Good day, thank you for standing by. Welcome to the Arcutis Biotherapeutics top line data call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone, and you will then hear an automated message advising your hand is raised. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Eric McIntyre, Head of Investor Relations. Please go ahead. Thank you, Michelle. Good morning, everyone, and thanks for joining. We are incredibly excited to be here with you again today to discuss pivotal phase II results from our INTEGUMENT-1 and -2 trials in atopic dermatitis, and certainly also proud of the continued execution on the clinical front, and, you know, progress towards realizing the long-term value for topical roflumilast. A couple logistical details before we get started. Arcutis management team is all here today, and we'll also be joined by Dr. Larry Eichenfield during our prepared remarks as well as for Q&A. You could find today's webcast and posted presentation under the Events and Presentation section of our investor website. Finally, I'd like to remind all of you of the safe harbor rules governing our remarks today, as well as any forward-looking statements that we make during this call. These statements are subject to any risks and uncertainties that could cause actual results to differ materially. With that, I'll turn the call over to Frank Watanabe, President and CEO, to kick us off. Frank? Thanks. Thanks, Eric. I'm on slide 5 now of the deck. Back in March of this year, we had an Investor Day, and we teed up for you all that 2022 is going to be a transformational year for Arcutis. I think today is the final installment in that story. I think that we have really delivered on that. You know, we have shown across now multiple different disease areas with completed phase III studies that topical roflumilast has a very highly differentiated clinical profile, very strong efficacy, excellent tolerability, and each one of the diseases, plaque psoriasis, seborrheic dermatitis, and atopic dermatitis all address about 2 million patients each just in the U.S. dermatology setting. Very large opportunities as well. You know, we, I think, have built a track record at this company for many years now of execution in our clinical trials. Again, today, I think, is the latest installment in that. We've now completed three phase III programs this year and four phase III studies, which I think is quite a remarkable accomplishment for a small company like ours. We continue to be very, very excited about the clinical profile of topical roflumilast, and I think Patrick and Larry will share with you more some clinical perspectives on that. I think the data today positions us very well to compete in the very large atopic dermatitis market. Then lastly, I'd be remiss if I didn't mention how things were going with the launch. We continue to be delighted with the progress on the launch of ZORYVE and plaque psoriasis. You know, the recently announced wins with Express Scripts and one of the large national health plans, I think is validation of our differentiated, let's say, access and pricing strategy. If you turn on to slide 6, this is just a reminder of our overall pipeline and where we stand. Obviously, ZORYVE at the top and plaque psoriasis is on the market. We're now in a position in atopic dermatitis, seborrheic dermatitis, and scalp psoriasis to be filing sNDAs, and we'll go into more detail as we go through the remarks today. I would also call out ARQ-255, which is the deep penetrating version of our JAK inhibitor, which we moved into the clinic just in the last couple of weeks. Good progress on our early pipeline as well, and remind everyone of ARQ-234, the biologic in atopic dermatitis from moderate to severe that we obtained through the acquisition of Ducentis earlier in 2022. On slide 7, for those of you who were at the R&D day back in March, you may recognize this slide. We teed up the time frames for various major catalysts for the year, starting with seborrheic dermatitis. We delivered phase III data on that. The FDA approval on time in Q3, the scalp and body data right around the beginning of Q4, the second of the two phase III studies in atopic dermatitis. Again, I think the team has done an exceptional job. I cannot give enough credit to our team for the outstanding execution that they've been able to deliver this year. Just briefly on slide 8, I wanted to remind you all of the opportunities as we see it across psoriasis, atopic dermatitis, and seborrheic dermatitis. You know, 2 million or more patients who are actually in a dermatologist office receiving topical treatment and who are eligible for receiving topical roflumilast once it's approved in all three indications. You know, close to 7 million patients we're talking about in the opportunity, just in U.S. derm. A very large opportunity outside of the dermatology specialty as well across all three diseases, but particularly in atopic dermatitis where, you know, majority of the patients are being treated by PCPs, pediatricians, and allergists. we will be looking in the coming years at how we address that opportunity as well. With that, I want to turn it over to Dr. Patrick Burnett, our Chief Medical Officer, to get to the data. Hey, Frank. Thanks a lot. I'm really excited to share these data with everybody. You know, as a dermatologist myself, I was a resident when Elidel and Protopic. Launched and recognized that atopic dermatitis is an area where we really have a lot of unmet need, especially for a non-steroidal treatment. I think that the clinical profile that you're gonna see here really delivers against that unmet need extremely well. You know, we have a really good efficacy and safety profile and particularly in atopic dermatitis, it's really important to have a drug with a strong safety profile because of the pediatric component. I'm very excited to have Dr. Larry Eichenfield as well here to talk to you about kind of contextualizing these clinical results. Moving to slide 10, we have the scheme for INTEGUMENT-1 and INTEGUMENT-2. Just to remind you, these are two identical phase III trials in patients with mild to moderate atopic dermatitis. You see on the left there, the eligibility criteria. We enroll patients ages 6 and above into these two trials. We studied the 0.15% cream. Just to remind, the psoriasis dose for ZORYVE is 0.3%, we're also studying a 0.05% cream for ages 2- 5. This is the ages 6 and above. These are the ages 6 and above studies, BSA greater than or equal to 3%, you can see the EASI score on the slide as well. Patients are randomized 2- 1, the sample size for these studies was quite large. We enrolled 654 patients in INTEGUMENT-1 and 683 subjects into INTEGUMENT-2 and treated them for 4 weeks. Our primary endpoint is validated IGA or Investigator Global Assessment in atopic dermatitis success at the end of treatment, which is week 4. Validated IGA success means that patients had to go from mild to moderate, so that's a two or a three, and reach clear or almost clear, which is a zero or a one, and have a 2-step improvement. Patients