Welcome to those of you in the room. Really appreciate you guys coming and joining us here in Boston, and those of you online, thank you for joining us as well. I'm Frank Watanabe. I'm the president and CEO of Arcutis Biotherapeutics, and I'm joined today by Patrick Burnett, who is our chief medical officer, and Ken Lock, who is our chief commercial officer. A little bit later when we get to the Q&A session, we'll be joined by Scott Burrows, our chief financial officer as well. We are gonna be discussing some forward-looking statements. When you get a chance, if you would, please review the legal disclaimers. I know you can't read them now. Just a quick overview of what to expect for today, especially for those of you who are a little less familiar with the Arcutis story. I'll start out with an overview of the company, an overall overview, and then Patrick and Ken, are going to drill in more on psoriasis. Patrick will give you an update on the clinical data on plaque psoriasis, and then Ken is gonna talk at some length about our launch preparations for plaque psoriasis, which are coming along very quickly. We'll pivot to talk about atopic dermatitis program, and both Ken and Patrick will talk about that as well. We'll then go on and talk about our foam programs in seborrheic dermatitis and scalp psoriasis. I'm gonna do something a little bit new today. Want to talk to you more about some of our earlier stage programs in particular ARQ-255, but we want to talk to you about some of the early stage pipeline programs too. I'll wrap up, and we'll get into a Q&A at the end. For those of you online as well, you can submit questions online, and we'll try and respond to those as well. Let me talk a little bit about Arcutis as a company. You know, we really see 2022 as a transformation year for this company. For those of you who've been following the story for a while, I think probably everyone has noticed, this team has built quite a track record on execution, and they continue to execute exceptionally well, both on clinical, commercial, our manufacturing team as well, and the finance team. As Ken will talk to you a little bit more today, we are very excited about the launch, and I think you'll see we're very well prepared for the launch of roflumilast cream in plaque psoriasis. We also are very confident in the outcomes of the atopic dermatitis phase IIIs, and Patrick will talk to you about why we feel so confident about our AD data. Then we're also gonna spend some time talking about the seborrheic dermatitis opportunity in particular, because our excitement level just continues to build, I think especially coming out of this week at AAD. We think this is a very large and largely underappreciated opportunity for us. Then lastly, as I mentioned before, we wanna talk to you a little bit more about other things that we're doing beyond roflumilast to build out our pipeline. Again, for those of you who are not as familiar with Arcutis as a company, a little bit of background. The company was formed about six years ago, with a very single-minded idea behind it, and that was to fill the gap in innovation in dermatology drugs. There's been a lot of consolidation in dermatology over the last couple of decades, and that really led to an atrophying, frankly, of the innovation pipeline, and we saw an opportunity to fill that void. In particular, our vision is to really elevate the standard of care, in the treatment of common inflammatory diseases, and in particular, to try and help doctors and the patients that they treat not have to make trade-offs between efficacy on the one hand and safety and tolerability on the other, which is unfortunately all too common today in the treatment of these diseases. Our strategy for doing that was really threefold. The first one was to focus on biologically validated targets, so things that we already knew worked in dermatology like PDE4 and JAK inhibition. That really reduced our risk profile, to focus on best-in-class target drugs against those targets so that we had that sustainable differentiation. To build a world-class team of dermatology experts around those products to develop them. That strategy has really, I think, done very well for us, and allowed us to build out a very robust pipeline in a fairly short period of time and not all that much capital, at least as drug pipelines go. This is our pipeline. Many of you are probably familiar with this. I'll start at the top again. Roflumilast cream or ARQ-151. We're currently in front of the FDA for plaque psoriasis. We have a PDUFA date of July 29. We have a large atopic dermatitis phase III program ongoing that Patrick's gonna talk a little bit more in detail later this morning about. We have a foam version of roflumilast as well that we developed to treat hair-bearing areas of the body, like the scalp. We have phase III studies ongoing in both seborrheic dermatitis and scalp psoriasis with the foam. We have our JAK programs. We have a selective JAK1 inhibitor that we formulated as both a cream, and a penetrating solution. The cream's been in the clinic. We're in the process of reformulating that, but we're looking at hand eczema and vitiligo as indications for our cream. You know, we've leveraged our unique development expertise to develop this deep penetrating version, ARQ-255, that we hope to be in the clinic soon, to treat alopecia areata. We've also been busily working, in particular, David Osborne, our Chief Technical Officer, has been busy working on new programs, and we'll talk about those a little bit, later in the day, but we have a number of other earlier stage programs in the preclinical pipeline. One of the reasons why 2022 is gonna be so transformational for us is, the richness of the catalysts, frankly, especially in the second half of the year. We've announced that we've finished enrollment in the seborrheic dermatitis phase III study, the STRATUM trial, and we'll read that out sometime around the middle of the year. As I mentioned, we have our PDUFA July 29. We expect to read out the scalp psoriasis study late Q3, early Q4. I think we're coming up very close on last patient enrolled. It should be done very soon. As we guided in the K, we expect to read out the first two phase IIIs in atopic dermatitis sometime before the end of this year. One of the other reasons why we're really excited, frankly, about the roflumilast opportunity is that we're addressing really large markets, right? So this is looking across psoriasis, atopic dermatitis, and seborrheic dermatitis. If you just look at those patients in a dermatologist's office currently, being treated with topical currently, that's about seven million patients. That's a very, very large market opportunity for us without really having to do much to get patients in the door and, you know, build a market. In addition to that, there's almost that many, probably around six million patients who are being seen by another specialty other than dermatology for either psoriasis, atopic dermatitis or seborrheic dermatitis. You know, really large established markets. This isn't one of these markets where we've got to go out and get people off their sofa and get them motivated. They're already in the office. They're already being seen by a dermatologist and are being treated topically. We think that roflumilast has a really unique profile that suits it well, that aligns it very closely with what doctors and people with dermatologic skin diseases want. In particular, and Patrick will go into this in more detail in just a minute, but we've seen efficacy in plaque psoriasis that's on par with the most effective topicals that have ever been developed, the combinations of high-potency steroids and vitamin D or vitamin A analogs. It is a non-steroidal, which is really important, with the ability to use it chronically, which you can't do with a high-potency steroid, and to use it anywhere in the body, which you can't do with a high-potency steroid. We don't anticipate any box warnings. And, you know, we've treated over 3,500 patients now with this drug, and we've seen no evidence of any application site reactions, which, you know, it. are very common, not only with the other, PDE4, topical PDE4 inhibitor, but with many of the other topicals that patients use, there are local, adverse reactions, which we're not seeing with our drug. One of the other important elements when you're a small company getting ready to launch is your ability to supply the market, right? You know, we have built a very robust, supply chain for our product, that we think de-risks our launch, but also our ability to supply the market going forward. We do formulation fill and finish in the U.S. at a very large, well-established, contract manufacturer. It's one of the leading manufacturers in the whole industry for topical drug manufacturing. They have a strong track record with the FDA and EMA from a regulatory standpoint, and they've been manufacturing our drug now for over five years. Many of those years, they've been manufacturing at commercial scale already. In fact, we manufactured all the supplies for phase III, at commercial scale in a commercial plant. In the commercial plant, I should say. That really de-risks from our standpoint, our manufacturing and supply chain strategy. Another important aspect, obviously, is having enough money to do all of this stuff. We topped up the tank in fourth quarter. Scott and his team negotiated, I think, a very attractive non-dilutive deal for us with SLR Capital. For those of you who aren't familiar with the terms of the deal, we took down a $225 million facility. We took down $75 million at the close. We'll get another $125 million at approval for plaque psoriasis. There's a final $25 million that's tied to a fairly modest revenue milestone. It's interest only for the first five years and very light on covenants. We think this deal really gives us very good optionality, particularly, you know, given the challenges that the biotech sector is facing right now, in terms of when we would do any future financings. I think importantly, it gives us runway out to 2024, and gives us the resources to fund both the clinical programs that Patrick's team is running, as well as investing in Ken's team and the launch for success instead of cutting corners. We also think there are opportunities for us to add to the balance sheet in non-dilutive ways through, for example, out licensing of our ex-U.S. rights, which we're actively looking at right now. Another important consideration, I think, is intellectual property. As many of you probably know, composition of matter of roflumilast is expired. Frankly, that doesn't really worry me because we've built, a very strong patent portfolio around topical roflumilast. We now have eight patents that have been issued in the U.S. and foreign territories on the formulation of topical roflumilast, both the foam and the cream. Late last year, we received the first pharmacokinetic patent, on topical roflumilast foam and cream. We really believe that that combination of formulation and PK patents puts us in a very strong position, to maintain exclusivity at least through 2037, which is when our first patent expires. In addition to that, we continue to add to the portfolio. We have multiple pending patents. We have three additional patents filed for pharmacokinetics of topical roflumilast. We have multiple patents filed on the formulation of roflumilast. We have some method of use patents in place as well. If those patents issue, you know, that will just continue to build on the strength of our intellectual property portfolio. We feel very comfortable about where we stand from an IP standpoint. Then we do have a couple of patents around the JAK programs as well. Okay, with that, you've heard enough from me. I'm gonna turn it over to Patrick to talk about plaque psoriasis. Thanks, Frank. I think Frank did a great job kind of setting up the size of this indication. Plaque psoriasis is highly prevalent in the U.S. As mentioned, nine million U.S. patients suffering from plaque psoriasis today. There has been innovation in this disease, but it's been very much focused on the systemic treatment. Despite all that, still greater than 90% of patients are treated in the U.S. with a topical drug, and that's for a couple of reasons. One is, the majority of these patients are in the mild to moderate severity, so they're not actually captured in the indication that is for biologics currently. As well, many of the patients who are on biologics are still being treated with a topical therapy adjunctively. There's other patients that are in the moderate to severe category, but either due to personal choice or due to access issues, they actually don't have availability of systemic treatment. That means that these greater than 90% of patients haven't been able to actually participate in the innovation in this space, and that leaves them using existing therapies, many of which have challenges and leaving them with the trade-off between safety and efficacy, especially when they're using topical steroids. I'm gonna talk a little bit today about how it is that roflumilast can kind of change this balance. We even see that reflected when we talk to patients, and we find that over 80% of the patients say that they wish that they had more topical treatment alternatives beyond just steroids. Now when we're treating psoriasis topically, it really you have to deal with some local issues around some different body sites. Although it's the same disease, when it manifests itself in some of these different locations, it can either be more recalcitrant to treatment, or it can be sensitive to some of the local tolerability issues or to some of the mechanisms of action that are being used to treat psoriasis. On the left, we have face and intertriginous. These are two areas where the skin is traditionally more thin, and as well, patients have a sensitivity to treatment, which may make it not really appropriate for them to be treated with some of these either for due to local tolerability, such as irritation, or in the face, for instance, in this area around the eyes, treatment with steroids can be associated with cataracts and glaucoma, so there is a sensitivity to that point. Intertriginous disease makes up about 15% of patients at any given time, more easily irritated. These are areas where skin are in contact, and so any irritation is magnified in that setting. In particular, steroids oftentimes can lead to atrophy or stria, which are stretch marks, and those can be permanent, lasting on the patient for many years. Now, moving over to the right side of this screen, what we see are two areas that are typically recalcitrant to topical treatment and even systemic treatment for that matter. Scalp disease is highly prevalent, being seen in about 40% of patients. The challenge here is that many of the treatments that patients are being prescribed are in creams and ointments and can't be used on hair-bearing areas, and that's where we'll talk about the use of our foam in this location. Then elbows and knees, I'm not gonna talk in detail about our data for treating elbow and knee psoriasis. We do have actually a poster that we presented at the American Academy of Dermatology meeting here in Boston, where we highlight those patients out of our pooled data set that have knee and elbow involvement. That makes up about 35% of patients and show what our efficacy looks like in that subgroup. Now, I'm gonna go through some of the data, but what we've captured here on this slide are some of kind of the key differentiation points that are present in our profile, both from an efficacy and a safety point of view. I think if you take a step back, what's really critical here is that this is a non-steroidal treatment. I'm gonna show some comparison to some of the commonly used therapies. Many of these may actually have efficacy that is in line with what it is we've been able to show, but they all still also contain a steroid, and that's what really is the hurdle for many patients to try and find a way to treat this chronic disease and avoid steroid use. We have a once-a-day treatment, which I think is very easy for patients to incorporate into their kind of daily treatment regimen. These are phase III data. As I mentioned, we have now pooled data that we brought to the American Academy of Dermatology meeting in a poster. These represent the individual study level data with DERMIS-1 on the left and DERMIS-2 on the right. These are two identical phase III trials. Here we're showing IGA success. That's Investigator's Global Assessment success. This means that on a five-point scale, with mild, moderate, and severe being two, three, and