VYNE Therapeutics Inc. (VYNE)

Investor Update

← View all transcripts

Oct 1, 2020

Good day and welcome to the Vine Therapeutics Physician Symposium on Amzik and ZILCZI. At this time, all participants are in a listen only mode. As a reminder, this webinar is being recorded and a replay will be made available on the Vine Therapeutics website following the event. We will be conducting 2 question and answer sessions during the formal presentations. If you would like to submit a written question, please use the Q and A function on your Zoom screen. If you prefer to ask your questions out loud, please use the raise your hand feature. Before we begin the presentation, let me remind you that some of the information on this webinar as well as the news release issued this morning by Vine contain forward looking statements as defined by the Private Litigation Reform Act of 1995. There are further details here on slide 2 as well as the company's filings with the SEC. I would now like to turn the call over to your host, Dave Domzalski, President and Chief Executive Officer of VINE Therapeutics. Please go ahead, Dave. Thanks, Sarah, and good morning and good afternoon, everybody. Thanks for taking time out of your busy schedules to join us for this event. We're excited. We have a lot to cover. Today is another exciting day for our company here at Vine. We announced earlier this morning that we officially are launching Zilksy, our topical minocycline foam product, 1.5% concentration of that product. That is indicated for the treatment of inflammatory lesions associated with rosacea for adults. So we are officially launching the drug today. We're excited about this. And I know Matt and the team will talk more about it throughout the course of our discussion today. So big day for our company. In terms of the agenda, I have a few opening remarks. Then I'll turn it over to Matt Wiley, our Chief Commercial Officer, that can talk about how we're progressing with the launch of Amzik. And then from there, we'll turn over to 2 dermatologists that can provide their experience since Amzik has been launched, Doctor. Ted Lane and Doctor. Julian Moore. We'll open it up then for a Q and A session for all of the panelists. From there, then we'll segue into a review of our commercial strategy and the market opportunity for ZILTI, and Matt Wiley will cover that. And then we'll have a presentation on the data that we have for ZILTI from Doctor. Linda Steingold. We'll open it up again then for a Q and A session for all the panelists and then I'll wrap it up with some closing remarks. So as I share, we're very, very fortunate to have 3 highly accomplished dermatologists that are joining us for today's session. If we can just turn to the next slide. First that will be joining us is Doctor. Ted Lane. Doctor. Lane is a Board Certified Dermatologist and Chief Medical Officer at Sonova Dermatology in Austin, Texas. He has a joint medical and master's degrees from Baylor College of Medicine and Rice University and specializes in diagnosis and treatment of skin disorders and hair disorders and is a physician trainer for Allergan on BOTOX, cosmetic, Juvederm and Voluma. We then can move to next slide. We're also very fortunate to have with us Doctor. Julian Moore, also Board certified dermatologist at Hollywood Dermatology and Cosmetic Surgery Specialists in Hollywood, Florida, Assistant Director of the Larkin Nova Southeastern University Dermatology Residency Training Program, has his doctorate in medicine from New York College of Phosphopathic Medicine, a postdoctoral NIH fellowship in dermatology and cutaneous malignancy at Mount Sinai Icahn School of Medicine. And then lastly, if we move to the next slide, we have joining us Doctor. Lynn Steingold, who's the Director of Dermatology and Clinical Research at Henry Ford Healthcare System in Detroit. She is the Division Head of Dermatology at Henry Ford Health System, has her medical degree from Pennsylvania School of Medicine, very active in a variety of clinical research areas for various dermatological conditions, is the treasurer of the National Activation Society and also a member of the National Psoriasis Foundation Medical Board. So again, thank you to Doctor. Lane, Doctor. Moore and Doctor. Steingold for joining us today. We look forward to your comments and discussion and then the question and answer session. So if we turn to the next slide, this has been quite a year of milestones for our company, Viant Therapeutics. As you know, we just changed the name of the company just about a month ago. If we look back over the last 12 months, it's been quite an active year for our company, with the initial approval of Amzik back in October of last year, so almost a year ago, then subsequent NDA filings for ZILSI, the merger with Menlo Therapeutics, the subsequent launch of ZILCY in January of this year, the eventual approval of ZILCY in May, and then in June, very positive results for FCD105, our combination product of minocycline and adapalene, had a successful capital raise on the heels of that Phase 2 data. And then obviously, it brings us to our point today, which is the launch of ZILTI. We also have scheduled our end of Phase 2 meeting for FCD105 later this quarter. So if we move to the next slide, again, it's been a great year for us, despite the fact that we're all navigating through unprecedented times with the pandemic around the globe. Despite that, we're very proud of the achievements that we've accomplished as a company. And as we look forward, our priorities as an organization are very focused. Obviously, we are in execution mode on the launches of both Amzik and ZILCZ. We intend to continue to progress the trial utilization of Amzik and continue to gain market share. And Matt will talk more about that today and some of the activities that we have ongoing as well as the underlying metrics that we're very encouraged to see. We are excited to leverage our operational infrastructure and our sales force, which we believe is second to none out there in the area dermatology, now with our 2nd launch with our product ZILTI. So we're going to focus on healthcare provider awareness over the course of the next several months and leverage the experience that physicians have had with Amzik and our molecule stabilizing technology to drive rapid experience and uptake for ZILTI. Obviously, for both these brands, Amzik and ZILTI, a key area of focus will be on payer acceptance and reimbursement. And then on the pipeline fronts, our most advanced asset is SED-one hundred and five. As I shared earlier, we had very, very positive results in the