Greetings, and welcome to the ruxolitinab cream phase 2 data in Vitiligo webinar and conference call. At this time, all participants As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Mike Booth, Head of Investor Relations. Please go ahead, Mike.
Thank you, Kevin. Good morning, and welcome to our conference call and webcast to discuss Vitiligo, the disease, the medical need, and the biological rationale for JAK inhibition, as a potential therapy. We will also provide some highlights from the presentation of the phase 2 data from ruxolitinib cream as a treatment for patients with Vitiligo that were presented at the World Congress of Dermatology over the weekend. The slides used today is in today's webcast, are available for download on the Investors section of insight.com as are the full data slides as presented in Milan on Saturday. I'm joined on the call today, not only by Herve and by Jim Lee, our Head of Information And Auto Immunity Development but we're also delighted to welcome Doctor John Harris from the University of Massachusetts.
Doctor Harris is a world renowned expert in Vitiligo. He is an associate professor and vice chair in the department of dermatology, and the director of the Vitiligo Vitiligo Clinic And Research Center, at the University of Massachusetts Medical School. Hervea will begin the call today with a few opening remarks before Doctor. Harris provides us with some important context On the disease of Vitiligo, the evident unmet medical need and the rationale and potential for JAK inhibition to be the first approved therapeutic for the disease. Jim will then provide some highlights of the ruxolitin and cream phase 2 data set before we open for your questions.
During the question and answer at time of the house. Before we begin, however, I'd like to remind you that Safe Harbor rules govern our remarks today and any forward looking statements that we may make. I therefore encourage you to review the risk factors detailed in Insight's SEC filings including in our Form 10 Q for the quarter ended March 31, 2019. And we'll now begin the call with
Thank you, Mike, and good morning, everyone. So, inside clinical portfolio is organized around 3 you know, so we have in oncology targeted therapies and immunotherapy. And several years ago, We give the new group of 10 or 15 scientists to review the use and indication for products coming out of the research and review where they could have, applications outside of oncology. And that was, the goal we gave them saying you have this immuno, impacting type of a mechanism coming from our research, tell us where it could apply outside of treatment of cancer. And that's what gave rise to our information and autoimmunity development group is now edited by Jim D.
Here today is part of the syringe Times organization. So we have small proof of contract trials already underway several indications for our oral JAK and oral delta program. So most advanced programs in this IAI franchise are with cream. So we have phase threes ongoing in atopic dermatitis and are recruiting well, and we'll have data from the phase race in the first half of next year. And now we have a successful phase 2 in City Lago, which is the subject of today's call.
So if you remember, last year, we had an IND there reviewing the full portfolio of insights And this year, and this will be the first instance of that. We want to replace it with more pemetic TCs based on the news flow. So today, we'll be around, the proof of concept in, Vitiligo. And I would like to welcome Doctor Harris to the call to start the presentation.
Good morning, everybody. And thanks, Mike, for that that nice introduction. I, just to remind everybody, I'm physician scientists who studies Vitiligo, I see patients a half day a week in Vitiligo Specialty Clinic, and then I run a research laboratory to better understand what causes this disease. And so, Vitiligo is an incredibly common disease that affects about 1 to 2 in a hundred people. That's a lot of people in the US and around the world.
And half the patients who get a bit of Largo DSO before the age of twenty. So, I'm, as a physician of managing patients over many decades of life, And we have to think about treatment in terms of, of decades, and as a as a scientist, it gives me an opportunity to study this disease over a long period of time. Vitiligo has a lot of disease associations. And so as we studied this disease, we know that, we believe that we're studying other, the mechanisms of other autoimmune diseases as well. So this is a typical presentation of Vitiligo, called Apache Deepigmentation.
This is on the hands. As you can see here, It can become a more widespread in some cases as well. We'll talk about, the the the surface area of Vitiligo and and how it can present in different patients. A little bit later. The great news about Vitiligo is that it it's reversible.
So this used to be a white spot. You can see that there's, repigmentation here coming back as little brown spots. And this is how it rebigments. And the reason why the spots come back as they do is because of melanocytes themselves live within the hair follicle. And, and and so this is where the the Vitiligo repigments from, as you can see here.
You can see, really can get very nice responses. It can take a very long time, however, so this is a patient treated with narrowband UV B top left, to bottom right is over over a year. But she got very nice repigmentation of her neck and chest. And, and and was very happy with it. She said she was wearing lope that dresses again and completely changed her life.
What I'm not showing you is the repigmentation on her face, which was complete. 100% to the point where I could not even remember that she had bit of lago on her face. In talking about the effect of Vitiligo on patients, it it it is huge. So we published paper called Vitiligo is not a cosmetic disease in the title, specifically to call attention to this, because sometimes in the past, it has been dismissed as such. But it it's actually, it's it's a well known mechanism.
It's an autoimmune disease, similar to psoriasis and in alopecia areata type 1 diabetes. We know that these run-in families, and and so we understand the mechanism is clearly at the disease whereas cosmetic treatments are or cosmetic issues are things that we all struggle with as we age, whether it's sprinkles or or thinning the hair, etcetera. And so Vitiligo is in its it's clearly in a separate category in in in the paper, second paper shown there, the burden of Vitiligo, concluded, that Vitiligo is a serious skin disorder when the adverse impact on an emotional state comparable without another major skin diseases. So I think it's clear that that Allego does not deserve a a separate category as being any milder than than the other diseases that we currently treat. On the right, we have a study that looked at Vitiligo patients in psoriasis patients and their quality of life using the dermatology life quality index.