four, that patients had to get to a zero or a one, which is clear or almost clear, and have a two-step improvement in order to be considered a responder by IGA success. You'll see this measure a lot as we kind of step through the data. I'm not going into great detail, but what you see is on our pooled data, we had 40%. That's combining a 42% DERMIS-1 response, and a 37.5% IGA success that we observed in DERMIS-2. Just to contextualize this a little bit, we have some cross-trial comparisons that are shown here. As with any cross-trial comparison, you have to caveat the fact that these are not head-to-head studies within the exact same study. Just to give an understanding of how our data on IGA success, stack up against some combination products. Again, all of these still have a steroid incorporated into them, so they're still also susceptible to all of those same caveats with regard to use of location. They've been combined now with usually either a retinoid, a vitamin A or a vitamin D containing second product. Those oftentimes are associated with irritation. What you can see is that the average of these three products is about 34%, which matches favorably against our 40% efficacy that was seen in our pooled data. You see IGA success for both DERMIS-1 and DERMIS-2 all the way to the left. I'll also direct you to what is a topical steroid. Kinda like the workhorse of treatment of psoriasis would be betamethasone dipropionate, and that's actually showing up under Taclonex in the purple bar. That is just monotherapy with betamethasone dipropionate. Just to give you an idea of what monotherapy with a steroid. That's what represents kind of the efficacy you would anticipate from a generic treatment with a steroid. Additional data that we've brought to the AAD is using these pooled data to do a subgroup analysis, looking at baseline severity as split out by body surface area. Body surface area is abbreviated here BSA, and patients then are kind of slotted into three different categories, which we'll call mild, moderate, severe, with mild patients being less than 5% body surface area, moderate five to ten, and then everybody greater than 10% would be severe. The first thing that you notice in looking at IGA success on the left, this is an endpoint that I've talked about previously. At week eight, you really see almost identical efficacy across these three groups. Maybe a slight numeric increase in patients in the severe end. These data are represented almost identically in PASI 75. I haven't talked much about this one, but PASI 75 is the Psoriasis Area and Severity Index, and it's a binary endpoint where a patient has to improve the amount of psoriasis that they have by 75%, in order to be considered a responder. One of the things, just kind of taking a step back, looking at these pooled data, is a very, very high level of consistency between IGA and PASI. Keeping in mind that these are two completely different assessments. For a PASI, an investigator is going in and looking in great detail at the amount of erythema, the amount of the thickness of the plaque, and then calculating the body surface area in each area and then plugging that into an equation, whereas IGA success is just a five-point scale. Despite the fact these two different methodologies, we have highly correlative data, which really suggests we have great investigators in our trials, and that the drug is working reproducibly. For a topical treatment, you wouldn't necessarily expect that it would work just as well in patients on the severe end of the spectrum. Just for comparison, we've taken our data here, IGA success on the left and compared that to Otezla. This is not a drug that we really see as a key competitor for us. It's a systemic treatment, but it has started to encroach into the mild to moderate population with data coming from their ADVANCE trial. Now that we have our pooled data and the subgroups, that we can look at our mild, moderate, and severe response rates, it allows us to do another cross-trial comparison with the same caveats. This isn't a head-to-head comparison. You can see that the you know, Otezla is roughly 20%-22% across these three trials, with advanced being in mild to moderate patients. You would compare that then to the left two bars on our on our BSA graph. ESTEEM 1 and ESTEEM 2 are in moderate to severe patients. That would be the right two bars. You can see that in eight weeks of treatment, we have efficacy that exceeds that which they can do in 16 weeks. I think looking at the fact that these are both PDE4 inhibitors, what you're seeing here is the benefit of applying a highly potent PDE4 inhibitor directly to the psoriatic lesion so that we can really optimize the response on this pathway. This is a new display for our data. Again, taking the pooled, the pooled data that we now have in-hand and looking in a waterfall plot across all the participants in our phase III studies. DERMIS-1 and DERMIS-2 combined here. On the left, we see roflumilast cream, on the right is vehicle. Every patient is represented by a bar, and what it's representing is their PASI total score% change from baseline at week eight. Any downward deflection then represents a patient who had improvement in their psoriasis, and any upward deflection represents a patient who had worsening of their disease. It's kind of hard to see on the roflumilast side, but all the way to the left, you can see, those would be the patients who didn't respond. But what you see most of all is that almost every single patient who went into treatment with roflumilast, had some clinical benefit from being on this treatment. That's really dramatic when you compare it then to the vehicle patients. The difference in the number of patients is because we randomized two to one, and that's why the vehicle arm just has less individuals being represented there. The nice thing about looking at our percent change from baseline in PASI in this way is that it then allows us to kind of visualize the other binary responder metrics that we're used to from PASI, like PASI 50, 75, and PASI 90. PASI 50 has been identified as a clinically meaningful response using this endpoint. Here we see that three out of four patients, 72% of the patients who are treated with roflumilast cream meet that endpoint, compared to 26% on vehicle. As we go up to the higher bars of PASI 75 and PASI 90, we're capturing 40% of patients and 20% of patients for PASI 90. You really get a good understanding here, of kind of what the expected response is in a large population of patients treated with roflumilast cream. Overall, what you see is that the vast majority of them are responding favorably to that. Another aspect of psoriasis treatment which is critical is that patients need to be able to treat their psoriasis chronically. It's a chronic disease. They'll have it for the rest of their life. We have two sets of long-term safety data. What we're showing here is our phase II open label extension data in plaque psoriasis. These are patients who either rolled over into this open label extension after being on vehicle, and those are represented in the darker bar, and those that rolled over after being treated with roflumilast in the preceding trial. Both of them, you see good sustainability of the efficacy that was observed in our phase II and then subsequently our phase III studies. Those patients who roll over from the vehicle rapidly kind of join their peers up in the 40%-50% range of clear or almost clear, and then continue that through the remainder of the 52 weeks of treatment. Given that the active patients were treated already for 12 weeks, that puts us at 64 weeks worth of safety data. Also at the AAD, we do have rollovers from our phase III, which are where we're releasing the safety data there, which shows another kind of just additional patients giving the same understanding of our safety profile. This is represented here on the bottom right, in that we had a very low number of patients who discontinued due to lack of efficacy, less than 1%, and less than 4% of patients discontinued due to any adverse event. These are numbers that were significantly lower than what we had anticipated going into the trial. Typically, in a topical trial, you'll have about 50% of patients who complete. We were very happy to see that about three in four patients, almost 75% of patients were able to complete our studies. I talked a little bit about intertriginous disease. This is where we have skin-to-skin contact. Our program, our development program has been unique, because we saw early on that the clinical profile of roflumilast cream, particularly the favorable tolerability and potency similar to even the combination products, would be a nice mix for patients with intertriginous disease because we don't have a steroidal component in our treatment. So we developed an IGA based off of intertriginous disease only, and we called it an iIGA, and we assessed that prospectively in both DERMIS-1 and DERMIS-2. We've shown these data before, but just to highlight them again, about 70% of patients across these two studies showed iIGA success. Importantly, of those that did show success on this endpoint, 90% of them actually made it to iIGA of clear, which means that they didn't have any intertriginous disease before. The tolerability profile in these patients who are very sensitive to irritation was very favorable as well. This is a differentiating point of our development program because these aren't data that we've seen previously in phase III studies. Just to highlight again data that we've shown previously, our itch response in DERMIS-1 and DERMIS-2. Here we're looking at what's called a WI-NRS, Worst Itch Numeric Rating Scale. This is a 10-point scale. To be considered for this endpoint, patients had to have an itch score of four at baseline, and then they had to have a four-point improvement over the duration of the treatment that's being evaluated to be considered a responder. I think the two key points to take away from this across both studies, which look very similar to each other, we have an early response with over a third of patients already responding at week two according to this metric, meaning statistical significance in DERMIS-2. Then by the time they get to week eight, we're up in the 65%-70% range for patients responding by itch. This is something that is being included now in topical labels we've seen recently, and really addresses the key symptom for patients with psoriasis. If you ask a patient with psoriasis what it is that drives their severity, it's not necessarily their body surface area. The number one thing that they'll tell you is it's the level of itch. Being able to control that symptom and have it respond early gives patients confidence that the drug that they're taking is working because it's addressing their kind of key concern about their disease. This is the safety data from DERMIS-1 and DERMIS-2 split out individually by study. You can see quickly that, at the top line we have like low and balanced, adverse event rates looking similar between vehicle and roflumilast cream. Both studies look similar to each other. Just to highlight adverse events. Well, start looking at study discontinuations. I always feel that this is really the best metric of tolerability that you have. Here you can see that our discontinuation due to an adverse event wasn't really different between active and vehicle, which is great to see. The only specific preferred term on an adverse event I think is worth talking about specifically is the diarrhea. Here we had an incidence of about 3% across both studies, which is very low. That's significantly lower than what you get with oral administration of a PDE4 inhibitor. Importantly, of those 18 patients, 17 of them were mild, none of them discontinued early, and the diarrhea was transient, occurring early in treatment and then resolving. I'm going to turn it over to Ken to talk about launch planning. All right. Thank you, Patrick. What I'm going to do is talk a little bit about the way we're thinking about a launch opportunity, our launch planning, some of the strategic pillars that we're thinking about, and then ultimately some of the metrics that we'll be using to track our progress. First and foremost, you know, topical roflumilast being a next generation PDE4 topical inhibitor really has the potential to simplify the overall treatment of psoriasis. I think we're in the unique position to actually have almost full alignment or full alignment amongst the key stakeholders that you see on this slide. First and foremost, healthcare providers. You know, we talked about what they're looking for in a product profile, efficacy of a steroid, you know, the ability to use chronically and the ability for it to be used everywhere. Beyond that, I think what's sort of another benefit of our product, is the simplicity it brings to their practice. If we think about what happens today when a patient goes into an office, they often leave with two or three prescriptions, one for the sort of more difficult refractory plaques, one for the sensitive areas, and maybe, you know, another product to sort of manage their scalp or their hair bearing areas. The opportunity to sort of rationalize and simplify what physicians have, you know, do, so to speak, and the number of prescriptions given, and ultimately also reduce the amount of concern that they might have about misuse of a product, or the counseling that they have to provide with that, leaving them a long list of directions with their therapies, may be essentially eliminated with a product like topical roflumilast. The same is true for a patient. While the patient is largely seeking the same things as a physician, efficacy, simplicity, once a day, you know, non-greasy formulation, these are all attributes. The end benefit also, you know, the reduction in confusion, number of prescriptions, number of co-pays. These are very tangible benefits that I think are important to look at. Lastly, from a payer perspective, you know, this category overarchingly has grown dramatically over the last two decades. It's about a $20 billion category today, but 90%-95% of that, is actually a systemic biologic spend. You know, having a product that is quite effective at a different price tier, significantly different price tier, is attractive to payers and for both from an absolute cost and a potential savings downstream, should we be able to delay, for example, the need to graduate to systemic or biologic agents. This is a very unique alignment, if you will, of key stakeholders. Often you might have two of the three, you know, in hand. I think this is very unique in terms of that. I often get asked by many of you here and in the audience sort of what is the best analog. Show me an analog for a successful topical launch. Very frankly I think owing to the profile or the dynamics of any given launch there are very few I think that are perfectly appropriate to pinpoint against topical roflumilast. If you look along the top axis here you see some of the more Elidel obviously being the oldest but some of the more recent launches in branded topicals whether they be atopic dermatitis or psoriasis. What you see is, essentially, there's some aspect of either the profile or the label, that I think impedes ultimately the ability to either get off the ground quickly or ultimately sustain that success that is seen, out of the gate. If we walk down to the parameters that both Frank and Patrick have mentioned, efficacy being on par with a topical corticosteroid. Legacy non-steroidal products or first generation, you know, PDE4 have not been able to demonstrate that type of efficacy, whereas we have in our phase III trial. The ability to be used chronically and everywhere on the body, clearly that's, you can't do that, right? With steroidal based products like Duobrii or Wynzora. With the topical JAK approval recently, also there's a limitation on duration of use to it, sort of embedded in the label. So we see that as a potential, you know, reason why that's not a perfect analog either. The box warnings, we don't anticipate a box warning, but the presence of a box warning has already played itself out particularly strongly, in the calcineurin inhibitor market, where by year four, that trajectory was dramatically reduced by the presence of the box warning. You know, Opzelura or topical JAK has been off to a fast start. I think with respect to that conversation with one of the key stakeholders in the decision making for atopic dermatitis being the parent, I anticipate that to be a little bit challenging downstream. Lastly, we talked about the local stinging and tolerability profile. Many of