Phase 2 study earlier this summer. We believe it has the potential to be a best in class treatment if we replicate those results in a Phase 3 program. We have our end of Phase 2 meeting scheduled for the Q4 of this year. And then we hopefully embark on a Phase 3 program sometime in the first half of next year. We obviously have other products that we continue to develop and move through the pipeline. But our focus certainly in the near term is on executing on these launches while being very thoughtful and prudent in managing our cash and operating expenses. So if we move to the next slide. To sum up, as we think about VINE as an investment thesis where we've morphed and have evolved over the course of the last few years from really being a very small clinical stage company to now a fully integrated specialty pharmabiotech company in the dermatology arena. We're now a commercial space company. We have 2 products that we will be launching and are launching effective as of today. Strong IP with patents that go out to 2,030 7. We're building a robust pipeline. We've got great synergies that we believe we can leverage operationally and from a commercial infrastructure perspective. We've got a very experienced management team that's demonstrated that they can launch products, they can develop and bring products to approval and launch them. And we believe we're well capitalized as we've shared with the markets, our shareholders in the investment arena. We have $100,000,000 in cash as of the end of the second quarter. And we believe that that should get us through the balance of 2021 as we continue to build our business and grow our products market share. So with that, I will now turn the meeting over to Matt Wiley, our Chief Commercial Officer, that could take you through our commercial plans and our underlying metrics for AmZ. So Matt, take it away. Thanks, Dave. Good afternoon. Good morning to everyone. We can go to the next slide. I'll walk you through the original strategy and you may have seen a slide similar to this in previous presentations, but the commercialization strategy for Amzik is predicated on these four key themes. 1 is to position the product in a unique and ownable way. I think that you'll see as I take you through it, our story reflects that. We want to be able to mobilize consumers and typically 6 to 9 months after launch, after you've gotten a foothold in the market, you typically would deploy DTC efforts. So I'll walk you through how we're approaching that as we're getting into Q4. Efficient deployment, we've talked about this previously, but I'll walk you through the sales deployment model that we have and some of the impact that we've had on our targets since launch. And then I'll take you through where we are with access to date. So go to the next slide. So positioning is important. As we do market research, typically we look for attributes of product that rise to the top. It's not surprising and I've seen in diligence products that I've worked on over the years where efficacy and safety typically rise to the top, sometimes convenience does as well. And as we look at the competitors in the acne space, we see a lot of these products that have their positioning really focused in their message platform, focused on these three things. And while they're important attributes in market research, typically they're not as ownable as something that's truly unique to the brand. So as we think about our positioning, we want to make sure that we had a message that had good resonance and was very bespoke to Amzik. So as we go to the next slide, you'll see this in our message platform. We have built out our story that's predicated on the fact that minocycline is a known molecule. It's trusted molecule that's been around for almost 50 years. We were able to use the molecule stabilizing technology, which is the cornerstone of our positioning by the way, to overcome the challenges of getting this molecule into a topical formulation. And then of course, that leads to the fact that we have this brand Amzik that is redefining topical therapy for inflammatory lesions in moderate to severe acne. And then of course, the balance of the presentation that we communicate on a daily basis runs through our efficacy parameters, our safety profile, tolerability of the product, how to use the product effectively, and the affordability components and tools that we have in place. Next slide. So our reps clearly go out and make these calls every day using that message platform. We also use peer influence programs, speaker programs to help communicate these messages as well. To date, we've had over 90 programs. Now a lot of these had to transition to virtual due to the pandemic shutdowns. But we've made really good impact on healthcare providers. We've had over 1200 attendees to date in speaker programs. We've had we have almost 400 estimated attendees that are going to attend future programs. And as you may recall, we had a satellite symposium back in the Q1 where we had 338 total attendees. So the ambition here is to have educated over 2,000 healthcare providers in 2020 on the ANSIQ story through peer programs. Next slide. Now, as I mentioned, the consumer approach typically you wait 6 to 9 months after launch, so you can get good trial and good uptake of the product with your healthcare provider targets. That has been impacted by COVID-nineteen. And so we have pushed that out to Q4. But we've already in this, in late September increased our presence in search engine, paid search term acquisition. We've also launched or about to launch the Amzik Facebook and Instagram channels. And we're doing exploratory work with acne influencers on how we can build content for channels such as YouTube, Instagram and Facebook to get real life promotion presentations from those influencers in social media. Next slide. So how are we doing with the targeting model that we deployed? As you recall, we deployed 51 representatives that cover 2 thirds of the acne diagnosed patient population and about 3 quarters of the total acne prescriber prescriptions. And one of the things that we've been able to accomplish here, 94% reach on all of our targets. We define our targets by platinums and golds. So the platinums think of those as the highest decile physicians who see the most patients and have the highest volume of prescriptions. We've reached that group to 99%, which is great. And then 93% of our gold targets, some targets just are not easy to see. And so this is pretty good result 9 months in, in a pandemic. Next slide. So what is our penetration into these groups? Well, we've penetrated