Greetings, and welcome to the ruxolitinib cream Phase III data in atopic dermatitis webcast. At this time, all participants are in a listen only mode. As a reminder, this conference is being recorded. It's now my pleasure to introduce Jesus, Head of Investor Relations, Mike Booth. Please go ahead, Mike.
Thank you, Kevin. Good morning, and welcome to our conference call and webcast to discuss atopic derm titus, the disease, the medical need, and the Phase III WESP Litinib cream data presented yesterday as the revolutionizing dermatitis virtual symposium. The slide used in today's webcast and those presented yesterday, are available to download on the Investors section at insight.com. I'm joined on the call today by Herve and by Jim Lee, ahead of inflammation and autoimmunity development, and we're also delighted to welcome Doctor. Larry Eicomfield from the University of San Diego.
Doctor. Ican Field is a world renowned expert in atopic dermatitis. He is a professor of dermatology and pediatrics, Vice Chair of the Department of Dermatology and Chief of Pediatric And adolescent Dermatology at UC San Diego School of Medicine And Raide Children's Hospital, San Diego. Given the Global COVID-nineteen pandemic, though they will begin the call today with a few opening remarks on business continuity, and how insight is reacting to the current environment. Doctor.
Eigenfield will then provide us with some important context on the disease of atopic dermatitis and the evident unmet need before Jim shares data from the ruxolitinib cream Phase III TRU AD program. We will then open up for your questions. During the question and answer session, I ask that you limit yourself to one question and if needed one follow-up as this will enable as many of you to ask questions as time allows. I will also ask that we seek to split the Q And A session. First, asking questions related to atopic dermatitis.
And towards the end of the hour transitioning to any COVID-nineteen topics you might wish to raise. Stephen and Cristiano will join us for the full Q and A session. Before we begin, I must remind you that Safe Harbor rules govern our remarks today and any forward looking statements that we may make. And I therefore encourage you to review the risk factors detailed in Insight's SEC filings included in our Form 10 K for the year ended December 31, 2019. In addition, I would like to caution everyone that the COVID-nineteen pandemic is an evolving situation and it is still relatively early to be able to assess the full effects of governmental, business and social actions and policies and overall economic conditions on our business.
Accordingly, it's important to keep in mind that our statements on this webcast speak as of today. We will now begin the call with Irvin.
Thank you, Mike, and good morning everyone. Thank you all for joining today's call. So before getting started, I would like to briefly address the ongoing COVID 19 pandemic. It's an unprecedented and very challenging time for people around the world, and our thoughts are with all of this impacted by the virus. I also want to thank our partners, our customers and all insight associates who are working hard to ensure that all of our patients that all of our patients continue to receive their medicine.
In terms of our business to date, we have not seen an impact on patients on JAKA Fi and IQOSIG or on our supply chain and manufacturing processes. In term of regulatory process, The three products that are currently under regulatory review at the FDA continue to move forward as expected As does, I will plan for the NDA submission of ruxolitinip cream before the end of 2020. That submission will include the primary and secondary endpoint data that we are sharing with you today as well as long term safety follow-up, which currently being collected. In terms of clinical development, we will continue to act in the best interest of patient and we believe that keeping our clinical trial programs open and deferring enrollment decision to study investigators and patients healthcare providers is most beneficial to patients. That said, we anticipate that short term effect may begin to emerge across the health aspect of our work clinical program.
For example, while we expect ongoing monitoring of already enrolled patients to continue, New patient recruitment in certain clinical studies may be impacted. We also expect the conduct of clinical trials may vary by disease state and by severity of disease as well as by geography as some regions are more adversely impacted. We are monitoring the situation closely, selectively preparing and implementing contingency plans across our global study. Such as sending drug direct to patients and adopting novel remote and tele monitoring tools as we to ensure continuity of care and data integrity for all participants in our studies around the world. Finally, last week, we announced that Insight and Novartis are working together with the FDA to launch a global Phase III trial to evaluate the safety and efficacy of Ruxolitinib to treat the cytokine storm associated with severe COVID-nineteen.
In these basic patients, a hyperinflammatory response in the lungs can lead to respiratory distress and the need for mechanical ventilation. And we have both anecdotal clinical evidence and a strong preclinical rationale that Japanese may have significant volatility here. We are also seeking to launch an emergency expanded access program for these patients in the U. S, and we can assure patients currently taking JAKA 5 for its approved indication, as well as just participating in clinical studies, but we have ample supply of opportunity for all our clients. I'll go to the next slide now, and I will end my introduction with a reminder of our oxalate cream development activities and the timeline for the expected NDA and subsequent FDA review in atopic dermatitis as well as the ongoing Phase III trials of restructuring equipment vitiligo with data expected next year.
It's now my pleasure to welcome Doctor. I can fill to the call. So, Larry, please go ahead.
Good morning, everyone. Larry, I can fill here as you heard. I'm a dermatologist and pediatric dermatologist in San Diego. Wishes of health and safety for everyone around the country. We've converted a lot of our practice to tele dermatology as we rev up our hospitals for changes in practice.
But, pay to be a part of the presentation, as insight rolls out some very great data that I think could be very helpful that a longstanding interest in atopic dermatitis and take care of lots of patients across the ages with, with eczema. So, what I will be doing is going through the landscape of atopic dermatology clinical need and then I'll be available for lots of questions on the disease state. So I'll be talking, from a mixture of what I know to be this evolving field on eczema, but also translated, like taking care of patients and families across the ages with atopic dermatitis. Just a short story, sort of my summary point. This is a high prevalence disease.
It's 10% to 20% in young children, 2% to 10 set of adults. It has variable course and severity with a subset of patients, with a lot of, active exiva with secondary impact of the disease. It has significant disease burden as well as comorbidities associated with it. Historically, limited treatments beyond topical corticosteroids and still a high unmet need or long term inflammatory disease control. Now one is atopic dermatitis.