those products, both steroidal and non-steroidal, have local safety tolerability challenges that we've not seen in our profile. I'd be remiss if I didn't speak about something that's sort of not part of the profile, but sort of broad patient accessibility, which is sort of a key tenet of our approach. I would also say, you know, many of these products are not necessarily perceived, either today or you know, maybe in the future to have the type of broad accessibility that we strive for. While I can't put the plus sign yet until we get to approval, certainly I'll be looking to enhance that perception in the marketplace. We know based on this and based on both the profile, the anticipated label and some of the other conditions, we feel very strongly that we're positioned for both a strong launch as well as the ability to maintain or to continue that success down the road. The other question I get often from the investment community is, some skepticism regarding the ability for a first time small company launcher. While you know I can't lay claim that we will repeat you know Biohaven's success, what I would like to just to point out is that there are some strategic parallels with respect to the evolution of the CGRP market. First and foremost, I believe that, you know, with the right product profile, which I strongly feel we have, the right execution, and importantly, the right strategy, it is possible. Walking down this chart, you know, and looking at some of the parallels that exist today, you know, the treatment of chronic large markets, chronic symptomatic conditions, large competitive markets with very significant unmet need. I think the third row is maybe the most important, which is that you're delivering meaningful innovation, to really supplant that sort of legacy, you know, standard of care, sort of an outdated generic standard of care. In the case of the CGRP market, that were the generic triptans. In the case of this marketplace, it's really the generic steroids, topical steroids. Then last but not least, the ability to build upon that initial indication from a portfolio standpoint to really build the halo of efficacy and ultimately improve the value and economics for both manufacturer and payers in garnering large volumes. Again, just as we think and sort of aspire to be successful in our first time launch, we look to some of these, you know, parallels as proof that it can be done. Let's talk a little bit about some of the critical success factors for launch. You know, beyond any of these pillars, it always starts with the foundation of a very durable and differentiated product profile, which I think you've heard quite a bit about today. The three things we think about that we must execute on clearly, is to drive prescriber awareness and ultimately use, to drive strong patient engagement and having a first positive experience at a patient level. Then importantly, broad high quality access. I just want to pause on the sort of high quality comment because I think, you know, it's one thing to say you're covered or not covered, but I think the devil's in the details with respect to how easy it is to actually get your product, and I'll talk about more of that as we get into our reimbursement strategy. With that, I'll first start on our first pillar with respect to what we've been doing around driving awareness and use. One of the fortunate things that we've had as a company, both from a foresight and a resourcing standpoint, is to make very early and strategic investments, in our community facing organization. Starting with Patrick's medical liaison team, we very early hired that team and deployed them into the field, so to speak, and really engaging with KOLs as early as the spring of 2021. If you think forward about our relative launch timing, our MSLs will have been out well over a year in advance, you know, engaging KOLs in scientific exchange and ultimately bringing back the type of customer insights that we really need to be successful. Really understanding where the product is gonna be used, how they want to use it, and how we can best partner with the dermatology community. This should not be taken for granted. As we look back at sort of the factors that are key success factors in any launch, typically you wanna have folks out as early as possible, particularly your medical science liaisons. From an access and reimbursement standpoint, again, it's been part and parcel to our strategy regarding thinking about broad and high-quality access, is to deploy the team early. I had the fortune of bringing on my payer lead more than two years ago. Ultimately, we deployed our payer team last summer so that the folks that engage on a day-to-day basis with both PBMs and health plans, we've been exchanging ideas and really setting the stage very early, very strongly signaling to each other what we're seeking in terms of the type of access that we're looking for. That's, you know, ideally gonna pay off ultimately with the type of access that we get. Last but not least, our sales team. We actually employed and brought on a team of very talented sales managers actually in the fall of last year. Again, well in advance of launch, you know, and really to set the stage, introducing themselves, I think, you know, ferreting out some of the things that sometimes make sales teams come out of the gate a little more slowly. Tackling maybe some of the logistical challenges of sort of knowing, where to go and these basics. Importantly, I think establishing relationships with the key customers early. You know, we're just gonna repeat the fact that we are thinking about 80 sales representatives hired in two waves. I'm very excited that in the next three weeks from now, our first wave will start. Half of that sales team will actually begin, you know, again, covering and obviously not selling anything, but more importantly, driving company awareness and awareness of our overall pipeline. Just a comment. I then think when we think about sort of the composition of the current commercial team, deep commercial dermatology experience in both dermatology and outside of dermatology, but importantly, you know, having participated and been in very highly competitive categories, whether we're talking about dermatology, oncology, lots of these very competitive spaces, and you see some of the brands you recognize today up here. The second thing that I'd like to talk about in the first pillar around driving awareness and use, is that the patient dynamics are quite favorable for us. Frank mentioned this idea that many of the patients are already in the offices that we seek to be in, and so activating that patient or finding that patient, is a little bit less of a challenge. We also believe that there's minimal behavioral change given that 80%-90% of prescriptions are being topical today, that we're not educating on anything new, right? We're not needing to teach you about a new injection technique. They're really just plugging into the everyday algorithm of the physician. That activation energy is quite a bit different, let's just say, and I think is in our favor. Also, you know, there's a highly dynamic market going on here in terms of the mild to moderate population. Owing to the structural limitations of steroids, there are forced switching opportunities that are going on quite frequently. The proverbial shots on goal, if you will, are quite frequent with respect to topicals, and there are many opportunities to either start or switch to an agent like topical roflumilast. I think this is very starkly in contrast to what you see with systemics, where you're waiting three, six, nine, 12 months to be the opportunity to the next product. We do not expect that at all. Then lastly, there's a relatively sparse competitive landscape for innovative topical therapies. We actually expect quite a bit of synergy, frankly, with our other nonsteroidal topical that's launching in the same timeframe to actually work together in driving, you know, some of the nonsteroidal market growth. These are conditions I think that are favoring that utilization. The last pillar of sort of phase I, which is the HCP awareness and use, is that broad sampling of our product and trialing we feel are very key to our uptake and ultimate success, for three reasons. First and foremost, we wanna establish a very early positive experience. The ability to immediately sense, you know, feel, experience, hand a patient that sample, and very frankly, I think, you know, it's expected, is key. Secondly, to enable strong differentiation from legacy PDE4s. We know that there is a perception in the market regarding currently available products, and we wanna quickly extinguish and differentiate, you know, any concerns, very frankly, over the known side effects of those products or profiles. But lastly, just touching again on the idea that this is an expectation, and despite what you might hear, this is truly an expectation in dermatology offices. We've heard it repeatedly, the ability to sample strongly and maintain that sampling is really key for both broad adoption and continued success. Moving on then to the patient pillar a little bit, I just want to talk a little bit about sort of the sentiment that the patients are exhibiting. We recently fielded a large scale 500 topical patient survey, just to better understand kind of what they were looking for and also the level of interest. As you can see, almost universally, nine in ten patients first and foremost wished that there were more efficacious topical options. Also, that, you know, it was a once-daily application. Many of these products are more than once a day. You know, they could use a single topical, again, rationalizing the number of prescriptions and effort needed and time, frankly, and are interested overall in trying a new topical for their psoriasis. Those conditions are very favorable with respect to heading into this and, again, capturing that engagement and interest. Interestingly, you know, Patrick talked a little bit about intertriginous psoriasis. While the literature suggests it's about 15% in this population, which is obviously a little richer in terms of these patients are already getting topically treated for psoriasis, on a lifetime basis, two out of three patients actually, mentioned that they have experienced at some point or another intertriginous psoriasis. The overwhelming majority of those patients, as you can imagine, said that they would be more adherent if they could use a single product across or all areas of the body. Then moving on to pillar three, which is about access and reimbursement, and again, I talked about high-quality access. This slide has really not changed at all since we've been doing this. The idea that, you know, optimizing patient access is really key, and that broad, high quality access and reduced prescriber burden would be key to maximization of volume. First and foremost, responsible pricing is something we've talked about from the beginning, and we believe that product pricing more modestly, even though we're delivering what I consider very high innovation, may allow for broader and more rapid payer coverage. You know, really focusing on patient affordability and the ability for the patient to actually get the drug that the physician has actually prescribed is key. Then lastly, you know, I think rapid introductions of follow-on indications. If you follow along in our pipeline, we're in a position to launch up to four indications over the course of 24-36 months, which actually allows for, you know, significant value there to payers as well in terms of the economics. I wanna double down on the prescription prescriber burden factor. Many of our physicians, even this week at AAD, have just mentioned that, you know, their willingness to sort of fight through continuously, you know, significant utilization management techniques is not particularly high for a topical agent. Only about half the offices have people who actually do this for a living. You can imagine that, for many of the offices in the community that don't have support, don't have on-site teams to sort of handle paperwork, the easier we can make it to sort of plug into their paradigm, if we can make it as easy as it is writing that next steroid or that next nonsteroidal, calcipotriene, for example, the better we are off. This is sort of the basis for some of those pricing, you know, philosophies that we've talked about. Let me just recap then here just so the overall landscape of branded medications today, and this is inclusive of both psoriasis and atopic dermatitis. Historically, the band for these products, which include also foams and creams, was about $400-$1,200 until the topical JAK was approved recently. The intent of this slide is really to show, the relationship, the relative relationship between payer controls and utilization management. Directionally, while this isn't perfect, I think it gives you a sense of sort of the higher the price you go, the more sort of typical restrictions you might experience. It's not to say that the product wouldn't be available, but the steps you might have to take to justify that or the number of therapies you need to demonstrate having failed, right? They're sort of directly correlated, I think, and we see this playing out in the market today. As mentioned for topical roflumilast, the way we're thinking about this is to still, you know, despite some of the newer pricing, I think stay within sort of the left side of this page, that's the lower middle left side, to try to optimize again, you know, the volume opportunity. I don't think it's changed our thinking at all, but you know, some recent events, and looking at some of the utilization management techniques, I think have validated our approach in terms of thinking about, making the product as easy as possible to get and where do you actually have to price to get that. Okay. Just, you know, bringing this full circle, again, here I've added a little bit more about the type of metrics that I think we'll be looking at, both short and long term, in terms of whether we're delivering on these critical success factors. From a driving prescriber awareness and use, some very typical metrics here that you would expect to see. TRX, NRX trends, breadth and depth of prescribing. Importantly, reach and frequency. We get a lot of questions, of course, about, you know, how do you think this is gonna go, you know, during COVID? And we have seen some impact, but fortunately in dermatology, both pre and I don't know if we're post-COVID quite yet, but pre, you know, the trends early on were always more favorable with respect to access, I mean, physical access of sales representatives. I think, as we are hopefully coming out of COVID, it's also rebounding quite faster, frankly, than other therapeutic areas. What we see is the greater ability to get into offices. We also see prescription volumes growing faster in dermatology, coming out. This is a trend that we'll obviously be watching. On the patient side, obviously, I think, you know, the best compliment you can get is repeat business in any business you can think of. Refills, adherence, compliance, all very important factors. I think for a product like ours that doesn't have specific label limitations on repeat use or extended use, we would expect this to be a strong component, particularly given our tolerability profile. We'll also be watching non-steroidal category growth. As mentioned, we have another company that's launching in the same timeframe, and we'll be both, I think, trying to do the same thing, which is effectively displace some of the older standards of care. Then lastly, getting patient feedback directly through any number of mechanisms. Lastly, the broad and high-quality access. Percentage of covered lives is interesting. I think, you know, everyone sort of talks about that in terms of and we will share that with you as well. But importantly, I think it's the quality of that, the details and the specifics of, how burdensome is it to get even if it is covered. I think that's really where you start seeing things start teasing out in terms of adoption and long-term success. Lastly, the co-pay card performance. Again, underpinning all of this is our durable and differentiated product profile is really the foundation. These are things you can look forward to hearing from us about with respect to how things are going. I will quickly now bridge over to atopic dermatitis, and then hand it off to Patrick. Atopic dermatitis from a market standpoint obviously is a very large market and at this meeting in particular, a lot of excitement around this market. You know, despite the advent of all these newer agents, if