who were mild then had to have a 2-step improvement and get all the way to clear in order to be considered success on this endpoint. The other key data that we're going to show today are the EASI-75. That's the Eczema Area and Severity Index 75. It means a 75% improvement in the disease, as well as the Worst Itch Numeric Rating Scale. I just wanna point out that the EASI- 75 and the validated IGA are really very different methodologies. The IGA is a five-point scale, and some investigators just compare against the verbal descriptions of each of those and determine which classes the patient falls into. For EASI- 75, each aspect of atopic dermatitis is evaluated based on different regions of the body, and then those numbers, including body surface area, are plugged into a calculation, and a number is then generated. As I mentioned, in order to be considered a EASI- 75 responder, that number has to be reduced by 75% compared to baseline. Two very different methodologies to assess the same patients in these trials. When I move to slide 11, this is the primary endpoint, validated IGA success, at week 4, you can see that we met statistical significance in both INTEGUMENT-1 and INTEGUMENT-2. The numbers were 32% in INTEGUMENT-1 and just shy of 29% in INTEGUMENT-2. If you look at the delta versus vehicle, you see that it's identical between the two studies. Vehicle came in at 15.2 and 12%. I think that's one of the things you'll see as we go through the data today. These studies, particularly potentially because of their size, showed very, very consistent results, across the different endpoints between the two studies. I think that that's one of the, the very strong aspects of this data readout. We met statistical significance all the way as early as week one in INTEGUMENT-2. I'm sorry, in INTEGUMENT-1. In INTEGUMENT-2, we met statistical significance at week 4, week 2, and narrowly missed it at week 1. That was really, I think, one of the only kind of key secondary endpoint that we missed the statistical significance on in the INTEGUMENT-2 trial. In INTEGUMENT-1, we met every single one of our secondary endpoints. Now looking at EASI-75, which is on slide 12, again, this is a separate methodology that evaluates the patients. Here, the responder numbers are at 43.2% at week four and 42% in week four for INTEGUMENT-2. Very similar EASI-75 response in patients. On this endpoint, we met statistical significance as early as week 1 in both INTEGUMENT-1 and INTEGUMENT-2. You're seeing that about 13%-14% of patients already after a single week of treatment are reaching this success criteria of a 75% reduction in the amount of their disease according to the EASI assessment, and around 30% of patients already at week 2. One of the aspects of the profile that we're seeing is that patients are responding quickly to treatment, even within the first week. Week 1 was the first day that we assessed and brought patients back into the clinic and evaluated them for EASI and IGA. As I move to 13, see the EASI-75 response of 42% and 43% all the way to the left. What we're showing here is week four data pulled from various different trials for other drugs that are approved or used for atopic dermatitis, just to help give a kind of comparison. I do have to acknowledge that the cross-study comparison here is one that has to have a lot of caveats associated with it. Obviously, there could be different patient populations that are subtly different enrolled across these, although these are really primarily mild to moderate patients as well. Some of these trials are a little bit older. So there are differences in making these are not a within study comparison. However, I think that it's important to kind of understand where it is that the efficacy on EASI-75 stacks up against some of the other approved drugs. EASI-75 has really emerged recently as, I'd say within the last 5-10 years, as the endpoint that is the most accessible for healthcare providers and patients. It's the one that is used most commonly in thinking about assessing the efficacy of a drug in AD. You see that 42-43% places us with a higher efficacy compared to EUCRISA, which is another approved PDE4 inhibitor. This is from a phase IIIB study that was conducted. In that study, it also included an Elidel arm, which came in at 36%. Again, showing slightly higher efficacy compared to Elidel, and very competitive efficacy with triamcinolone, which I think is really the most important comparator on this slide. That's because the majority of patients who are being treated with topicals for atopic dermatitis, and that's the majority of AD patients actually, are being treated with a topical steroid. That is kind of the first treatment that is often given, and that's because it can help patients to respond quickly, and it's well tolerated. I think you'll see in our efficacy and safety profile that not only do we match up well with regard to efficacy, but you'll see that the safety profile is one also, that doesn't include stinging and burning, which has been historically some of the problems with non-steroidal treatments, especially in atopic dermatitis. To the right, we give the Opzelura week 4 data. Their primary endpoint was at week 8, just for kind of an apples to apple comparison, we pulled the phase III week 4 data for EASI-75, and you can see that the comparison there. It's important to note that given the label around Opzelura, that this is something that's positioned later in the treatment paradigm for patients. I know Larry will probably talk a little bit more about the treatment landscape later. Moving on to slide 14. Itch is really the hallmark of atopic dermatitis. It is the most common symptom. Here we're using Worst Itch Numeric Rating Scale to evaluate the response according to itch. Here we included any patient who had an itch of four, and the maximum you can have is the scale is from 0- 10, so a maximum of 10. Anyone with an itch of four or greater when they entered the trial was able to be included in this population. To be considered a responder and to be considered a success, you had to improve that by four over the duration of treatment. Again, we're showing very, very rapid response to itch, with about 10% of patients getting to WI-NRS success already at week 1 and meeting statistical significance there. Then moving up to week 2 and week 4, we have between 30% and 34% of patients responding WI-NRS success already at week 4. Key symptom for atopic dermatitis is also responding quickly, and they continue to progress over the 4-week period. Moving on to slide 15. Just a couple of slides on the safety profile. Most importantly, we had overall low adverse events rate between 13% and 23% of patients with any adverse event. The most important AE metric I would say that you have is really the discontinuation due to an adverse event because subjects can always just stop their participation in the trial. They don't have to really go through any trouble to do that. If they're seeing something in the trial from an adverse event profile that they're