Well, it's really as a type of eczema, the term eczema is a broader term, but it's the most common type of eczema that presents with its typical morphology and distribution. So inflammatory skin disease with a chronic or persistent cord And as manifest as eczema, I'll show you some more images of sort of typical eczema that we see. It also relates to bacterial colonization and secondary infections and the disease impacts multiplied by its associations with but allergies, which include food environmental allergies, asthma, hay fever, as well as neuropsychiatric effects. Which I'll mention in more detail. So first of all, EXHIM is a worldwide issue.
We know that the eczema rates it used to be and in non industrialized parts of the world around 4% to 5%. But they increased to 12% to 15% in many Westernized industrialized countries. And there's more data on the persistent and or adult onset atopic dermatitis as well. There's this whole experience in China, for instance, where they had rates of 4.5% now in the major cities 12% to 18% with a lot of it developed on so they canopic dermatitis. So The reason isn't necessarily known.
It may be a mixture of changes in environment, both, avoidance of of a parasites or early stimulants that might affect the immune system development as well as pollution and other factors. We have pretty good datasets now that have come out in the last 10 years on rates in teams and adults. The disease can persist or you can get new onset disease in 5% to 7% of adults in the U. S. In recent estimates have atopic dermatitis.
I added this slide because it's important. One of the takeaways that I want people to get is that there's a lot of atopic dermatitis that's that's mild or moderate, and then there's another set that's moderate to severe. And that moderate group probably splits in half. But whether it be adults or children, we have a lot of mild to moderate disease. And even though there's been a lot of excitement in that have been approved and developed for more severe disease.
It's still going to be still now and will still be in the next 10 years that most atopic dermatitis is going to be managed with the topical agents. Just goes along with the the severity data of the population. So a few images to make sure you get a sense of what we're talking about. There this variable severity with eczema, but eczema has this inflammation in the skin where you see redness in any of these photos. We know there's inflammation that's in that skin.
There's, of course, also some degree of, skin effect and you can see both oozing and crusting, as well as scale that develops a promo. There can be a lot a bleeding in more severe disease, pigmentation changes, cover changes that happen from the disease as well. And then you can get in more chronic cases, which is very common. We get what we call like canification. You get thickening, as well as erosions.
So this inflammation, the skin creates this secondary changes, but a lot of this is tied to pruritus as well. Because you can have dry skin that causes pruritus, inflammation that causes pruritus and pruritus perpetuates this cycle. Before we go through a quick discussion of pathogenesis, I wanted to discuss the a secondary consequences disease and relationship to infections. And it's very common with atopic dermatitis there's increased bacteria in the skin predominantly staff, so we can get what we call impetigenized atopic dermatitis, as well as increased rates of infections, even cold sore herpes can cause something called eczema or PEDICOM. I evaluated 2 patients over the weekend with the teled dermatology who are in the emergency room for, possible eczema or pedicone.
So secondary infection is a big consequence of the disease. The medical consequences of disease, there are chronic rashes, there's pruritus or itch drives disease manifestations. And we're definitely looking for products that can help to control that itch infections, as mentioned. A lot of secondary consequence of disease is tied to sleep disturbance, because that clearly hasn't impacted on quality like. We're performance, and is very much tied to pruritus.
And then there's the set of what we call a non atopic morbidities. So we're talking about atopic dermatitis, but there's a tradition of comorbidities that are also considered atopic or relatively allergic in nature. This includes asthma, a fever, allergic rhinitis conjunctivitis, food allergy, and then contact allergy or which fits into allergic contact dermatitis also known as occupational dermatitis and these images you see a patient with asthma through some peanut butter up there, a common, a food allergy that can develop in patients with atopic dermatitis. And then the bottom right showing allergic contact dermatitis where you get localized reactions to chemicals or metals on the skin and that's the sort of patch testing those little white things that we do as we try to figure out what particular allergens are maybe, instigators of breakouts in atopic dermatitis. The rate of allergic co morbidities is really quite high, across the ages, whether it be infants, children or adult with hay fever, allergic rhinos, you need almost 50% of adults in more moderate severe disease.
It's at least a third of even, younger individuals with a fever allergic rhino conjunctivitis as of about 40% as well. And food OGSight, while it can trigger a subset of atopic dermatitis generally develops, after the onset of atopic dermatitis. So these are things that are sort of secondary issues that bring up the importance of atopic dermatitis. The other, thing we've recognized in the past decade is the mental health effects, neuropsychological effects of atopic dermatitis at very high rates of anxiety and depression with more severe disease with what had 5 adults meeting diagnostic criteria for major depression. The literature on attention deficit hyperactivity ABA HD.
When the first paper came out, we were a little questioning. Maybe they were just fidgety kids. It was a Java paper. So it really superb We're still we were appropriately skeptical, but the data is really strong now that there are higher rates and a lot probably ties to sleep, disturbance and fatigue. So the way I put together a sense of that burden, if you start looking at 9 o'clock, okay, on this circle diagram.
We have
a quick tour manifest with the itchy Rasha's side the symptoms of disease, which is tied to them. We'll work clockwise to the symptoms with pruritus and frequent intense itch. Sleep disturbance very much associated with those findings in the itch, both falling asleep problems, staying asleep problems, which has a huge impact on quality of life. Atopic comorbidities, as mentioned, other comorbidities, including the mental health, back bacterial viral and other risk factors of some immune diseases and potential cardiovascular impacts. And then of course, the impact on quality of life's social functioning, life course and school and work performance of affected individuals.