you look at what's happening in this market, almost 90% of the prescriptions generated in 2021, were topical steroids. You can see quickly the slices there. You see a little bit of Dupixent there. You see some calcineurin inhibitors, and then the 1% there is the legacy PDE4. But overwhelmingly, you see the opportunity is despite the advent of all these new medications, topical therapy is really the mainstay of treatment for atopic dermatitis. On the right is the expected growth. You know, nearly a $9-$10 billion market by mid-decade, and this is prior to the introduction of all the things that are coming in this space. But we really feel confident that, you know, the unmet need is still there, and we are very much plugging into the preferred, you know, way of treating today, and probably tomorrow for dermatologists. Atopic dermatitis, again, remains a very compelling opportunity, very large market, nearly 25-30 million patients with this condition. Importantly, 12% of that are children. When we say children, you know, six and below. There's a very, very strong need in this particular segment to have a very safe and effective therapy, which, you know, even with some of the newer approvals, that excludes that population, frankly. There are still significant unmet needs here. Recently with some of the JAK approvals, either topical or oral, the labeling that's occurred, and I think the way that people are thinking about those products, has really been a clearing event for us with respect to confirming our opportunity, very frankly. In fact, I think there may have been a sort of cloud over that until those labels landed. It really makes us emboldened as we think about atopic dermatitis. Again, on the right, what we do see is a very nice alignment, again, of the key stakeholders, and we think about physician, payer, patient. In this case, there's actually a fourth stakeholder, which is the parent. The ability for a parent to choose something that's very, very safe and tolerable with no warnings, and no concern over steroid side effects and things like that, it really is, I think highly aligned with this fourth stakeholder as well. With that, I'll pass this to Patrick to talk a little about the profile. Thanks, Ken. I'm going to talk a little bit about the data, and I think Ken did a really good job of setting up, just how it is that our profile in atopic dermatitis is very well suited for this indication. I think all the things that we really said about psoriasis are true here as well, but this additional piece of this being predominantly but not completely a pediatric market really highlights the need for a safety profile that's very strong in this area, as well as the interest of patients and their parents to have a non-steroidal treatment. I think the desire here is very, very strong and hopefully kind of coming out of this, you'll be able to understand why it is that we're so confident in our phase III success as we move to read out INTEGUMENT-1 and INTEGUMENT-2, at the end of this year. These are the data from our phase II study that was conducted in atopic dermatitis. You can see there are three arms. We have 136 subjects that were enrolled into this trial. It was a fairly small trial that was conducted and again, split across three arms, so about 45 patients in each of these arms. We tested two doses, 0.05 and 0.15. Keeping in mind that the psoriasis dose is 0.3% that we've been studying, and that's the same dose that we're also using in our foam program. We dropped the dose a little bit here. Again, atopic dermatitis is a disease with high body surface areas and also with a skin barrier defect. Traditionally, it's easier to get drug into the skin in patients with atopic dermatitis. You can see that we had very good response at both doses. We felt like we were at the kind of plateau end of the dose response curve. You'll note that we did narrowly miss on the primary endpoint of absolute EASI score, and that was due to a higher than anticipated vehicle rate. I'm going to talk a little bit later about that. We also kind of saw that as something that would spur us on to look a little bit more closely at our vehicle and what it could be doing in these patients where moisturization is really kind of the key foundation of treatment for atopic dermatitis. The right two endpoints are EASI-75 and validated IGA atopic dermatitis. These are both binary endpoints, with EASI-75 being the eczema version of the PASI score, which I talked about earlier. Here you see again, the roflumilast 0.15% and 0.05% behaved similarly, both of them showing statistical significance at the 0.15% dose versus vehicle. The range of response here is in the 50%-60% range. Just to contextualize what that means versus other therapies that are out there, again, cross-trial comparison, these are not head-to-head comparison of these products. We're showing now our EASI-75 response for both doses and vehicle, compared to Opzelura and Eucrisa. These are both studies that were conducted with topical treatments in mild to moderate patients, and after four weeks of treatment. You can see that the efficacy that we observed in our phase II study matches very well versus both of these treatments, similar to Opzelura, and actually higher numerically than what we saw with Eucrisa phase IIIB/4 study. To the right, we have two systemic treatments, Dupixent, which I'm sure all of you are very familiar with here. It takes 16 weeks to get to the efficacy that we're showing. This is in a moderate to severe population, but again, kind of numerically, just to give you an idea of how the efficacy numbers for EASI-75 compare to Dupixent and then also Rinvoq, four weeks of treatment, JAK inhibitor also systemically administered. We feel like we're in a very good range, with our efficacy that was observed in the earlier study. We didn't really have any other questions to answer for the program, so we moved directly into phase III from that point. We did want to look a little bit closer at what it was that our vehicle was doing in these patients. Again, atopic dermatitis is a disease where you really need to have a moisturizing vehicle if you're not going to add additional insult to the skin barrier. One of the key aspects of our vehicle is it has no lipid-extracting emulsifiers. Oftentimes, when you're trying to deliver a drug, what you need to do is disrupt that skin barrier so that your drug can penetrate into the epidermis. That's kind of the purpose of the epidermis. To be able to deliver ours without disrupting, that is one of the kind of key aspects of our cream, and I think why it is that we saw a very good vehicle response in our studies. To follow this up, we conducted a trial in mild eczema patients. This is an intra-individual comparison between our vehicle, again, no active in this, and a leading commercial moisturizer. This is one that uses ceramide, and is really a favorite of dermatologists because it has such great moisturizing properties. Our primary endpoint in this 40-patient trial was to look at what's called TEWL or transepidermal water loss. It's pretty easy to envision what this is. If your epidermis doesn't have a good skin barrier, then water leaks out. We're all very wet inside, and if you don't have a good skin barrier, it leaks out. It's like you're missing kind of like a waxy coating on your skin. By measuring the amount of water that's penetrating, you can get an understanding of what's going on with that skin barrier directly. What we looked at is no increase, no change in the skin barrier for these eczema patients over the 15 days of treatment. That looked very similar between the ceramide-containing moisturizer and our vehicle. Again, this is unusual because normally you need to disrupt that barrier to a certain extent. Just to give you an understanding of what this actually looks like, we're going to have Elaine kind of come through. She has both our foam as well as cream, so that if you want, you can actually sample what the vehicle for each of these looks like. Again, no active in this either. While you're going through with that, let me just kind of finish up on this slide. In these 40 patients, we also asked them about the overall assessment of efficacy. Here we were looking at things like dryness, redness, roughness, irritation, key aspects of eczema, and asked them how they did over time as they were being treated with the vehicle versus the ceramide-containing moisturizer. You can see that the response from them are virtually superimposed on each other over this 15-day treatment, which is really unexpected for a vehicle. I'm not going to go into great detail about our tolerability and safety profile. It looks very similar to what I've talked to you earlier about. I think again, this is one of the key aspects that makes this a great fit for atopic dermatitis, because we also don't have the burning and stinging that may have been seen with the earlier generation PDE4 inhibition. Just to kind of give you a preview of what's coming up with our readout for INTEGUMENT-1 and INTEGUMENT-2 at the end of this year. These are two identical phase III studies. They're relatively large. We have 650 subjects in each of them, and I'll kind of talk to why that is in just a moment. That means we're going to have 430 on active and about 220 on vehicle. Relatively similar eligibility criteria, with the exception of here, we're enrolling patients ages six and above. Atopic dermatitis, you really need to study pediatric patients. In INTEGUMENT-1 and INTEGUMENT-2, we have ages six and above, and we're looking at a 0.15% dose. That was the higher of the two doses we looked at in phase II. We have another trial that is a very similar design to this, called INTEGUMENT-PED, where we're using the 0.05% dose, and we're studying that in two to fivefour year-olds. Primary endpoint here is validated IGA success at week 4, but of course, we'll look at EASI-75 itch and then clear or almost clear as well as key secondary endpoints. We really feel like these studies are designed to optimize the visibility of the efficacy that we've already seen in our phase II study. I mentioned that had 136 subjects. Here we're going to have about ten times as many patients on active compared to vehicle, 430 compared to the 45 we looked at in phase II. We saw that higher than anticipated vehicle rate as an overall benefit to patients, because they're going to get a moisturization and that efficacy. Superimposed upon that, we also have the PDE4 effect on inflammation. It really just becomes then a powering issue. This size of trial gives us greater than 95% statistical power to detect the level of IGA success than we saw in our phase II study. We feel very confident in our ability to read these out and to have success in our overall program as we go in to next year. With that's kind of the end of the cream portion of the talk. I'm going to switch over now and just talk a little bit about the two foam programs that we have in seborrheic dermatitis and scalp psoriasis. I'll start out and then hand it over to Ken. As I mentioned, for scalp psoriasis, this is typically considered a recalcitrant area of the body to treat. Oftentimes, there will be other treatments that don't actually have a formulation that allows them to be used on the scalp. Patients don't actually have access to that innovation as well. We made an early decision to develop a foam formulation because we felt that the safety and efficacy that we were seeing really made it well suited for scalp psoriasis. I think the phase II data that we have really bears that out. We're going to spend most of our time, though, on this part talking about seborrheic dermatitis. We think that this is really an underappreciated part of our pipeline. This is a big market. Ken will speak to that. We don't really have competition here. There hasn't been any development in this area for 20 or 30 years, and we're going to have a guest KOL speaker elaborate on what it's like for patients and doctors trying to treat this. We really see a lot of similarities here to atopic dermatitis 10 years ago, where patients were using very old medicines and primarily for anti-inflammatories, topical steroids. They were quite dissatisfied with those and really looking for innovation. We think that creates a great opportunity for us. First, just a couple of slides on scalp psoriasis. I mentioned highly prevalent, and we really think that the foam is a key aspect of this because this can be used in all areas that patients have their psoriasis. It can be used on the scalp, it can be used on the trunk, it can be used in intertriginous areas. We're studying that in our phase III trial, where we're actually applying it everywhere. We have co-primary endpoints. We're going to look at scalp IGA as the primary endpoint, but also body IGA as a co-primary, so that we're looking for a broad label that would allow this to really be a one treatment for psoriasis wherever it appears. We're expecting top-line data late Q3, early Q4, for that phase III trial. These are data that we've shared previously about our phase II study. Really exceeded our expectations, around 60% of patients getting to scalp IGA success at week eight. Itch data that looked very similar to what we had in our DERMIS-1 and DERMIS-2 studies, with 70% of patients getting to a scalp itch numeric rating scale response. That's very similar to the WI-NRS, but just focused on the scalp. I think really the most important part of this is the bridge from our phase III trials, DERMIS-1 and DERMIS-2. Along the bottom, you see that 40.3% of patients, reached body IGA success in this study. If you remember the pooled data that I mentioned earlier, when you pool DERMIS-1 and DERMIS-2, that number is 40% as well. Not surprising, these are very highly related, almost identical formulations, just with the addition of a propellant for the foam and changing the percentage of some of the excipients. As well, the dose is the same at 0.3%. I'm gonna have Dr. Raj Chovatiya talk a little bit in a moment about, this disease and really kind of set up how it is that that doctors treat these patients and and what are the challenges for that. First, I just wanna talk a little bit about one aspect of this of roflumilast that may make it uniquely suited for the treatment of seborrheic dermatitis. That's because, as you'll hear from Raj, there is a component of yeast overgrowth in the skin. There's a Malassezia yeast, and some individuals are sensitive to that, and that's what stimulates the kind of cycle of inflammation and changes in the skin as these yeasts are kind of left unchecked and overgrow in these sensitive individuals. We presented earlier that we have some data that suggests that we may have a dual mechanism of action where we actually impact the ability of these yeasts to live on the skin, which is kind of a key pathogenic feature of the disease, as well as the inflammation that they cause. We're continuing to look into this. I'd really just wanna say watch this space because I think that's gonna be a uniquely differentiating aspect of this program. Now let me turn it over to Dr. Raj Chovatiya to talk to you about seborrheic dermatitis. Hi there. My name is Raj Chovatiya. I'm a dermatologist and assistant professor and a director of the Center for Eczema and Itch at the Northwestern University Feinberg School of Medicine, where I specialize in seeing a variety of inflammatory skin disorders, including atopic dermatitis, eczema, and seborrheic dermatitis, which we're gonna be talking about today. Seborrheic dermatitis is one of the most common things that we see in the dermatologist's office. Arguably about 10 million people, on average are affected this condition, but I would suggest this is even lower than probably the actual number, in part because we don't have great population-based studies of this condition. Now, seborrheic dermatitis, I would very easily describe as a condition where people have redness, flaking, itching, scaling on the scalp, the face, the neck, and the chest. Aside from the obvious concerns you might have on the actual skin itself, the symptoms you might be experiencing, there is a huge quality of life burden when it relates to this condition. Patients' social lives are impacted, their personal relationships suffer due to the inflammation of the skin, and embarrassment is rampant when it comes to the symptoms and signs related to the disease. Now, as far as our current treatment paradigm, it's largely based on what we understand about the pathogenesis of this condition. We know in the case of seborrheic dermatitis, there's overgrowth of the normal skin yeast species on the skin, and this leads to a lot of