And I like to study because it it's a direct comparison and shows the effect on quality of life in both diseases. And so Vitiligo patients who are affected either moderate to severe to very severe, is 51%. And in psoriasis patients, that number is 56 something. And so they're actually quite comparable in terms of the impact on quality of life, in in both diseases. And so both diseases deserve to be treated.
The unmet medical need in Vitiligo is clear to the poor quality of life. As I mentioned, it's similar to psoriasis, but also eczema. Actually, there are studies that show that the willingness to pay for a cure, from patients is higher in, in Vitiligo than even in Exela. So that's the amount that someone is willing to pay out of pocket security disease. And so it just shows the impact of this this disease.
There are as no FDA approved medical treatments to improve. Vitiligo, there is one FDA approved medication medication called monobenzone, It's a cream that actually makes Vitiligo worse. It's what Michael Jackson used to bleach his skin. And and so we we certainly must do better. We use off label topicals right now, and and they have side effects that we'll talk about, in the next slide here.
So the current bill I got treatments are listed here. The market is segmented and incomplete. We we're not able to take care of all of our patients for But limited efficacy, the the, the burden that it puts on patients in psychotherapy, and I'll show you and then also the the side effects of these treatments. So the oldest treatments that we have are topical steroids. They can be effective, with this con with continued use, they cause stretch marks are streathe and atrophy of the skin.
And dermatologists are very careful with topical steroids. Non dermatologists are actually quite fearful of topical steroids and then refuse to use strong steroids, in their in their practice. Topical calcineurin inhibitors are newer. They don't have, these same side effects as steroids, although they they are symptomatic, they can cause a burning sensation, which has caused discontinuation. They often cause hyper pigmentation around the edge of the border in and and so people have concerns about using them as well.
Narrowband UVB for the therapy is currently the best therapy that we have. But it requires a visit to the dermatologist's office 2 to three times per week for over a year, as you can see, for very time consuming. Very difficult for pay people patients to take time out of their schedules to to do this. And and we have modern efficacy, and we can talk about that. Surgical transplantation is there just for completeness.
It is only for patients with very stable disease, which is a very small population of patients, but we can a transplant to get cells from one part of the body to another as a treatment. But it it only helps less than 5% of the patient population and it is only conducted in three locations in the entire US. So there's not a lot of access to it. And then deep pigmentation I mentioned earlier, this is the the monomensone cream We only use this if disease is very severe. And this is, represents a very small part of the population of Vitiligo.
It actually worsens the disease, and so it's it's not commonly used. So in summary, the current treatment that we have they have pretty significant limitations due to side effects in in in the population, which they are useful. And so at this time, without an FDA for treatment, we we we believe we've penetrated only a very small part of the market where we estimate less than 20% of of market. Next, so I I've put here just my simple treatment algorithm. This is how I treat Vitiligo.
First, I look to see if it's active. And if it is, I give some oral steroids for a short period while we get patients on something else. If it's not active, or after we put on the steroids, we look at the total body surface area. If it's greater than 5% body surface area, then, or if it's not greater than 5% body surface area, we'll use topicals alone. And right now, we have to use clobetasol because it's the most effective treatment that we have, but because of the side effects, we have to use it in a discontinuous manner.
So we will use clobetasol for a week, and then they'll use tacrolimus for a week back and forth, and we continue alternating in this way. Right? It's very confusing for patients, and tacrolimus doesn't have the same the same efficacy as clobetasol, which is why we use it this way. But it it's complicated because we can't use the strong steroids continuously. For for focal disease, we can also consider XMR lasers, a phototherapy option, and as I mentioned, surgery.
If if the body surface area is covered greater than 5%, then, we we strongly consider using narrowband UVB if the patient has access to it. They'll do that. I think they'll, we'll just continue to treat them with topicals in in a smaller area of their body. If they'll use UV and topicals, we certainly do that because we see better efficacy when you combine topicals with UV, And if they're not willing or able to apply topical, then we just use phonotherapy. So the question frequently comes up in this in this avenue, in this venue, how many patients actually have less than 5% body surface area and can be treated with opicals alone?
And so 3 specialty clinics around the world, gathered data including mine, a meat pandy of clinic in Dallas, Texas, and Colin Edeliz Clinic in Paris, And actually, we, we analyzed the, the body surface area of our patients in that breakdown. It was really very interesting in these different areas of the world. We we had very similar numbers. And so the number of patients who had less than 5% bottom surface area was 58% of our So those are patients that we would, most of those patients we would start on topicals alone. And then the remaining population 42% have greater than 5% body surface area.
And those patients, we try to get in onto narrowband EBB photo therapy, but then we also combine topicals. So this is a summary of how we would use FDA approved treatments in the future, assuming we had a topical and a systemic available. First, we would look for signs of activity. If that was if if they were present, we would use a systemic plus topical. We estimate this would be 20% of the population.
If there are no signs of activity, and there was less than 5% body surface area, we'd use a topical alone. That would be about 48% of patients we estimate. And then those without signs of activity be more than 5% body surface area. We would use a systemic and topical again, and that's about 32%. The take home here though is that a systemic would probably be used in about half of patients, but a topical would be used in 100 out of patients.
This is what we do today even. So if I have a patient with widespread disease and I put them on a, honest, on full therapy, full body therapy, we add in topicals as well. And so the, the the those that would be eligible for a topical is is every patient. Currently, therapy for Vitiligo is reimbursed at a high level, even though we don't have, FDA approved treatments We use narrowband UBB. It's reimbursed at $24,000 per year.