not comfortable with, they will just drop out. Here what you can see is that our discontinuation due to an adverse event rates are very low, 1.4% and 1.8%, and very similar to what you see with just vehicle. Overall, we had over 90% of the subjects that completed these studies. Really good completion rates, which is historically what we've seen with our trials. On slide 16, we have a comparison here between INTEGUMENT and INTEGUMENT-1. On the adverse events, this is showing all adverse events that were greater than or equal to 1% in the trials. You can see that the overall AE profile looks similar to what we've seen with others, with other trials, that the specific numbers are given here. Similar AE profile between INTEGUMENT-1 and INTEGUMENT-2. The most common adverse event now being headache. If you remember from our psoriasis program, we had diarrhea of about 3% in patients. We're not really seeing those same numbers here. In fact, 1.5% is the highest that we saw. That was in INTEGUMENT-2, that's compared to a 0.9% in vehicle. COVID-19 shows up, was actually more common in vehicle patients. It's important to note here that we do have 2.1% versus 0.5% on application site pain. This is a component of atopic dermatitis itself. I think interestingly, you'll note on INTEGUMENT-2 that rate was actually balanced at 0.9% versus 0.9%. Really good adverse event profile here, matching similarly what we've seen in earlier studies and other indications. I think that's starting to emerge as a consistency across different programs. My last slide on 17, just wanna give you a reminder on what our plans forward are with these data before I turn it over to Larry. What we're gonna do is we're gonna submit INTEGUMENT-1 and INTEGUMENT-2 in the second half of this year. I'm sorry, on next year, 2023. That's gonna then that submission will support an approval after a 10-month FDA review timeline, potentially in ages six and above for atopic dermatitis. We've note down there, and Ken's gonna talk about this, that really captures the majority of the U.S. dermatologist-treated AD population, ages six above. really bringing this drug to the largest population of AD patients in the U.S. We are, as I mentioned, conducting a study in ages 2- 5 with a lower dose, a 0.05% dose. we expect those results from that 2- 5-year-old study in 2023, and then that will be submitted as a supplemental NDA after we get the potential approval in ages 6 and above. It'll be a two-step process with the first one taking these data that I just walked you through today, and bringing them to the FDA with a submission in the second half of 2023. With that, I'd like to turn it over to Larry Eichenfield to contextualize the results for you. Thank you, Patrick. Good morning, everyone. I'm Larry Eichenfield. I run the pediatric dermatology unit at Rady Children's Hospital in San Diego, and I'm Vice Chair of Dermatology and a Professor of Dermatology and Pediatrics. Quite excited to hear the results this morning, I'd like to sort of put this in perspective. I'm on slide 19. Just by background, yeah, atopic dermatitis, this is an incredibly complex disease. It's, you know, chronic skin disease, genetically predisposed inflammatory skin disease, but also associated with intrinsic dry skin and barrier dysfunction. It presents across the life, the lifespan. Childhood disease is quite common with a prevalence in younger children of 12%-15%. That's actually a pretty conservative number around the United States. With a high prevalence throughout life, we're really aware now of either persistence or new onset atopic dermatitis in adults. Actually, a quarter of cases are new onset. We have pretty strong data of 7% prevalence in adults as well of atopic dermatitis. Atopic dermatitis, there are some children, for instance, born with intrinsic barrier dysfunction, and then they get sensitized and/or there's this neuroimmune dysregulation, but it manifests as not just the rashes, but dry skin, itch, eczema with secondary changes as well. Once there's inflammation in the skin, that further compromises the skin barrier. Itch or pruritus, as we say, is clearly a most burdensome symptom. I have active videos where someone takes their clothes off on a young child, once the clothes are off, they start working at their skin 'cause air on the skin is an itchy sensation. We still have tremendous unmet therapeutic needs for atopic dermatitis. If you'll move with me to slide 20, I just put some images of not unusual patients in our practice. You can see, you know, an abdomen with the red swollen skin of atopic dermatitis. On the lower left, a sort of crusted eczema. Eczema in the Greek means to boil over. Facial eczema, you can see thickening that we get in the middle picture on the bottom. You can see various presentations with excoriations and swelling as well. Skin of color patients have a lot of pigmentary changes as well. As you can imagine, the symptoms that come with this, there are sleep disturbance associated with it. There could be impact on neurodevelopmental aspects and a whole set of comorbidities that go along with the core rashes and signs and symptoms of atopic dermatitis. Therapeutics, basically topical corticosteroids have been a mainstay of therapy. There's a problem with them. There is a limited limitation on their duration of use. There's certainly concerns about systemic absorption and mixing and matching of multiple agents. They're not suitable for long-term care due to local side effects and safety concerns and potential for steroid withdrawal and/or rebound with discontinuation and flaring. Topical calcineurin inhibitors and crisaborole have twice-daily application. Probably bigger issues are safety warnings and tolerability and stinging and burning with those tolerability issues being present both with what we call the TCIs and crisaborole. Topical JAK inhibitors, you know, ruxolitinib, topical RUX has been approved. It has a pretty profound black box warning mimicking the box warning of all the JAK inhibitors, including the orals. It prohibits first-line use or use with biologics. There's significant concern with systemic absorption and tolerability, limits in the quantity of use you can put on the skin, and it's twice-daily application. As Patrick said, sort of niche differently in our therapeutic regimen. From a, first of all, I have to state that, while we do have newer systemic agents over the last few years for atopic dermatitis, which are marvelously important in our care, most treatment of atopic dermatitis spectrums across the ages is still topical treatment. With this, you know, with this new data set, with both studies showing that high consistent response and great tolerance really seems to fit a patient need. Clearly, once-a-day product's easier to use than twice a day. This is a non-steroid that's appearing effective. We have rapid itch response. You saw the EASI-75 results at week 4 looking quite good, as well as the IGA clear or almost clear. It has what you would call separation from vehicle. I'll come back to that in a minute, also