inflammation on the skin. There's probably issues related to both the skin immune system, the skin barrier itself, the skin microbiome, that lead to a lot of the flaking and itching and scratching and redness we think about with the condition. Most of our treatments fall into two categories currently, topical antifungals and topical anti-inflammatories. That already highlights one issue with our current management. We have to use multiple products to try to keep things under control. In the case of topical anti-inflammatories, topical steroids are largely what we use. These are sort of a blunt tool that grossly turn off inflammation across the skin. Now, the problem here is that we're limited by the potency of these agents. Low-potency agents don't work that well. High-potency agents can have a lot of side effects, including thinning of the skin, dyspigmentation, even leaching into the eyes and causing glaucoma and cataracts. When it comes to topical antifungals, these largely don't work that well either, and these come in a variety of different fashions such as shampoos or creams, and you can already imagine how this might be difficult to treat in areas like the scalp, where there's big differences in hair care behavior from patient to patient. Now, you can also imagine that there's a variety of other products that patients use over the counter. When I talk to my patients, two, three, four, five extra things on top of everything we're already prescribing. That's already raising some more issues as well. We have problems with efficacy. We have problems with the vehicle. We have problems with the number of treatments that individuals are using. Bottom line, what do we need in this space? We need effective treatments. We need safe treatments. We need to simplify our treatment approach and really have a formula that can work across all these different body parts, including the chest, the face, the neck, and the scalp. Okay. I think Dr. Chovatiya did an excellent job in sort of articulating, both the unmet need and some of the challenges that patients go through and physicians have in treating this condition. I want to walk through a little bit about some of the numbers again and some of the marketplace conditions here. You know, just reiterating that the opportunity here is actually comparable in size to psoriasis. On the left funnel, you can see 10 million patients. Dr. Chovatiya mentioned this might be actually under accounted for. About 70% of those patients are being topically prescription-treated today. If we sort of go down in the next step in thinking about those being treated by dermatologists, which again is the focus of our promotional efforts, you can sort of get to the bottom there and see that the ultimate. Addressable population for us, about 2.2 million, is very similar to that what we talked about in psoriasis. This opportunity is as large, frankly, in comparison to psoriasis. On the right, the upper right there just sort of speaks to the average monthly patient volume. 75 patients per month on average are being seen for seborrheic dermatitis. That number is 80 for psoriasis, so very close in terms of patient volumes. Importantly, in thinking about sort of the bottom there is a very high correlation or very high medical urgency to treat. If the patient's diagnosed with respect to being moderate or severe, ninsix out of 10 times they're going to actually get something for that. That is the sort of everyday algorithm, is that they will be prescribed some sort of topical agent for the treatment of seborrheic dermatitis. Just building also on the commentary that Dr. Chovatiya said about sort of the need for multiple treatments. We did a survey, actually at the time of our readout in phase II, but also just repeated this in a large study here of 300 patients who are seborrheic dermatitis patients. What you see is sort of startling. On average, 6 therapies being used on average for any given patient. The breakdown of that is about, you know, two-ish prescription, a few OTCs and in some cases alternative treatments. This polypharmacy approach, you can imagine, can be really, really rationalized with a product like topical roflumilast foam. When we presented the idea of, you know, what if you could get something that you could, you know, dramatically cut that down, nine out of 10 patients said, "Yes, absolutely. You know, we'd be much more likely to stick to it if I didn't have to spend half an hour a day and six different things treating this condition." That's really the, again, sort of tying back to the idea of simplifying the overall treatment, not only of the other conditions we talked about, but in seborrheic dermatitis specifically. In the same survey, you know, nine out of the 10 patients agreed that they were interested in trying something new. Patrick mentioned there's been zero innovation in this space for 30+ years. Antifungals are not new. Topical steroids are not new. High interest level in trying something new. Then, again, on the tail of our phase II data last fall, we conducted a physician demand and interest, and nine out of 10 physicians were actually either very or extremely likely to prescribe the roflumilast foam after seeing the profile presented in our phase II data. Patrick. Thanks, Ken. We have a lot of parallels between these two foam programs. We're running a single phase III study in both seborrheic dermatitis and scalp psoriasis. The phase II studies had a lot of similarities in how that they were designed and conducted. You can see here that even the results in seborrheic dermatitis, which really were far exceeding at least my expectations of what could be done. We didn't really have a lot of analogs going in. We would've been happy to see a efficacy on IGA success in the kind of 50% range. To have it come back at 74% of IGA success at week eight and patients already being in that 50% range by week four and week two results of about a third of patients meeting that response criteria, was really fantastic to see. Just as important to the response on Investigator Global Assessment, is the fact that the worst itch numeric rating scale, that itch measure I talked about for DERMIS-1 and DERMIS-2, also responded very early. Half the patients were considered responders at week two, and that continued to increase to 65% of patients by week eight. As you heard from Dr. Chovatiya, the itch in these patients could be very distracting and have a significant impact on quality of life. We actually have another poster here at the AAD meeting that really looks at the impact of seborrheic dermatitis on different aspects of functioning in this patient population from our phase II trial. New data that we have here today, this is the first time we're talking about it, is from our open label extension in seborrheic dermatitis. I'll just kind of prelude this by saying, like, in an open label extension, you don't really want a lot of surprises, any like, you know, new findings. That's what we saw. We saw that this is behaving exactly the way that we would anticipate it. We're seeing it in two different populations. Some subjects rolled over from other studies. That was 133 of the—a clear close to 400 subjects that we're looking at here. As well, we enrolled a de novo cohort. These are patients that this is their first time on treatment, and they really give you an understanding of, you know, a new set of patients going through treatment. How did they respond? That's about 267 subjects. They were all treated. It's an open label trial, all treated with the 0.3% foam. What you can see along the bottom is that we do have different durations of treatment. We only have about 59 patients who came into a cohort that were intended to be treated for 52 weeks. When I show you the data, you'll see that we do see a fall off in the number of patients as you get out past 24. That was intended. That was kind of how the trial was designed, because given the absolute number of safety, data points that we already have with roflumilast, this was the number of patients that we wanted to capture safety data on. The primary endpoint is around safety, but we do have efficacy data coming from them as well. Again, no surprises here. We would've anticipated that we could have really good sustainability to our efficacy based on what we saw in psoriasis, and we see the same thing here. Now we're looking at IGA clear or almost clear. This is a zero or a one. Looking at the de novo patients in yellow, you see that they start out at zero, and they quickly get up into the 50% range by four weeks, and then into the 70% that we saw, at the primary endpoint for the phase II study, and then kind of sustain that throughout, even to the 52 weeks for those subjects that were included in that longer treatment cohort. The pooled patients includes 133 more subjects who were also rolling over from other trials. They behave exactly as you would expect as well. The safety data that we've seen, in this trial, again, no new surprises here, looks very, very similar. We have relatively low, overall adverse events rates at 32%. Discontinuations due to an adverse event, low and consistent with our other trials at 1.3%. In particular, for a study where we follow patients all the way out for 52 weeks, that's a very low number from my experience. Then just looking at the most common adverse events, unsurprisingly, you know, we had COVID-19 showing up at the top. Headache is something that you commonly see in trials. Everything else is less than 2%. This looks very similar to what we've seen in our earlier trials. Doesn't really change our understanding of the safety here. Now, you know, we've kind of checked that box for what does it mean for seborrheic dermatitis as far as sustainability, of efficacy and efficacy as well as the overall safety. This looks like a very good chronic treatment for this condition. Our phase III trial, we've enrolled the last subject in this. We press released that earlier in the year. We're expecting to read this out in mid-2022. This is the study design. It's about 450 subjects. Very, very similar in design to our phase II trial. In fact, we actually are going to have a lot of the same sites that participate as were in phase II. We did extend that age down to nine years of age. This is a disease that's it seems to have an onset around the time of puberty. This really captures a very broad spectrum of patients with seborrheic dermatitis. Our primary endpoint is going to be investigator global assessment success at week eight, just like the data that I already showed you from the phase II study. With that, I'll turn it over to Frank to talk about our early pipeline. Thanks, Patrick. We've been talking to you all about roflumilast for what, about an hour and 15 minutes now. I'm going to take a few minutes to talk about some of our other programs, especially those in our earlier pipeline. The team will tell you that I'm fond of aphorisms, and one of my favorites is, when all you have is a hammer, everything looks like a nail. Many types of companies sort of live by that principle, right? They have one formulation, they try and pack every drug they can into it. That's really because they don't have a lot of internal drug formulation expertise. We're in a very different position. We have probably the greatest top formulator in the industry as our Chief Technical Officer. We're really able to develop, each formulation uniquely for the drug, and I think even more importantly, for what doctors and patients are looking for. Ken talked about the foam and its importance, and Patrick talked about the cream. You know, what we have built is an engine that allows us to continue to innovate and develop new therapies. Obviously, roflumilast foam and roflumilast cream are the first examples of that, and Patrick talked about some of the innovation that we have there. We have a sustainable business model with expertise that allows us to really do some very innovative things that we want to share with you all as we're talking about our pipeline. This is some of the earlier stage programs. I mentioned at the beginning our TopoJAK programs, ARQ-252 and ARQ-255. As many of you may know, 252, the hand eczema study was a failed study, so we're in the process of reformulating the cream, and then we'll be looking to bring that back in the clinic in the future. 255 is one that we're really excited about, and I'm going to ask Patrick to talk about in a little bit, in greater detail. We think we've sort of unlocked the secret of treating disease in the hair follicle, which is really revolutionary and is really built on the expertise that the team has. Earlier on in our pipeline, we haven't talked about this previously, but we have active programs to develop new therapies in acne, in palmoplantar psoriasis, which is a rare but very serious and challenging form of psoriasis, in nail psoriasis, which is fairly common and also very difficult to treat, and then in rosacea. We look forward to sharing more data with you about those earlier-stage programs as we continue to advance those. In addition to our internal efforts, as you might imagine, we continue to be active on the business development front as well, looking at opportunities. I think the key for us really is that they are best in class, and they go after validated targets, right? That's really been foundational to our success to date, and we don't really see any need to change it. I will also say that we are modality agnostic. Everything we've talked about so far is topical. We do have a lot of topical expertise. It's dermatologic conditions, so sometimes topicals are the best option. But we have a great deal of expertise in the company in the development of systemic therapies, biologic therapies. Patrick's had two biologics approved. Ken and I started in the biologics space. So we're really agnostic as to the modality as long as it's a really good drug against a validated target. With that, I'm going to turn it over to Patrick to talk a little bit more about the 255 program. Yeah. This is a little bit of a pivot for us because we tend to talk a lot about clinical data. This is a program that we're going to be hopefully bringing into the clinic. We anticipate doing that in 2022. Just wanted to talk a little bit about this new indication for us. There is development that's going on in this area, but there are no approved therapies. Primarily what's being developed are systemic treatments for alopecia areata. It's an autoimmune disease where the inflammation is directed against the hair bulb. I'll show a representation of kind of what that means, where it's located within the skin and why that represents a challenge for topical treatment. This disease, because patients lose hair in these patchy locations, as you see on the screen, has a significant impact on patients from a psychosocial perspective. You could imagine self-esteem, body image, and self-confidence are all impacted here. The fact that there aren't any FDA-approved treatments means that patients are either using off-label, very potent immune suppressors if administered systemically, or a lot of times they get injections into these areas. If you just think about getting many injections into a patch like you see here on the screen, you can see why patients would be quite eager to have something that can be administered topically without a needle. JAK inhibitors, we know from systemic administration, do work in this condition, but these are healthy patients, and they could have this disease for a very long time. It's a chronic condition. That represents a challenge for them. I mentioned, you know, there is a desire to have a topical therapy for this, especially as you move into the mild to moderate range of this condition. In a situation where other topical therapies have failed, in particular, topical JAKs, but you have an oral treatment that works, it really looks like a drug development question. That's there must be hurdles. Sorry, not drug development. It's a penetration issue where you're not getting your active drug actually down to where the inflammation is being located. Where is the inflammation in alopecia areata? It's located around the hair bulb. On the right, you see a cross-sectional representation of the skin. There are hair follicles with a hair sticking out of each one of those. Underneath that, starting at the top, you see the epidermis. This is the activity area for, you know, psoriasis, for atopic dermatitis, seborrheic dermatitis. This is where most of the kind of inflammation and action is going on and where the drug is being kind of active and being delivered. We have to go much deeper here. In addition to the epidermis, which is