I spent a lot of time on pathogenesis, but there is now a sort of a holistic sense of the pathogenesis of atopic dermatitis system children who were born with, barrier dysfunction, which is a lifetime thing. If you look at adolescents and adults is there as well, drier skin, more open skin, as the skin to be more sensitized, which sets up the immune reaction that gives you these overactive cytokine production in the skin, which manifests as the rash. And you can see, on this diagram that there are a set of mediators of the disease, especially the TH2 modulators and a variety of cytokine that are the targets. We'll be discussing later on the in the data set. Jack inhibition can disrupt the inflammation in atopic derma the tightest unit IL-four thousand five hundred and thirteen thirty one, but these are mediators of the inflammation and itch.
And atopic dermatitis. So what therapeutic needs are there? First of all, we start off with atopic dermatitis. Is moisturizing is important because patients can have a dry skin tendency and dryness also tends to increase the it's of atopic dermatitis. And we have many different approaches, but this does not handle the inflammation of atopic dermatitis that we see in most of our patients and we generally then need effective anti inflammatory therapy that hopefully will be anti pruritic as well.
Traditional mainstays are topical corticosteroids. We have about 70 different topical corticosteroids. They range in potency. They were used for tube flare management intermittently for maintenance management. There are significant concerns worldwide phobias with topical corticosteroids concerns because of steroid absorption, especially with higher potency agents as well as local effects with skin attributes, stretch marks, etcetera that limit its use and while we often try to have patients use topical steroids and use them in regimens, there's a lot of concern and they have to be managed so that we does stay away from side effect profile.
Topical calcium neuron inhibitors came out in around the 20,021,001 as non steroid topical agents to chromis and pembrocholimus they're officially listed as 2nd line therapy that can be used intermittently, not continuously, as we know, they have concerns with labeling due to concerns about, the latency that were raised by the FDA. That fair to good efficacy is not that strong. They are approved either to mild to moderate or moderate severe atopic derm depending upon which drug you look at and definitely are limited by tolerance with stinging and burning, which can occur. The relative new kid on the block is topical Chris Aboro, which is a topical PD4 inhibitor. Used BID.
Safety looks good. They recently had an expanded indication down to 3 months of age, but a lot of stinging and burning and not I'd say limited efficacy, not that strong anti inflammatory for eczema. So still in play, I think that the market that was expected in terms of use, but that's sort of where we're at with it. There's reasons for that. As systemic therapy, being niche for moderate, severe atopic dermatitis, traditionally we use very fuses systemic agents in patients in the United States, methotrexate was the most commonly used, but was uncommonly used and not approved.
We also used the cyclosporin azathioprine, mycophenolate, lots of toxicity associated with them. Fasenex steroids are most commonly used for sort of acute rescue therapy, but not advised at dupilumab now approved 12 plus? As the first systemic agent, I'm sure you're well aware of the evolution of systemic agents and the market in your relationship to this with both oral JAK inhibitors, specific IL-thirteen blockers, IL-thirty one blockers and we could go in detail, but that's not really what we want to stress today because it's very important in clinical practice to understand that most eczema is mild to moderate that topicals will still handle most disease. And from a political perspective, there's a great need for more potent, well tolerated, non steroid. And if I could get a well tolerated non steroid agent that really more effectively controls inflammation and effectively decreases itch.
That's something that would be very, very exciting to the patients and to the patients who take care of them. Also think the market of atopic dermatitis is still relatively untouched. There's still a lot of work getting patients back into the office and to understand that we're sort of revolutionizing therapy with new tools that allow us to establish more long term disease control rather than just occasional player control. I regularly see pay with loss of eczema on their skin, and lots of the secondary consequences. And this is how we have an expectation that we can fix it and get it under control.
But with new agents such as what Insight is producing, we'll have more ability to do that. So I thank you for listening and we'll have an opportunity for some questions. But at this point, I will turn over the material that Jim Lee who can discuss the great results on the AD drug.
Great. Thank you, Larry. This is Jim Lee. I lead the inflammation and autoimmunity group here at Insight. And I have the pleasure of representing the phase 3 study results that were presented yesterday, if you could slide to the next slide, at the revolutionizing apac dermatitis conference, the virtual meeting held yesterday, presented by Doctor.
Kim Papp, one of our lead investigators in the phase 3 study. Go to the next slide, please. Yes. So before I, present the data. I just wanted to remind people of the scientific rationale and previous clinical work that was done with RUC cream in atopic dermatitis.
Doctor. Eichenfeld mentioned, in terms of the pathogenesis of atopic of dermatitis. I think we've learned some of the main culprits, specifically the TH2 cytokines as well as IL-thirty one. That really drive both the inflammation and the symptoms of this disease. And we've learned, over the years, that a lot of that is driven by the JAK STAT Pathway, specifically, JAK1.
And we know that the cream, or ruxolitinib, excuse me, has the ability to block those inflammatory pathways. So a few years ago, Insight conducted a Phase 2 study in atopic dermatitis, where they looked at a number of different concentrations. Dosed twice a day and once a day for 8 weeks. And those results have been published in the journal of allergy and clinical immunology. And, based on the results of those studies, Insight conducted, the 2 Phase 3 studies that I'm going to share with you today.
So if you go to the
next slide, please. It's the study schematic or the study design. We tested 2 concentrations a 0.75% and the 1.5% Rux Cream. And in the 1st 8 weeks of the study, we compared it to vehicle cream. And after week 8, which is the end of the vehicle control period, patients who were originally randomized to vehicle, were re randomized to either 0.75% cream or 1.5% cream.
And in the 44 week long term extension portion of the study, patients were instructed to retreat when they had a flare. So when they either saw new lesions or felt the itch that drove their disease, they were instructed to retreat, and then treat until the itch went away or the lesions cleared. And we'll have results from the long term extension sometime later this year. But today, we're here to present the, results from the vehicle control period. So if you could go down to the next slide and then one more, This, this summarizes the study endpoints that were looked at.