the itch is an early indicator of clinical response. It has very high tolerability, unlike some topical corticosteroids where you mix and match by strength in different parts of the body, it can be used on essentially all body locations and sensitive skin. It has safety for chronic use, which is important, people don't need to stop it because they're avoiding a side effect profile like you might get with skin thinning with topical corticosteroids. Formulation is very well tolerated without sensitizers or associated allergic contact dermatitis. We're very excited to see those incredibly low rates of adverse events topically because that's been an issue with some of our agents. I would like to comment that the, you know, what matters for the FDA, right, is the separation from not placebo in the case, it's vehicle, and the vehicle can have effect, but also the sort of hardy outcome measure, the clear, the itch clear or almost clear in EASI-75 shows that it works, which is fundamentally what's very important for us. Very exciting data in terms of how it can fit in into many of our patients with eczema. With that, I'll turn it over to Ken Lock All right. Thank you, Dr. Eichenfield. Very exciting. I'm now on slide 24, and I'll talk a little bit about the commercial opportunity regarding atopic dermatitis for roflumilast cream. You know, very aligned with the our Arcutis sort of strategic approach, atopic dermatitis is a very, very large market with significant unmet need. The market size, as you can see, around 26 million individuals by our estimate affected by the condition. That's roughly 2.5, almost 3x, you know, as much as the psoriasis market. In 2021, there are around 26 million prescriptions in the U.S. for this condition, and again, roughly twice that of psoriasis. Very large market here. Dr. Eichenfield talked earlier about the prevalence in children as well, and that being a strong driver for even further need for safe and effective topical therapy. On the right, we can talk a little bit about the roflumilast cream and once again, similar to the psoriasis profile, we find ourselves very aligned with all the respective stakeholders in the ecosystem. Physicians, you know, going back to March, I think Frank was referencing our investor day. When we ask physicians primarily, you know, what are you looking for in a, in a, in next generation topical? It's really about having the power of a steroid, but the ability to be used everywhere and the ability to be used chronically. We do see ourselves here with this type of profile. Dr. Eichenfield already mentioned what patients need. Here we have a slightly different and additional stakeholder in parents in that the condition being primarily that of being children, the parents are highly involved in the therapeutic option and selection. So having a profile like this could be very, very congruent with the needs of parents. Lastly, payers, which again, with our differentiated access and pricing strategy, should fall in line there as well. On slide 25, I want to comment a little bit on the market size and again to break down further the 26 million prescriptions that we saw in 2021. You know, a full 95% or so of those prescriptions were topical, and nearly 9 out of 10 there were topical steroids specifically. We do see steroids playing a very, very strong role here and an opportunity for us to change that paradigm with a product like topical roflumilast in atopic dermatitis. The market you can see on the right, the significant expected growth in the overall sales potential in this particular market over the next 5 years. Moving on to slide 26, we did recently conduct a large scale quantitative study in both dermatology clinicians on the left, as well as allergist primary care and pediatricians on the right. Of note, on the right there, you know, that speaks to actually the larger opportunity. Frank alluded earlier to the within derm, outside of derm opportunity for atopic dermatitis. In many cases, the allergist primary care or pediatrician or all of them in some parts are involved early on, particularly in young children and actually treat quite a bit and prescribe quite a bit. We did a quick survey just to assess their perception of unmet needs with topical therapies for atopic dermatitis on the left. I'll direct you to the top two box scores. These are essentially separated by age groups at the bottom, under 12 to 17, and 18 and above. In the dermatology clinician subset, the greatest need was really identified, you know, nine out of 10 in both cases. For the 17 and under population was probably the highest unmet need, followed only ever so slightly lower, for the 18 and over, but still a great degree of unmet need for topical therapies for atopic dermatitis. Pivoting to the right, you can see an allergy, pediatrics, I'm sorry, and primary care. That unmet need is perceived to be even higher than that of the dermatology community, where greater than 90% in all cases, agreed or strongly agreed, that there was still very much unmet need with topical therapies for this condition. Slide 27 speaks to some of the differentiation and Dr. Eichenfield alluded to the approved crisaborole product. I want to just take a moment to so talk a little bit about the differences here. Obviously, while PDE4 inhibition is a validated mechanism in atopic dermatitis, you know, it's a very well understood mechanism of action. The safety profile is extremely well characterized and is suitable for chronic use. Now remember that roflumilast cream is actually a next generation topical PDE4. The only thing it has in common there with either other products is the mechanism of action or the pathway. Roflumilast is actually 25x- 300x more potent than other approved PDE4 inhibitors, and that includes the oral. Importantly, our formulation, which is a key facet of the treatment, really leverages our proprietary HydroARQ Technolog y, and I'll talk about that in a moment. Importantly, you know, it addresses the skin barrier as well, which is one of the key challenges in this condition. Despite the experiences that clinicians may have had in the past with PDE4s in atopic dermatitis, you can see on the right, you know, 9 out of 10, both derm clinicians as well as allergy, peds, and PCPs would be interested in a new and improved PDE4 inhibitor topical for treating this condition. On my last slide, on 28, just speaks to the importance of vehicle itself in atopic dermatitis treatment. Being as though or as it has a skin barrier defect involved, and the skin barrier is compromised, you have significant moisture loss. It's very, very important to have a high quality vehicle to accompany your actives. With our proprietary HydroARQ Technolog y, we find ourselves with a very highly moisturizing vehicle. It also uses similar to the formulation in our psoriasis product, the emulsifiers being used are non-lipid extracting, so therefore does not allow for lipids to be extracted or loss of moisture. Lastly, and very importantly in this condition, our formulation includes no common contact