a significant barrier, that's one of the purposes of it, is to actually block things from getting into the skin. You have a superficial vascular plexus, which then can draw away any drug that's being delivered into the skin, which is why you then, once the drug is administered, sometimes you don't actually see it getting any deeper, even if it makes it through the epidermis. In order to hit alopecia areata, you have to get down around the hair bulb. In order to do this, what we've done is designed ARQ-255, to deliver drug to the site of the inflammation by going down through the hair follicle. That's the concept behind this technology. What we've done is to do an in vitro study looking at scalp skin. This is ex vivo scalp skin, analyzing, well, what kind of drug delivery are we able to get, and where is that then located within the skin? Just to orient you, very similar to the cross-section I showed earlier. All the way to the right is what we call a serial H&E. That's a hematoxylin and eosin stain that's used by pathologists just to look at the histopathology of the skin. You see some of the same structures that I showed you earlier. At the very top is the epidermis. You see some follicular structures that are identified there, and then going down into the dermis and then the subcutaneous tissue below. In the middle is an overlay between the MALDI drug concentration, which you see in the left. MALDI looks at drug that's been administered in an adjacent section. This is a section that would have kind of preceded this one. It should have exactly the same structures. You can see a heat map of where the drug is actually located after application to the top or the, you know, epidermal component of this, tissue in vitro. White is the highest drug concentrations, not surprisingly, located as close up and within the epidermis, and then going down into green and blue for the lowest concentrations there. What you see is in the superimposed between that, the overlay, is that the levels of drug concentration in the 20 micromolar range in this particular section then are showing a range of 20 micromolar at the same level that we have follicular structures. In the bottom left, we plot the depth of this section versus the concentration, and then we've put a box around that range where you would see dermal follicular structures. This gives us confidence that we're actually getting drug, substantially deeper than what you would get with a normal formulation, and in a range where you would find the inflammation for patients with alopecia areata. Again, as I mentioned, we anticipate entering the clinic with this in 2022. Okay, we're going to wrap up quickly, and then we'll get to the Q&A session. You know, obviously, one of the key parts of our success is continuing to fund all of these activities. You know, we're in a very strong position from a financing standpoint. I mentioned the SLR deal earlier this morning. We ended 2021 with $385 million on the balance sheet. That includes the $75 million initially that we received at the close of the SLR deal, but it doesn't include the additional $150 million on the debt facility that we haven't taken down. We've got quite a bit more cash yet to bring onto the balance sheet as we move forward. That $385 million plus the $150 million gives us cash runway into 2024. After the completion of all the phase III trials that Patrick talked about, and frankly after the launch and well into the commercialization of topical roflumilast. We think that puts us in a very, very strong position from a financing standpoint. You know, as I mentioned earlier as well, it gives us optionality in terms of where, when, and how we might do any additional financings in the future. One of the things I want to talk to you about is the commercial opportunity, and we've talked about the number of patients and sort of the treatment paradigm. You know, at the end of the day, what matters to investors is also dollars. You know, we think that topical roflumilast alone is probably something like a $2 billion-$4 billion opportunity just in the U.S. dermatology market. You can see on the chart on the left here, broken down by indication, you know, plaque and scalp psoriasis, atopic dermatitis, and seborrheic dermatitis, all probably something like three-quarters of a billion to a billion and a quarter per indication. If you add that all up, you know, $2 billion-$4 billion in potential peak revenue just in U.S. dermatology. You think about the additional opportunities to create value beyond that. Obviously, I mentioned the six million patients being treated outside of the dermatology practice for these diseases. That's a very large additional opportunity. We haven't talked at all about the ex-U.S. opportunity for roflumilast. Patrick just talked about the JAK program, and I mentioned earlier the pipeline program. You know, we really think that we're in position to build a very strong and financially commercially successful company with the pipeline that we've got. One of the other things that we haven't talked about in the past, but I know is very important to investors, is ESG. We actually have a very long-standing and strong commitment to ESG, and we recognize we need to be more transparent with you all about that. I'm gonna talk about it a little bit today, and you will see increasingly us talking about our performance and our strategy. I'll walk you through. On the corporate governance front, seven of our nine directors are in fact fully independent. The other two are myself and Howard Welgus, who used to be an employee. We have only one class of shares. We don't do dual class shares, and we do have a head of ESG at the company, as well. You know, Ken talked a little about the patients earlier and responsible pricing. You know, I would mention we have six dermatology clinicians at the company and a seventh on the board, so we really understand where dermatologists and the patients are coming from. Also Ken talked about our commitment to responsible pricing so that we can maximize access to the innovations that we're developing. Obviously, DE&I is a really important area of ESG. I'm really proud to say that three of our nine directors are females, and three of our nine directors are people of color from underrepresented groups. So that, you know, from a diversity standpoint, that's pretty remarkable for a board of nine people. And we have a strong commitment to clinical trial diversity. You know, I think we've performed well already if you look at our trials in terms of enrolling non-Caucasians into our trials. We also have a commitment to continue to improve that, and Patrick and his team have a number of efforts ongoing to improve our clinical trial diversity. Then at a macro level, in terms of our demographics, you know, you look at our leadership team, a third of our leadership is female, and about a quarter are people of color. The overall organization, we're about half female and about 40% people of color, so very diverse population. We think that makes us a stronger company. From an employee engagement and culture standpoint, I personally believe this is a critical success factor for any company, and spend a great deal of time working on this. I'm really proud and humbled, I guess, to say that last year in a survey, 97% of our employees said that Arcutis was a great place to work. I'm still trying to figure out who the 3% that are unhappy are. Not to punish them, just to make sure that they're happy. That led actually to us being certified as a great place to work last year as well. We have a professional development program in place to develop our staff, and I'm very proud of the fact that last year our staff donated over 2,200 hours of community service across the organization. Then lastly, you know, obviously environmental is an important part. It's the E in ESG. This is an area again that we look at very closely, and we're a largely virtual company, so we don't generate a lot of carbon footprint ourselves. We do look very closely at what our key partners are doing. Every one of our key partners has an environmental program in place, and we monitor their performance against that. We have very strong supply chain oversight. We track our own recycling and the team will attest to the fact I don't like paper, so we don't print very much at Arcutis. We're very concerned and attuned to our environmental impact. One of the ways that we reduce that is that we're a hybrid company. About two-thirds of the staff doesn't actually work in the headquarters on any given day, and that reduces, you know, obviously commuting time and so forth from the environmental standpoint. That's just a first look at what we're doing in the ESG domain. It's more than just a slogan or philosophy. We track this very closely, and you'll be hearing a lot more from us going forward. I started out by talking about 2022 being a transformational year. Hopefully, now that you've heard myself and Ken and Patrick talk about our programs, you recognize the team's ability to execute not only clinically, but also commercially and in the manufacturing and finance realms. Hopefully, after hearing Ken talk, you will agree that we're well prepared for this launch. I think you can see all of our excitement for the launch. After hearing Patrick, hopefully you're feeling more confident as well about our results in atopic dermatitis, and hopefully you're sharing with us the excitement, the growing excitement we're feeling about the seborrheic dermatitis opportunity. I can't wait to turn over those cards. Lastly, you know, as we wrapped up, you know, you've had a little bit of insight into the efforts that we're doing to build out the pipeline beyond roflumilast. I think with that, we're gonna ask Eric McIntyre, our head of investor relations, and Scott Burrows, our chief financial officer, to join us, and we're gonna switch into a Q&A session. Seven seconds behind schedule. Close. Great. Yeah. In keeping with kind of the hybrid, I think we'll have some mic runners for folks that have questions in the room, and then I can manage kind of the queue of questions that come in online and continue to. Maybe Amanda, I see you going to Chris first here. Thank you. Chris Shibutani from Goldman Sachs. Appreciate this presentation today, especially coming at this in-person meeting, so it's great to see everybody here. As I think about the opportunity in atopic dermatitis, obviously you had the phase II data, and most of us are trying to figure out how to predict the probability of success on the phase III. Can you put some context for us about what you think are the key ingredients, to transition to a successful phase III? In part, one of the mixed blessing components of your armamentarium is this vehicle, right? It almost behaves too well. It does a lot of good on its own. You almost want that to thread the needle to a certain extent. A related question almost is, by the way, is there another opportunity for this vehicle? It almost seems as if it could have a life of its own. Probability of success around phase III, is it patient selection? Is it something about the protocol, something about the backgrounds that we can understand that might gain that success? Tell us a little bit more about this vehicle. How can you get it to behave? Thank you. No, just kidding, Patrick. Yeah. Thanks for the question, Chris. Yeah, I think that you touched on it to a certain extent. You know, we got a very good understanding of the efficacy of roflumilast cream in atopic dermatitis patients from that phase II study. In order to be successful in phase III, I think there are a couple of things that we need to do. One of them is just built into the design of the trial. The fact that we have a vehicle rate that is where it is, for me, it's not about trying to knock that vehicle rate down. I think it's an intrinsic part of the treatment itself, as you mentioned. It's more about how is it that we can design this study so that we can be successful and accommodate that. That's where the increased size of these trials, which actually doesn't put us, I mean, it still puts us in a very reasonable range from an ICH E1A kind of overall safety database position. I don't feel like these trials are really oversized in order to accommodate that. It does give me the confidence in the readout. Again, about 10 times as many patients on active, in this study and these two studies compared to what we had in the phase II trial. The other piece that I will say is really critical, and I think it's something that my team does fantastically well, is select clinical trial sites. That is a really, like, absolutely critical collaboration that we have. Those investigators are the ones who are actually recruiting the right patients. They're recruiting appropriate patients for a clinical trial, carefully following the protocol and then doing the assessments. In dermatology, these are not assessments that are coming from a machine that you point at the thing, right? These are clinical assessments being done by people who need to be skilled and trained in how to do it. I think that aspect is part of the success as well for this. I think one of the challenges there is just scaling that up from a smaller study to a larger study, and making sure that even though you're treating more patients and you have more sites, that those sites are well selected, and that your trial is designed right with the adequate power. I think that puts us in a good position. With regard to the commercialization of our vehicle, Ken, I guess that's in your range. It's not what we do. Yeah, it is not what we do. At this point in time, there's no plan to do that. I think it's really something unique to have a product that, you know, while applying it, you're getting this sort of wonderful aesthetic experience, which is probably not anything that anyone would actually, you know, comment on. It's a little two-for-one there, but no current plans to market the vehicle. I think we have Seamus next, and we'll maybe come to Luis. Great. Thanks. Seamus Fernandez from Guggenheim Securities. So a couple of questions here. Maybe just first on, you know, timing of FDA inspection of the manufacturing facilities. Just wanted to get a sense of when we'll get timing around that, or at least just where your expectations are. I know you guys are buttoned up super tight on the manufacturing dynamics there, but just wanted to get a sense of how FDA's inspection scheduling is going, just because I know that that's been a little bit of a challenge. The second question is, you know, not a challenge for you, but just broadly speaking. The second question is as we think about, you know, I think, Ken, you mentioned the opportunity for the pediatric patient population. Something that we're particularly excited about is INTEGUMENT-PED. It's very clear you guys are excited about that as well. Can you talk about, you know, I think this is something you've talked about in the past, but the consistency in the data, that you guys have seen as you've gone to younger patient populations. And so, you know, what your expectations are for the consistency in the AD data, as you kind of proceed INTEGUMENT-PED. Then just the last question, as we consider the gross to net dynamic that has really evolved quite significantly over the last two decades, can you guys help us understand a little bit better where you think your product can operate in a healthy way from a gross to net perspective? Thanks. I'll take the inspection question. Patrick, maybe you can comment on the AD consistency, and then Ken, you can talk about gross to nets. I think with regard to the inspection question, you know, the FDA obviously has a right to inspect at any point in our supply chain. When they do that is up to them, and they don't give you a lot of advanced notice. We're about five months, I guess, now from PDUFA. You know, it really could be any day. You know, I mentioned we do formulation fill and finish in the U.S. You know, some of the issues that other companies have run into, I don't think are gonna be a problem for us. There was a very brief period the FDA wasn't inspecting earlier this year. The plant that we use has been frequently inspected by the FDA. While they certainly have a right to do it, I don't know whether they're going to do a PAI or not. I think it's anyone's guess. As I said, you know, they unfortunately don't give us much heads-up. Seamus, as you said, you know, I have a great deal of confidence in both our manufacturer and in our team's preparedness for those inspections should they come. You know, our head of manufacturing used to be the contract manufacturing head at Amgen, so she has a great deal