Exumer lasers reimbursed at $42,000 per year. And so we do get coverage, for patients, even though we don't have the the approved therapy. The opportunity in Vitiligo, I think, is probably best appreciate it if you compare it to, psoriasis, which is another disease that has grown significantly over the last 25 to 30 years. 30 years ago, psoriasis was in the same place that Vitiligo is now. We were treating the topicals for the therapy, oral immunosuppressants like methotrexate.
Now psoriasis is in the $8,000,000,000 market, shared by 10 to 12 drugs, many of them biologics. And the market is expected to grow significantly in just the next few years. And part of the reason for that is the very highly effective biologics that have now been developed. Psoriasis is, in in 2 to 2 a half percent of the population, but Eligo is similar to that. 1 to 2%.
And so, we we estimate a large unmet need there in the Vitiligo population. And as I mentioned, there's no effective FDA approved medication for this disease. So to introduce the rationale, for targeting Jackson Vitiligo, a put a few slides here on some of our work. We developed a mouse model of Vitiligo early on about 10 years ago where we adaptively transferred auto reactive T cells into a mouse that has black skin and black hair. And over 6 to 7 weeks, we see white spots appear, up here so you can see them on the tail.
They're on the feet, the nose, and the ears of these mice for him to quantify that. The mouse model actually is is a great representation of human disease. So clinical and histological appearance is the same gene expression, which I'll show you in the next slide is the same in mouse and human skin. It's the only mouse model that we have of skin depigmentation, others, haus hair depigmentation, which is a different animal altogether. It's the only reversible model of the liga that we have.
So to be able to to test new treatments that rehearsed disease, we need to use this model. We, have found that ongoing studies, including the one we're gonna today, parallel observations in mouse and healings, and the drugs that work in mouse, working human. The the mouse model is predicted JAK inhibitors that are now in clinical trials that that they would be effective. And, we use this model actually, now for for many companies that are want to perform preclinical testing. So this is the gene expression profiling that we did early on in the mouse and human skin.
Can see a loss of melanocyte transcripts as you'd expect to see in Vitiligo. And then, the other, obvious, pathway that's turned on is is interferon gamma and the interferon gamma induced genes. So we see nothing from the type 17 immune response or the type 2 immune response. And this is where we have psoriasis drugs and dupilumab for atopic dermatitis. And so this really predicts that those drugs would be ineffective for Vitiligo.
And that's what we find. So at least psoriasis drugs have been thrown at Vitiligo many times, and and they're completely in So we we need drugs that target this, interfer gamma pathway, which is the vitiligo specific and relevant pathway. So we had based on this data, we hypothesized, that interferon gamble is really the driver of this disease in mice. We found that was true. So if we knocked down an interferon gamma, the receptor for that, we were able to prevent Vitiligo and mice.
If we knocked out a downstream, chemokine CL10, which on the previous slide is one of the highest expressed. GAMA induced genes, we also found that that prevented disease. But probably more importantly, we found that even if we let disease So this used to be a black tail on the top, turned completely white, through Vitiligo. And then we blocked CXCL10 or interferring gamma or other things within antibody, we found that the the the picnic came back. So we got very follicular reconmentation.
On the tail, as we see with with treatments in humans. So we're very excited that we had identified the key pathway that drives Vitiligo. And and so, summarized here, interferon gamma initiates the pathway, cygnus d, the interferon gamma receptor. JAKs 1 and 2 are required for a intracellular signaling through this receptor. They activate stat 1 and then turn on chemokines, 6, field 9, and 10, and others.
That signal through CXCR3 and recruit more T cells to the skin. And so this creates this positive feedback loop that drives the progression of Vitiligo. So we have found, over the last, 10 years or so that when we knock out interfer gamma, the receptor, stat 1, the chemokines, or the receptor for those chemokines, able to prevent disease really indicating that this pathway is important to to development progression of Vitiligo. We've also found that if we use antibodies, to to the soluble factors of the receptors. We can not only prevent disease, but we can reverse it, which is fantastic and and and clinically relevant.
And then, most importantly, for today, we found that JAK inhibitors are effective in our mouse model, and I won't take the time to show you the data. Have not published that data. They're they're highly effective in the model, but it'll prevent and reverse disease. Next, we we we put ruxolitinib, oral ruxolitinib in a patient's the Vitiligo I see here. On the far right, you can see before and after treatment, 5 months of treatment, the amount of repigmentation he He had almost nothing left on his face, and he he's nearly completely repigmented in in just a few months.
This was about 50% improvement, actually. And and we found, we had saved up his serum over a year, before this treatment, and we found that it's CF field 10 model, but, you know, for again, I'm just KeatonKine, was very high and stable for over a year in this patient, until he started the Resolute NIM treatment and then it dropped. And so not only did we see that ruxolitin was affected in a patient, but we saw that, it seemed to be working the way we hypothesized with, blocking interferon game and dropping the the chemokite. And so this is allowed for, this in in other clinical studies have allowed for 3 ongoing clinical trials right now up by Aclaris Insight in Pfizer. We're talking about Insight today, which is the furthest along by far.
And and so we have one more question because those were systemic therapies. We wanted to know what a topical JAK inhibitors, would be effective for Vitiligo. So we're back to the the Interfer And Game of Pathway. And the way we tested whether topicals would be effective, definitively and mechanistically was to, to look at stat 1. So we were able to remove stat 1 genetically, only from keratinocytes in our mouse model and then ask did this have any effect on saliva?
So the keratinocytes, the question is whether the keratinocytes played a role in driving disease. So this is how we did it. We put T cells into the black mouse again. To the black mouse, we're able to completely remove interfer gamma signaling by removing stat1 only in keratinocytes. And what we found was, if the keratinocytes cannot respond to interferon gamma, we were able to, significantly protect from disease development progression.