The primary efficacy variable with with the proportion 2 point grade improvement from baseline or what we call IgA treatment success or TS at week 8. The secondary endpoints included the proportion of patients achieving at least a 75% improvement in their EZ score from baseline, EZ75, and then the proportion of patients with at least a 4 point grade improvement in the itch NRS score from baseline at week 8. The next slide summarizes the eligibility criteria. And, essentially, this, the criteria was, was almost identical to the criteria used in the phase 2 study. The only change was the expansion of the age range.
So in the phase 2 study, adults were evaluated in this study, we went down to age twelve. So adolescents and adults, in terms of their disease severity as mild or moderate, so IGA 2 or and the baseline body service area involvement range from 3% to 20%. In terms of key exclusion criteria, These are very common criteria used in most atopic dermatitis studies. So let's move to the patient demographics summarize on the next slide. As you can see, the distribution of the Democrats at baseline was very similar across treatment groups.
So as I mentioned, this included the study included adolescents and adults. So we had about 80% of the patients where adults, the rest were adolescents, about 60% of the patients were female. And in terms of race, about 70% were white, about 23% black and the remainder were others and those others primarily were Asian people of Asian descent. And in terms of where the studies were done, about 70% of the patients came from the U. S.
And Canada and the rest thirty came from Europe. On the next slide shows the clinical characteristics of the patients And again, as you see, the distribution was similar across treatment groups. But in terms of the clinical characteristics, in terms of the body surface area involvement at baseline. It was around 10%. And in terms of the mean easy score, we saw a mean easy score of 8 across the groups.
In terms of the baseline IgA score, about 75% of the patients were moderate the rest were mild, in terms of the main baseline, each score, it was 5 across treatment groups. And the proportion of patients who came in with an NRS score of at least 4 or greater was about 2 thirds. In terms of the duration of disease, the population with longstanding duration, the median duration was around 16 years. And about 38%, 39% of the patients had facial involvement. And this is important, but there are a lot of top of treatments, where, you really can't use it on the face at all or for very long periods?
So the next slide, summarizes the safety that we observed in the study. What we saw from a safety perspective was that rux Cream was well tolerated and was not associated with clinically significant application site reactions. Again, with a lot of topicals, you see high rates are modest rates of application site reactions, pain, itching, burning, and we didn't see that in either study. In terms of the adverse events, all treatment related treatment in urgent adverse events were mild or moderate in severity, and that was very, very good to see and that we didn't see any adverse events that were suggestive of any systemic exposure. So in terms of the specifics, we see the overall rates of adverse events, was around 25% to 30% And in terms of those adverse events that were felt to be treatment related, and again, a much lower percentage And in fact, if you see, it looks like the vehicle control treated patients had the highest rates.
And specifically to those application site reactions, as you can see there. And again, you see that it looks like the vehicle treated patients had the highest rates of those application site reactions. In terms of discontinuation, you'll see on the next slide before I go there, the discontinuation rate was fairly low. And it actually, the number of patients who discontinued due to adverse events was also very low. And again, you see the highest number of discontinuations occurred in the vehicle arm And in terms of SAEs or serious adverse events, again, a very small number, none of them were believed to be treatment related.
The next slide shows the disposition of the patients that were randomized in both of the studies that we had about 1250 patients or subjects randomized. As I mentioned, the discontinuation rate was low was around 10%. And as you can see in the boxes themselves, majority of those patients withdrew for personal reasons over a loss to follow-up. And so we had about 90% of the patients complete the studies And so let's turn to the efficacy. On the next slide, this is the primary efficacy variable the IGA treatment success.
And as you can see, significantly more patients treated with Rux Cream, demonstrated achieve the primary endpoint IGATS compared to vehicle. As you can see, there's a breakdown here between the two studies on the left there. TRU AD1. And as you see, by week 8, in the 1.5% Rux Cremar, about 54% of the patients achieved this endpoint, 50% in the 0.75% arm and 15% in the vehicle. In the TRU AD2 study, on the right, about 51% in the 1.5% arm achieved the IGA 0 or 1 with the 2 point grade improvement, 39% in the 0.75% arm and 7.6 in the vehicle arm.
So that was a very exciting data. Well, how about the EZ75, which is another very common efficacy variable, and that's shown here in this slide. And again, very similar pattern where you see a higher response rate in the 1.5% arm, and then both arms shows fiscal significance compared to vehicle. So in TRU Eighty 1, 62% of the patients achieved an EZ75 by week 8, 56% in the 0.75% arm, and 24%, 25% in the vehicle arm. In TRU 82, we see about 62% of the patients in the 1.5% arm, achieved an EZ75 score, 51.5% in the 0.75% on and 14.4%.
In the vehicle treated arm. In terms of the main percent reduction in EZ score that's shown on the next slide, You could slide the the next slide. That would be great. There we go. And it oh, I think can you go back 1?
There it is. This is the easy percentage change from baseline. And as you can see, this gives you a sort of a time course. You can see that 77 percent or excuse me, the easy reduction in the 1.5% arm in 281 was 77% and the 0.75% arm is 72% and in TRU 82, the easy reduction in the 1.5% arm was 75% and a similar reduction was seen. In the 0.75% arm, much higher than what we've seen in the vehicle treated patients.
In terms of itch in the next two slides, if you go to the next slide, please, shows you the reduction in itch. And as Doctor. Eichill referred to, the inflammation is obviously a very important component that drives the pathogenesis. But what in terms of what the patient feels, it's really itch. And so we collected the itch scores.