irritants, nothing that will drive allergic reactions or contact dermatitis as a reaction to the product. No propylene glycol, no polyethylene glycol, no alcohol, et cetera. A minimization of those things that cause additional irritation of this already inflamed and sensitive skin. We believe with the formulation, we have a very unique water-based cream that will, should, or may, excuse me, promote better adherence and ultimately better therapeutic effect with the product. With that, I'll hand it back to the team for our Q&A. Yeah. I think before we jump into Q&A, maybe I'll just very briefly wrap it up. You know, I think we remain very excited about the profile of topical roflumilast across psoriasis, atopic dermatitis, and seborrheic dermatitis. You know, the product consistently shows efficacy that's comparable to or better than the standard of care across our targeted diseases. We continue to show a very rapid onset of efficacy. We've seen a consistent dramatic impact on itch. It also continues to demonstrate exceptional safety and tolerability both in the clinic and in the real world, which is really unique amongst topical therapies. The product is easy to use, which I think is very important. You know, our somewhat contrarian pricing and access approach is beginning to pay dividends for us as we are acquiring differentiated access for ZORYVE for commercial patients. We're We're excited to now be in a position to progress multiple regulatory filings, you know, seborrheic dermatitis in sometime probably in Q1 of 2023, atopic dermatitis, as Patrick mentioned, in the second half of 2023, and then for scalp and body psoriasis sometime down the road post the seb derm approval. We also look forward to updating you all on the progress of the ZORYVE launch early in 2023 at our Q4 earnings call. I'd be remiss if I didn't end by thanking Larry Eichenfield for getting up very early. He's in San Diego, so this is a very early morning for him to join us. He's one of the world's leading authorities in atopic dermatitis, if not the leading authority. We're really honored to have him join us on the call. Thank you, Larry. With that, I'm gonna turn it back over to Eric for the Q&A. Michelle, we can open the line. As a reminder, to ask a question, please press star one one on your telephone. Please stand by while we compile the Q&A roster. Our first question comes from Ken Cacciatore with Cowen. Your line is now open. Thanks so much. Congratulations team on the great data. Dr. Eichenfield, I guess I would just start with you. You gave a nice review. Just wondering, though, if you could give us some sense of what% of your patients you think will actually touch this. You talked about maybe where it would be slotted, but maybe what% ultimately do you think would have would be useful of the roflumilast cream? Also maybe there's some discussion often about absolute effect or placebo-adjusted effect. I know you talked about it briefly, but maybe just get your view of that once again. Thanks so much. Yeah. Let's start with the first. It is an incredibly high percentage of, children and teens who could use this. You know, the situation is that, if I have a, you know, a new patient who hasn't been on treatment before, they're coming in fresh, we may still start with topical corticosteroids, as a quick fix. It's a quick fix and, we all have concerns sometimes even with that initial topical corticosteroid use. As we're building then regimens of care to keep people in good shape and to minimize their disease, going to a non-steroid is something we consider with pretty much every patient who we see. The non-steroids have been limited, in terms of stinging and burning, you know, safety warnings, so tolerance issues. With Rocaltrol, it's just a different ballgame. It's has effectiveness, but it's limited, and its body surface area, and has its own set of warnings associated with it. You know, I truly believe that there is this need for a non-steroid It'd be very useful, you know, facial dermatitis, delicate skin areas that otherwise you don't like to use topical corticosteroids for other than a few days. Facial disease around the eyes is very, very common, so it's gonna be a significantly high%. As long as, you know, access is there, the company's done a very good job, I believe so far at playing the access game, getting it into the hands of patients at a reasonable cost. I'm very positive about that. In terms of placebo adjusted and vehicle adjusted, you know, this is a principle that's easy for me to understand having done it for so many years. Our placebos can have an active component to them in the clinical studies, because when you put moisturizers on the skin, you might minimize your skin barrier dysfunction and have a mild anti-inflammatory effect. When studies are designed, you know, for topicals, you have to show that they were much better than the cream or the ointment that you have as a base, that the active chemical is delivering the stuff, right? Delivering the anti-inflammatory effect. On the other hand, having a well-formulated vehicle matters and can help to bring overall efficacy. This performed very well, you know, incredible consistency in the two studies with that delta. The delta, I say the delta's important to get your approval because you have to show that your active is works as compared to vehicle. Fundamentally, you want a drug that's gonna work well on the patients because that's what's gonna have them happy that it's impacting their symptoms and their signs of their disease. If it is tolerated well, that's when they're gonna wanna continue to use. Thank you. Please stand by for our next question. Our next question comes from Seamus Fernandez with Guggenheim. Your line is now open. Great. Thanks everybody. Congrats on the data. Just a couple of quick questions. Maybe first, Patrick, if you can, help us understand the opportunity in the younger patient population, you know, particularly given the choice of the 0.05% formulation. It did look like in the previous phase II data that the 0.05 actually performed quite well. Just wanted to get a sense of the choice of the 0.05 in the 0- 2 or sorry, the 2- 5 patient population studied. For doctor, for the physicians, if you can just give us maybe a sense of, you know, the opportunity that you see under the age of 6 as well, just to kind of give us a sense of, you know, sort of the frequency of disease and the concerns of parents at that age, in that age range. Just a last question. Do you guys see opportunities to really expand your coverage in 2023, perhaps with some off-cycle potential reviews? How do you feel about those opportunities? Thanks. Sure. Patrick, maybe you can take the first one around dose selection. Yeah, absolutely. Thanks, Seamus. Thanks for the question. What we're looking for with that 0.05% dose is really to find the kind of optimal safety and efficacy in that younger age group. I think you hit on the key point, Seamus, which is that in the Phase IIB study, we looked at 0.05 and 0.15. What we saw in that trial was that both of