So this indicated to us that all we have to do is turn off interfer gamma signaling in keratinocytes alone and we could have a big effect on disease progression and develop a treatment. So this is what topicals do. Topicals hit the keratinocytes first. And, David Rosemarin, at Cops sees this as as rationale to perform a small topical clinical trial. That was published in the JAD 2017 where you saw significant repigmentation, through topical treatment with ruxolitinib.
That's the end of my presentation, where I'm ready to trans transfer this back to, to insight. Great.
Thank you, John. That that was a great presentation. What I'd like to do now is to provide some highlights of, the presentation by Doctor David Rosemarin at the World Congress of Dermatology. He presented the phase 2 data, this past Saturday and like to do is provide some of the highlights, of his presentation. I think, as, Doctor Harris mentioned, this was the 1st large randomized study, in Vitiligo.
And on the next slide, it provides a very high level overview of the study design and some key inclusion at the exclusion criteria. We evaluated 3 concentrations of ruxolitinib cream, the 0.15 the 0.5 and the 1.5. With the highest concentration, the 1.5% concentration, We tested both once a day and typed twice a day, and we compared it to vehicle cream. And, and and that portion of the study, again, the comparison against vehicle cream was done for 24 weeks, and that's the data that we're sharing today. After the 24 week visit, all the patients were crossed over to active therapy.
They're crossed over to either continue with the the 2 higher concentrations the 3 highest dosing cohorts, and then vehicle patients and, patients on the lowest concentration were crossed over to higher concentrations. At week 52, all of the patients were started on the highest concentration of Rux Cream, the 1.5% BMED. In terms of some of the key inclusion exclusion criteria, we we tested Luxolitinacream in adult patients with Vitiligo. They had to have approximately half of palm, body surface area involvement on their face, and at least 3% of their total body had to have, vital item. We we excluded patients, that had other skin conditions that would have confounded any of the evaluations as well as uh-uh screening them or at least requiring a washout period.
For previous therapies, of their Vitiligo. In the next slide, we highlight the key demographics and clinical characteristics of the patients that were enrolled in the study. You could see the average age was approximately forty eight, about a fiftyfifty split between women and men. And in terms of Fitz Patrick's skin type, about a third of the patients, were darker skinned individuals, Fitz Patrick 4 through 6, a third of Fitz Patrick skin type 3 and a third, just Patrick's skin type 2. In terms of the the disease, the doctor doctor Harris mentioned, some of the the clinical characteristics of patients that he sees.
I think the the clinical characteristics here provide, a view of the of the patients that we're enrolled in this study, the total BSA involvement was 22. So 22, that mean, a percent body surface area involved was 22%. So so quite a high number. In terms of the length of disease that the patients had, the median duration of disease was 14 years. And doctor doctor Harris mentioned that there are other autoimmune conditions associated with Vitiligo.
We had about 25% of patients who reported another autoimmune condition. And in and in terms of of prior therapies, about half of the patients had been treated with topical corticosteroids, another half treated with topical calcineur inhibitors, and about a third of the patients had received prior phototherapy. On the next slide, we present the primary efficacy variable, which was the facial Vazee 50 response. So of patients who achieved at least a 50% improvement from baseline in their facial Vazee score. Couple points to highlight.
One, as you can see, you can see over time, the response continues to improve and get better. But interestingly, see, responses early as week 8. And then at week 24, we see that the the best response are in, the 2 highest dosing group the 1.5% dose once a day and the 1.5% dosed twice a day. One of the things that we've heard from feedback, and I think Doctor Harris mentioned, is that both physicians and patients truly want the best response for the Vitiligo as possible. So another efficacy variable that we looked at was the Vazee 75 score, which is shown here on this slide.
And and this is that the proportion of patients who experienced at least a 75% improvement in their Vazee score from baseline. And again, you see the same pattern you see the response show up fairly early at week 8 and improve over time. And in this case, you see that the best response was seen in the group that was dosed with the 1.5% cream dosed twice a day. In about 30 percent of the patients achieved a facial Vazee 75 at the week 24 time period. In terms of the safety that was observed in the study, that's pilot here in the next slide.
We see that, rux Cream was very well tolerated. We do see, some reports of acne. In the study, a low a low percentage, but, and none of them led to discontinuation from the study. Patients also reported some itch, both at the application site and at other body parts. In terms of the discontinuation, we had only 3 patients who discontinued due to adverse treatment events We had, one patient, in the vehicle arm and one patient in the lowest concentration, the 0.15% Cueday arm that this continued due to headache, and we did have a, serious adverse event, occur in the 1.5% the ID arm However, that was not, related to treatment.
The patient actually injured himself, and and had to withdraw, from the study. So overall, very well tolerated, in the 1st 24 weeks of treatment. So in the next slide, it's just a very high level summary and the conclusions that that we see from the study. We see that significantly more patients achieve the facial VISTA 50 improvement. After 24 weeks of treatment, we're forced to let them cream.
In terms of the specific arms that that, achieved the best response, we see that the 1.5% those twice a day and the 1.5% dose once a day, both were significantly, better than vehicle crane In terms of the facial Vazee 75, again, the higher, more robust endpoint, we see that 30% of the patients and the twice a day arm and, 16 or 17% of the patients in the the once a day arm, we're able to achieve a 75% improvement. And the facial body score at week 24. And again, from a from a safety perspective, we saw that the rux cream was very well tolerated. In terms of next steps, obviously, we're very excited about the data and we're, we're moving very quickly to initiate the phase 3 study. We hope to, start the study sometime this year.