This is the change from baseline in daily itch NRS score. And as you can see, we see significantly greater reductions in each NRS, observed with both active arms. And in fact, with the highest concentration, the 1.5, we see the reduction as early as 12 hours after the first application of Rux Cream. As you can see, we're showing the 1st 28 days that it continues to improve throughout the 8 weeks of the study. But as you see it's a very impressive reduction, and more importantly, a very rapid reduction in itch with the mean easy reduction in the in the 1.5% arm of 3.39 in the TRU 81, and 2.88 and TRU 82.
If you could go to the next slide, the next slide summarizes, one of the major secondary efficacy variables that we collected, and that's the Go to the next slide, please. Yeah. That is the 4 point improvement in each NRS. And this is important, but this is what FDA has has defined as a meaningful endpoint in terms of its reduction. And as you can see in both studies, we see significantly more patients treated with Rux Cream, demonstrated clinically meaningful reductions in their NRS4 or at least a 4 point grade improvement in their NRSH versus vehicle.
And by week 8, in TRU 81, we see 52% of the patients in the 1.5% rux arm, are able to achieve this efficacy endpoint about 40% in the 0.75% on and 15.4% in the vehicle treated arm. In the true 82 studies, in the 1.5% arm, 50.7% of the patients achieved this endpoint, 42.7% the 0.75% arm and 16.3% in the vehicle arm. So very exciting data as well. So if you could go to the next slide, to finish up the presentation, to, conclude and to provide the conclusions from what we saw in the study. So what we see in this study is application of Rutscream brought about a rapid and substantial and sustained its reduction, which was very exciting to see for patients.
In terms of the efficacy, Rux Cream showed superior efficacy versus vehicle in all of the major efficacy endpoints. And, in terms of the itch and the inflammation, I think this is the first time that we demonstrated a dual mode of action for cream is not only displays the anti inflammatory activities you would expect with the JAK inhibitor, but also the anti itch anti pruritic activities. In terms of safety, again, we're very excited to see that the Rux stream was very well tolerated we didn't see a very many local systemic or local side effects nor any evidence of systemic side effects. And so, very excited about the, the data from both studies. We think that the data will support the application of RUX, excuse me, the submission of RUX, and we're hoping to move that forward later this year.
So with that, I'd like to turn over
step in the program is to get the long term safety data. And when this is available to us, we intend to submit the NDA seeking a cohort in dermatated before the end of this year. The last slide here, summarize the commercial strategy and the exciting opportunities that we seek for accelerated cream in the U. S. If approved by the FDA, we expect to launch in atopic dermatitis late next year and in Vitiligo in 2022.
We plan to create a dedicated dermatology division and we will be targeting our efforts towards the 8000 or so medical dermatologists using a specialty field model. Okay. So operator, that concludes our prepared remarks. Please give your instruction and open the call for Q And A. Thank you.
Thank you. Our first question today is coming from Cory Kasimov from JP Morgan. Your line is now live.
Hi, this is Gavin on for Corey. Thanks for taking our calls. We just wanted to understand the key barriers to commercial adoption for this product. And then, we had one follow-up as well. Thank you.
So do you want to take that one? The key barriers to come actual, adoption and, and maybe, Doctor. I can field if you can add. Are they you on mute?
Oh, sorry. Oh, okay. Sorry. I was, I wasn't on mute. No, I think, I think, I mean, as you know, I mean, the number of patients we are potentially able to treat here is very large.
These are patients who today have unsatisfactory treatment sometimes with steroids. So there is a question of will be addressing that need. You can see the efficacy data in term of each and anti inflammatory effect. Is really key to understanding why this product could be really changing you know, the options for these patients. And as we discussed, our, plan is to really work with medical dermatologists that launch for the 1st months, if not years of the launch of this product to educate everybody on how it could be really helpful.
On the other hand of the spectrum, when you go to the TV, type of atopic dermatitis. Obviously, using injectable antibodies today, one of the option, what we are also looking at is that for patients who have limited size of a lesion that using a cream could be so very good option. And as you can see from the clinical result, the lack of systemic exposure is leading to a very interesting, efficacy safety ratio for this strategy. So maybe Doctor. I can feel if you want to confirm on that from your experience?
Yes, certainly. I think that the when we see a new drug maybe on the launch pad as a in the dermatologists and to a degree, a more primary care position. People are looking to see, okay, how would this complement what I have now? And is it going to have something different that's really added? And so I think that's the hard part in rolling out is to make sure that there's that some a drug is bringing something new and novel and better, as it fits its way in.
What's very exciting about this data is that We don't have number 1, there's very limited efficacy to the non steroid medicines that we use. They're just not that strong in terms of their impact on eczema and the data set actually. It's hard to know without living within these data sets, but the easy score, the separation from the vehicle response to the active looks really, really good. Both the absolute EC score decrease, the percentage change as well as the percentage of patients who get a lot better, that EZ75, meaning those people are getting 75% better.
So with
a non steroid, you don't have to worry about atrophy, you don't have to worry about steroid and cortisone absorption. There's this can be used across the spectrum of eczema. So patients with milder and more localized disease could use it as an alternative or in addition to regimens with topical steroids, more severe patients may be able to prevent people needing systemic therapy. Even in those on systemic therapy where we were even dupilumab, which has been a marvelous drug. There's a lot of surface area, a lot on it.
Across the spectrum, I think it can be taken up. So I think the novelty is the what looks like the relative efficacy And the other thing is their topical side effect data is where you're seeing stinging and burning that's that's higher in the vehicle in 1 of the 2 studies that were around the same. That's remarkable because of the drugs well tolerated. It also means there'll be a lot of excitement to people using it.
Kevin, next question please.
Thank you. Our next question is coming from Mark Frahm from Cowen and Company. Your line is now live.
