Hello. Good morning, or I guess good afternoon. My name's Mutya Harsch, and I'm the company's General Counsel. Thanks to everybody for coming today. I have to read this disclaimer because we are being recorded, and this webcast is going to be recorded and posted on our website. Hopefully, I don't have my glasses, but welcome to Foamix's R&D Day. To the extent that statements contained in this presentation are not descriptions of historical facts regarding Foamix, they are forward-looking statements reflecting management's current beliefs and expectations. Forward-looking statements are subject to known and unknown risks, uncertainties and other factors that may cause our industry's actual results, levels of activity, performance, or achievements to be materially different from those anticipated by such statements.
In some cases, you can identify forward-looking statements by terminology such as may, will, should, expects, plans, anticipates, believes, estimates, predicts, potential, intends, or continue, or the negative of these terms or other comparable terminology. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding the timing of anticipated clinical trials for our product candidates, the timing of receipt of clinical data for our product candidates, our expectations regarding the potential safety, efficacy, or clinical utility of our product candidates, the size of patient populations targeted by our product candidates, and market adoption of our product candidates by physicians and patients, the timing or likelihood of regulatory filings and approvals, and our revenues under our agreements with our licensees, including LEO Pharma and other companies.
Although we believe that the expectations reflected in the forward-looking statements are reasonable, various factors may cause differences between our expectations and actual results, including but not limited to unexpected safety or efficacy data, unexpected side effects observed during preclinical studies or in clinical trials, lower than expected enrollment rates in clinical trials, changes in expected or existing competition, changes in the regulatory environment for our product candidates and our need for future capital, the ability to protect our IP, and the risk that we become a party to unexpected litigation or other disputes. Please check our registration statements and our filings filed on sec.gov and also on our Foamix website.
Dr. Hilary Baldwin, Associate Professor of Clinical Dermatology at the Robert Wood Johnson Medical Center , and Dr. Jonathan Weiss, Adjunct Assistant Clinical Professor of Dermatology at Emory University School of Medicine, are participating in today's presentation on behalf of Foamix. Dr. Baldwin and Dr. Weiss were principal investigators in our clinical studies for both FMX101 and FMX103. They are paid consultants to Foamix and are receiving remuneration at their standard rates for their participation today. The trademarks included herein are our property and are used for reference purposes only. Such use shall not be construed as an endorsement of the foam technology or product candidates of Foamix. On that, I'd like to introduce our CEO, Dave Domzalski, who many of you are familiar with. Dave is going to get us started, enjoy your lunch.
Well, thanks, Mutya. That was a tough job for today's session. Again, thanks to everyone for coming. We have a full house, and we have many people that are participating live on our webcast. Thanks to everyone that's dialing in. Looking forward to an exciting afternoon. We are very fortunate that joining us today are two incredibly experienced board-certified dermatologists with significant expertise in the fields of acne and rosacea, amongst a whole host of other dermatological conditions. We have Dr. Hilary Baldwin, who is the Medical Director of the Acne Treatment and Research Center in Morristown, New Jersey, an Associate Professor of Clinical Dermatology at the Robert Wood Johnson Medical Center New Jersey, and was past President of the American Acne and Rosacea Society.
We also have with us Dr. Jonathan Weiss, who is with the Gwinnett Clinical Research Center and is an Associate Clinical Professor of Dermatology at Emory University, and also is a member of the Board of Directors for the American Acne and Rosacea Society. I want to thank you both for taking time out of your very busy schedules to join us today. In terms of the agenda, I have a few opening comments regarding our corporate focus and objectives in the near term and midterm. I will turn it over to Dr. Baldwin, who will talk about the current acne therapy landscape and review our key pivotal data for FMX101. We will then turn the podium over to Dr. Weiss, who will do the same for the rosacea marketplace, as well as review our data for FMX103.
After that, we have Dr. Iain Stuart, who is our Chief Scientific Officer and Head of Research and Development, that will take us through some additional recent data for FMX103 and also talk about our medical communications plans for approximately next year. We will introduce then Matt Wiley, who is our Chief Commercial Officer, who will talk about the commercial plans for FMX101. Dr. Stuart will come back up and give you a high-level overview of some of the pipeline activities that we have. At the end, I will wrap it up, and we will save Q&A for just one Q&A session with both Dr. Baldwin, Dr. Weiss, Dr. Stuart, Matt, and myself. If you could just hold your questions until the end, and then we will have a comprehensive Q&A session.
I believe we will also have the ability to take some questions from those that are participating on the webcast as well. In terms of our objectives as a company, 2018 was an exceptional year for us. We completed successfully our third confirmatory phase III trial in acne, which again, Dr. Baldwin will speak to it shortly. An exciting time for us, an exciting milestone. We also successfully completed our two double-blind pivotal studies for rosacea, and also filed our NDA for FMX101 in acne before the end of the year. In terms of milestones for the companies, these were crucial milestones for Foamix. We are very excited about the past year and very much looking forward to what is in store for us in 2019 and beyond. Obviously, if you take a look at corporate strategies, and I could obviously speak to you about very long-term horizon objectives.
I don't believe they provide a whole lot of value right now. I want to try to keep our discussions tight on what are we doing over the next, call it, 12 to 36 months. Certainly in a near-term perspective, our focus has been, as you know, to leverage the synergies of both FMX101 and FMX103 and to establish our development commercial presence in these acne and rosacea marketplaces. When I took the CEO post approximately two years ago, we had three fundamental areas of focus. One was to execute on our pivotal trials, two was to manage our cash burn, if you will, and then three was to start advancing our pipeline.
I believe the team's done an exceptional job, certainly on all of these fronts, especially the first two, and then now we look forward to providing at least some insight on what we're looking at from developing our pipeline. If I go beyond, say, the next 12 to 24 months, it's important for us to create durability of these franchises, for acne-rosacea, and begin to diversify our portfolio. We'll do that through our own internal developments, and we're also open to selective acquisition opportunities as they may deem be appropriate, whether they be technologies or assets. In terms of our imperatives, it's important obviously, that we establish a very efficient commercial model to successfully launch FMX101 and FMX103, and Matt will talk about that to some extent a little bit later on this afternoon. We've obviously been working to expand our R&D and our drug development capabilities.
Quite pleased with how that has begin to come into focus, especially over the course of the last 6- 12 months. We are clearly looking at identifying complementary markets for product developments, again, using acne and rosacea as, call it, a beachhead and to build off of that. Certainly since we've gotten very positive phase III results for FMX101 and FMX103, the dialogue on out licensed partnerships with other potential collaborators has increased significantly, and these would be for ex-U.S. rights. We also look as we move towards midterm initiatives, I do believe that we have an opportunity, and we will look to advance our development programs, first and foremost, for the next generation products in acne and rosacea. We are also in the process of advancing what I would call adjacent clinical development programs in medical dermatology as well as aesthetics.
We are clearly looking at and doing quite a bit of work in areas such as atopic dermatitis, as well as we believe our platform has a lot of utility for areas such as aesthetics. As I have outlined here in the slide, we'll look to leverage our platform and our development capabilities to expand additional collaborations with partners. For purposes of today's discussion, when we move towards our dialogue around our pipeline activities, we want to focus on what I have here boxed out, is how are we going to create durability for the acne rosacea franchise. We'll spend our time focusing on that. In a future session, we'll talk about some of the other categories that we're developing products for. With that, I'm going to turn the podium over to Dr. Hilary Baldwin, that'll talk about the current acne landscape and FMX101. Thank you.
Thank you. It's a pleasure to be here today to talk about the current acne landscape and the way in which I predict that FMX101 will fit into our acne toolbox. We have quite a few drugs in our toolbox. It's always nice to have a new one, and I think this is going to replace several of the things that are currently players in my toolbox. I'd like to start really briefly going off over pathophysiology of acne, not in any kind of detail, but because I think most thoughtful dermatologists, when we sit down and see a patient in front of us, have this in the back of our minds.
You may already know that the average successfully treated acne patient is on 2.53 acne medications, that shows you that the pathophysiology of acne is multimodal, what we're trying to do is to come at the problem from several different directions so that we can reduce the burden on the patient to the greatest extent. We're thinking about the increased sebum production. We're thinking about follicular hyperkeratosis, which ends up giving you the clogged pores. We're thinking about P. acnes living in the follicles. I will continue to call this P. acnes. Many of you probably know that it's now referred to as C. acnes. I am way too old to change at this stage in my life, I'm going to continue to say P. acnes. All roads lead to inflammation in the acne world right now.
If we think about what drugs we might use to treat those different aspects of this whole process, when we're talking about androgens, when we're talking about sebum production, we're talking about androgens. We're talking about suppressing male hormones with hormonal therapy orally, generally. We can also use a topical anti-androgen if we had one. We don't yet, m any of them are in development. Isotretinoin is a great drug to reduce sebum production. We might think about topical retinoids, maybe benzoyl peroxide, and certainly isotretinoin when it comes to decreasing the clog in the pore. We're going to be thinking about antibiotics when it comes to reducing the P. acnes in the follicle. Isotretinoin also reduces P. acnes in the follicle, not because it's directly antibacterial, but because it starves the little suckers to death by depriving them of sebum, which is what they eat.
It makes them starve to death. The number of P. acnes go down. We used to think of acne as being an infectious disorder, and now we're thinking of it as an inflammatory disorder. P. acnes still plays an important role, but it plays a role mostly in the fact that it causes this whole inflammatory process to occur to begin with and maintains it. Acne process now is considered inflammatory from birth to the very end resolution of every single acne lesion. Inflammation is the name of the game, not anti-infection. All the medications we're looking for, yes, they will kill P. acnes, they will reduce P. acnes concentration because P. acnes leads to inflammation, but they also ideally will be anti-inflammatory drugs as well.
Lastly, we're looking at inflammation again with our antibiotics, with our topical retinoids, which are also anti-inflammatory drugs, and finally, once again, isotretinoin. You can see here why it is that isotretinoin is such an effective drug for the treatment of acne. When we're talking about our antibiotics, what we're looking at primarily is the tetracycline class of antibiotics. To a lesser extent, trimethoprim is also helpful, although you don't hear much about it. It's a very good anti-inflammatory and antibiotic in the treatment of acne. The tetracycline class of antibiotics are highly effective in treating our acne patients, both because it kills P. acnes, but also because of all of these anti-inflammatory activities that it has. It's why it's such an effective medication in both acne and in rosacea, as Dr. Weiss will show you in a few moments.
The question remains, is topical minocycline, what we're talking about today with FMX101, also anti-inflammatory? You're going to see some more information on that in a few moments. I think some of the data that you have seen and will be seeing support the role of topical minocycline also as an anti-inflammatory medication. When a patient walks in the door and I take a seat, and I take a look at the patient, how am I deciding which one of those 2.53 medications I'm going to use on this particular patient? If you ask a dermatologist how long it takes them to make up their mind how they're going to treat an acne patient, probably most of us say maybe five seconds, two seconds, 10 seconds. It's very obvious what we need to treat them with.
The reason for that is that we have an algorithm that we all go over in our heads, and it may be different for each person. For me, the first thing I'm looking at is lesion type. Is the patient primarily comedonal or inflammatory, or is there a combination of the two? If it's primarily inflammatory, I'm going to start thinking about antibiotics, topical and oral, maybe topical dapsone. If it's primarily blackheady kind of stuff, I'm going to be thinking about topical retinoids. If it's both, I'm going to need both medications. I'm looking at the number of lesions, the size of them. We could have 100 tiny little papules, and I'm going to pick a different treatment than if I have 10 big, huge inflammatory lesions. Then I'm going to, in my mind, put them into mild, moderate, and severe, comedonal, inflammatory, or both.
That's how the decision is made so quickly. Location also matters. Is it face only, or is this chest and back and arms and face? At which point, using topical medications gets very cumbersome. Am I going to use 2.3 on the face and a different 2.3 on the back and chest? That is never going to happen in real life. You're not going to get those prescriptions filled. The patients are never going to use them. That's when we start to think about using oral medications, for example, to take care of all of the problems with one particular drug. Presence or absence of scars is very important, both psychological scars as well as physical scars. The psychological overlay of this condition is very, very great, especially for our teenagers and our adult females. The physical scarring, obviously very important as well.
We're treating acne both to get rid of the pimples that they have now and to make sure that they don't have scars for the rest of their lives. The last issue, which I've saved for last but is sometimes the biggest issue, is all the baggage the patient brings with them. Is their insurance company going to pay for the treatment that I thought of in only five seconds? Do they play a sport where the use of the topical medication is going to be a problem? How do they work? What kind of job do they have? Is this a reporter for whom one zit is going to ruin the entire day or maybe even her entire career? Then, of course, patient preference. Some people like pills, some like creams. Some tolerate irritation, some don't.
The patient baggage is often the biggest part of the visit that we have. I've converted this patient into mild, moderate, severe in my head. Here we have a picture of some mild to moderate acne patients. I might consider topical retinoids alone, topical benzoyl peroxide alone, topical dapsone, combinations thereof, and I might even think of an oral antibiotic, especially for the patient on the left. Now, that's where the baggage might come in. If his baggage was, "By the way, my prom is in a month," well, then I better haul out my oral antibiotics because it's going to take a while for this patient to get better with topicals. That's part of this whole decision-making process. A topical retinoid can make this patient better all by itself.