And then, depending on enrollment, have the results sometime in 2021, with, with, hopefully, a submission at that time point. Hello, Kevin. That that ends our prepared remarks. If you could, please give
the instructions for for Q And A. Thank you.
Absolutely. We're not picking up any question and answer session. If you like to be placed in the question queue, please press star 1 on your telephone keypad. We ask you to please ask one question and one follow-up. A confirmation tone will indicate your line is in the question queue.
For participants using speaker equipment, maybe necessary to pick up your handset before pressing the star keys. We do ask you to ask one question and one follow-up then return to the queue. Our first question today is coming from Brian Abrahams from RBC. Your line is now live.
Hi, thanks very much for taking my question and congrats on the data. I was wondering if you could talk about any interim results you saw on T Gazi scores? Any reason to think that would trend differently? And do you have clarity from regulators on what registrational endpoints might be, and I'd love to hear doctor Harris's views on on that as well. Thanks.
Sure. This is, this is Jim Lee. Great question. So I'll start with your second question around the regulatory endpoints and say that we are working with, both the FDA and the EMA to finalize the phase 3 study designs and, we'll share those shortly when we start the studies. In terms of the total BOSI, we did collect, obviously, total BOSI, as I mentioned, the average our body surface area was about 22%.
Patients were, we were restricted to treating only 20% of their body, and and we did collect the treated areas, and we'll we'll provide that data at a future scientific meeting.
So, Eric, if you'd like to add anything?
Yeah. Yep. Copy to to to add to that. So, In terms of the total improvement that patients are looking for, we've published this, we've asked, we've done, panels with patients asking them kind of how much improvement they want, and they consider 75% improvement, successful. Successful therapy.
So, but that is not 75% at 6 months. It it's 75% of by a year or more. Ultimate improvement, they want 75%. They said that they would be happy with 25% at 3 months as long as they know that they're they're gonna get more over time. So in this study, we found that 30% of of the treated patients in the highest group actually achieved a successful treatment in only 6 months very fast.
And, and then the VASC50, with its upward projection at 6 months, we fully expect the 52 week data, I would anticipate gas just based on the the traits in that, it would improve significantly. So I think we're completely within the realm of what patients want. Thanks so much.
Thank you. Our next question today is coming from Mark Frahm from Cowen and Company. Your line is now live.
Thanks for taking my question. Maybe, Doctor. Harsh, who can follow-up on that last question in point. I think in your studies in talking to patients ourselves, we see there is kind of a range of goals for patients. Could you talk a bit about kind of if you could bucket the patients into the ones that are willing to accept say, 50 to 75% versus people who really want, you know, how many patients really want just full or near full repigmentation before they would want a therapy.
Yeah, there is a range, of patients. So some patients are very demanding and they say, you know, it's 100% or nothing. They're the minority for sure. But but the good news is actually that the face is capable of responding to a 100%. And What we see is is the response, extensive response really varies by anatomical distribution.
And so as I mentioned earlier in my talk, the the refigmentation comes from the hair follicles. And so what we find on the on the body is the areas that have the highest density of hair follicles respond, the fastest and the most complete to therapies, any type of therapy. The face has the highest density of hair follicles. And so the face actually is capable of responding a 100% as I mentioned in in in my patient and what frequently happens, is after after a successful therapy, I'll forget that the face actually ever had vitiligo. So so that, unfortunately, is the most important patients that their face is usually the most important area, and that that location is capable of responding a 100%.
At the same time, there are other areas that that don't respond at all. So fingertips with no hair follicles or or the underside of the wrists in a very few other places that have no hair follicles typically respond 0%. And so what what patients need to be educated on in their expectations set about what can be expected. The good news is even the patients who want 100 percent, the small number who who demand that that much representation, can get that on the on the fixed that is achievable. You know, they'll usually usually take a year.
But patients, the good news too, is is after 3 months, they've got 25% regigmentation. They're on board. They're excited. And they'll treat for a full year to get the to achieve the full effect. So that it's not that it takes a full year to see anything.
We see improvement early on. And that that continues at a pretty, slow cliff for the whole time.
Thank you. Our next question is coming from Tyler Van Buren from Piper Jaffray. Your line is now live.
Thanks guys. Good morning and congrats on the data. It looks great. I guess, more of a commercial question. Can you guys speak towards your potential capacity to launch and strategically how you would do that, and how much resources you'd have to put forth upfront and how you would change that over time.
And just briefly, maybe as a follow-up, is there the ability to price differentiate in Vitiligo versus atopic derm?
Okay, thanks. I'll take this one. So, starting with your last question on the pricing, obviously, the phase threes are ongoing already for atopic dermatitis. There are 2 different concentrations that are are tested in the phase 3. So when we'd be able to answer that, and we don't I have not yet started the the first really meeting I go.
So that's something that is discussed. So when we see the different concentration, then we have a question of the size of the tube in some way. And the and the and see if it will be easy or less easy to have a a price, differentiation when we when we know the result of the history, at the big Regarding the commercial aspect, so obviously, we are, seeing this as a very significant opportunity for inside. In the case of Vitiligo, it is treated by specialists, mostly, or entirely. In fact, and the and the commercial deployment that will be feasible from the financial standpoint very different in Asia, Europe, and the US.
So the way we look at it is, Italy, 3 different analysis that we are doing the program in terms of development is targeted at each of the 3. And then we have to answer the question of saying, what does make the most sense to make optimize this opportunity in Asia, in Europe, and in the US. I can tell you from the US, that the number of people that would be required for launching it indefinitely is around 200 and that will include, like, commercial and medical affairs and the the team required to do it. So in terms of resources, it's something that is somewhat feasible and we are, going to get an answer, so precise answer to the question more or less on time so that when we do the submission, next year or when we get the results in atopic dermatitis, we will we will have a full commercial deployment plan in place. At this stage, we we keep everything open in somewhere as we are trying to, to see that, you know, what what would make the the most sense there is.