Some of the data. Maybe one just technical thing for Jim. In the patient disposition slide, noted that for TRU AD1, the analysis was done on an IT basis versus ensure 82, some patients were excluded. Can you kind of describe why some patients were excluded? And then also if you did the analyze true AD to on an ICT basis, would any of the primary key secondary endpoints like each have lost, statistical significance?
Sure, Mark. So you did notice that there were a decreased number in the efficacy analysis. And so during routine monitoring, a quality issue was identified at one of our sites in Europe. And we did a thorough investigation and it looks like there are some some quality concerns around the data that comes from that site. And so we've decided to actually move site from the efficacy analysis.
And the fact that analysis, by removal of the site, that actually lowered all of the top line efficacy in the in the rux arms, but we felt this is the right thing to do. In terms of the imputation method that was used, this was This was the NRI. So we use the most conservative, which is actually what we use in the phase 2 study as well. And when you take a look at per protocol, analysis, actually all the numbers go up. And so, or if you use an LLCF, the values actually all go up, but we were actually sticking with the NRI analysis because it's the most conservative.
Thank
you. Our next question is coming from Brian Abrahams from RBC. Your line is now live.
Hi there. Thanks for taking my question. And congratulations as well on the data. Doctor. Reichanfield had mentioned that many comorbidities or the amount of morbidities associated with atopic derm like leak disturbance, etcetera.
So I was just wondering if you're seeing any concurrent benefits in these Phase 3s on a quality of life score scores alongside the leasing and niche improvements as well as on score ad, which I know is important for Europe. And then just as a follow-up, your level of confidence that you'll be able to collect adequate reliable data in the long term follow-up just given the current pandemic and how you're managing through potential challenges there? Thanks.
Yes, absolutely. So we did collect a number of additional PROs, including quality of life. That data is still being analyzed and collated. And we'll present that data at a future scientific conference. In terms of the impact, the potential impact, you're right.
As we mentioned, we're monitoring the situation very closely. And we're putting into place in working with the sites to try to get the patients in within their visit windows. But right now, we don't have a full measure of what the potential impact is. But in terms of the specific long term data, yes, we're still monitoring that, but the goal is to submit the NDA by the end of this year. And, right now, we, we still have that on track.
But, obviously, everything will depend on, what happens with the COVID-nineteen
Our next question is coming from Salveen Richter from Goldman Sachs. Your line is now live.
Thanks for taking your questions. This is Andrew on for Salveen. Maybe just one for Herve. If you think about the benefit that was demonstrated by both of the doses, How are you thinking about the regulatory path forward? Are you planning on seeking approval for both doses, or how are you thinking about that?
Yeah, maybe Jim can speak about the regulatory. I mean, you saw from the data that obviously both doses are very effective. And it looks like on most of the endpoints that we have seen today, the higher dose, is showing a little bit more efficacy and there is really no difference in safety. So that's really what we see from the data. Now how the FDA is going to look at it?
It's frankly something that I would say difficult to predict. And I think that this season at the end of the day we've been made together with the FDA. Arjun, do you have any?
No, I think that's a great summary. Yes, no, I think that's right. I think, we have some additional analysis that are ongoing. We'll have the long term safety data that'll all come into play obviously in terms of the dose. But I think everybody is right.
It'll be a negotiation with the FDA when we submit.
Kevin, next question please.
Our next question is coming from Alexander Duncan from Piper Sandler. Your line is now live.
Hi, thanks for the question. Could you provide any information on how much Rut screen patients used on average or on a percent DSA basis? If there were any site specific differences or types of lesions in terms of where Rux Cream works better? Thanks.
That's a great question. And we're still analyzing the data. We're, we're, you know, still doing all of this sub analysis. Including amounts of drug. But all of that is being done now and will be shared at a future scientific meeting as well as future publications.
Our next question is coming from Jay Olson from Oppenheimer. Your line is now live. Mister Olsen, perhaps your phone is on mute.
Oh, Congrats on the data. Really impressive P values and thank you for the presentation and taking the questions. If I could ask Doctor. Eichenfield, could you describe the factors that would drive preference for a topical JAK inhibitor And are they mostly related to the body surface area involved or do comorbidities also play a role like if patients present with atopic dermatitis plus asthma or food allergies, would that make you more inclined to treat with a systemic therapy? And then as a follow-up, Can you talk about the systemic long term adverse effects that are associated with high dose topical steroids?
Thank you.
Sure.
So it's there may
be an evolving approach to considering comorbidities in the decision tree for systemic therapy. One of the issues that I think we've seen Regeneron and Sanofi deal with with dupilumab is they have a drug that's approved for more than 1 TH2 associated disease state, but they sort of had parallel programs. And there's the in the Dermatology world, people are sort of aware of the comorbidities, but they don't necessarily want to manage them. So I don't think that makes a big a big in the plate for a decision for systemic. I think probably the biggest thing is that being able to bring different regimens in that will have more, more effectiveness where one could use non steroids in long term disease control more effectively to the present ones, have their limitations and or a mix and match between that, there'll be a subset of patients who can be really well taken care of with the systemic effects of top the the politically incorrect analogy is alcohol.
If someone says, I drink wine every night and a bottle lasts 5 months, I mean, why don't go bad, but I won't worry about the quantity imbibed. But the problem with top corticosteroids, the difference between an over the counter or lowest strength prescription topical corticosteroid which are 1% or 2.5% hydrocortisone for instance and point of 5 saw numbers don't correlate clobetasols about a twenty times stronger. So you truly can get, just continuously in large quantities, then you could get absorption and what happens to Cortisol's producer, your adrenal plants stops working Very uncommon clinical practice to have, so much systemic corticosteroid yet that can occur. But the consequence of that is that there's, you know, under use of a of a corticosteroid, I'd say, because people are so fearful of it. And, while it's great for us to encourage use of topical corticosteroids as part of regimens of care, perspective is really having a move to other patients or a mix and match depending upon the disease severity.