This is from the tazarotene 0.1% cream study originally. You can see at week 12, this patient is dramatically better just with a topical retinoid. That took 12 weeks. Acne patients don't wait 12 weeks to get better. They want results much sooner than that. The next problem, of course, with topical retinoids is often the patients get very dry and very red. Ideally, we would like a topical that works that fast, that well, and does not create this kind of a problem. Benzoyl peroxide's been a workhorse. It's now 80 years old. It's a very old drug. We're still using it as a standalone for inflammatory and, to a lesser extent, non-inflammatory lesions, has a rapid onset of activity, and it's not associated with any antimicrobial resistance. It has a lot of baggage in and of itself. We have concentration-dependent irritation.
About 5%- 10% of patients are said to be actually allergic to it, although I think it's mostly people who are irritated by it, we just never really got a chance to look at whether it's irritation or allergy. In addition to that, it bleaches the heck out of clothing and stains white fabrics. That's a really big problem. Often people poo-poo that, but the patients hate it, especially if you expect them to be putting benzoyl peroxide on the chest and back. You're asking a patient to get up in the morning, take a shower, then to consider, "What color am I going to wear today?" If they're wearing white, they can put on their benzoyl peroxide, if they're not, they can't really. I'm going to ask that of a teenage boy.
That stuff is never going to end up on them. What I'm looking for is a topical that does not cause irritation, does not cause contact dermatitis, does not bleach fabric. When we're talking about moderate and severe inflammatory acne, the current topicals that we've been talking about don't work well enough or fast enough to take care of most of these problems. We're going to be adding oral antibiotics to our topicals. Never oral antibiotics as a standalone. If it's a woman, we might think of hormonal therapy with topicals, we might even consider isotretinoin for this woman. It depends on her baggage. If her baggage includes suicidal ideation, you betcha, I'm onto isotretinoin right away. If it includes scarring somewhere, absolutely, isotretinoin immediately. Let's talk about the oral antibiotics then.
Oral antibiotics, as we said, tetracycline class, usually because it's both antibiotic and anti-inflammatory. They work very well. They give us our fastest onset of activity when a patient needs to look well as soon as possible. We have a lot of systemic side effects with our oral antibiotics, including GI distress, photosensitivity with our doxycycline and tetracycline, vestibular side effects primarily with our minocyclines, hyperpigmentation issues, rare severe side effects with the oral medications, concerns about antibiotic resistance, which is a real issue now in this day and age. We didn't think much about this 10 years ago. We kept them on it for years.
Now the CDC, of course, is calling for us to be better stewards of our antibiotics, I think dermatologists are finally listening to this, we're turning away from the use of oral antibiotics whenever possible. What about our severe nodular inflammatory acne? I was on an interview yesterday with a reporter, all she really wanted to know is what are our alternatives for isotretinoin in patients who look like this. I said, "I'm sorry. We can just stop this dialogue now because the treatment for this patient is isotretinoin, or isotretinoin or isotretinoin." That's what this patient needs, that's what they're going to get if they come to our offices. This is the sort of thing that isotretinoin is capable of doing.
I want you to keep that image in mind when you think about all the potential side effects for isotretinoin, which I would like to suggest are much more perceived than they are real. I think Jon will agree with me that the bulk of the things that our patients are concerned about don't really happen. They're hyped or internet hyped. Isotretinoin is one of those 1-800-bad-drug drugs because there's a lot of legal issues surrounding it. In reality, if we take good care of these patients and check their blood tests and follow them carefully, this drug has less side effects than many of the others that we use for treating our acne patients. Teratogenicity, of course, being the only one that's of major concern because you can't go back once you create a problem of that sort.
This whole thing is really a problem, and the reason why we're talking about all these medications is that acne is a chronic disease. This is not a one and done. Patients come in to see me with this chronic relapsing course over many years. They have all of the psychosocial overlay. I'm going to treat them acutely right now with something, and then moving forward, we're going to be treating them with something else for maintenance purposes. That maintenance phase is going to be years. It could be easily six or seven years in a teenager. It could be 20 years in an adult female.
When you're looking at medications and their importance in our toolbox, and frankly, as investment issues, the medicines that are going to be used for maintenance are the ones that are going to be refilled over and over again as time goes on in order to maintain the improvement achieved by the acute therapy. Acute therapy is almost less important in terms of the pharmacoeconomics than is the maintenance. Maintenance also, however, adds to frustration. Patients don't want to be using medicines forever. Unfortunately, that's a reality for a lot of our adult female patients with acne. We have to find something with a delicate balance of efficacy, tolerability, and acceptability. Can't expect them to be using benzoyl peroxide and worrying about their fabrics bleaching and switching over to white sheets and pillowcases for the rest of their natural life.
It's bad enough for a couple of weeks, right? The need for maintenance therapy also adds to this whole bacterial resistance issue. Even if I can get you under control with oral antibiotics, can't do that forever. Going to have to stop it in a couple of months, so I've got to find an alternative. What might be one of our alternatives? We're going to turn now to the top-line pivotal study results for FMX101, and I know that you've all had access to this, so I'm going to go over it relatively rapidly so as not to bore you. What we're looking at here is the third study, the phase III design for the third study. As you're well aware, FMX101 had a little problem with its first phase III trial. 05 met its endpoints, 04 met most of its endpoints but missed the IGA.
They had to go ahead and do a second study, which was called 22 instead of 06, which is what I would have called it. Study 22. In this study, there were 1,500 patients who were nine years of age or older, and they applied this medication once a day for 12 weeks. The co-primary endpoints were IGA of success, which was 2-grade improvement and clear or near clear. If they started off as severe, they had to go to moderate, to mild, to near clear. This is a very tall order. The average number of lesions at baseline was very high at 31 inflammatory and 51 non-inflammatory. We are talking more than 80 acne lesions on the face of the average person who entered this study.
Rather than just glossing over that, I would like you to think about what you would have done this morning if you had woken up with 80 acne lesions on your face. Would you be here? Would you have sent somebody else? I would not be here, for sure. What we are looking at here is 1,500 patients with moderate to severe acne, with a lot of acne, with a very high, very tall order for success. Now we are looking at the patient demographics and baseline characteristics of Study 22, which was very similar, with the exception of being a much larger study to the successful 05 study on the right. Otherwise, all of these match up quite similarly, including the number of lesions at baseline and the fact that about 85% of patients were moderate and 15% were severe.
Now we are looking at the efficacy data. This first one is the co-primary endpoint of the absolute change of inflammatory lesion counts at week 12. On the left, again, in Study 22, we see a nice, healthy, statistically significant difference between the drug and the vehicle, with a reduction of 17 of those original 30 to 31 inflammatory lesions, compared to 13.5 in the vehicle-treated side. Study 22 did much better than the original Study 05. Looking now at the other co-primary endpoint of the IGA, which is treatment success. Again, a highly statistically significant difference between the drug and the vehicle, with a success rate of 30.8%. That is an extraordinarily high number for any acne study. In fact, it is about 10 points higher than the newest oral acne medication to enter into the marketplace just last week.
Compared to Study 05, it was even more highly statistically significant than the original study. Here we are looking at the key secondary endpoint, which is percent change of inflammatory lesions over time. You can see at the end, at 12 weeks, we are talking about a 56% reduction in Study 22 and a 43% reduction in Study 05. Those numbers also comparable to that which is reached with the use of oral medications for the treatment of acne. You can also see that it became statistically significant as early as week three. That is no small issue. You have to get into the patient mindset. At week three, with most topical acne medications, they are already experiencing a great deal of cutaneous irritation, and they look into the mirror, and they see no change whatsoever. They are hoping to see an improvement in their acne.
They see none, what they see is more redness and more dryness than they did before they started using the medication. It's a moment that I like to call the crisis of confidence. They have lost confidence in that drug, and they have lost confidence in me. It's highly unlikely that they will continue with the medication past that point if they don't see signs of improvement and if they continue to see a lot of cutaneous side effects. As you'll see in a few moments, these folks did not experience a great deal of cutaneous irritation, redness, and dryness, and they did see improvement at week three. I think they're liable to continue to use the product moving forward at a much higher rate than they would have had it not kicked in quite as early as it did.
Now we're looking at absolute change of non-inflammatory lesion count. I think this was kind of an actual little boost for you. We don't usually think of topical antibiotics as having an effect with non-inflammatory lesions. That's usually the bailiwick of topical retinoids. Our topical antibiotics are generally, we're using them more for our inflammatory lesions. Here, a nice, healthy reduction, statistically significant, of non-inflammatory lesion count as well. Not as big a number. We subtracted here at 19 lesions, but that's a nice big number. If you asked me to speculate, which granted you didn't, but if you asked me to speculate, I would think that maybe that adds credence to the thought that maybe topical minocycline is anti-inflammatory, because how else would it result in a diminution of non-inflammatory lesions? There has to be some way in which it accomplished that.
Since inflammation precedes the development of those comedonal lesions, perhaps this is demonstrating to us an anti-inflammatory activity to this medication. What about safety? Talked about this a few moments ago. What we're looking at here is treatment emergent AEs, these are all AEs, which as you are well aware, could include things like hangnails and being hit over the head with a baseball bat. Right? On this list, I think you'll appreciate that most of them don't have anything to do with a topical acne product. For example, a ligament sprain, unless you sprained your ligament while putting on your cream, I can't see that as being an association. It was quite low with no treatment-related serious AEs reported in either group. Now let's look at the AEs that really might be related to the medication.
We're looking at our local tolerability issues, here we see that 95% of signs and symptoms were classified as mild to moderate. It was uncommon, and when it did happen, it was mild to moderate. You can look at the separation of erythema, dryness, hyperpigmentation, skin peeling, and itching, and you can appreciate on the left, which is the drug, and on the right, which is the vehicle, no difference between those columns, and most of them weighing in as mild to moderate. I'd like to spend one moment talking about the hyperpigmentation. You're all well aware, I'm sure, that oral minocycline has been associated with hyperpigmentation. It's associated with this after a long treatment duration of about 4 g of total dose and probably four to five years of use, especially now with our use of lower dose of oral minocycline. It's a long-term problem.
Of course, it was important to make sure that this didn't occur with the topical minocycline. This hyperpigmentation, as you can see, no difference between the vehicle and the drug. It was not the kind of hyperpigmentation that we see with minocycline on the face, which is in the base of pitted acne scars. It was the kind of hyperpigmentation that we see as inflammatory acne lesions resolve. Especially in our patients of color, when their lesions resolve, they, for a short period of time, have brown dots on their face. That's what this hyperpigmentation was in my experience and in Dr. Weiss's experience as he shared with me. It was not the hyperpigmentation that one might see from minocycline. Safety summary. Again, very few AEs. The ones that were probably related to the product were mild and rare. The severity was none to mild.
No treatment-related serious AEs were reported. One of the markers of how much an irritation bothers the patient is did they pull out of the study? Right? If patients complain of irritation, but they didn't decide to leave the study, that irritation becomes much less important. What was the discontinuation rate? It was extremely low and similar between the vehicle and the treatment group. Overall, the safety results for the third trial, Study 22, were similar to those of Study 04, Study 05, and the long-term safety extension. No red flags. The overall summary is that we had a statistically significant disease improvement with FMX101 compared to vehicle with all of the co-primary endpoints and secondary endpoints, with an additional bonus of non-inflammatory lesion count reduction at week 12 being statistically significant. A percent reduction in inflammatory lesion count, statistically significant at all time points.
Treatment emergent AEs were few and mild, as we said before. No serious ones. No discontinuations, other than a couple that was the same in the treatment and the vehicle group. Patient satisfaction, as you'll see in a few moments, high in all of these studies. I've been asked to talk a little bit about where I think FMX101 might fit in my acne regimen. I see this as monotherapy for inflammatory acne. Maybe even for non-inflammatory acne, frankly. Monotherapy probably for my milder patients. I would probably be using it in combination, I think probably with a topical retinoid, the first thing that springs to mind, give me a little extra boost dealing with my non-inflammatory lesions. With moderate to severe, I'm going to add it on to my oral therapies and onto my other topical therapies as well, especially hormonal therapies.
Most importantly, I think is for maintenance. I see a big role for this drug in maintenance, which of course, again, can extend for years and years. As monotherapy, maybe. The numbers look as if it's good enough to just be used as monotherapy, which again, is not going to bleach their clothes, it's not going to be irritating, it's not going to cause contact dermatitis. All of the things that were on my initial wish list for a topical product. I may also end up using it in combination with a retinoid as far as maintenance therapy is concerned, especially for our our adult female acne patients, which of course, off-label, kills two birds with one stone, since the topical retinoid can be utilized as an anti-aging medication as well. What's it going to replace in my toolbox? For sure, clindamycin.