Obviously, a probability of going alone and being able to book the revenues that is higher for the US. Probably lower for Asia, which is a very complex market in the field of dermatology. And we are still, not sure exactly how it's going to end up for Europe, but that would be the the picture I would I could draw today is a higher probability to go on in the US or to go and book the sales, lower in Asia, and still, deductible for Europe.
Great. Thanks so much.
Thank you. Our next question today is coming from Evan Siegelman from Credit Suisse. Your line is now live.
Hi, all. Thanks for taking the questions. When I look at the F Bazi 50 score, I see that there's not much of a difference between the once daily and twice daily at the 1.5% dose. However, and you look at the 75, you see a much greater, separation. Is it practical patients to apply this twice a day and actually adhere to that longer term to get that 75% resolution.
And then my follow-up is you know, we have this pretty encouraging data set. What do we actually need to see in a phase 3 for regulatory approval? And why is this data set not sufficient given the unmet need in Vitiligo. Thank you.
Oh, those are those are great questions. And maybe I can ask doctor Harris to to address the question around what patients, would need to compare, you know, comparing the VASI 50 to the VASI 75.
Right, in in the in the practicality of the ID dosing. So, yeah, I I think I I'd go through this every week when I see patients in the clinic. I explain to them, you know, what the application. So we use all top I use all topicals, at BID dosing. So everybody's using topical steroids and topical, calcineurin inhibitors at twice a day.
They don't always keep up, every day. And I tell them once a day is better 0, twice a day is better than 1, and they're usually very happy with that, and they're motivated. And so the majority of my patients actually follow the the application of twice a day. If you get the results they want.
And to your second question regarding the FDA, just maybe could you clarify, I I I understood it as, was there a thought of of of of submitting this data rather than then moving I don't
know if the truck's
really thought of submitting this data, but it's more that it seems that there's such a high unmet need in Vitiligo. I guess, what would you need to see in the phase 3 trial? And would there be any situation with this data set could be used for some sort of accelerated approval?
Sure. And and I I can speak to the regulatory requirements. Sure. That'd be great. Sure.
So so in general, you know, obviously, for a phase 3 program, you do need to show statistical significance, difference between the the active arm and the vehicle arm. But in addition to that, you you also the the FDA typically wants to look at response over time. They want want to look at durability of response, and very importantly, the safety, of a treatment over time. And so all of those components need to be included in a submission. And, obviously, this is a a great study, a very robust study, but it was a 100 97 patients.
And so we we are including it and we'll have long term data, but I think we need to expand the patient data set to increase the reliability as well as, look at a larger patient population from a safety perspective.
All right. Thanks so much for the questions. I appreciate it. Can I have one more comment just in terms of the practical aspect of applying the cream? So what we currently have available in steroids and protopic is, that they're an an ointment base in order to get the efficacy that we currently have.
It's a very thick ointment, like Vaseline And patients really they they apply it. They do it, but they don't enjoy it. They they that the biggest complaint about using these treatments that I didn't mention in my slides is how greasy they are. And the great thing about the new pre and the ruxolitinib cream is that it is indeed a cream and not an ointment in the subject to actually really prefer the And I think that so if anything, I think they'll be more willing to apply this twice a day than what we currently have.
Right. Thank you.
Our next question today is coming from Michael Schmidt from Guggenheim Securities. Your line is now live.
Hi. This is Kelsey on for Michael. First, I guess we're just kind of wondering in terms of the FS VAC E50 dose response, It looks interesting and that there isn't really clear separation until week 12. I guess what are your thoughts on that? And then follow-up, I guess, what kind of duration of therapy should we expect should this hit the commercial setting?
Thank you.
Sure. And I can address the, the F Vazee. The F Vazee, was developed, a number of years ago. And in the publication, there you know, one of the limitations is that it's a fairly blunt instrument. And so with the 50% improvement, you know, one of the reasons why we're we're likely not seeing a large separation between the the various dosing arms, especially the point 5 Q Day and the BID is is the the sensitivity of the 50% improvement versus the sensitivity in the 75% improvement.
So if you if you actually look for a more robust endpoint, you can really clearly see the dose response, between the various dosing groups. So it's, I think, effect of the the 50% improvement versus the 75% improvement
I can comment on the duration if you'd like. The the expected duration of therapy. So, you know, I I fully anticipate, that most patients will be on a year of therapy, in order to achieve the results that they want. The, there are 2 options after that in terms of the potential for relapse and and so patients currently with current therapies, at least, and we and we don't know, the rate of relapse that will occur with this drug. But with the current therapies, patients have a choice of either stopping their therapy once they achieve what they've they've been seeking to achieve and then waiting for relapse, which may happen a year or 2 years or later, and then restarting the therapy.
So a lot of patients do that. I also have patients who who really never wanna see a white spot again, and they use a a maintenance therapy, of topical application, instead of twice per day, twice per week. And I would anticipate that that would be an option here as well. So patients for the rest of their lives could apply, a topical just twice per week. To maintain, to maintain their their their benefit.
And the only the only thing
I would add there is that, those are all very important, clinical endpoints that that patients and, physicians would like to see. And we are, we are trying to, integrate as many of those
into
Thank you. Our next question today is coming from Alethia Young from Cantor Fitzgerald. Your line is now live.