We can bring long term disease control. And I think that's where this product 6 is something that brought something very exciting that will allow more patients to be managed effect without the need for systems.
Thank you. Next question is coming from Ren Benjamin from JMP Securities. Your line is now live.
Hi, thanks for taking the questions and congratulations on the data. Just one for Doctor. I can tell, you have a quite a few options on your hand. And I'm kind of curious, a newly diagnosed new patient comes into your clinic. Just what is the, kind of the gamma that you run through before you get to, let's say prescribing a rough screen or a Eucrisa, in how many options do you go through?
Is this kind of like a last ditch option that you give these patients or do you start losing them, moving it up kind of front line? And then as a follow-up, maybe for Jim, you have 50% of patients that are not considered IGA responders. Do those any of those patients getting better over time, or do you wind up switching them to other medications? Thanks.
The when used question is something that I have to be honest, we're talking a lot to both people and company people, people often want to know, oh, is this 1st line? Can this be 1st line? Did I say don't fight line as a label. I mean, as a verbiage because someone who comes in for nuance of atopic dermatitis. So the first one, they're probably going to get cheap topical corticosteroid to see how quickly we can get the disease under control and then see see what happens because whether it will stay, it will come under control and then stay under control.
Or is it one of those persistent cases where it keeps they stop the topic of corticosteroids, there's recurrence. And that's almost besides the point because there's so many who aren't managed by just a week of 2 atopic corticosteroids and a little topical corticosteroid now and that's if you had that, that would be that's one thing. The patients where that regimen doesn't work. And so I have a patient who's a new patient for me who has a history to use a type of steroids is usually the case. Even if they're too little, it's very, very early may visit or second visit that, that will prescribe a non steroid like this in the regimen of care.
And many times it's the first time, especially you have to realize that there's topical corticosteroids on the face issue, around the eyes that can cause cataractions, very thin skin on the body. So, a well tolerated medicine that's not going to have that and get to still control the eczema very exciting. Yes. Yes. And the second question was for Jim.
That's right. And the question was around the percentage of patients that weren't able to achieve the IGA score IgA treatment success at week 8. So, I think in the study schematic, I showed you that all patients were on active drug, either the 1.5 or the 0.75 beyond week 8. So we'll be able to collect those patients and see how many of those patients who didn't hit the IGATS at week 8 and how many of them are able to achieve that at subsequent visits. I will add though that, this is the first time, I think any product has been able to achieve an point grade improvement of end of '50s.
I think I mean, Larry, correct me if I'm wrong, but I think this is the best efficacy that any product has been able to achieve in an AD study. So I do just qualify the IGA at 50% as probably some of the best efficacy that's been seen so far. So just wanted to add that there.
Yes, I totally agree. The IGA scores. The FDA approach is what percentage of people get like pretty clear. A high bar, but if you look at that's why you look side or the absolute easy decrease, an absolute increase of 75% when we're in the easy score of around 8 is marvelous. You're down to really, really low numbers.
And I think showing a lot of answers.
Thank you. Our next question is coming from Vikram Parekh from Morgan Stanley. Your line is now live.
Hi, good morning. Thanks for taking my question. So I have one for Doctor. I consult. Wanted to go back to a question on commercial considerations and thinking through uptake.
So if the product is eventually approved but is approved with a black box warning, due to it being a JAK inhibitor, how do you think uptake would be impacted versus if the product were approved without a black box?
Well, the easy answer is it's hard to know that. A lot going on what the sensibility is of the safety data that comes with it. Dermatologists are way more sophisticated now with what box warnings means since they're an expanded number of this that may have them. I think, if the safety data for the drug itself does not show signs of systemic effect no systemic giving us suppression, none of the side effect concerns that may get labeled for what you're seeing with our oral JAK inhibitors or oral rux. If it's labeled, but not seen in any of the population, very comfortable using it.
And, I think that's, I mean, we totally live in this world of ideation of side effect profile between topicals and systemic delivering efficacy locally to areas that are inflamed without taking the systemic approach to try to avoid systemic side effects So I think, it's the safety aspect of this, which looks so good, remains that way. It will allow them to move forward. At least amongst the hands of most dermatologists. Now if there is touring requirement for monitoring that that might be a big barrier, but I wouldn't foresee that happening.
Thank you. Our next question is coming from Matt Phipps from William Blair.
Hi, thanks for taking my question. This was kind of asked a little bit earlier, but just curious what this rapid response you see in skin involvement. Does that essentially mean that the amount of cream used, I guess, as in grams or such, will show a similar pattern, just assuming there'd be I guess, much less volume being used by 8 weeks as opposed to when these patients start with about 10% PSA.
Sure. This is, this is Jim. Let me just, can you rephrase that? I'm just, I want to make sure I want to answer your question. Are you asking around, do you think the cream, because it's topic you applied directly onto the skin, that that is the explanation for the rapid response in its reduction?
No, sorry, just as far as volume being used in thinking about, I mean, ultimately thinking about pricing it versus a tube and how much patients are using. And that's just pretty rapidly. This rapid response leading to just the patients not needing as much volume over time to cover the surface area?
Yes. And so that's a fair question in terms of the clinical trial. We'll obviously provide an instruction and we will we're looking at that I can ask Doctor. I can feel to address in terms of patient compliance in the real world. Yes.