of experience. Our head of quality used to be the head of quality for Kite in Europe, another very experienced person. We're very hands-on with our manufacturing supply chain, so we have a good sense of everything that's going on in the plan. I'm sure if the inspection comes, it'll be fine. Do you want to talk about AD? Yeah. With regard to our own data for pediatric atopic dermatitis patients, as I mentioned, the phase II study that we ran was relatively small. We had 136 subjects in that. Just given the age range in that early study, we don't really have an understanding from our own trials as to efficacy of our roflumilast cream in those younger age populations. I can kind of point you to two different sources that address that. One would be in our psoriasis program, when we look across different age ranges, we don't see any differences in the response of patients. We think from a drug delivery perspective and just an ability to control inflammation, we don't anticipate any issues there. The other is kind of looking to topical PDE4 in general in atopic dermatitis. Obviously, there are previous studies been done with an earlier product. There, when we looked very closely at differences in ages, just to understand, is this mechanism potentially different at different ages in patients with atopic dermatitis? There's no evidence to really suggest that. We feel very confident, just given everything that's understood about this mechanism in in AD, that we're going to see a response that's similar across the entire age range that we're studying. I think it might be just worth reiterating it. INTEGUMENT-1 and INTEGUMENT-2 actually capture 6 and above. INTEGUMENT-PED is really on the only the really, really young kids, the two to five year-olds. Ken, you want to comment on GDN? Of course, yes. Thanks for the question. You know, unfortunately, this has become a little bit of a flashpoint, but which is taking away from an otherwise very successful launch by Incyte. In general, you know, gross to net trends we've seen historically looking back, there's a correlation between the level of innovation and the degree to which you can bring down those gross to nets. We see older legacy products, steroid-based, vitamin D-based combinations or standalones, operating at a very high gross to net, 80%+, is not unexpected. And as you move into the more branded, on-patent, still under patent protection, innovative medications, you start seeing that come down into a middle range of between that 40% and 60% that we often talk about. I think one thing, we'll be, you know, while stopping short of like actual giving guidance, the directionality of, you know, higher gross to nets at the beginning, and then moving to stabilization by, you know, 12-18 months out is a trend that should be expected. I think I personally was surprised at seeing some of the numbers, you know, being what they were recently with recent launches. I think it's more about the directionality and the fact that we have, also, you know, with the pricing that we're looking towards, are trying to optimize rebate expectations. As you go higher and higher in the price tier, what also happens in addition to, I think all the other dynamics you see is that rebate expectations start growing as well. You're trying to manage that expectation and keep it reasonable on top of the other things that drive gross to net, including patient support and things that we will do. You know, we don't want to have an outsized number, sort of a self-inflicted wound, if you will, you know, driven by excessive pricing. I see, I see Georgie with the mic, but then maybe we'll keep coming forward for Luis. Luis has been waiting. Yeah, I know. I promise we'll get you. Thank you. We're just sanitizing the mic, too. All right. Okay. Thanks for taking my questions here. First question I had for you is, what gives you confidence in a full approval versus the CRL, which has been popping up unexpectedly in some places? Second question I had is, what has the physician feedback been at AAD for both roflumilast for psoriasis and for atopic dermatitis? And then lastly, can you prescribe your product virtually or do you have to go into the physician office for it? You guys are killing us with multiple questions. I I got to remember them all. On the CRL, you know, you can get a CRL for a variety of reasons, right? You know, you have questions about your efficacy. There are concerns about your safety and your tolerability. You don't submit the right data, or unfortunately, a lot of times it's around manufacturing. You know, I think with the data that we have, the efficacy is very clear. This is a well-trodden pathway too, so we know what the FDA is expecting. I think our safety and tolerability are also very, very clear. I don't think those are particularly high-risk areas for us. with regard to the manufacturing, as I mentioned earlier, you know, that's another area that we think we've largely de-risked, partially through our selection of partners, partly through the oversight that we provide, and then partially through just having done all of the things that they want you to do in terms of manufacturing commercially in the right site, you know, multiple tech transfer and so forth. You know, you can never say never, right? You know, I sleep pretty well most nights. Okay, the second question was on- Feedback from AD. Feedback from AD. I'm going to actually ask Patrick and Ken to see if they have thoughts. You two have spent basically the entire last week talking to doctors, thoughts on feedback that you're hearing from physicians? Sure. You know, largely the conversations, Luis, have been focused on psoriasis, given it's the most near-term opportunity. I think, you know, I'm feeling very positive, frankly. I think the clarity of the unmet need and as we come into focus, near-term launch, I think physicians are getting very excited about the product. They're asking us, you know, when can we have it? How soon are you going to have it available post PDUFA, things like that. The profile and I think the overall interest in sort of these next generation, you know, nonsteroidal agents is really, you know, if you think about the topics that were discussed at the hot topic session in psoriasis, you know, two of the four things that were the two nonsteroidal agents and, you know, the TCI, too, and one biologic. For 50% of the session to be about nonsteroidal topicals, clearly they're coming into focus and the unmet need, people are getting very excited about that. You know, Patrick, you can talk about the AD a little bit in terms of, you know, the feedback there, probably more involved with talking clinically. Yeah, I think what, you know, what we see a lot of times when we talk to dermatologists is an interest from what they've heard or the data they've seen to kind of get involved in our clinical program to join us as a clinical site. I think that's a really nice conversation to have because what it really represents is that they're looking for kind of the earliest way that they can get access to this for their patients. I mean, where we are right now, we're, you know, running, I think about seven phase III, six phase III trials right now. We're kind of, you know, have a tremendous clinical program that's ongoing. It is nice to hear from physicians about their interest in how soon can I get this for my patients. The other thing I would just reiterate is as a dermatologist, I have to say, I'm really surprised by how quickly that switch has happened in the discussion about steroids. You know, derms historically have been very comfortable with steroids. I kind of anticipated it might take a little bit longer and these products to be approved to really have them start kind of thinking carefully about it. Already here at the AAD, and keep in mind that we haven't had one of these meetings live for several years, you know, so it's not like they've even had a lot of opportunity to be able to kind of digest this. Very quickly, even the kind of structure of the conversation in the program has changed. I think that really signals an interest in changing the way it is that we take care of patients with these inflammatory skin diseases. Sorry? Oh. Oh, yeah. Yeah, I'll take that. It's prescribable, I think, in any fashion you want, Luis. You know, we obviously, with the advent during COVID of sort of virtual and telemedicine, you know, there's no prohibitions to prescribing it either live or virtual. I think, you know, based on feedback this week, we were actually talking about with physicians, you know, how are you starting to see, you know, more and more patients, and the return to sort of face-to-face is really real in dermatology. There's a desire to sort of touch and, you know, see the disease and just connect with their patients. We won't sort of be limiting in any way, for example, you know, only face-to-face versus virtual formats. We wouldn't anticipate any testing requirements. No. before initiation of therapy. Correct. That would be an obstacle potentially, which we won't have, so we'll go to Georgi next. Yeah. Thank you. This is Georgi Yordanov from Cowen. Maybe firstly, taking a step back, maybe could you talk about some of the historical challenges that existed with solubilizing roflumilast, and actually making it into a topical formulation, and then your proprietary approach to it. Then secondly, for psoriasis, if you could just comment a little bit more about the commercial strategy, the number of physicians you plan to reach with the 80 sales reps, and what percentage of the topical steroid prescriptions do these targeted physicians write. Then I'll do a couple follow-ups. Got you. I'll take the formulation one, and then, Ken, if you maybe can address the prescribing one. Yeah, from a formulation standpoint, one of the things that David Osborne discovered very quickly when he started working with roflumilast is that it's exceedingly hydrophobic. It's about 100 times less soluble in water than gasoline, and anyone who's mixed water and gasoline knows those two things don't like each other. But when you want to make a moisturizing cream like ours, you need a lot of water. Ours is in fact 50% water, and so the trick was how do you get roflumilast to dissolve in water? David tried every FDA-approved excipient and discovered that there was only one that would dissolve roflumilast in the water. He then discovered that once you got it dissolved in the water, roflumilast likes to crystallize back out of solution from these very large drug crystals. He had to go back to the drawing board and try all of the excipients again, and he discovered one excipient of FDA-approved excipients that will prevent the formation of crystals. Those two discoveries really form the basis of a lot of our intellectual property. How do you solubilize roflumilast in water, and how do you maintain that solubility in water over time? There's only one combination, two things that work, and we have patents on them. Well, we have a patent on one and a pending patent on the other. I think that was really a key element of developing roflumilast. Subsequently, Patrick mentioned this earlier, we chose an unusual excipient to act as the surfactant in our formulation. You always have to have a surfactant when you're making an emulsion of water and oil. We chose one that has not been used previously in the pharmaceutical industry, although it's literally used by the metric ton in cosmetics and lotions and moisturizers and sunscreen. We discovered over time that, as Patrick I think mentioned, it is unable to extract epidermal lipids on application to the skin. It's one of the things that makes our formulation so moisturizing. That is now the basis for a third pending patent. You know, this is why I said earlier, you know, that we feel very confident about the strength of our formulation patent portfolio, and then you layer on top of that the PK patent portfolio, and you get some sense of just how strong our intellectual property really is. Ken, you want to talk a little bit about sort of our reach? Certainly. From a commercialization standpoint, I mentioned about 80 sales representatives, and our goal is to address approximately 94% of the topical value. What that means is, you know, if you look back in the past periods, there's about 11 million prescriptions being generated for topical psoriasis. It's concentrated, and clearly not every physician, you know, uses branded. We're focused on branded topical value, 94% being covered, of the market being covered by those 80, in terms of our overall reach. The math is about ultimately, you know, 12,000 physicians and allied healthcare that drive the majority of that value. 90% something like that. 94%. 94%. Yeah. Yeah, this is great. Just a couple follow-ups on the other programs. On Seb-Derm, maybe we learn about the cost of these topical steroids. Maybe can you talk about the cost of the topical shampoos and the antifungals, and the polypharmacy, what is kind of like the total cost to both like a patient but also healthcare systems as well? Finally on the JAK program 255, just the importance of having a selective JAK1 inhibitor versus what some of the competitors in the space might be going after. Ken, can you comment on overall costs and- I don't know that we've dimensionalized fully the array of products being used. What I can say is, you know, the standard of care, we talked about antifungals, steroids obviously tend to be less expensive and generic. What ends up happening, though, when you start piling them on top of each other, is probably more of a cost burden to the patient than the system there, in the sense that you have multiple co-pays and, you know, steroids are actually priced from as low as, you know, sub $400, as we talked about, all the way up to $1,200 plus actually is what we're seeing. It's a little bit hard to give an average, but what I'll say is, you know, there's definitely a consolidation of the need for all those scripts and I'm sure from an out-of-pocket standpoint, in all likelihood, a strong reduction. Because even though things might be over the counter, it still doesn't mean it doesn't cost anything, right? There's some component of that will be dropping down, but I don't have a great feel for the sort of cost per patient. Patrick, can you maybe comment on the importance of JAK1 selectivity? I mean, I think it's pretty clear that the primary effect on immune suppression from JAK is taking place through the JAK1 pathway. You know, we anticipated this, and it's been represented as well as the labeling has come out, right? I think the real importance of treating is finding that balance between the JAK safety profile, reassuring patients that, especially with a topical treatment, that your safety profile is going to look different from systemic administration of those drugs. I think having JAK1 selectivity on top of a topical approach, puts us in a very good position, especially when we're talking about alopecia areata, which is a disease, as I mentioned, there are no FDA-approved products right now. Very different from atopic dermatitis, where the patients have a choice between multiple different treatment modalities, some of those biologics, some of those, orally or topically administered, all of them giving some level of efficacy, and then really being able to choose on the, on the kind of efficacy and balance to safety. In alopecia areata, it's just a very different environment. What we're trying to do is provide a treatment that will have the best possible kind of risk benefit for patients. I think JAK1 selectivity allows us to have that. I think it's worth just reminding everyone that you know there are a couple of other JAK1 selective molecules like upadacitinib and abrocitinib, but we have the only topical JAK1 selective molecule, so. I see Vikram with a mic, and then we'll come to Uy Ear next. Okay. Thanks for taking my question. Two for me on roflumilast in psoriasis. First, I mean, on the topic of duration of use, I know you've spoken about this previously, but just based on any work you might have been doing leading up to a potential launch, it would be great to get your updated thoughts here. What do you expect in your best case to be, the course of treatment throughout a year for a typical patient? Would you expect more continuous use throughout the year, or would you expect patients to go on therapy, get better, and then go on, like a drug holiday or move to something non-medical until they need product again? Secondly, on the topic of launch metrics. You mentioned some metrics you'll be providing, as the potential launch progresses, but do you think sales guidance could be a possibility