3 months, then you're risking relapse.

And the data that we showed around regaining the pigmentation after relapsing, that would reassure you that you would restart that patient on Opzelura?

Right.

And perhaps we'll take one more question and then end the evening, if there is one more question.

The last question comes from Evan Seigerman with BMO.

This is [ Keith ], on for Evan. Congratulations on the data. I have 2 quick ones. The first is, could you -- for the upcoming Phase II data for rux plus phototherapy combo, just wanted to know what your expectations are in terms of the step-up in efficacy. And any feedback on the FDA on the outcomes of the trial -- for the combo trial. And then secondarily, more of a practice question. One of the doctors today mentioned a 4-month waiting list for appointments. And I imagine in dermatology, this is the case broadly. Just wondering what you could expect in terms of evolving clinical practice. Given the safety of Opzelura, would you expect this to extend to primary care, at least in terms of maintenance therapy?

Okay. Maybe I'll address the first part and then have Dr. Pandya address the second part. So the Phase II study in combination with UVB light therapy, Dr. Pandya was actually intimately involved with that study and helped us design it. And so after 12 weeks of Opzelura therapy, if a patient doesn't have a response, and I believe it's facial VASI 25%.

25. T-VASI.

Or T-VASI25, excuse me, T-VASI, then that patient is -- continues with Opzelura but UVB light therapy is added. The patients who actually are able to achieve with total VASI25 at week 12 continue with monotherapy of Opzelura. So that's how that study is designed. It's ongoing, and we hope to have the data as soon as possible. So -- and again, that's basically to guide -- help guide physicians, right? Because for a fast responder, Opzelura is good just by itself. There's no need to add anything else. But for the patients who melanocytes are senescent and not waking up, then that's where the light therapy can certainly help boost that response in those patients.

I fully expect that T-VASI -- I fully expect the vast majority of those patients will have a T-VASI75 at month 12 with the phototherapy. And the second question was, once again?

Around the wait times, 4-month wait times?

Right. Yes. So 65% of skin care in Americas is taken care of by primary care doctors. And so primary care doctors do treat acne, psoriasis, eczema. And I think that vitiligo is something that they're not so comfortable with, but this is an opportunity with Opzelura and with Incyte educating physicians and patients coming in to see doctors. They can't see the dermatologist and for 5 months, but they can see their primary care doctor perhaps next week, then it's actually a very easy medication to prescribe.

Okay. On that, we'll end. Thank you, Dr. Pandya. Thank you very much. Thanks, everyone, in the audience and online. Have a good evening. Cheers.