Hi. This is Emma on for Alethia. So in the commercial setting, would you expect patients to continue receiving photo therapy or other treatments in addition to Rec Cream? And if so, I guess, how would that factor into pricing and reimbursement discussion?
Maybe, John, you can address the thoughts around combination therapy. And, and then perhaps we can, we can try to address the, the pricing issue.
Sure. Yeah. So the the way we use topical now as I mentioned in the slides is is we like to use them, in combination for patients who have greater than 5% body surface area. If patient comes into me, with less than the 5% body surface area, which is five hands worth of Vitiligo all over their body. Then we'll start with just topicals, because it's practical to be able to, a practical amount of skin to be able to apply topicals to play today.
Beyond 5%, it's just too much body surface area. So so the majority of patients have less than 5%. So we would use topicals alone there. If they have greater than 5% body surface area, we would wanna put them on on phototherapy as well, because otherwise they'd have to bathe in the cream. And, as I mentioned though, we get better responses with current, topical and phototherapy than phototherapy alone.
So I would anticipate, we're using them in combination for the subset of patients that have widespread disease.
And for, what are their benefits
on this one? Thing. Maybe I can I can say what? I mean, I was just saying we are in the process of working on the how it would, it could be covered in the, I think, for the US and Europe, we are we are we are in that in that process. What we know is that photo therapy is Sally well reimbursed, and it can be up to $24,000 a year.
And, and, obviously, the question will be for different types of patients, how many of them would be using combination of the 2 versus single agent with the cream. Of course, the view is that the medical need is well understood. It will be first approved product for this, for this condition. And we think, we think reimbursement, you know, would be achievable. I mean, it would take certainly some some evidence, to to get there, but we are we think it would be well covered at which level is certainly something we will not discuss till the day of the launch of the product.
Just to add one more thing to that in terms of practicality. When we add phototherapy and patients continue on topicals, they usually are not treating a large body surface area. So patients will often, when they go on phototherapy, they may just treat their face and their hands at that point. And so they they would probably use less cream if they're on phototherapy until the total reimbursement might end up being similar.
Great. Thanks.
Thank you. Our next question today is coming from Salveen Richter from Goldman Sachs. Your line is now live.
Yes. Hi. Thank you for taking the questions. This is Mariana Breichman for Salveen. I have a quick question.
In the study, the median duration of disease was 14 years. Do you think it will be advantageous to start treating earlier in the course of the disease? And also, do you get any additional benefit from some kind of for the therapy or a life therapy? I mean, would the great exposure to life have an effect of characteristics being reprocessed. Thank you.
Sure. Maybe Doctor. Harris, John, could you handle that?
Yes. Sorry. Can you repeat the question again? I had it. And then I was ready to go on the second question.
Yeah. So the duration, the median duration that we saw in this study was 14 years.
Oh, right. Yeah.
And if we saw, patients with, with less, longer, you know, lower durations of disease with, I think, What do you think would be the impact, if any, in the Phase
III study? The good news here,
and it confirms what we've seen previously, that the duration of disease itself does not indicate, the response to treatment. So I've had patients with 20 year duration disease respond just as well or better than patients with shorter disease duration. Certainly, there there's a huge advantage to starting early. And it's not because of the binary response, the treatment will work. Or not work, if it's treated earlier late.
But, really, the amount of body surface area affected directly correlates with how long disease has been present. So if you've had the news for 10 years, you're gonna have much more body to treat new pigment, than than if you started earlier, And then also, remember, some parts of the body don't respond to treatment. And and so those can be protected if started early. And cannot be if started late. There is, like, a clear, result, though.
So it's, so, the longer duration of disease, the more likely it is that the hair growing in the stock will also turn white. And when that happens, we generally don't see repigmentation. So there's that risk. It's more of a binary if you had disease for 20 years, it's more likely that the the hair within your spot will be white. And in that case, you won't respond.
But if you've had disease for 20 years and the hair is still pigmented, then there's no problem.
Great. Thank thank you for that. And I can address second part of that question around, the the potential for, combining light pair view, ruxel and the cream, into phase 3 studies. I I can say that the the phase 3 programs will be designed as monotherapy. So ruxolitinib cream versus vehicle But, but, obviously, we're thinking about, future studies beyond the phase 2 program, that we'll look at a combination of rux Cream and light.
Got it. Thank you.
Thank you. Our next question is coming from Matthew Harrison from Morgan Stanley. Your line is now live.
Hi. This is Costa on for Matthew. Can you elaborate a little bit on, the double selection for phase 3 And the how high the batteries for success in phase 3? Thank you.
Yeah. At this time, we're still finalizing phase 3 program. We'll we'll obviously have that with the press release, but also in clinical.gov. The details release then, but at this point, we can't comment on it.
Okay. Thanks.
Thank you. Next question is coming from Carter Gould from UBS. Your line is now live.
Hi, this is Andre on for Carter. Thanks for the question. How does the phase 2 data shift? How are you thinking about your inflammation in autoimmunity portfolio and strategy around business development, both from an in licensing and out licensing standpoint.
Yes. I asked exactly that and we can, we can, you know, discuss it. The way we we started this program was really agnostic to any indication. We were really working on the biology, where does it make sense, where there's a medical need, know, you see it in a great example of a, you know, sort of the strategic aspect of it. And when we reach proof of concept, which is what we have done now for both at the big derm and Vitiligo is where the question becomes, like, do we partner this?