So, well, first of all, patient compliance are real miserable, but that's one of the issues, partially because they're fearful of their medicines. But what normally happens, even with any of our topicals is that we'll start off with a higher quantity of use over the 1st week or 2 of the treatment And then if you start to get if you have an effect of intonation, you start to get, skin healing, then you'll decrease the quantity you use as parts of areas, heal, but many times for many patients, we go into maintenance mode, where we call proact of treatment, sort of using the asthma model where we don't we don't wait for patients to layer. And start wheezing again before we treat to keep their wheeze away. So, in atopic dermat, there are these hot spots that may recur, you cool them down, then they may they may use the drugs intermittently in that should not the way this drug is studied at this point in the phase 3 studies. So it's not as though people will turn off their use totally, but there will be a higher volume to use probably in the 1st few weeks, but that's because you're bringing healing that portion of the skin.
But over the long term, there should be continued use, not just for flare control, but in this long term disease model.
Our next question is coming from Michael Schmidt from Guggenheim Securities. Your line is now live.
Jim. We were just kind of wondering if you could provide some of your thoughts around existing peer control in the AD space. And maybe kind of some color around your strategy to secure patient access. Thank you.
Maybe
the first part of it I missed. I'm sorry.
Oh, that's okay. I can, I can go back to, yeah, just kind of thoughts on existing payer control in the space, and your strategy to secure strong patient access?
I'll take it from my standpoint, which is and then I'll turn it over to Jim for the real answer. So As a clinician, this is we spend more time in energy and staffing, trying to get drugs approved, but it's usually it's there are 2 ways of doing it. There's, patient by patient and then there's group by group or payer by payer. And increasingly, as a standardly used in regimens of care that we can get it approved. Now many times they may require that someone's used a topical corticosteroid to get an odd steroid, but that's not a problem as long as you document it.
So, there's advocacy that needs to be done, but that's pretty much part of the standard of what we do in practice.
Yes, I mean, like any new product, I mean, there is a phase where we will be working with the payers to try to see where they see this new product in in the, you know, the step edit program, what the prior therapy that we need to see, etcetera. I mean, it's a very classic phenomenon is that as we go through the 1st month of the launch, there will be more and more availability of the product earlier in the disease On, on the pricing side, we have not made a decision on where you're going to to land. So that would be done later when we are close-up to the launch date. But, obviously, the goal is to have a product that will be widely available because we leaves the benefit of this cream can be seen in a very large number of patients with a big dermatitis.
Thank you. Our next question is coming from George Farmer from BMO Capital Markets.
Hi, thanks for taking my question. I want to talk a little bit about systemic exposure and whether you actually looked at systemic exposure and whether, application of the drug perhaps on open lesions might increase any risk?
Sure. This is Jim. I'll take that and I think, Doctor. Pat mentioned it during his presentation. We're still working on getting the PK data.
So we did collect, PK during the fee of control period. That data is being analyzed and we'll share that at a future scientific conference But if you take a look at the adverse event profile, clearly, there's, it's hard to say or hard to see if that the systemic exposure was clinically meaningful as we didn't see any side effects associated with that. So And then in terms of the open lesion, we'll see. We'll see what the PK data, but I will share with you that the PK was also done in the Phase 2 study in that data or that information was shared in the Phase 2 publication, the main script.
Thank you. In the interest of time, we have time for one further question. Our final question today is coming from Tazeen Ahmad Bank of America. Your line is now live.
Good morning guys. Thanks so much for taking my question. Maybe one, and congratulations on the data, maybe one about, on the question of commercialization. So on the competing drug that's on the market that's applied topically, One of the complaints that physicians have had is that, patients sometimes complain that the clean can be messy. Now based on the comments that were made already on the call, is it your view that a cream is something that would be more attractive to patients who potentially have, less of their skin involved in a breakout?
Or do you still think that once the case gets to a maintenance level that the Ukraine that he or she might need to use would decrease over times. Thank you.
So, Frank, if you want to take that one? And, Jim, maybe a follow-up. Sure.
So first of all, we know the you asked dermatologists, they prefer ointments over creams, patients clearly prefer creams overall admits. And that's partially because the sort of gooeyness aspect of it really matters to them. You know, most patients recognize that there's a part of their skin that's not just the inflammation that has dryness as well. Some degree of skin care as part of the sort of the obligation, but trying to make it as minimal as possible is what we're going for and what patients want. So people are going to be looking for, efficacy, a number 1, efficacy and whether it can be put in a regimen of care not going to create a burden of work.
So you can, which itself will decrease inflammation as well as decrease inflammation. People will use it in ResMed secure. As I said, they might use less over time, but that's fine. We're going to have more patients who use more proactive therapy, as I call it, treating to keep inflammation from coming back and that's fine. They only need a small amount of product for that.
That's marvelous because it decreases the burden. People are trying to minimize the disease, but they also want to minimize the work thing you can do to do that. So you want an effective, of product that were rated. I think that's very important.
Jim? Yes. And the only thing I have to add, I think that's a really good description. I think the only thing I have to add to that is that our cream itself is very cosmetically elegant. It's vanishing.
It doesn't leave any tacking as they're seen. So I think, I think patients will find it very acceptable from a cosmetic perspective, aesthetic effective. So, but I think Doctor. I can tell it's absolutely right. I mean, I think ultimately, it's really going to be finding something that works for the disease to provide that both the acute, but also the long term control.
And obviously, if you have a percent of your body of surface area involvement, a topical doesn't make a lot of sense. Because it's very impractical to ladder yourself up in such large areas. But I think for the vast majority of AD patients, I think a topical product makes a lot of sense. And it's probably, as Doctor. Eckfill mentioned, in his presentation, still where the greatest unmet need is.
So with that, I'll turn it back over to Kevin.
Thank you. We've reached the end of our question and answer session. I'll turn the floor back over to Mike for any further or closing comments.
Okay. Thank you all for participating in the call today. The IR team and I will be available for any follow-up questions that you may have. I know we weren't able to reach all of the analyst questions that were pulled for. I'm sorry about that.
But for now we'll close the call. Thank you.
Thank you. That does conclude today's teleconference and Webinar. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.