I have to admit that my toolbox didn't have much clindamycin in it to begin with. Our fellow dermatologists love standalone clindamycin. Apparently, the last number I saw was like 26% of topical acne products are still being written for clindamycin. I don't get that. I never use clindamycin, bless you, unless it's in combination with benzoyl peroxide. It's not a terribly good product to begin with in my mind, and the antibiotic resistance problem has increased that issue dramatically. It's always been said to be an anti-inflammatory. It may have anti-inflammatory properties, but it's never been shown to be anti-inflammatory in the disease of acne itself. Dapsone, never been a favorite of mine anyway. If minocycline has anti-inflammatory properties, that's what dapsone does for a living, so why wouldn't I use something that both suppresses P. acnes and is anti-inflammatory?
Benzoyl peroxide, one of my favorite drugs, that staining issue is a real problem for maintenance therapy. If the numbers are correct, this is giving oral minocycline a run for its money. Again, if I could use the topical minocycline without systemic exposure, without the risks of the systemic symptoms that can be associated with minocycline, why wouldn't I use a topical? That's what I have to tell you about acne, I'm going to turn it over now to my colleague, Dr. Jonathan Weiss, who's going to talk about rosacea. I'll be happy to answer any questions that you might have.
Well, thank you, Hilary. That's a tough act to follow. Also my Apple Watch is telling me I should be taking a lap around the room at this point. I won't do that, but it's great. Wearable technology is wonderful. I'm going to start talking a little bit about the history of rosacea. Unlike acne, which we've had a pretty good handle on how to treat it and what we need to do since the 1950s or 1960s, rosacea is a condition that has evolved a little bit since then. Before 1992, when a small company called Curatek came out with a product called MetroGel, which I believe they may have licensed from 3M, and then was bought by Galderma. Rosacea was a sort of condition to dermatologists that reminds me of a quote by Potter Stewart. Does anyone here know who Potter Stewart is?
You're all very young. Potter Stewart was a Supreme Court justice in the 1960s who was quoted in an opinion on an art film that was banned, I believe, in Alabama. It made it all the way to the Supreme Court, and they were trying to decide what is free speech and what's pornography. Potter Stewart famously said, "I can't define it, but I know it when I see it." That's how dermatologists felt about rosacea through the 1980s and 1990s. That we didn't have a definition of it, but we had someone present to us, and we knew they had rosacea, and we basically treated them with an oral tetracycline. In 1992, this small company came out with this product, MetroGel, as all good drug companies will do, they try to define the condition, and they created the National Rosacea Society at that time.
This was a good thing because it got dermatologists thinking about a condition that we all took for granted, and it started a cascade of research that has helped us define it much better today. As a result of that and the National Rosacea Society and the American Acne and Rosacea Society, which followed later in the late 1990s, early 2000s, we have two classifications of rosacea: the 2002 classification and the 2016/2017, which I will refer to as the 2017 classification because that's when it was published. The 2002 classification was largely based on clinical presentations of rosacea. Not a bad way to go. We really did not understand the pathogenesis of rosacea at that point, and they broke it into four categories. Erythematotelangiectatic rosacea, or ETR. Papulopustular rosacea, basically the pimples we see, or PPR. Phymatous rosacea, which was best encompassed by W. C. Fields.
Fields' nose, an old actor who had this bulbous nose that was lobulated. And ocular rosacea or the eye rosacea. The weakness of this is that it segregated rosacea into groups, and there was not a whole lot of accounting for overlaps, which we do see a lot. In contradistinction, by 2017, a group of experts got together and said, "We really now have a large understanding of the pathogenesis of rosacea." And that understanding encompasses that it is a disease of vascular blood vessel reactivity and inflammation. And this new classification accounts for overlap.
With this understanding of the pathogenesis, we now can diagnose rosacea if one of two factors are present, just absolutely, and that is central facial erythema or redness of the central face that may periodically intensify, or the phymatous changes, those bulbous changes of the nose, the cheeks, the forehead, or the chin. Most patients do not present like that, however. Most patients present with two or more of what we call the major phenotypes, and that would be the papules and the pustules, the inflammatory bumps, the flushing, telangiectasia, or the ocular manifestations. I would say over 90% of the patients who present to my practice for treatment of rosacea or not for treatment that I then wind up treating have papules and pustules and either flushing or telangiectasia. That's how we make the diagnosis most of the time.
However, there may be someone sitting in front of me who has that central facial erythema. It's just that becomes a much greater conversation and a much more difficult type of patient to treat. We don't do that. Again, the ocular manifestations are really somewhat poorly defined and understood. Now, adding to those major phenotypes are what we call the secondary phenotypes or symptoms that help us make the diagnosis if someone's borderline. One or more may be present with the other diagnostic features, and that would be burning and stinging, edema, little bit of swelling in the face that patients complain about, and you can see if you know them quite well, or that dry appearance, that flaky appearance, which is somewhat different from seborrheic rosacea overlap.
Again, ocular rosacea, I'm not going to deal with that anymore today because it's very poorly understood by both dermatologists and ophthalmologists, and it can occur with or without dermatologic disease. If they have no other symptoms, which is very rare, if someone comes with papules and pustules and they have rosacea, they almost certainly have some telangiectasia or flushing. It might help a little bit. My treatment, if I treat them systemically, may actually help the ocular rosacea. One final note is that ophthalmologists and other doctors who treat the eyes have a very poor understanding of this disease. They actually are putting steroids in the eyes, and if ocular rosacea is anything like cutaneous rosacea, you do not want to be putting steroids on cutaneous rosacea.
I can't imagine that the pathogenesis is that different that they're not causing rebound in their patients by putting steroids in the eyes. I think that is an area that is ripe for research, and as a group of investors, you might want to spur some companies in the ophthalmologic realm to kind of look into that. I think it is an area that has vast potential. How do we treat rosacea in 2019? Currently, most of our colleagues are treating according to the 2002 criteria. Anytime you get relatively new criteria, they take about 5-1 0 years to take hold. I'm going to present these in both contexts. ETR, erythematotelangiectatic rosacea is largely treated with topical alpha adrenergic agonists, the vasoconstrictors for the background erythema. Those would be brimonidine or Mirvaso and oxymetazoline or RHOFADE.
Two products that have not done well, quite honestly, because these drugs tend to be used more episodically by patients when they need them. The coverage has not been great to this point. Hopefully, they're going to correct that. Those two drugs do need some boost to help their use. There are surgical options for the telangiectasia or procedural options, including laser, IPL or what I like to call the poor man's laser, electrodesiccation, which is a 1950s or 1960s technology that actually works quite well but is not quite as specific as laser or IPL. For phymatous rosacea, you're looking at procedural or surgical options. Electrosurgery or hot loop is probably the best way to go about this. Interestingly, whenever I've sent patients for that, I think there have been about five or six in my community that I've sent for it.
Whenever they send the shavings off, they do the hot loop to pathology, there is skin cancer underneath the phymatous rosacea. I am five for five, and this is something that's not well known. It is another reason to treat rosacea because the I don't know what your experience is, Hilary. Yeah. It is something that has not been publicized, published that I know of or anything like that, but it is a very strong reason to treat rosacea to keep it from getting so bad that that occurs. Other ways you can treat it are with laser surgery or cold steel surgery. Cold steel, just standard treatment. Not a great idea because of the amount of bleeding, which is why they use hot loop and/or laser.
Where we're going to focus today, papulopustular rosacea, you have obviously topical therapy with antibiotics or antihelminthics, metronidazole, azelaic acid or Finacea, ivermectin, Soolantra, and sodium sulfacetamide sulfur, which is really actually a pretty poor medication. It's available in a wash, which nothing else is, and patients love washes. Systemic antibiotics are well known, largely the tetracyclines, doxycycline, either in what I call full dose, and I'm not saying you use 100 mg twice a day, but I'm talking about the full-size pill or the sub-antimicrobial dose, which the name brand would be ORACEA but there's also a doxycycline 20 mg that's available generically. Minocycline is used in multiple brands and is highly effective.
For patients who are tetracycline resistant or tetracycline allergic, there are various others, amoxicillin, again, Bactrim or trimethoprim, and the macrolides, quite commonly erythromycin, which is hard to get, but clarithromycin or azithromycin. I want to share with you something that is a personal observation, and I'd be curious what Hilary thinks about this. When I think about rosacea, I've observed rosacea for 30 years, there are basically three paths that a patient can take. A very few patients, probably far less than 10%, have a single episode of rosacea related to some trigger factor. They get treated, it never comes back. The vast majority have what I have come to call chronic relapsing rosacea. They have a first episode, they get a remission from our treatment, and that remission may last for weeks, months, or even years, but they are going to flare again.
That's what I tell most of my patients when they present. "You are likely to have this more than once." Maintenance treatment in that group prolongs remission. I try to get my patients onto a maintenance regimen. There's what I call chronic constant treatment, chronic constant rosacea, which is the patient who you put them on medication and you go to take them off, or you try to reduce it, and they relapse almost immediately. That's probably a 10%-20% group of patients. How is rosacea treated in clinical practice today? Well, for me, I generally start with a full-dose oral antibiotic, probably doxycycline or minocycline, 100 mg once a day, sometimes 50 mg if it's a smaller patient. Rosacea can be exquisitely sensitive to even lower doses, and the majority have vast improvement in one month.
I combine that with a topical agent, I try to continue them on a topical agent, plus or minus a sub-antimicrobial doxycycline. The minority have partial improvement in one month, and those patients require two to three additional months of a full-dose antibiotic with the topical agent. I try to wean them to sub-antimicrobial therapy with the topical agent. For long-term management, I like them to use a topical agent daily. Some patients use intermittent treatment, and you can read that as patient-directed or non-adherent. It's not the best way to go, but some patients, especially men, just don't use it constantly. How does FMX103 fit into what I do? I would like to point out that FMX103 and FMX101 are very different medications. FMX103 is a 1.5% doxycycline and FMX101 is 4%.
Minocycline.
Minocycline. Sorry. It's topical minocycline. It's 1.5% versus 4%. It is because I believe they are very different pathogenetically that you can use a far lower concentration of minocycline topically to treat rosacea. This shows the program design. We are going to focus on the double-blind studies that were done. There were two studies. They were 100 sites total. Over 1,500 patients enrolled. Self-applied once daily for 12 weeks. Inclusion criteria were 15 to 75 inflammatory lesions. The lesion count was much higher than one would normally expect in a topical study of rosacea, which speaks to the management of the study by Foamix. The IGA five-point scale was on a five-point scale of zero being clear, up to severe being a four, a five-point scale.
The co-primary efficacy endpoints were a mean change from baseline and absolute inflammatory lesion count and the proportion of subjects with IGA scores of clear or almost clear with an improvement of at least two grades. This is also an important point in these studies in that you had to hit both of these endpoints for success. This is no minor feat for a topical product to attain. The safety evaluations were fairly typical of the adverse events, anything that came from physical exams, vital signs, tolerability, or from labs. The demographics for this study, very similar to what you see in most rosacea studies. Around 750 to 770 enrolled in the two studies. Number of sites, about the same. Interestingly, I believe we were in the 11 because my site has terrible time attracting rosacea patients for studies. The mean age, right around 50 years old.
Gender break, about what you see in most rosacea studies, about 30%, 70% male to female. The ethnicity, largely a Caucasian population. I will point out that we are seeing more and more skin of color rosacea patients, and I would expect that to shift, maybe not in studies over the next several years, but for those patients coming into the dermatologist, I am seeing more and more patients with skin of color, both brown and black skin coming in to see me that we recognize with rosacea now. The baseline inflammatory lesion counts, these were quite impressive, sitting right around 30, 28.5- 30 lesions, with a median of 25- 26 lesions. These are patients with a lot of rosacea.
When Iain goes through with you the patient satisfaction, I think that's very important to keep in mind because the standard for patients with rosacea is they expect to be clear in about a month to three months. Anything short of that is active disease to them. It's not like acne, where I tell a patient "We're going to have you, it's going to be five to six months." I usually give my acne patients target dates. If I'm seeing them at the end of the school year, May-ish, I say, "We hope to have you better for homecoming, but think about Thanksgiving." That's when I want you to get better. In rosacea, they're thinking a month to no more than three months down the line to be better. The breakout of moderate to severe for IGA was about 90/10, 85/15.
The efficacy results, on the left you see 17.5-18.5 lesion reduction, and that's a mean lesion reduction, and high statistical significance in both study groups. Very nice to see. One thing I would like to point out is you're looking at the vehicle group. Topicals are not studied against placebo. A topical drug is a combination of its vehicle and its active. I wouldn't worry about separations, because what a patient is getting is the combination. The reason you go against vehicle is to get it approved by the FDA. I think it is outstanding that they got such strong statistical significance. With regard to IGA, you're looking at a 50% level of clear or almost clear. Very unusual for a topical rosacea drug.