at some point in the future? If so, how many quarters of execution would you need to see, and what sort of metrics evolution would you need to see to have that make sense? Ken, you want to take it first, then maybe Scott, you can take the guidance question. Sure. With respect to utilization, you know, I think topicals are a little bit different. Patients don't typically treat clear skin. What we would expect is, you know, treat to clear, should the disease recur, then treat again. I think it's a largely sort of a intermittent use. What we've talked about in the past is an expectation somewhere for psoriasis, depending on body surface area between three to four, three to five units per patient. That’s consistent, but certainly not sort of continuous and particularly treating clear skin areas. Scott? Yeah. I think sales guidance is tough in the early phases of launch. You know, when you're trying to understand your script trends, you're trying to understand the gross to net, gross to net dynamics that Ken was mentioning. You know, in 2022, we've talked repeatedly that it's probably pretty modest revenue expectations. We haven't talked quantitatively. But if you think about even going into 2023, that's gonna be pretty early in the launch still, if we're getting approved in Q3. It's probably unlikely that we'd give kind of formal, you know, quantitative sales guidance for 2023. You know, we'll monitor progress and we'll update the, you know, the street as we progress. Got it. That makes sense. Just one follow-up from my side. On gross to net, to follow up on a question that was asked earlier. We're now kind of all familiar with gross to net for ZORYVE that was launched. When it comes to psoriasis, in terms of kind of gross to net expectations numerically, do you have any sort of guidance that you would provide as to what could be expected in the first couple of quarters? We have not provided guidance. I just point you at the historical precedents. You have steroid and steroid combination branded products operating at about 80%-90%. You have innovative products at more like the Eucrisas and Dupixents of the world operating between 40%-60%. Those are the ranges that we're talking about. That's steady state. That's steady state. Yeah. Not at launch. That's correct. Just looking currently at what's happening, and you see the sort of less innovative generic components put together kind of operating at this very high altitude with the inability to actually manage downwards. Those are long-term sustained high. That's something you want to look at, I think. We've sort of stopped short of saying explicitly. To be perfectly honest, we don't know until we know and all the contracts are signed ultimately with the payers and things like that. It's more about, to me, again, directionality. Do I expect to be able to manage that downwards? Yes, I do. I do think also it's important to remember that, you know, the payers all have their cycles for when they review new drugs and when they'll put them on formulary. Used to be they'd put you on formulary until they reviewed you. Now they don't put you on formulary until they reviewed you. You know, right out of the gates, we would expect not to have commercial coverage anywhere, and so basically we won't be booking much sales. Right. As Ken and his team pick off. Well, pick off, that's bad choice of words. Acquire. As we acquire coverage, right, with the various commercial payers, you know, as the year progresses, that's where, you know, Ken was talking about over the next 12-18 months, it would improve and get to some point that would be stable. Expect very bad growth rates at the beginning, getting hopefully to something that's pretty reasonable. Yeah. Historical precedent would say, looking back, about 12 months, achieving 80%, you know, covered lives in 12 months is a good benchmark. Anything short of that would be upside. Anything longer than that, you know, we're probably not doing our jobs. I think frankly, that's about the estimate you would look at. Got it. Okay. Thank you. Mm-hmm. I think you had a question. Yeah. There's questions coming in online. If for the folks online, if we don't get to those, we have the questions, and we can come back to you. Uy Ear? Thanks. Hi, this is Uy Ear from Mizuho. I guess to follow up on the usage question, in your guidance, what do you assume in terms of bottles per year? In our guidance. Tubes per year, yeah. Do you mean the ranges with the two to four range? Is that what you're talking about? No. We've not provided sales guidance. Is that what you're? Four. The sales guidance. Yeah. I think we just talked about that in psoriasis, you know, the three to four tube per year expectation, I think is where we've been. But not anything, I think, more specific than that. It might be worth pointing out, I mean, the three to four tubes per year is based on looking at actual Actual data. Actual claims data and seeing what patients are consuming. That's right. that's capturing the intermittent nature that Ken mentioned, as well as, you know, unfortunately, my buddy Steve Feldman likes to remind me, you know, lack of adherence, patients just forgetting to take their medication or not taking it as directed. That's a pretty real-world, I think, realistic number. You know, you spoke about ex-U.S. opportunities. Could you sort of just share with us like how large the opportunity is, ex-U.S.? Then you also spoke about the six million patients that are not in the dermatology setting. Could you sort of also talk about how you plan to capture those six million- Sure. -patients? Sure. Yeah. From an ex-U.S. standpoint, you know, again, we don't have a forecast, but, you know, every therapeutic area, the majority of sales and even the larger majority of profits are generated in the United States, right? I think dermatology, my experience has been dermatology is even more skewed to the U.S., especially on the profitability side. Having said that, there clearly are commercial opportunities ex-U.S. I think Asia is probably the most attractive, especially Japan and China, I think, are very attractive markets for topical roflumilast. You know, Europe is a large population. I think the challenge in Europe is the reimbursement system. The reimbursement is hard in Europe anyway, regardless, right? It's particularly difficult in the topical space because you're generally being referenced to, you know, older generic products, and the European systems tend not to reward innovation in the same degree that the United States does. There's still an opportunity in Europe as well. With regard to how are we going to access those patients outside of the dermatology office, I think primarily we would be looking to work with a partner. Most of those patients are in primary care and pediatrics, so there's a large number of patients, but they're spread across a very, very large base of physicians as well. Frankly, it's not really cost-effective for a company like us to build a primary care sales force. You need a lot more than 80 reps to be an effective primary care sales force. There are a number of other companies out there that have existing primary care sales forces where you can partner with them to promote your product in primary care, and I think that's likely what we'll do. Having said that really is primarily atopic dermatitis and to a lesser degree, seborrheic dermatitis, not really psoriasis, the ex derm opportunity. It's gonna be probably a couple of years before we need to have that partner in the primary care space. There was a follow-up that came in online, you know, I think to Seamus's question. We talked about kind of the comfort around our CMO, but the question is kind of around, you know, the comfort on your API supplier. If you could comment on that, given they received an FDA warning letter in 2016. I'm actually glad that question came in. First of all, in a nutshell, no, I'm not worried. So let me maybe back up a little bit and explain a little bit about how the FDA operates when it comes to manufacturers. You know, as I mentioned earlier, they have a right to do a pre-approval inspection, a PAI on every manufacturer, including our formulation fill finish plant as well as our API manufacturer. When they do an inspection, one of three things happen. They say there's no action indicated. They can say there's voluntary action indicated, or they can say there's obligatory action indicated. So those are the three levels. If you get voluntary action or obligatory action, you get a warning letter or a 483. Everyone's probably heard of 483s. You know, I've been in this industry a long time, and our head of tech ops and the head of quality has been too. It's very difficult to find any manufacturer that doesn't have a 483, right? So the details matter. With regard to our API manufacturer, our API manufacturer did receive a VAI warning letter in 2016, so six years ago. It wasn't so severe that they got an obligatory action. They got voluntary action, and then they could choose what they would do about it. I will also say they've been inspected three times by the FDA since then, with no warning letters. They've been inspected by the PMDA since then. They've been inspected by the EMA since then, no warning letters. They have two products that have been approved from that factory since the 2016 warning letter as well. We are confident that they sorted out whatever issue happened a long time ago with the FDA that generated that VAI, and that's no longer an issue. I would just also add, as I mentioned earlier, you know, we have very extensive oversight of our manufacturing supply chain with Patricia and Bethany really directing those efforts. We're in regular contact with them. We really don't have any concerns about the API manufacturer. All right. Maybe one more from Greg. I know we're at the bottom of the hour, so. In atopic dermatitis, some patients are pretty effectively treated with intermittent corticosteroid use. Is that type of patient, do they make up a pretty significant portion of the population you'll be targeting for roflumilast? Are they also at material risk of developing skin atrophy and other side effects of corticosteroids? Patrick, do you want me to handle that? Yep. Yeah, I think so. Atopic dermatitis is a disease that is fairly sensitive to topical corticosteroids. There still is this kind of relationship between the and the trade-off that happens where you need to find the right potency of topical steroid to get control. Oftentimes as you're doing that, you're reducing, let's just say the safety and tolerability locally in the skin as well as especially in atopic dermatitis, you have systemic absorption that's taking place from those steroids. That's one of the key aspects of any steroid development program that the FDA makes you do, is as the potency of the steroid goes up, the suppression of the HPA axis in patients becomes more and more of a concern. That's also true as the body surface area increases. AD is, again, the situation where you have high body surface areas and a skin barrier defect. They're kind of on the high end of sensitivity to that. You combine it with the pediatric nature of the disease, and you have steroid administration kind of over the period, even if it's intermittent, where patients are in a developmental part of their life. I think that's what raises the concern that Ken was talking about. You have this fourth stakeholder in the discussion in addition to the patient, which is the parent. Even for those patients who are now adults, right, they've been using steroids their entire life, and I think they're just even if they've been using them intermittently, they're probably ready to transition to something non-steroidal. The one other piece of data I would point you to, which is in psoriasis, but I don't think there's any reason to believe it would be any different in atopic dermatitis, is that the risk of bone fracture from topical use of steroids has been shown now to be related to the cumulative exposure to topical steroids, not to the duration of your particular use. Coming back to intermittent use, you're still adding cumulatively to that. We know at least from psoriasis patients, and it's probably true in atopic dermatitis, or at some point someone should look to see if it's true in AD patients, that that probably is having an impact overall on safety, on bone mineralization, and all of these things that we know from systemic exposure to steroids that are best to be avoided. Yeah, maybe if I could just build on Patrick's answer, because I think this is a really key point, the role of the parent, especially in atopic dermatitis, right? You know, I talked earlier, and I think Patrick talked earlier about this conundrum that doctors and patients and parents have between efficacy on the one hand and safety and tolerability on the other. I have a good friend who has a very young son with atopic dermatitis. He's only about seven months old now. She wakes up every morning, and there's blood all over the crib because he's excoriated his face, and he's bleeding all over the crib, which is very traumatic for the mother, right? You can imagine how she feels when she wakes up to that every morning. On the other hand, she won't put a TCI on the kid because of a box warning for cancer. It doesn't matter whether dermatologists believe it or not, a lot of parents think that that's real or don't want to take that risk. She's tried another non-steroidal, and it's not tolerable. He's constantly cycling on and off steroids. When it gets intolerable, she'll put him on the steroid, and she puts him on for a week, and then he gets clear, and then she gets scared of the steroid, and then she stops. Two weeks later, it's back again, and then she starts him on steroid again, and he's on for a week, and then she stops. That's a very typical sort of treatment pattern driven by aversion to TCIs because of the box warning and aversion to steroids because of just the generalized steroid phobia in our population, you know, across the whole country. That's the problem that we're trying to solve for, is reducing or eliminating ideally this need to make trade-offs between efficacy and safety and tolerability because no parent or patient should have to make that choice. AD has been a little bit better than psoriasis and Sebderm, but you know, in the topical space, there's been almost no innovation in any of these diseases for decades, literally. You know, Howard Welgus, our first Chief Medical Officer, was trained 40 years ago, and most of the drugs used today topically were available when he was trained 40 years ago. That's the degree of lack of innovation, and that's the problem that we're looking to solve at Arcutis. Can I sneak in one more? Sure. Yeah. We'll fit in one more, and then we'll let everyone go get some lunch. On pricing, you've been very clear about being responsible from day one. Based on all the conversations that you've had with payers, is it your expectation with a list price in the $400-$600 range that most payers probably won't require a prior authorization? While they will not tell us point blank, yes, no, I mean, I think right now, you know, we are signaling strongly to each other sort of the type of access that we want. It's more corroborated, I think, less so by direct acknowledgments of that in the moment, but more so about the multiple rounds of research we've conducted, advisory settings, in addition to just waves of actual research. I think some of you too have done your own checks and sort of like talked about that price point with various payers. I think the general consensus is that, you know, the amount of sort of utilization management at that level would likely be kind of congruent with what we're shooting for. Again, can't lock it in until, you know, we announce that and/or, you know, the access that comes with it. I think directionally, payers are very interested in this idea, right, of high innovation, moderate pricing, less restrictions that like lines up with where we wanna go. Okay. Well, let me thank everyone here in person for coming. I know it's a cold morning in Boston, and thank also everyone joining us online. A lot of great questions, and sounds like we've got some more that we'll follow up on. Eric, I'll turn it over to you to wrap things up. Yeah, no, I think it's just that, you know, thank you all for coming. For the folks that are in the room, we have some boxed lunch outside. The team will be sticking around, so if you wanted to grab it and come back in, or if you have to grab a flight and go to the next meeting, then we will hopefully see you back here in person sometime soon. Thank you all. New Orleans next year.