them performed very, very well. They also had a comparable response across multiple endpoints, including EASI-75 and validated IGA clear or almost clear, as well as the percent reduction in the EASI score, which is a continuous endpoint. The safety profile looked very similar. We were in a situation there where we had the ability to be able to kind of choose between the two of them. Now, we went with the 0.15% for the age of 6 and above because in that older population, we wanted to make sure that we had, you know, the most amount of drug that we could to really optimize the efficacy. In 2-5-year-olds, given that the profile was similar in the phase II study, we felt with the skin barrier defect and the lower body weight relative to the body surface area, that a better choice for that patient population would be the lower dose. You know, based on the results that we have, we don't feel like we're going to be giving up any kind of efficacy in that, in that population. We will be able to kind of maintain, we feel, the strong safety profile that we've shown in INTEGUMENT-1 and INTEGUMENT-2. Larry, do you wanna maybe address Seamus's question? Yeah, sure. I think there's tremendous opportunity when you get to the younger age kids as well. I think there are lots of, you know, basically a few months of age onward, they're a high prevalence. You know, the data about, you know, 12% in California is up to 15%. Basically 8%-15% of children in the first few years of life. Families are quite concerned about topical corticosteroids. I think most families who come in are concerned, especially if, you know, after 1 week of use or 2 weeks of use, if that's where someone starts, then what? What are they gonna do? You know, there's significant percent of patients that are gonna have continued diseases, basically a chronic disease. I think there's tremendous opportunity. Just to be clear, it's partially because the this. Type of drug. This is a PDE4, and the PDE4 inhibitors are considered to be an incredibly safe class of drugs. They don't have systemic effects in different formulations that some of our other drugs do. I think that there'll be a tremendous opportunity in younger age children. You know, there's younger age children even more so are gonna be managed with topicals as compared to systemics. There's this variability in the severity of the disease. I think use of use in regimens of care can be very high in that under six group. Thanks. Ken, lastly, do you wanna maybe take the question around access? Sure. Seamus, it's just so I'm clear, you're referring to, an topical review for psoriasis as it relates to this data or... Yeah. Sorry. Yeah, for psoriasis. Thanks. You know, as we previously talked about, the expected or anticipated timeframe typically would be that of 12 to 18 months. I think we are very pleased with our progress thus far. I think for psoriasis, you know, would expect a strong progression. We're not quite, you know, obviously announcing all these different deals quite yet, but I don't know that this data necessarily sort of portends to the psoriasis sort of access picture. Basically what I would expect is, you know, this will be a standalone indication that will secure its own access at the time of approval. What this won't necessarily lean into the psoriasis or weigh into the psoriasis decisions that will be made. Thanks so much. Please stand by for our next question. Our next question comes from Vikram Purohit with Morgan Stanley. Your line is now open. Hi. Good morning. Thanks for taking my questions. Two from my side, both on commercial. The first, Frank and team, could you talk a bit more about how you plan to detail dermatologists versus PCPs, you know, if and when the approval comes through? Speak a bit more about, you know, what you'd be looking to establish in terms of a commercial infrastructure and field force, et cetera. Secondly, now that you have both phase III data sets in hand, do you have any updated thoughts on, duration and tubes per year that you think patients would be using, for AD? Thanks. Sure. Ken, you wanna take those? Sure. Good morning, Vikram. We've spoken about this before in terms of to really unlock the full potential of this indication, we'd likely have to partner with a company that has a footprint in primary care, pediatrics or both. The numbers you see earlier on the slide, I think this was in Frank's section that talked about, you know, there were 2.6 million mild to moderate in the derm setting and another 4 million or so outside the derm setting. Really I think that's the linchpin there for us. We've also talked about kind of the timing of that. Previously we said that we thought that we'd want to potentially wait till approval. You know, we are continuously scouring that landscape to see what the best partner and fit would be. I think that situation would be, you know, probably a bifurcation of audiences given that we are clearly focused on medical dermatology specifically. We wanna keep that for ourselves and have our team work on promotion of that to that audience and allow the partner to really focus on the primary care capacity part. It doesn't change our thoughts. In fact, it probably, you know, this emboldens our, you know, desire to really leverage this data and leverage this opportunity outside and both within and outside of dermatology. Again, I think the timing is TBD, we've talked about that in the past. As for the unit consumption, I think also we've talked about this in the past, to be somewhere between, I think the three and five units per year. I think our profile, you know, again, with the extreme tolerability that we have and kind of profile that's played out, we think that we should have some additional adherence. We won't have the limitations of body surface area, nor duration and likely or any sort of other, you know, prohibition of use with another agent. I think that sets us up nicely for, you know, an additional adherence with a profile like ours. Got it. Thank you. Please stand by for our next question. Our next question comes from Chris Shibutani with Goldman Sachs. Your line is now open. Hi, good morning. This is Steven on for Chris. Thanks for taking our question. Maybe one on the data and one on the commercial opportunity. Just wondering if you expect that additional patients would respond in terms of IGA success or EASI-75 responders with additional exposure beyond week 4, and if we should expect to see any of that data in the future. On the commercial opportunity, have you talked with physicians about feedback on having two or potentially three different doses of this cream that something that they're managing right now with other therapies? I'm just wondering if you see that as a challenge in the marketplace. Thank you. Yeah, I think, Patrick, probably you're the best to address the first question, and then maybe Ken, you can address the second question. Absolutely. Yeah, thanks for the questions, Steve. You know, we don't have data yet beyond week four, and our phase IIB was also a 4-week study. I don't have data