Again, clearly getting good penetration, clearly getting strong results, both also with strong statistical significance. Secondary endpoint, again, is you're looking at the percent reduction in lesion count, the mean percent reduction in lesion count. You get statistical significance by week four. Again, very important, like we talked about, people want to be seeing results by week four, and you're seeing a mean of 64%, 61%-64% reduction in mean lesion count. Adverse events, just like the acne study, largely non-cutaneous in those that are occurring in over 1% of the subjects. A lot of things you would expect to see in the population that was studied, over 18 Caucasians, and studies that occurred during influenza season, a couple cases of flu. Nothing that you could really attribute to a topical agent.
To summarize the safety, the most common systemic adverse event was upper respiratory tract infections, both studies with incidence rates less than 3% for both FMX103 groups. Treatment area cutaneous treatment emergent adverse events in the FMX103 treatment groups were few, most mild, and included instances of dermatitis rash. There was a cyst or two, pain, pruritus, hyperpigmentation, which again, was post-inflammatory hyperpigmentation, not that bluish gray dyspigmentation that we see with long, long-term oral minocycline therapy. Some people, not surprisingly, developed actinic keratosis, little sun damage precancers. Again, unrelated. No treatment-related serious adverse events. In total, nine subjects discontinued the studies due to treatment emergent adverse events, including seven in the FMX103 treatment groups and two in the vehicle groups.
The overall summary, again, statistically significant improvement in the FMX103 versus vehicle was achieved for both co-primary endpoints of absolute reduction of inflammatory lesions and IGA treatment success at week 12. Treatment emergent adverse events were few in type and frequency, and most were mild in severity. No treatment-related serious adverse events. Subject discontinuations due to treatment emergent adverse events were low in both studies, and FMX103 was shown to have a favorable safety profile. Now, again, I've been asked to give you my impressions of where might FMX103 fit in the rosacea regimen, and I would suggest that for the patients that present to my practice, as opposed to those that were studied, it would be in just about every patient type.
Certainly monotherapy in milder patients, which it was not studied in, a lot of my rosacea patients who come into my practice are coming in for other issues, and I happen to notice it, and I ask them if they want something done. Right now, to give them something that I know is effective, I have to go with some form of oral therapy. What I feel this gives me, based on my experience in the trials, is a topical agent that will work well in monotherapy for the patients who are to the milder side of moderate and maybe less than that, even though that will not be an indication for the drug. Once it's out there, I expect in my experience, it will be used in patients in whom it could not be studied.
Combination therapy, obviously, I think it will be a great first-line therapy with the systemic agent. It will be natural to bring a patient down to that. I think it can also be used in those patients who have systemic antibiotic phobia in addition to another topical agent. I think it will be great, especially a non-antibiotic topical agent. Then for maintenance therapy, this is a no-brainer. This is exactly what I want in a maintenance topical therapy. Where does it fit in my treatment toolbox? It definitely falls ahead of metronidazole.
When I first spoke on metronidazole back in the 1990s, part of my talk, in order to legitimize the fact that I was speaking on it, was to explain how these studies were done for FDA approval and not for clinical use, and that there were ways to use metronidazole in the clinical setting other than monotherapy like they were used in the study. With ivermectin and azelaic acid, I feel it will supplant a lot of those patients in my armamentarium and will also be used in combination, as I stated before. With oral doxycycline and systemic therapy or oral minocycline and systemic therapy, I see it again being used in combination with those agents. To me, based on what I've seen of rosacea therapy and topical rosacea therapy, this is a great boon to my practice. I believe that is my last slide. Now, it's Iain's.
Thank you, Dr. Weiss and Dr. Baldwin, for your review of the respective landscapes and review of our data. My name's Iain Stuart. I'm the Chief Scientific Officer for Foamix, and it's my pleasure to present some new data that has come from our pivotal studies, FX2016-11 and FX2016-12. Starting with local tolerability, Dr. Weiss touched on that. We didn't present it earlier on. These are the local tolerability assessments that we are regulatory mandated to follow, but also touches on the disease state itself. For example, telangiectasia, or what's colloquially known as spider veins. I'm sure people who know people with rosacea have seen this. The burning and stinging, what we talked about clearly causes a major impact on quality of life. Flushing and blushing is certainly an element of disease. The dryness that can happen both during therapy and fundamentally with disease.
Itching really does speak to tolerability of the product itself applying to the skin. Remember, these patients expect, and they should expect, good resolution of disease with very little irritation at all, if any. The peeling and desquamation that you can see, both the natural disease state itself and therapy, and hyperpigmentation we talked about. Patients deserve to have none, and what we are seeing here is a baseline. The patients who actually came into the clinics, the centers, the 100 centers that we had, who had none of these symptoms. You can see there, if you think almost inversely, if you only have 12% had no telangiectasia, the vast majority did. They're mild, moderate, or severe. Same with burning and stinging, flushing and blushing. Majority of patients had some degree of that, et cetera.
After therapy, you can see in all cases, all of these factors improve. Starting on the left-hand side, we did see some resolution on telangiectasia. The burning and stinging, these percent of patients that actually had no burning and stinging. We're not talking about almost or slightly, we're talking about no evidence of self-reported burning and stinging. The flushing and blushing, which is very clearly an important clinical manifestation of disease and is obviously very embarrassing to have people having these flushes, these episodes that can be triggered for a variety of environmental considerations. Dryness is very important because that does speak also to peeling and desquamation. Hyperpigmentation, again. In all of those categories, there's improvement.
I think what it's actually telling you, if you look at it at the category level, we managed to, of six of those seven assessments, over 50% of those patients had none. Nothing. No evidence of those clinical manifestations of signs and symptoms. This is pooled data from both studies on the active treatment. 1,000 patients were assessed at baseline, with 895 at the end of the study. Obviously, you have dropouts in studies like any other study. These are real patients. This is not imputed data, and this is quite impressive to have a topical therapy where really you managed to get the number of local signs and symptoms and proportion of patients with these signs and symptoms effectively to none. Moving on to clinical erythema. Again, this is something we also assess. This is a 5-point scale.
This is one that's used primarily when we're assessing the background erythema, or ETR, a subtype of rosacea that Dr. Weiss talked about a little bit earlier. Just cast your eyes to the plot on the left-hand side. At baseline, we had roughly two-thirds of the patients had moderate background erythema. Remember, this is not the basis of the study. This is a papulopustular study. This is the lumps and the bumps. This is the lesions that Dr. Weiss was talking about when he was reviewing our data. What this actually does speak to is the multifactorial clinical presentation of rosacea. Some patients may not have any material erythema, some may have very intense background erythema, as well as the papules and pustules.
We had two-thirds of patients had moderate disease, and at the end of therapy at week 12, we managed to reduce that down to under 20%. That's a material stepwise improvement on background erythema, as well as Dr. Weiss had presented earlier on, the papules and pustules. Looking at the other side of the coin, which is looking at clear or almost clear based on clinical erythema assessment. As I said earlier, you don't always have to present with erythema at baseline. There is going to be a proportion of patients who really don't have much of a background erythema, but clearly qualify for the study based on lesion counts and ultimately IGA. We had roughly around 6% of those patients at baseline, which you would recognize as clear, almost clear of background erythema.
At week 12, we managed to get nearly 45% of patients clear or almost clear of clinical erythema. This really does speak to the multimodal action of minocycline. We talked about its effect on acne earlier on, and here we're really as it's driving primarily as an anti-inflammatory agent and the effect it has on clinical erythema. Moving to subject global assessment. We talk a lot about investigator global assessments as the primary endpoint. You see that if you work in dermatology. It's a very important regulatory hurdle that drugs need to cross to ensure that there really is a minimum clinically meaningful resolution of disease. Normally, it's clear or almost clear. This is the other side of the coin, as it relates primarily to the patient experience.
They're not looking, obviously, at specifically clinical assessment, but we ask very basic questions comparing them to before they started treatment and where they are now. Were they slightly better? Much better? Was their disease status basically the same, slightly worse, or even significantly worse? What you will see here, that we had approximately 50% of patients not only say they were slightly better, that they were a lot better. This actually jives very neatly with the corresponding IGA treatment success. If you remember back to Dr. Weiss's presentation, we had approximately 50% of patients in the active arm that were clear or almost clear of disease. This is very encouraging data, clearly, and is highly consistent between the IGA and the SGA. Moving to satisfaction. Three questions we obviously ask, again, of the subjects. Overall speaking, what is their satisfaction level with the product?
You had nearly 72% of patients were very satisfied or satisfied with FMX103. With respect to ease of use, we had 90% of patients thought it was easy to use. Supporting patient compliance through a topical therapy is key. If they find it complex to use, they will not use it. If they do not use it, guess what happens? They don't get the clinical response that we all hope that they will. This, again, very encouraging perception of how easy it is to use FMX103. On the right-hand side, "How does the product feel on your skin?" This is really an acid test. Dr. Weiss talked very elegantly about burning and stinging. These patients have extremely irritated skin, and anything they put on their skin that could potentially impact on their satisfaction, they will obviously speak to through this product.
Again, we have nearly 2/3 of patients, and if you include the ones that are somewhat neutral, nearly 80% of patients were satisfied with the feel on the skin. This is critical because, again, speaking to the ease of use, speaking to the application experience. If they don't like how it feels on their skin, they're not going to use it. I'm also pleased to give you an update on the pipeline. I'm sure you've seen this slide many times before, but it's pleasing to actually give you a little bit of an update and a change of guidance here. In relation to FMX101, Dave Domzalski's talk at the start in relation to our NDA filing. We're pleased to do that just before Christmas time this year.
I'm very pleased that the R&D group put up a huge amount of effort to convert our FX2017-22 phase III study, get it ready for registration in record time, we're very pleased that we did that. Of course, the projected PDUFA action date will take us into Q4 2019. The corresponding timelines for FMX103, we presented the top-line data in early November, as you're aware. I am also pleased to update, this is new information, we have actually had our last subject out of the open label extension, what's called FX2016-13. That has already happened in early January. Our team are working very quickly and judiciously with the corresponding clinical sites to make sure that our clinical data is cleaned and ready for data lock, and we will present top-line data in due course after that.
What is key here is that we've been talking for the last year or so that there would be approximately a year of gap between our FMX101 and FMX103. We're pleased to announce that we will actually bring that NDA forward. We plan to submit that in mid-year 2019 rather than towards the latter part of the year, which was the earlier guidance. Of course, you have a consequential move on the equivalent PDUFA action date. We're very excited that the team has put a lot of effort in here to continually move our pipeline forward judiciously with high quality, but also ensuring that we have all this good clinical data and this great product actually makes the market as soon as we possibly can do. We're pleased to announce that. Changing gears a little bit differently.
What are we doing just now in relation to medical affairs? Clearly, our commercial footprint is a little bit further out just now. We are doing the regulatory process for FMX101. I want to give you an idea of what the basic themes that we will be communicating to the dermatology community over the next year as we move through this kind of pre-launch, peri-launch phase, and ultimately into commercialization. Really, it speaks to three matters beyond our clinical data. We will clearly be communicating that widely, and we continue to do that through one-to-one discussions with thought leaders such as Dr. Weiss and Dr. Baldwin. A lot of work done at conferences, and I will touch on that as well, and of course, our publication footprint.
These three areas of the triangle really are pretty critical points of scientific communication in relation to both of these products, but primarily starting with FMX101. Vehicle matters. You have already seen that from our presentation. We have a very sophisticated, well-tolerated, and elegant vehicle system that in of itself has direct effect on the disease status. Understanding why this happens is going to be very important for physicians to understand as they make their prescribing decision making. Minocycline disposition, what does that mean? How does minocycline actually get to where it needs to get? It is very important to understand when you apply a product to the skin, is it getting to your site of action in sufficient concentration, but no more? We certainly do not want to have significant systemic exposure because then that plays back into some of the limitations you have with oral tetracyclines. Mi crobiology.
Microbiology is a key. We are dealing with an antibiotic, we have to address some of these concerns upfront. Speaking on these areas in a little bit more detail, I am going to have a few slides on each one of them about the key messages that we will be communicating over the next year. It is a unique hydrophobic form. No one has done this. This is first time that a micronized topical minocycline formulation has been produced. The key words in and around this is stable. Many people have tried it over the years, not many have succeeded, and we are certainly the most advanced of those who are currently looking at these types of products. Sebum liquification.
We are going to talk a little bit more about that and how that actually impacts the disease status, that our vehicle itself actually has the capability to interact with sebum, which is a key progenitor to acne, and actually help as a partner with the antibiotic and disease resolution. Microbiology. We have a highly potent antibiotic. We will talk about C. acnes. Sorry, Hilary. The young folks are talking about C. acnes these days. We have a tremendous direct impact on C. acnes, which is our target microbe. It is pro-inflammatory, not in of itself, but as it replicates, it does generate pro-inflammatory molecules within the pilosebaceous unit that really does trigger additional inflammatory cascades. Low resistance potential. We will talk a little bit about this in a few slides time. We actually have some very interesting data from our own in-house work.