Do we find somebody who would be better, fitted to, to, to, to make it a success in phase 3 and then on the commercial side? So as you have seen for the Durham and Vitiligo, we decided to do the phase 3 ourselves. And now we are at the stage where the same question comes up for the commercial side of could we have, benefit from some help, or could we benefit from, like, something out of the the project? As I said, there is so much value we can see here that we are looking at it, you know, for a good period of time. And we are also looking at how we could do it ourselves.
And for other indications, and you could see from the the list of the ongoing talk studies, we will be going through the same process as we see the data coming. We have studies ongoing in the United States. We have studies ongoing in in maletic anemia, in a TS, in Shogram. So all of that will be, subject to a very specific maximization, business development, kind of, approach and there is no rule that applies to all of them. It will be a week in my case.
Thank you.
Thank you. Our next question is coming from Pete Lawson from SunTrust Robinson Humphrey. Your line is now live. Mister Lawson, perhaps your phone is on mute. Please pick up your handset.
Thank you. Doctor Harris, just on
the on the drug when it's
if it's approved, what percentage of your patients would
you think about using, like, topical looks on? So, yeah, I I think as a assuming it's FDA approved treatment, I anticipate that the coverage will push us toward toward that toward that drug. Right now, it can get to my denial for coverage. It's it's because there's no approved drugs for Vitiligo and everything's being used off label. In terms of the looking at the efficacy and side effects, I think that it would be very high on our list.
If covered, I I I would anticipate going straight to to rocks, you know, if the insurance companies didn't require us to go through other drugs first. And I think it would be hard for them to do that because there are no FDA. You know, if it's the only FDA approved drug, it'd be strange them to say, well, you have to try all these offsetable things first, although we just don't know what their what the insurance companies are gonna say. The the efficacy of this is is you know, my estimation much better than any of the topicals that we currently have, and the side effects certainly much lower than the other other topicals that we have. You know, the side effects really in my in my view, for the drug, at least, are limited to acne, which is was pretty well tolerated.
10 to 15% of patients had had acne really only as a side effect, and and then the remaining had none. So I I think that this this the safety profile, the efficacy profile is is so good here, that if we can if we can get coverage, then that it would be one top, if not the first.
Thank you. Our next question today is coming from Jay Olson from Oppenheimer And Company. Your line is now live.
Good morning. Congrats on the data, and thank you for taking my questions. I had 2 of them. At the beginning, you described the quality of life impact. And I was wondering if there are other long term, dermatological or systemic morbidities associated with Vitiligo it's left untreated.
And then separately, I think you mentioned there are 2 systemic therapies in development for Vitiligo And I was wondering if you could please talk about the pros and cons of a topical treatment for Vitiligo versus a systemic therapy. Thank you.
Sure.
Go ahead. Is there a problem?
No. I'm sorry, Doctor Harris. Do you wanna take both of those questions for us?
Yeah. In terms of the the topical versus systemic, okay. First, I I think that it's It's important to have both. As I mentioned, just the the extent of disease really dictates the need for topical and systemic. And honestly, I think we need both.
And so for for, small areas of disease, we love the the side effect profile of a topical and and and feel very comfortable with that. A systemic would would, you know, we really eventually, I think, need for the widespread disease, which is a minority of patients, or or patients with rapidly spreading disease and active disease. So I I really think there's a need in a place for both. And then sorry. Can can someone remind me of the first question?
Yeah. The first question was, the they were,
quality of life measures indicated, but what are the other Oh, right.
Yes. So for patients and their family members with Vitiligo, they're at a much higher risk of developing other autoimmune diseases and particularly Hashimoto's thyroiditis, so about 15% to 20% of Vitiligo patients that develop Hashimoto's, which is unrelated to the Vitiligo. So if you treat the Vitiligo, we we don't necessarily know that that will affect the shimotos, although, in serving out a topical, but a systemic might might be able to decrease the incidence of that. In addition, what's more directly related at Alaga, we think, is a hearing loss in patients. So there are probably 4 to 6 studies that have been done in the Alaga patients looking at hearing loss and and showing that there's a greater incidence of hearing loss in Vitiligo patients.
None of the individual studies was was very well done or, in a large proportion are well controlled, but just a number of the fact that all all 4 or 5 of them are are 6, show that there's some hearing loss is a good indication that that's true. There is some vision loss as well. Again, the data is weak but there are a couple studies out there suggesting that long term Vitiligo predisposes you to worst vision as well. There are rare forms of Vitiligo that clearly affect vision and hearing, patients with, syndrome called VOKoint. I mean, Gerata Syndrome actually can become blind, from this very severe form of at Allego.
But I've I've only seen one in my career so far, so it's very rare.
Thank you very much.
Thank you. Our next question is coming from Stanley Lee from SVB. Your line is now live.
Hello? Hello?
Hello. This is Ganley for, and the veterans. Just to have a quick question regarding this study for the follow-up study for the 52 weeks and the double blind data for the 28 weeks for the randomization. When do we expect that the data and how do you expect that the data, is it more like, close to what do we have for this study, or just that's gonna have for info regarding the, the double blind study and open label study. Thank you.
Thanks for that question. We, We plan to to present and share the week 52 data, at a future scientific meeting. And And I I I, unfortunately, I can't comment on the data now, obviously, until we, we present it publicly. So, So just, you have to wait until, the next, scientific meeting where, we'll be able to share that data with you.
Thank you. We've reached the end of
our question and answer session. I did turn the floor back over to Mr Booth for any further or closing comments.
Thank you. Thank you all for your time today and and for your questions. We look forward to speaking with you at our 2nd quarter call, in a couple months' time, as well as seeing you at upcoming investor and and medical conferences. But for now, thank you again for your participation in today's call. Thank you, and goodbye.
Thank you. That does conclude today's teleconference webinar. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.