to be able to answer with regard to the, you know, potential increase in efficacy beyond. We do know, however, just kind of looking across all of our studies, that this is a mechanism of action, especially with the potency of roflumilast that gives an early response. We saw that very clearly in INTEGUMENT-1 and INTEGUMENT-2 data with, you know, clinical responses, especially on itch. As early as week one, we met statistical significance in INTEGUMENT-1 on IGA response as early as week 1. Then extrapolating those results over to where we do have data, which is in psoriasis, we saw that once we moved beyond that, efficacy was sustained over the treatment period through a year. Just kind of taking a step back and looking, you know, we expect that we're probably pretty close to our kind of optimal efficacy with this week 4 data. We'll kind of have to wait and see once we get the open-label extension readout that would kind of support our NDA. Hey, Steve. On the second question, with respect to, the comfort level, I think, you know, dermatologists are very comfortable with different strengths, of therapies, whether you're talking about steroids. You know, in the case of, for example, psoriasis, you're using a much higher potency steroid, first line therapy in atopic dermatitis, much more of a mid-potency steroid. Sort of moving between those does not seem to be a problem. We also see that with the calcineurin inhibitors, in which there are two doses. I think it's a very well and understood, you know, common phenomena to have, different dosing. I don't believe that's gonna be a problem, frankly. Yeah, I would just add, I think the key is, and Dr. Eichenfield mentioned this, is the ability to use the same dose for an individual patient, right? One of the struggles that dermatologists often face is that they're having to give multiple different steroids or different drugs to the patient for different places in the body, and that's not an issue with topical roflumilast. That, you know, just simplifies adherence. It saves dermatologists time during the visit and so forth. So that's really the key, I think, complexity you want to try and avoid, is giving the same patient two different concentrations for different parts of their body. Got it. Thank you, team. Please stand by for our next question. Our next question comes from Louise Chen with Cantor. Your line is now open. Hi. Thanks for taking my questions. I had a few for you. First one I wanted to ask you was this WI-NRS. It appears to be better on the second study than the first. Just curious which one you think will, you know, more reflect real world usage. Second question I had is, do you have any more specific timing on the INTEGUMENT-PED data coming in 2023? Is it first half, second half? The last question I had is, do you have any update on branding for roflumilast in AD? Will you use the same name for the drug? Anything to think about that will expand your sales force? Thank you. Maybe I'll take the last one first, and then I'll ask Patrick to comment on the others. The trade name will be a matter of review for the FDA. We obviously will, you know, ask to probably use ZORYVE, but that will be something that will be reviewed as part of the sNDA, whether the FDA wants the same trade name or not. Then Patrick, do you wanna talk about WI-NRS? Yeah. Louise, thanks for the question. The WI-NRS, which assesses itch, I would say is pretty similar across INTEGUMENT-1 and INTEGUMENT-2. If you kind of take a look at the numbers, we're sitting right at around 10% at week 1. By the time you get up to week 4, on active, we're at 33.6 for INTEGUMENT-1 and 30.2 for INTEGUMENT-2. I see those numbers as, you know, 3 out of 10 or a third of patients getting to this response. You have to keep in mind that WI-NRS is evaluating a subjective report from the patient, and these kinds of subjective endpoints sometimes have more variability in them. I'm actually really happy with how closely aligned the numbers are, and I think that's really reflective of just the overall size of these studies. Keep in mind, WI-NRS is assessed only in patients who have a 4 or above an itch, so the sample size is slightly lower than the overall trial size itself because it really is a subpopulation of those patients who had clinically meaningful itch at baseline. I think I would think about it as about, you know, a third of patients are getting to that itch response at week 4. With regard to the INTEGUMENT-PED readout, we'll give further guidance on that as we get down the road with that trial. You know, enrolling patients ages two to is always challenging. You know, we're making good progress, we feel, on that trial, but we wanna definitely be able to kind of refine that guidance only once we, you know, are able to do that confidently. We're gonna stick with the current 2023 guidance right now. Thanks for the answers. Actually, just to be a little bit more clear, I'm sorry I wasn't more clear, and I know you don't like to look at it like this, but just the placebo-adjusted result on the WI-NRS is what I was asking, the difference there. Yeah. Oh, I see. Remember, it's not placebo, it's vehicle. You know, as Larry mentioned, the vehicle does have some therapeutic effect. Yeah, Patrick, do you wanna maybe comment on the vehicle-adjusted difference? Yeah. I mean, I would say that difference, you're talking about the difference between 20.7 and 12.4 on those. Yeah, I would say if you look at the sample size for vehicle, keep in mind that it's a 2-to-1 randomization. We got, let's just focus in on INTEGUMENT-1. We've got 278 subjects on roflumilast and 135 subjects on vehicle. Your vehicle size is about half the size of the roflumilast cream population. That means that you're gonna have a slightly wider confidence interval on the vehicle just because of the smaller sample size. You know, if you wanted to say what's the true vehicle response there, I think the safest thing to do is probably go split the difference between the two of those, which is what happens when you pool the efficacy results. We will take these data from INTEGUMENT-1 and INTEGUMENT-2, that's part of the NDA process, and we pool them together, and then that gives you a sample size that's gonna be effectively twice the size of it. What you end up with there is that that vehicle rate is then gonna sit right between 20 and 12. It's gonna be around 16%. That might be another way to think about them. Okay, thank you. Please stand by for our next question. Our next question comes from Uy Ear with Mizuho. Your line is now open. Hey, guys. Thanks for taking my questions and congratulations on the positive study. Just a question on IGA success versus EASI- 75. The IGA success here, on an absolute value basis seems a little lower than in INTEGUMENT-1, but the EASI- 75 seems relatively comparable. Could you kind of explain the differences between the two and why one might be more important than the other if that's the case? I guess my second question is, now that, you know, you have, I guess, data from both studies, what do you