We actually did a phenomenal amount of microbiology of profiling of minocycline as part of both of our NDA and of course, part of our scientific communications moving forward. Minimum collateral effect in systemic and commensal organisms. Where you have very low systemic exposure, then the fitness cost of a microbe to adapt really isn't there. One of the biggest concerns we have with systemic antibiotics is you're providing an environment where you are allowing them to potentially develop or trigger resistance mechanisms against that particular antibiotic. Disposition. Targeted delivery to the pilosebaceous glands. This is where we want to go. This is the idea of outside in rather than inside out. We really want to make sure that we target where the C. acnes resides, that we have that direct inflammatory effect directly into the pilosebaceous unit.
Ultimately, where we're trying to get to is resolution of disease. We do have high concentrations in the stratum corneum, and that's really important to make sure that we suppress C. acnes as much as we possibly can do, and as I talked about, a very low systemic exposure. I want to pick on one just now on the vehicle/matter side. Sebum liquification, why is that important? The sebum plug really does provide the optimum physiological environment for C. acnes to replicate. C. acnes is the anaerobic bug, so it doesn't like oxygen. It likes to grow in an oxygen-depleted environment. The lid, if you like, that sits on top of the follicular mechanism really does provide that environment so that C. acnes can actually develop. There's two components to the sebum plug. One is dead corneocytes.
This is cellular debris that happens, the natural shedding of cells from the follicular shaft out into the epidermis, and then there's sebum itself. Okay. Many sponsors have looked at should we remove sebum, deplete sebum is a very important part of maintaining good skin conditioning. If you don't maintain good skin conditioning, drying, irritation is really a factor of that. Bringing these two things together provides this plug that sits in the pilosebaceous unit. What we've done is actually compared our vehicle system to what's called an oil-in-water emulsion. Really what that means is your classical dermatological cream. You've seen them in CVS's. Any dermatological acids have been based on primarily these basic creams, these are oil-in-water emulsions. What's actually happening is that the skin temperature is a little bit under body temperature. It's around 36 degrees.
Sebum itself doesn't melt until 37 degrees. Sebum in its natural physiological state within the follicle is in a kind of jelly-like semi-solid state. Okay. It's a perfect environment for things to stick to it and provide this plug. When you actually mix oil-in-water emulsions or creams with sebum, that actually increases the temperature of the combination. If anything, it's making the sebum harder, becomes a little bit more solid-like. When we mix it with FMX101, it actually reduces the effect of temperature. The thermodynamics of this process allows that you have much improved miscibility of our vehicle system with sebum. Let's show pictures. What we have here on the left-hand edge is really that kind of yellow interface here, that is sebum.
The kind of pink interface is our vehicle, FMX101, and below that is the equivalent interface in combining the oil-in-water vehicle with sebum. This is at 25 degrees. Basically, sebum at 25 degrees is solid. As you start to increase the temperature to 35 degrees, so just below skin temperature, again, focusing on oil and water, that margin between the two, both the vehicle system and sebum, is still pretty defined. You can start to see with the vehicle system for FMX101, that barrier start to break down. What's happening is they're beginning to become miscible with each other. When you hold at 35 degrees temperature, you can see it in the top right-hand, they are becoming very much miscible. The system is becoming liquefied at 35 degrees.
Whereas at 35 degrees with the oil and water system, you still have this very clear margin. What we're already seeing here, that the vehicle itself has a direct impact on the physical state of sebum, potentially in the pilosebaceous unit. Microbiology. This is some very key, and I'm quite excited about this because I've been doing this for a while. It's very rare for the opportunity actually to reshape thinking in relation to something as important as the use of antibiotics, particularly with the dermatology community. Here we'll be actually introducing some new concepts to the dermatologists. One is called mutant prevention concentration, and the other one is a mutant selection window. I talked about earlier that against C. acnes, our drug is particularly important, one of the key concerns with the prescribing dermatologist isn't so much resistance developing against the target organism. A C.
acnes superinfection is not life-threatening. Their concern is primarily cross-resistance with other commensal bacteria such as Staph aureus and other microbes that could be potentially life-threatening should resistance develop against a particular therapy. We have evaluated the MICs against 102 C. acnes isolates, clinical isolates, and we have very, very potent on-target effect against that. It's not just about potency, it's about consistency. Sometimes you can have some isolates have very, very low MICs, and some are very high. You may have a patient basically walking in, have a great treatment response or be a clinical failure, and it's extremely difficult to determine which is which. We have that consistency across the 100 that we looked at. Frequency of step and step mutations is very, very low. Always remember that bacteria are always in balance with each other.
You have susceptible bacteria and you have resistant bacteria, and it's a little bit of a war between the two of them. As an antibiotic comes in and starts to degrade susceptible bacteria, the possibility of growth of resistant bacteria does accelerate. What I want to talk about here is this concept about mutant prevention concentration. In the body with FMX101, we have extremely low systemic exposure. It's actually 100-fold below the MIC against our target organisms. What does that actually mean? That means there is no fitness cost. This is evolutionary biology 101. Microbes will only develop a resistance against a particular microbe if they feel the cost benefit is there for them.
If they feel that it's not, that the levels within the system are so low, they do not have the energy, they do not want to expend the energy to develop that resistance mechanism because it does take energy. It's classical Darwinism. In the body, which is really the primary concern about effect on commensal bacteria, we have a very, very low systemic exposure. On the other side, in the skin, we have a very, very high exposure in the skin. Many hundredfold higher than the MIC. What actually happens, and this is something that we will be discussing at great length with dermatology community, is that the opposite actually happens. There really isn't much potential there for resistance to have a meaningful impact on clinical failure as it relates to resistance.
You're delivering so much of the antibiotic there that the ratio of wild type to the resistant species actually goes back the other way. The current thinking is that the more antibiotics you use, this ratio gets worse and worse and worse, the resistant species become the most dominant one. It's not, it's actually a bell-shaped curve like this. It reaches a maxima and then goes back down the other way as the ratio re-corrects itself because you're actually delivering an antibiotic at such high levels where it matters the most. What does that mean looking at comparing to oral minocycline? The mutant prevention concentration really is that minimal concentration will actually, or the MIC for the least susceptible microbe. When you compare that with oral minocycline, you have dose-limiting toxicities that come into play here.
Ideally, in the body, we want to make sure that we continually remain above the mutant prevention concentration. Quite frankly, pharmacology and toxicology dictates that that will just not be feasible. Our colleagues who are working on oncology are well aware of you kill the issue, but you could kill the host as well. Basically, the therapeutic index just basically disappears to nothing. Here we're talking about Cmaxes of 3 ng per mil, well below the MIC. If you compare that with oral minocycline, which is about 1 μg per mil, really what's happening in there is you're providing an environment for the microbe itself or microbes itself to kind of get used to the presence of that antibiotic. Really, this is what's commonly known as the mutant selection window.
You're allowing an environment to develop within the body that actually supports the development of resistance. You can see the ratios between concentrations in the skin and concentrations in the plasma are greatly favoring, obviously, the skin versus plasma for FMX101 in relation to when compared to oral minocycline. Okay, minocycline disposition. Again, this is all well and good, if we can't actually get minocycline into where it needs to be, which is deep within the pilosebaceous unit where C. acnes resides, then it's all for naught. This is ex vivo work that we've done with human skin, looking at the penetration profiles, not just through the strata of the skin itself, but again, looking directly down the follicular shaft to ensure that we are actually delivering sufficient concentrations of FMX101 or minocycline deep to where it matters.
On the bottom axis here, you can actually see the concentrations in the epidermis and the dermis. Again, it should go down. If you're dealing with a topical, it'll be higher concentrations in the epidermis, lower concentration in the dermis, as minimal as possible going through the basal cell layer, because that ultimately relates to exposure. The plot in the middle is called FMX101SA. We actually managed to pluck out the sebaceous appendage of the skin itself. Allows us actually to look at concentrations deep within the pilosebaceous unit, not just meaned out across the skin. As you can see there, we nearly have 3.5 μg per sebaceous unit of minocycline being deep into the follicular apparatus, which is particularly important. The corresponding side of it, exposure, this is the receptor solution, so this is a surrogate for systemic exposure, is extremely low.
You'll see alongside that, we have the equivalent data for FMX103, and you can see there's a dose dependency, a ratio, and obviously we have different concentrations. Medical communications. We have a lot of very powerful scientific messages and a lot of work that we have done over the last year and will continue to do, but that's all for naught if we don't communicate it to the prescribing community. I want to take you very briefly through the plan. I am not going to go one by one, you'll be pleased to know. This year, we are actually greatly accelerating our medical affairs activities, both a combination of presentations at conferences. My VP of medical affairs is actually back from Winter Clinical, which has happened last week.
We will continue to be very present at conferences throughout the whole year as we lead up to our perceived action date and of course, beyond that. The boxes in the top there are really our poster presentations that we plan to communicate. I'll pick out a few key ones here. The FX2017-22 poster is obviously a marquee study for us for FMX101, and we'll continue to communicate that information broadly and widely through the dermatology community. Dermal safety is critical, and it isn't just about local signs and symptoms. Hilary actually talked about photosensitivity as it relates to the oral tetracyclines, so part of our regulatory work is to assess in phase I studies things like phototoxicity, photoallergy, cumulative and repeat insult patch testing. It's a very classic battery of tests that need to be done as you take a topical dermatological product through to market.
We will communicate that broadly as well. Pill safety is important, particularly in safety. The bigger the N, the more likely you're going to see any potential issues. We clearly haven't seen any of that, and we will communicate that broadly. Looking onto manuscripts, everything will be published. We will put them into a variety of journals over the course of the next year. Again, starting with the 22 study, the phototoxicity. The work that we've done on microbiology, we think is extremely exciting and quite revolutionary, and especially as it relates to the current understanding in the dermatology community about the judicious use or stewardship of antibiotics, as Dr. Baldwin talked about earlier on today. We're extremely excited for the work that we're doing here, and we'll continue to report on our activities as time moves on.
I am going to pass over to my colleague, Matt Wiley, who is our Chief Commercial Officer, for an overview on our commercial activities.
Thanks, Iain, good afternoon. As this is the first time that I'm presenting in front of a group like this, I'll give a little bit on my background. I've spent over 20 years in the industry, all of that in commercial, most of that in marketing. I've worked in small startup companies like Salix during the launch of COLAZAL, and also Azure Pharma. I was the third U.S. employee at Azure. I've also worked in mid-size companies like Cephalon and Jazz, most recently heading up the sleep business unit there. This is my first time working in dermatology, but I can assure you that I've worked in virtually every disease state beneath the skin. This is a discipline of breaking down markets that I'm familiar with, and I've had the opportunity over the last 10 weeks to gather some pretty good insights on this market.
Why did I join Foamix? I think about it in three different ways. First of all, I worked with Dave at Azure, I knew the management team here. The management team that I met, I have a high degree of confidence in their ability to bring drugs to market, both near term and long term. The products themselves, I spent some time doing my diligence on FMX101 and FMX103, I think, as you saw earlier this afternoon, the data is very favorable. I also looked at the market sizes of these drugs and previous launches to better understand the opportunity that I'd be walking into. The third is the opportunity to build out a commercial infrastructure from the ground up. This is something that I've been a part of in previous lives and one that I'm very excited to build out here. Okay.
Let's talk about some early market entry considerations in the acne market. First of all, this is a large market. I'll spend a little bit of time going through the size of the market and how we see it. Consumer activation and engagement. This seems to be a forgotten cohort, I'll walk you through some data that we have about the consumer play that may be available to us here. Market access is something that every new launch is dealing with. As I left Jazz, we were working on an NCE launch plan and understanding not just where market access challenges are today, but where they're going. You want to skate to where the puck's going to be, not where it is. Finally, competitive spend. This is a competitive space. There are a lot of players in the market.
There's a lot of noise in the market. How are we going to cut through that? First, let me talk about I want to juxtapose acne and rosacea here because I think it's important as we're talking about the launch strategy for FMX101. First of all, the acne market, the prevalence is about 50 million U.S. acne sufferers. 80% of those are between the ages of 12 and 24, and I'll get to why that's important momentarily. As we look through claims data over the last five years, there are about 7.5 million unique patients under physicians' care. In looking at longitudinal trends, we see that this is a fairly durable market, one that's evergreen. This is a market that doesn't need to be built. There is a ready-made market here. The same can be said for rosacea.
The prevalence in rosacea is 16 million in the U.S. The patients here are generally over the age of 30 years old, and we see a durable population here as well, 2 million unique rosacea sufferers over the last five years via claims data. Again, this is an evergreen population. As you look at the age groups for these two categories, you see that they are discrete. That's important as we think about any direct outreach to patients and consumers. We're not tripping over ourselves with different messages. A couple of reasons to have a look at recent and maybe a little bit further back for launch surrogates. The first reason is you look at the most recent launches to understand whether or not there is any impact due to market access in the first 12 months.
As we look at the most recent launches in acne, we see that there is a decent uptake. When we look at dollarized prescriptions here, it's anywhere between about $100 million-$230 million in the first year, dollarized. As we look at five-year surrogates, we can see that the dollarized volume here is anywhere between $200 million and about three-quarters of a billion in dollarized revenue. It's important as we look at surrogates, not just to look at the five-year history because it's going to tell a different story in uptake in the first 12 months, again, because the market access landscape has changed so dramatically over the last three years. Both of these are instructive, but both point to the fact that these are markets that have been successfully penetrated with new brands and have good, successful uptake over time. Okay.
As we think about targeting, this is from a slide that we've presented at investor conferences in the past. I would say that this is the more traditional approach. You define your prescription volume market basket, you relegate that then to the specialty that you want to call on, and then you do a top-to-bottom volume decile exercise. That's basically what we did five, 10 years ago. It doesn't account for where the patients are. When you're only looking at prescription volume, not all of those prescriptions are necessarily going to be in your target population. That's important, especially from a market access perspective. The way I think about it is slightly different, is I go to where the patients are, not where the drugs are. The drugs do follow these patients.
When we decile based on patient volume, I've boxed out over here the top six deciles. When you think about deciling is important in so much as it gives you a 10% block of the patient volume from top to bottom. We can see here that about 5,000 physicians manage 60% of all of the acne patients in the U.S. As we think about field force size, I know that we've stated publicly somewhere between 50 to 100. This number of targets would give you a good idea of where on that spectrum we're likely to be. I put the rosacea data up here as well because I think it's important as we think about the sequential launches of FMX101 and FMX103, to see that there are 2,500 physicians that account for 60% of the rosacea volume in the U.S.
There's only about a 50% overlap between these two groups, which means it's actually a very good thing because we're going to have discrete targets for rosacea, we're going to have discrete targets for acne, and we're going to reconcile through incentive compensation how we deal with the 1,300 or so that overlap. This is a preliminary view of how we intend to target, but there's a lot more that we do from a predictive perspective as we move forward. We'll look at things like brand versus generic preference. We'll look at access, et cetera, and we will sharpen our pencil on these models between now and launch. Let me talk about market positioning. This is the one thing in pharmaceuticals that costs us no money. A market position is the cheapest thing we do.
If you get it wrong, it's the most expensive thing that you can do. I've been fortunate to work on relaunches of several products over the course of my career, and I can tell you, it's a better experience to understand where previous commercial companies got it wrong, because you really learn what can trip you up, and what can make for either a successful launch or not. Positioning is one of those. Typically, what happens in market research is you share the attributes of the drug. The physician will certainly give you a hierarchy of what's important to them. Most marketers will then position around those attributes. I have yet to see a market research study that doesn't list in this order of importance for physicians, efficacy, safety, and convenience.
If you position around those things, there's only one way to cut through the rest of the market, and that's to shout louder. If you have a unique positioning that doesn't focus on those things but ties back to them in a certain way, that's a much better mousetrap to launch with. We believe that there's a built-in position here, and there are pros of topical products, obviously, that we're going to tout. Those of oral tetracyclines, we're taking the best of both worlds in this formulation. A lot of what Iain just talked about in the uniqueness of FMX101. There are great differentiators that we have. We think we have a unique story, and we'll be able to tie that back to the clinical results in a very hopefully unique way.
We think about competitive spend, we looked at some audit data from 2018 to understand where the current players in the space are spending their money. 88% of the spend is in physician-related activity, 12% in consumer. Why is this important? Well, as we look at the consumer spend, we can see that only about 16% of that is in internet search and internet display. This appears on the surface to be a relatively unique opportunity, especially as we consider what we talked about earlier, is that this population is between 80% of the acne population is between ages of 12 and 24. This is Gen Z. Gen Z spends about seven hours a day consuming media. Mobile accounts for well over half of that, anywhere between 50%-65%. They spend some time on their social platforms like Instagram, Twitter, and Snapchat.
85% grab their smartphone multiple times a day. I'm sure we all do. This group spends more time on Netflix and YouTube than they do on traditional television. The way to access this market wouldn't be from a DTC play, would never be through television. There are some very unique and innovative ways to get to this audience, where they spend their time. We're exploring that now, doing social media audits, et cetera. We believe that this is a market opportunity that still exists. As we talk to payers, one of the things that we have to consider is where they stand with dermatology. Before you read this slide from left to right here, what I'd like for you to do is think about where the payers' heads are as it relates to dermatology generally.
We did this study, 10 payers in this market research, and they cover over 230 million lives. Their impression of dermatology and dermatology drugs is not favorable. They look at this class primarily through an economic lens en masse. However, when we shared with them the product profile for FMX101, we saw that there was a pretty favorable reaction. They did not look at this as a me-too play. They looked at this as something innovative, a novel route of administration. They did believe that this would go to a full P&T. That's an important learning early on. As it related to that product profile, what was the expectation for net-to-plan pricing?
That was anywhere between $200-$400 net to plan, which means that, at least for this group, the value proposition spoke to this type of expectation of cost to them with some minor restrictions. And by the way, this shouldn't necessarily connote how we're going to price it. We have a lot more work to do with payer strategy and pricing. This is some good early signs, at least from a payer perspective, that there's a path forward here. Finally, as we think about how the competitors are spending. I talked earlier about the importance of positioning, as you look at the competitors of this space, there seems to be an arms race, who can shout the loudest, who can own the messages.
We believe, and I've seen this done in other markets, where you can cut through that noise very effectively with a sharp and unique positioning, we intend to do that. From a targeting methodology, certainly you can call on the 15,000 dermatologists that are out there, you can deploy a large footprint to get to them, you're going to get to all of the acne patients in some regard by doing so. The smarter approach is to go where the acne patients are, understand the predilection of the physician group for brands versus generics, new market entrants, et cetera, and really focus in on a tight target model. Finally, fiscal discipline.
We want to deploy some resources where maybe others aren't in the market and think through things that are a little bit more innovative, a little bit more outside the norm in dermatology, and invest in some of those high ROI tactics that we know through experience do work. Just to wrap up here, these are large markets. Acne is a large market, 7.5 million unique patients over the last five years. There may be an opportunity to engage and activate the consumer. Market access is always going to be, I think on the go forward, an area that we have to understand and work on, we do have some green shoots from the research we've done.
From a competitive spend, I think we can be smart about where we spend our money and have a focused and financial discipline that I think is important for a company our size. With that, I will turn things back over to Iain to talk about our pipeline. Thank you.
We've talked a lot about FMX101 and FMX103 and of course, Matt's presentation and about our commercial preparedness and our overall strategy is important. What's next for Foamix? Dave framed up at the start of our presentation today. We will talk about what is our other research interests and primarily in the acne foam areas. We do have additional researches in other dermatological conditions such as atopic dermatitis and others, of course, in the non-medical dermatology arena such as aesthetics. What I want to do today is talk about lead four projects that we have in development just now. You'll see these codes. I'll refer to them frequently throughout the presentation. The first one is a combination product, minocycline with adapalene.
We've already heard from Dr. Baldwin earlier on today about the appropriateness of combination therapy as it relates to targeting multiple areas of pathogenesis of disease. We feel this is a natural next step for the FMX101 chassis or formulation concept in acne vulgaris. FMX109 is nicotinamide, commonly known as vitamin B3, and the retinoid foam for acne vulgaris. I'll go into this in more detail clearly in the next slides. FMX110 is a topical doxycycline hyclate gel. This is our first move outside of the foams arena formulation, looking at papulopustular rosacea, ETR, and hidradenitis suppurativa. I'll explain what those particular disease states are in a minute. The last one, again, speaking to combination therapy, minocycline and benzoyl peroxide as a combination product. Starting with FCD105, combination with adapalene foam. Dr. Baldwin's already set this up primarily.
We really do need to target multiple areas of the pathogenesis of disease. We see this in combination therapy throughout the treatment and management of acne. Retinoids themself normalize keratinization. I talked about the combination of sebum and corneocytes. If they are not differentiated adequately, we do form this plug, and then really cleaning out the follicular apparatus is one of the key mechanisms for retinoids. Minocycline mechanism of action in acne, again, we talked about as being a bacteriostatic against the target organism C. acnes, which is a primary driver for inflammation. But we know that minocycline itself is also anti-inflammatory. The status of this project just now is formulation is actually complete, and the product is on formal stability. I'm pleased to say we put in a meeting request, a pre-NDA meeting request with the FDA.
Before we actually submitted the NDA for FMX101, we've completed a three-week dermal mini pig toxicity study with no remarkable findings. So we see the product at this stage at least to be well-tolerated, albeit a non-clinical model. We're about to initiate a three-month, which is the classical clinical dosing for acne, three-month dermal mini pig toxicity study basically this quarter. We actually anticipate having first subject into a phase II study in Q2 2019. So that's right around the corner from a clinical development perspective. I want to talk a little bit about that study. It's a proof of concept study. It's a classical monadic comparison study, where we compare the formulation components to each other versus vehicle. This is actually quite a substantial phase II study. It's 400 subjects, the moderate-severe disease.
It's not quite a one-to-one-to-one randomization, but we have a little bit more because we want to get as much safety information for FCD105 as possible. So we have a minocycline foam comparator arm, we have an adapalene foam comparator arm, and of course, we have vehicle itself. The inclusion criteria are very similar for the moderate-severe acne vulgaris group. In this case, we will actually attempt to have the full indication for acne vulgaris. I think this makes a lot of sense because we're dealing with multimodal impact on the disease state. So the moderate to severe acne vulgaris, and the primary efficacy endpoints that you've seen before is the absolute change in inflammatory and non-inflammatory lesion count at week 12, and a proportion of patients who have had treatment success, EG and IG of zero or one. This is certainly an exciting project for us.
This is our first foray into combination therapies, we're excited to get on with this clinical program FMX109, nicotinamide and retinoid foam. Again, Dr. Hilary Baldwin set us quite nicely. We know that the retinoids are effective therapies, but they also have their challenges as it relates primarily to irritation, onset of action. We already talked about this moment of crisis, where patients really are having quite a significant irritative profile or reaction to the product, but we're not really seeing the clinical benefits yet. That really is quite a challenge to do this. Nicotinamide is a vitamin B3 product. Really what it does is it actually enhances barrier integrity and actually has the potential to offset the thinning that occurs through retinoic acid therapy. Really to rebalance this irritative profile. Nicotinamide has been used for years in other OTC products.
It's always been known to have an effect in of itself in acne, but this nice interplay of offsetting some of the deleterious effects of retinoid therapy is interesting. It's also an antioxidant and is used in a lot of OTC products. What it does there is really prevent lipid peroxidation. Peroxidizing lipids deep in the pilosebaceous unit is one of the triggers for poor inflammatory cascades. It's not quite anti-sebum, but prevents sebum becoming a problem. What is very interesting is it actually improves this barrier repair and the cosmetic outcome. We feel this is actually going to be quite beneficial, particularly in patients or women who have late incidence acne.
It's very difficult to say to your patient, I'm sure Dr. Hilary Baldwin would agree, that you say, "Yeah, your lesions are clear, but you have a lot of this dyspigmentation afterwards." I mean, that's a nuance. They still look as if they have acne. They still look as if they have scarring. We want to see if there's a possibility we can at least reduce some of that. Where are we with this one? This is the clinical benefits that I talked about. I think one of the key things here right at the end is do we have a potential to offset some of this post-inflammatory hyperpigmentation, as well as having the power of two different modes of action directly onto the disease.
We could just take this forward and go straight into phase II, but what we actually have doing, we're looking to start this study in February. This is a proof-of-principle study. This is a small study. It's a bilateral acne models. What does that mean? It means that the patient are actually their own control. We can treat one side of their face with one therapy and the other side of the face with the other. There's no need for a vehicle comparison there, because as I say, the patient is their own control. We're actually evaluating two retinoids. We can do this with only 20 subjects. A very cost-effective way to understand the clinical rationale. It's clear that we actually do have this multimodal impact and potential cosmetic outcome that we all hope to achieve.
What we're really looking at is a relatively short four-week therapy. This is really the crisis point, as Dr. Baldwin talked about. The first few weeks on retinoid therapy, that's where the irritation comes hard and fast, and this is we really want to ensure that this concept is proved. The patients are treated with adapalene, and then one side of their face has 10% nicotinamide, the other side is a vehicle control. We're evaluating tazarotene and adapalene at their prescription strengths. It really is a dermal safety. We're actually looking at the irritation profiles very, very carefully. We're also looking at stratum corneum integrity, looking at transepidermal water loss, which is the model to actually determine the extent of dryness. We will look at efficacy, clearly.
We'll look at lesion counts, we'll also be looking at sebum production, and whether or not there is an actually impact directly on sebum as well. As, again, Dr. Baldwin talked about, that is one of the progenitors of acne itself. Most importantly, also at the end of here, we'll be looking at complexion analysis. What is the cosmetic outcome? Is the thesis proved that we have the potential to repair the mechanism and actually reduce some of the potential residues subsequent to inflammatory acne? The status just now, we've done penetration studies already for this, for the combinations. What we're looking at is prescription strength retinoids with an OTC product here. Proof of principle study is actually ready to go in February. We've submitted the IND to the FDA. We expect to have top-line results from this small study Q3 2019.