think you need to have in the label that could help you differentiate, I guess from, you know, what is already. We kinda know what could help differentiate from what is already out there, but, in terms of perhaps other products that are coming into the market as well. Thanks. Yeah, sure. Patrick, maybe you can take that. I don't know if Dr. Eichenfield, if you have any other thoughts you wanna add after Patrick's responded. Hi, Uy. Thanks for the question. Yeah, I think you strike on a really important point with this question about EASI-75 versus IGA. You know, when we look at psoriasis, we find a very tight correlation between PASI-75 and IGA. Those are very, very similar methodologies between eczema or atopic dermatitis and psoriasis. The EASI score is or the EASI methodology is very similar to the PASI methodology. In psoriasis you have this kind of crutch where PASI-75 and IGA almost always track hand-in-hand. They end up with very similar responses, and we saw that in DERMIS-1 and DERMIS-2. When you look at atopic dermatitis, the EASI-75 does not track, and I'm not just talking about our trials. When you look across multiple trials, the EASI-75 does not track with IGA. We've actually spent quite a bit of time internally thinking about this even before we got these data because we wanted to understand, you know, what are these two things really assessing. I think the reason why in atopic dermatitis that you start to see a difference between these two is that the diseases between psoriasis and atopic dermatitis are quite different. With atopic dermatitis, you have a typically a higher percentage of body surface area. You also have, you know, uninvolved skin, which we know has a, has an abnormality to it in the skin barrier defect. It's also a disease that can change relatively quickly, even in a day's time. These are all very different from psoriasis. I think the inclusion of a body surface area component in EASI-75 allows that measure to be much more sensitive to changes than IGA. If you look at the IGA, validated IGA readout, it really is just a description of what the patient has on their skin. It doesn't include a body surface area component to it. Body surface area is so critical to a patient's experience of atopic dermatitis. If you have a 2% body surface area, that's very, very different from 20% body surface area. That's not captured very clearly in IGA. In EASI-75 it's captured very, very well. That's why I think the atopic dermatitis community, especially with the advent of biologics, has really moved towards EASI-75 as how they think about understanding improvement in the patient. That's why we really focus on that, endpoint as well. Yeah. Larry here, I'll reiterate. I think that's really the right approach. Just the VIGA to get your clear, almost clear success and with the miles you have to be totally clear. It takes very little leftover to not make it for that parameter even though the IGA is this general description, it's hard to get there. EASI-75 is really, you know, assessing what percentage of the population makes that 75% approval. I think that these are consistent with other studies. We always read both. We like to, you know, try to see what's been driven to clear, almost clear within the time using that vIGA. It takes very little. You know, if you clear means there's nothing other than maybe post-inflammatory changes that are allowed on the skin that'll keep you from being judged clear in a mild patient who's biologic responded, but they may not make it to that particular endpoint. Patrick, I think there was a question on just like, what are we looking to see in the label that might be differentiating? Yeah. I would say, you know, what we see in, you know, the potential like label that as we take these studies and translate them in our mind as to what could appear in that label, and again, you know, the piece that's still to come is the, you know, long-term safety. I think safety is really critical for this. You know, our initial indication we're looking for is gonna be ages 6 and above. Dr. Eichenfield spoke clearly about the need for tolerability and safety as we go down into those younger ages. That's what's really gonna clearly differentiate us from what is standard of care right now in patients, which is topical steroids. The ability to use a treatment which is once daily. You know, if you look at even the nonsteroidal treatments that are out there, they are twice daily applications. You know, something, you know, like Eucrisa or Protopic, those are also in an ointment formulation. We have a moisturizing cream that's a once daily nonsteroidal treatment and a safety profile that we think is really gonna be consistent with long-term treatment as I extrapolate the kind of what we've seen in other indications as well. Then I think that this efficacy profile, which I put stacked up against, you know, some of the other most important approved drugs that are out there right now, is very, very competitive. I think that overall profile, which will be reflected in the label, puts us in a good position for a potential approval here. Thanks. I know we're kind of up on time, but maybe Michelle will just do one more and then we'll close out. Please stand by for our next question. Our next question comes from Greg Fraser with Truist. Your line is now open. Great. Thanks for squeezing me in. Congrats on the result. I apologize if I missed this, but on tolerability, what were the AEs that led to discontinuation? I realize the numbers are low, but I'm curious about what those were. Our adverse event rate leading to discontinuation was low as I mentioned, and that's in the slide. When we look across those AEs leading to discontinuation, there are couple important things to note. Like, one is that there wasn't a single adverse event that led to discontinuation that was actually repeated in another patient. If I look at INTEGUMENT-2, right, we had eight patients, there wasn't an event that was seen in more than one patient. We're not seeing any trend towards a patient who's having, you know, or a trend towards any kind of like group effect on adverse events. We're also not seeing any local tolerability that's leading to discontinuation there. We did have some patients who had worsening of their atopic dermatitis, for example, things like that. I, you know, I think it's, you know, but obviously those data will eventually be released in a published form, but, you know, there's no pattern there that worries me with regard to, you know, what's driving discontinuation. Seems more related to the individual patient's experience. Great. Thanks for the additional color. Well, thanks for all the great questions, everyone. I would now like to turn the conference back over to Frank Watanabe for closing remarks. Thanks. Yeah, no, I'll just say thank you for taking the time to call in. You know, we're obviously delighted to be able to share these results with you. We look forward to releasing more details at a major scientific conference sometime in the near future. I appreciate everyone's time.