Pending all those results, we expect to have first subject into a phase II in the earlier part of 2020. Formulation developments are obviously work in parallel with all of this. Moving to FMX110, doxycycline hyclate for papulopustular rosacea, ETR, and hidradenitis suppurativa. I think doxycycline itself is a very well-used product in rosacea space. Very similar mode of action to minocycline itself. As an anti-inflammatory, its impact on matrix metalloproteinases really does protect the capillary membrane that really is ruptured when you go through these blushings, and this is where really telangiectasia is the ultimate outcome of this. Also has down-regulated cytokines. Again, we talked about this a little bit earlier on today, and its impact on erythema and inflammation. We already saw that with our local signs and symptoms data, where we actually see the erythema with FMX101 dosed topically is materially improved.
Oracea, we've referred to before, is first and second-line therapies for more severe papulopustular side, again, we have systemic adverse events comparable to SOLODYN. There is no topical product for doxycycline, which is where we see a very clear value. Of course, we're going to be progressing based on our clinical evidence from FMX103, the effects on clinical erythema. The status just now, development candidate selection is mid this year, where IND-enabling toxicology, we expect the Q3 2019, pre-IND meeting in Q4 2019, and we're starting the phase II dose finding study of the gel in the first half of 2020. It's important to say here that not only will we be progressing our rosacea indication here, we'll be progressing a indication in parallel called hidradenitis suppurativa. I want to introduce you that to what HS actually is. Really this is immune-mediated dermatological condition.
It is a serious condition of the hair follicle, sebaceous and sweat glands, and it is primarily affecting the axillae and the flexures of the body. If you can imagine the worst possible cystic acne in your armpits, groin, and flexural areas. This is extremely life quality limiting disease. The clinical presentation is manifestly large comedones, very large and painful weeping inflammatory nodules. It is folliculitis-like. These are boils, colloquially used terms.
What can actually happen is that these cysts and boils, they burst, they leak, they heal. And because you are dealing with flexures where you have skin-on-skin contact, the possibilities for deep scarring is there. And what you actually get is a concept called tunneling or sinus tracts. What happens is that the skin itself folds back on itself and you get really deep indurated scarring, up to the point where it can actually impact on mobility of limbs.
If you can imagine scenario where you can't move your arm up because the scarring is so dense in your armpits or buttock areas. Treatment options, there really is nothing indicated. What I would say is that antibiotics, corticosteroids, anti-TNF alphas, adalimumab or commonly known as HUMIRA, had orphan designation for moderate to severe HS a few years ago. Methotrexate, hormone therapy, all of these have challenges. We have already talked about many of them. What I would also say, particularly for early stage 3, this is, if you like, severe HS, skin grafting is actually an option for these patients. It is that serious. It is that life quality limiting. There is possibilities here in orphan and these indications, and we are certainly progressing that. I just today wanted to introduce to you, it is an acne form like disease state.
Certainly plenty of utility for tetracyclines in this space, and we are looking forward to progress this project in parallel with our rosacea activities. What does 2019 look like and 2020? This is our 18-month view of deliveries almost by quarter or what we anticipate. At the top end of the slide here, we have our late-stage assets we have talked about a great deal today. We expect our Day 74 action letter will be in Q1, if all things go well. We expect kind of in the mid-year FMX103 will have our NDA submission, as I talked about earlier in today's presentation. Our action date will happen in Q4 for FMX101, and the launch in the earlier part of Q1 next year. Of course, consequentially, the PDUFA for FMX103 would be a little bit later after that.
On the earlier projects, I talked about FCD105 will start our phase II study in Q2 this year. We spoke to have the clinical proof of principle data for FMX109. This is a nicotinamide combination with the retinoids in Q3. Moving into next year, clearly a lot of these projects are moving into maturity in the clinical environment. We expect to have top-line results in Q2 for the phase II study for FCD105. That is a combination of minocycline and adapalene. FMX101, we will start the study for phase II in Q1, and we expect to have our first phase II open for FMX110, doxycycline hyclate gel, again, somewhere between Q1 and Q2. I think with that, I will pass the floor to Dave.
Thanks, Iain, and thanks everyone for a robust discussion. Just to wrap it up before we turn over to Q&A. As I'm proud of saying, as a company, we continue to execute on our milestones on or ahead of schedule for all of our initiatives. As Iain outlined earlier today, we're pleased to be able to accelerate the NDA submission timeline for FMX103, bringing it up almost two quarters worth. We do believe from our discussions today, from our esteemed key opinion leaders in dermatology, that we do have the ability to address significant unmet needs for patients and healthcare providers with these two launches, which could be within inside of a year of each other. The new data for FMX103, I think again reflects positively on the impact of our key secondary endpoints, especially around tolerability of our product and patient satisfaction.
We have a very unique scientific message platform to talk about for our products. Obviously, this notion of the vehicle matters, I think plays a very big role. Certainly seems to be in today's day and age, if you can get a favorable view from payers, that certainly bodes well as you prepare for commercialization. At least all the indications continue to reflect positively on that for FMX101. We were very pleased to see those initial results. As I've often talked about, when we look at launching FMX101 and FMX103, there's a lot of efficiencies, a lot of synergy. That's almost as if you're getting two launches for the price of one, as we like to talk about here. I think that continues to make sense.
It continues to be reiterated from some of the comments that Matt was alluding to earlier. Our near-term pipeline activities, we could be very efficient utilization of our cash to get these done. These are not massive phase III programs, we can create meaningful catalysts inside the next 12 months for our shareholders. Also, as we have outlined today, I wanted to focus our pipeline on the potential durability of the acne and rosacea franchises. If you look just at face value, the programs that Iain outlined, we believe that gives us traction to 10- 12 years just on these particular products in acne and rosacea. These are meaningful franchises that we can develop, address significant unmet needs for patients and for caregivers.
I would say stay tuned as we continue to work on our pipeline activities for adjacent markets in medical dermatology, such as atopic dermatitis, leveraging our platform for medical aesthetics and the like, we'll provide more insight on that in the future as we come back together. With that, I'll ask Matt to join me up here, and we'll take some questions from the audience. I appreciate it. Thanks.
For those of you listening on the webcast, if you'd like to ask a question, you can send an email to questions@lifesciadvisors.com. Once again, that's questions@lifesciadvisors.com, and we'll direct your question to the panel here.
Hi. Thanks for taking my questions. Louise Chen from Cantor. I had a few here for the doctors. First, what do you expect for the pace of uptake for FMX101 and FMX103, assuming they get approved? Second question I had was on the reimbursement for dermatology drugs. How has this changed? Is it still good for patients? Has there been any obstacle to uptake as a result of reimbursement? Last question I get a lot is with respect to RHOFADE and if your product, the FMX103 product, can be used in combination with RHOFADE. Thank you.
I never do well with more than one question at a time. I think I remember the first question, which was the expected uptake... , I'm sorry?
Pace of uptake.
Pace of uptake. Okay. I'm sure you're aware that dermatologists are very fond of new products. Lots of people are practicing dermatology these days, pediatricians, the internists. What we want is a new product. We want it because when a patient comes to see us, we're supposedly the experts, and if everybody else has already used a product, we're recommending the very same thing that people have used before. Our uptake is always very brisk, for that reason, if nothing else. Here we have a product that is actually efficacious as well as new. We've had new products that weren't terribly efficacious, but we prescribed the heck out of them anyway, because we just needed something new and a new brand name. I expect it to be very brisk, especially for acne. The second was what?
Reimbursements.
Reimbursements? I have no idea. No clue whatsoever. It's usually pretty good for the first six months, and then we have to see about it afterwards. Certainly, reimbursement matters a great deal in terms of uptake for some derms more than others. I think Jon and I are unusual in that we work very hard to do the best thing for our patients to make sure that coupons are used, that we use specialty pharmacies, and we make sure that we really work to get the branded products out to our patients. Not everybody's like that. A lot of our colleagues say, "If I get callbacks from the pharmacy, I'm done here." It all depends on how well that whole thing is set up before the drug comes out.
Okay. The third one was RHOFADE, which I'll take. I'll go back and mention a couple other things. For RHOFADE, I think there's no reason to think that they aren't compatible. The question will be, if we see the degree of erythema improvement with the topical minocycline, the FMX103, will patients need to use the RHOFADE? That, I think, is the big question there. Compatibility, I see nothing about them that would make them incompatible with each other. Going back to the pace of uptake, Hilary mentioned a lot of different prescribers. Don't discount the number of mid-level providers or advanced care practitioners in dermatology right now. There are some factors that I think are very important there.
I think where dermatologists were 20 and 30 years ago before the Sunshine Act was in place, they appreciate what the pharmaceutical industry can do for them in terms of advancing their agenda in dermatology. I think they are very quick on the uptake. They are seeing a lot of the medical dermatology patients. This group of executives is very aware of that and has a group of advisors that make them very aware of that. I think that the uptake will be probably a little more brisk than you have seen with some of the other products, both based on that mix of dermatology providers and the sensitivity of this group to that.
That's good. Anything else?
Okay. Thanks. Anthony Vendetti from Maxim Group. Just a quick question for both Dr. Weiss and Dr. Baldwin. Iain mentioned that there's a low resistance potential for topical minocycline. Both Dr. Weiss and Dr. Baldwin mentioned using the topical minocycline for maintenance.
Right
Right, for many, many years. I was wondering if you It's early yet, what's your view of long-term risk? Obviously, oral antibiotics over an extended period of time have a much higher risk, what's your view of the long-term risk in the maintenance mode? Maybe Dr. Baldwin, you can answer this question, because on a certain type of acne that you had up there, and I can't remember which one, you said the first three lines of defense were, if I'm pronouncing this correctly, isotretinoin, isotretinoin. In what acnes or what situations would the topical minocycline be used instead of that product or in conjunction with?
I'll take resistance potential first. I think quite honestly, rosacea is an area where you'll get people to use it more because it's a longer lifespan of the disease, if you will. Based on my understanding of the science behind it, I think low is an overstatement of how much resistance potential there is. I think this is mainly a systemic issue, the absorption is so low. If we look at the left side of the S curve, I think that's our biggest concern. I think low resistance potential is overstating how much resistance potential there is. You look at the other side, it's all sitting on the skin, you're way above. I am not particularly concerned about developing resistance. Further, with systemic minocycline, we're not seeing much anyway, it is falling in that range.
Of all the tetracyclines out there, the number of resistant strains to minocycline is incredibly low. There's something about this particular molecule, now giving it topically with low absorption, low concentration systemically, where I'm thinking it's going to be almost negligible. Time will bear that out. I don't know how Hilary feels about that's how I feel about that.
I totally agree. First, I'm way more concerned about systemic resistance than I am topical. Affecting the gut is a much bigger story than affecting the skin, because the gut is the seat of much of our immune response, we now see association between gut health and Alzheimer's, atopic dermatitis, even learning disabilities. It's very widespread. The fact that it is not systemically absorbed greatly reduces my concerns about resistance in general. The second is that, what was that, three or four months ago that we learned about your mutant prevention concentration? We were flabbergasted. We got to this meeting. We had never heard of any of this stuff before. This is a completely different way of looking at antimicrobial resistance.
We were just sitting there stunned, we actually ended up thanking them for allowing us to come to their advisory board when we were finished, because it was such new information, we thank them greatly for bothering to do this and to instruct us on all of this. It's a completely new way of looking at things and has changed the way that many of us felt about the possible use of topical minocycline as a monotherapy. I think we all went into that meeting saying, "Well, this is going to be nice. It's going to be helpful. It's going to be a new drug. It's going to be better than clindamycin.
You know, I'm still going to use it with benzoyl peroxide because I would never feel comfortable using this without benzoyl peroxide because of the risk of resistance." I think we all left the meeting saying, "You know what? Not sure I have to do that. Think this might be useful as a monotherapy." Really, it was a complete mind change in a two-hour period of time.
The people at that meeting were some of the biggest names in acne treatment, both young individuals and people over the last 30-40 years.
If I could just quickly follow up and thank both Dr. Weiss and Dr. Baldwin for their comments. Echoing both questions, really comes back to the core of why we're doing what we're doing. I've said all along for the last several years, we certainly do not believe these products that we're developing for patients and caregivers are me-too products by any stretch. This is novel technology. This is novel work that we're doing from a clinical perspective. I think that makes a meaningful difference in the minds of caregivers, and also we're seeing it makes a meaningful difference in the minds of payers. Which when, as we are getting ready to introduce these products, are certainly critical in today's day and age.
That's why I think the information that we shared today is actually quite compelling and seems to be that as we've introduced this to, again, payers and to fellow dermatologists. I know we have more questions.
There was part two to that question? Which was-
Yeah, the isotretinoin. The picture was...
Right
..quite stunning.
Right.
The improvement with that particular treatment.
Those patients would not get better with topical minocycline...
Right
...in my opinion. If they did, oh my gosh. Right?
Yeah.
It would be a life changer. That's the kind of acne that requires isotretinoin. Minocycline, topical minocycline, in my mind, would be thoroughly replacing clindamycin, kicking a lot of patients out of topical dapsone, kicking a lot of patients out of benzoyl peroxide, only because it's a pain in the neck to use. Maybe giving oral minocycline a run for its money. There are lots of places in which I see this drug surpassing and supplanting the currently existing products, but not isotretinoin.
Hi, I'm [Ogesevar Patne], HCR Partners. On topic of antimicrobial resistance again, have there been any long-term studies or papers that have demonstrated actual development of resistance in acne for overuse of oral antibiotics? I guess what's driving the AAD or other bodies to kind of recommend decreased use of oral antibiotics? The second question is, with the launch of sarecycline, obviously it has a narrow spectrum design that's targeted against P. acnes. How may that fit into your treatment paradigm with FMX101, given that profile?
There are many papers, to my knowledge, about resistance to long-term use of oral antibiotics in the general medical literature. Maybe not with individual antibiotics, but especially in the macrolide group. Erythromycin, for example, is basically worthless in acne, both systemically and topically. Tetracycline, just plain tetracycline, which we can't even get in this country anymore, pretty much the same story, though doxycycline and minocycline have fared better. Sarecycline, again, I'm not sure we have the proof. It is supposedly narrow spectrum, but it's hard to know with systemic agents and plasmids and everything that can go on with cross-resistance, what's going to happen with this drug. It's just a little bit too early. We're thrilled to have it, don't get me wrong. We did those studies as well. I'm sure Hilary did as well.
The results we saw were actually, if you look at the data, were not quite as impressive, not nearly as impressive as it was with the topical agents. With this topical agent. Now, different populations, difficult to know exactly who went in, monotherapy. It's hard to know what the vehicle effects were of this. If you compare, it was probably similar investigators. It's hard to know patient populations, but they could certainly be used together, and whether or not you would replace it, I think that's just going to be a long-term feel.
We're increasingly concerned about this worldwide problem with antibiotic resistance, and the very medications that we use are on the list of drugs which have lost their potency over the years. To Jon's point before, minocycline has been a particularly hardy antibiotic. Things are changing, especially in Asia, and I think it was Dirk Elston who said that means that resistance here in the U.S. is only a plane ride away. We are seeing minocycline catching up to the others, and we would obviously like to avoid that if at all possible. The tetracycline class of antibiotics have long been considered by dermatologists to be a non-issue because they're sort of a garbage pail antibiotic, right? It's not something that's important, and it's like sixth line now.
It was important when we were residents for syphilis and gonorrhea, it's lost all that importance, but it's still first line for Lyme disease and for nongonococcal urethritis, it's still a very important antibiotic. Also for MRSA infections. We really don't want to lose the tetracyclines to antibiotic resistance, I think it's crucially important that we do our best to curtail that, and part of it is not using the orals. Trying to avoid it if at all possible.
Yeah. That was part of my point about sarecycline. Given that it is in the tetracycline family, could it breed cross resistance with the other tetracyclines? We just don't know. As Iain's graph showed, with the low concentrations that kind of fall in that mid-range of the bell curve, if it falls in those, and I do not know that PK data, that could potentially at some point be an issue. Especially with MRSA, would be my concern.
Hi, Inanç Caner here from Credit Suisse, filling in for Vamil Divan. I just had a question for Foamix management. I just wanted to know if FMX101 has been accepted by the FDA, or if you've seen any impact from the government shutdown that could throw off your review timelines. Sort of related to that, have you given any thought to commercializing the vehicle alone as an OTC product if there were to be some sort of impact?
Sure. First of all, regarding the dialogue and timeline with the FDA regarding our NDA filing of FMX101, everything continues to remain on track. We've actually had continued dialogue and exchange of communications with the FDA since the government shutdown. We anticipate, again, that we should receive final notification of acceptance of the filing before the end of the quarter. Again, all signals, indications suggest that there is no change to that. Which would continue to keep us on target, assuming the product was accepted for filing. We'll put a set of PDUFA somewhere in the fourth quarter, and if approved, again, a launch somewhere around this time next year, right at the turn of the year.
Thank you.
Regarding commercial opportunities for the vehicle itself, obviously we're quite proud of the unique technology as well as the intellectual property capacity of our vehicle, which has served us well for the products we've developed. I would just say we look at all possibilities. A product such as that is a different commercial entity, if you will. It's an OTC type of product. We'll certainly explore those options amongst others. I think as you can see, we have a pretty full plate right now in preparing for the launch of these products and then advancing some of our near-term pipeline candidates. It's not the first that this topic has come up, and one that we clearly take a look at on a routine basis. Thanks.
Hi, Patrick Dolezal, LifeSci Capital. Just a couple for the KOLs. Starting with Dr. Baldwin, could you just elaborate on some of the rare but serious AEs associated with oral tetracycline use? Perhaps touching on how they're managed and any potential costs associated.
Sure. Since tetracycline we don't use it anymore, we'll talk about doxy and mino. They have different side effect profiles. doxycycline, in my opinion, has more upfront nuisance side effects, nausea being the primary. The Achilles heel of doxycycline is the gastrointestinal tract. We have a lot of patients with pill esophagitis and nausea and such. minocycline and phototoxicity. minocycline has virtually no phototoxicity, and it has very few initial side effects unless you're using the immediate release minocycline. The extended release minocycline like SOLODYN greatly reduces the vestibular side effect, nausea and headache and blurred vision, which is really a very difficult issue for patients to deal with when taking it for long periods of time. It has more end-loaded issues.
They're very rare, but there are some oral minocycline problems that are of considerable import, like lupus-like drug eruptions and drug hypersensitivity issues. Minocycline is a more highly prescribed medication, and in my opinion is more efficacious, although there is no head-to-head between them that actually shows that to be the case. I think most of us believe that mino is a slightly more effective medication than is doxycycline. How we manage those with the GI is with the doxycycline is going to the enteric-coated delayed release formulations that end up getting absorbed later in the stomach and into the small intestine to reduce the GI distress, making sure they're consumed with large quantities of water, that patients don't lie down right after they take the medication. Perhaps take it on top of food, although we know that decreases the absorption of the medication.
You're trading a decrease in side effects for perhaps less efficacy when you do that. For minocycline, the answer in my opinion is to go to the extended release formulations, which does away with most of the side effects. Since it also decreases the dose, the extended release formulation is at one milligram per kilogram. You also reduce your chances of long-term side effects like hyperpigmentation.
Great, one for Dr. Weiss as well. When you're thinking about optimal product characteristics in rosacea, what level of emphasis should be placed on purely lesion reduction versus some of the more holistic aspects such as quality of life, and tolerability factors like improving stinging and burning?
I think they're both important. I think it's a conglomeration of everything. I think you have to present the whole package to people, quite honestly. I don't place one over another. I'm thinking about all of that when the patient's sitting in front of me. I know that's probably not answering your question the way you want it's the honest answer.
Thank you.
Hi. This is a question for both the doctors. What is the average cost sharing by a patient in your practice, and where do you think the dollars will come from for an FMX101 or FMX103, but probably more like FMX101 product? Do you think it'll be a net add for the patient in terms of incremental dollar outspend or a neutral because the dollars would come from something else?
You're much smarter at this than I am.
I wouldn't say that. Your term cost sharing and I was an econ major, so I kind of know the, if you will, the econ speak or the finance speak a little bit. I don't think of it in terms of cost sharing. I think of it as maximum tolerability of the patient for their dollar spent.
I think that is increasing over time. Started at $0 to $10, and I see it inching up where they don't bat at $25 and it's getting closer to $50 for a lot of patients, especially in the Northeast market. In beautiful Snellville, Georgia, where I practice- it's probably not quite that high. My patients can tolerate about $25. For the economic modeling of percentages of cost sharing, I think that is still complex and that's under evolution. I think by the time these products are approved, we're going to have a very different model than what we have right now. The current model is not sustainable, where you have the company that owns SOLODYN losing $15 on every prescription. That's not going to happen anymore. It just can't. They can't be a startup and do that.
What we're starting to see is acne products released, some of them at a certain dollar where they're going cash only.
The latest formulation of tretinoin did that, and it's a wonderful formulation. Previously, the uptake would've been much greater. Companies are going to have to model that as to how it works. Sarecycline, SEYSARA, is currently coming out under the old model. That will only work for so long. While I can't give you an absolute number, I think if they can make this product $25- $50 to the patient by today's dollars, I don't know what that will be when it's available, I think the uptake will be quite strong, especially for the rosacea variant when you're talking about adults, and the amount of product that they will use over a specified period of time.
It's going to be probably about $15 a month if you go to the high end of that for the patient, $15- $20 a month. Because all of our canisters were returned with a fair amount of product in them.
Especially if that's coming out of the patient's pocket, they're going to use it judiciously and appropriately. I hope that answers your question to your satisfaction.
We'll take the next question. Please state your name and affiliation before asking the question.
Hi, Bill [Mau], Cowen. For the doctors, to expand a little bit on an earlier answer, can you talk in any specifics that you're willing to give about how the availability of generics and the pricing environment does in any way limit your accessibility to branded drugs? Along similar lines for management, what have you seen in the pricing environment for specific products that are continuing to get reimbursed that gives you confidence in the environment.
I'm sorry, I didn't hear that last question.
That was for management.
I don't need to hear it. You were asking about the availability of generics. I'm one of those old-fashioned dermatologists who believe wholeheartedly in branded topical products for acne. I'm not always prescribing brands for eczema and for psoriasis, but I think in acne it makes a huge difference in terms of efficacy, but especially in terms of tolerability and also in terms of acceptability for the patients. I don't think that those things should be undervalued. Many patients come to me as a tertiary acne person, already having been on many of the generics that they came off of because of tolerability, or they came off of it because it's not effective. I merely switch them over to the branded products with the designer vehicles. They get better. It's all it takes. I'm a firm believer in, whenever possible, utilizing the brands.
Now, as Jon pointed out, things may change greatly over the next year. I may not be able to do that anymore, but right now it's a priority for me. I spend an inordinate amount of time, as does my staff, working to get people branded products. Not sure that's the case in your average derm office where time is money. That might not work quite as well. For me, brands are the answer. Generics are subpar second-line products for me.
Yeah. Just to, again, I'm going to turn your question or the answer around a little bit. To me, it's not availability of generics. It's all about reimbursement. Okay? Generics don't matter. It's is it covered or is it not covered?
That's true.
To me this is. Please don't take any offense to this. This is a question for the management team to ask them what are they going to do to do that. Because it has nothing to do with what else is available. The reason we're here is exactly what Hilary said. We believe the name branded products. Like I said when I showed you, don't look at the vehicle line so much, look at the combination line because the vehicle is doing so well because it's been formulated exactly for the conditions we're treating.
That's right.
It has utility in that, I've always said that some products ought to go over the counter with their vehicle, to treat the conditions that they're looking at, because it really would do well in an over-the-counter world. I think I would put it to them at a later commercial stage, maybe Matt, what are you going to do to make it so people like Hilary and I, and the PAs and NPs who really want this product for their patients can get it for the patients?
Right. That's an important point because there's got to be a balance between price contracting, patient access tools, synthetic access tools, things of that nature to make sure that the patients can get our drug. That's all work that's being done. Regarding your question on competition and where they price and what the access looks like, there's a full battery of analyses that we're embarking on to take a look at just that. Understand where products are coming into the market, where they're priced, what the access looks like over time. We'll also do the same on our drugs so we understand where our access at Cascade will fall over the period of time. We do know that in the current environment, new-to-market brands typically don't have reimbursement until they go through a full P&T review. That can take anywhere from three to nine months.
There are synthetic options that we can use to make sure that the patients get drug in that period of time. That's why targeting is so important to make sure that we are focusing on the right patient population so when there is coverage through their insurance that they're not boxed out due to an alternative diagnosis, et cetera. Does that make sense? Okay, good.
Yeah. To just add some additional color, I think as Matt outlined earlier today in his presentation, you can see clearly where the net cost of plan needs to be. Certainly seems, and these again, were 10 of our largest payers in the category, view this as being a full P&T review product, which is not often the case, especially for products in various derm categories. All the initial signs, which is actually a continuation of what we've seen in previous research, remains quite positive, and we're quite enthusiastic about it. Don't want to at all underestimate the work that will need to take place, and we continue to do this and have continued to do this for the better part of a year, and we'll be doing this for the next several months leading up to launch.
I think also one important point that goes to some of the pipeline products that we were outlining. The bar continues to be raised for us to bring new innovative products to the space that are going to address unmet needs. I think our dermatologists here outlined some of the challenges with today's existing topical therapies and also needs to not just clear lesions, which is obviously a major goal when dealing with conditions such as acne and rosacea. Can you actually improve the skin itself? Can you actually improve skin health? When we're looking at a combination of products that may have cosmetic benefits, again, that opens up a whole another realm of patient benefits and can bring a whole another group of patients to products like ours if approved. That's it? Okay. I think that exhausts all the questions.
Once again, I want to thank everyone for taking time out of their busy days and schedules, especially for those that are here in the audience working your way through the rainy streets of New York City. Thanks again for joining us and for those that are listening and participating on the webcast. Thank you all again very much. Look forward to providing you additional updates in the coming months and quarters. Thanks. Have a great rest of the day. Bye-bye.