our target universe by over 50% year to date. And importantly, we're over 60% in our platinum group. Now the productivity of these overall, if you look at total target productivity, it's over 18 prescriptions per target and our platinum targets are generating over 27 prescriptions per target. Keep in mind that if a target had just written their first prescription, they were included in those averages. So these averages are weighted down by those that are coming on board. Part of our incentive compensation plan for Q3 was predicated on getting targets who had not previously written to right. And we've seen a lot of physicians come on board since that effort. And that's going to contribute to these numbers. But ultimately, as we continue to penetrate the market, we can count on at least 18 prescriptions per target and grow from there. Next slide. So where are we with market access? To date, we have roughly 63% of covered lives under contract. We're still waiting on one outstanding PBM. And so that contract is in motion. It is with legal. However, it is not yet inked. And so we're looking forward to getting that last PBM under contract. We feel like we've had great dialogue with them. But of that 37% that's not covered, 42,000,000 of the 65,000,000 lives in that bucket are due to this one PBM contract. And so we are cautiously optimistic that we get to 80% or better market in acne? These are branded new prescriptions and I've referenced these in other conference calls that we've had. But as we think about where the prescription volume was on a weekly basis back in 2019 in September, October, Where the market has healed to is just shy of that right now. It hasn't fully come back yet. We have seen some continued growth over time. Obviously, there's the Labor Day holiday in there for the most recent dip. But we expect to see that this market continue to heal over the balance of the year and get back to what we think will be normal levels. Next slide. One of the things that we're really proud of is how we've bounced back since the COVID-nineteen shut down. So obviously we're off to a very good start through mid March. The COVID-nineteen shutdowns happened in mid to late March, which impacted our growth through that month, but also really impacted April. And so from that point forward, we've seen nice steady growth at about 20% compounded over the last 5 months. Next slide. So this is a cumulative look at unique patients. And these are based on claims records. So this is not these are unprojected or raw counts. But based on these numbers, we have at least 36,000 patients that have now been on Amzik since launch. And that's a really nice number. Obviously, we do these things to help as many patients as we possibly can. So we're off to a great start and we believe that we have hundreds of thousands of patients to go. But it's good to that we're making an impact on these patients' lives. And I think you'll hear more about that from Doctor. Lane's and Doctor. Moore's presentations. Next slide. One of the things that we do measure is how many unique prescribers we have actively prescribing the drug over time. And to date, we have over 5,200 physicians or healthcare providers that have prescribed AmZinc at least once. And one of the things that's really impressive is as we had to pivot during the COVID-nineteen shutdown period, we were able to continue to grow the exposure of the brand and continue to grow the prescriber base over that period of time. Now that's a really important thing that we were able to do in that virtual timeframe because as the market comes back and as things get back to somewhat normal where the throughput of the patients in the practice heals and our ability for reps to go back and make details live in those offices also comes back that these patients have been exposed. They've at least tried the drug. And so this is a great thing to measure. We also measure how many unique prescribers are prescribing on a weekly basis. And we've seen anywhere between 1300 1400 unique prescribers on a weekly basis. So again, as the market comes back, that's a really important metric that we focus on every week. Next slide. One question that we get asked quite frequently is how many of our prescriptions are either new to market, or So this breaks that down for you. About 20% of our overall business launched to date are patients who have been on Amzik before. So that's those are refills. The new to market is right around 40% and those that are either switched to or added to something else is around 40%. And so when we break down the data that we have now, we don't have this broken down specifically by just pure switching. But we have done a little bit of digging into this to help inform which of these products are being switched versus which are being added to. It makes sense that most of the antibiotics are being switched from previous therapy to Amzik. And then products such as Akleif, Epiduo Forte, etcetera, we're surmising that that's being added to. There's ongoing analytics to break this down further. But just wanted to give you this view for your edification. Next slide. So this information is hot off the press. We have an awareness trial and usage study. We did a baseline back in Q4 of last year. We just got this information a couple of nights ago that we were able to call here. So these are physicians who are in our called on universe. So they're in our target universe and asked prompted whether they recognize or are aware of the products in the acne space, we can see that 88% of the respondents knew Amzik. And I think that's pretty good response in our called on universe, not surprising with those numbers. Given the fact that we've been on the market for just 9 months, and drugs like Seysara have been out a year ahead of us, to have similar awareness in our target group is a testament to our sales team and what they've been able to accomplish over the last 9 months. Next slide. This is also from the same study. And so we ask both in our baseline market research and in the most recent market research, what the anticipated usage of products on the market are. And so in our baseline, you can see that drugs like Seysara, Altreno, etcetera, the anticipated utilization on a go forward basis was relatively high. And you can see that after Amzik was launched in the most recent wave that we've done, the anticipated utilization of Amzik is better than 50% on a go forward basis. And you can see the products that we've displaced there. We're encouraged by this. We anticipate that those physicians who are just dabbling with the product to begin right now, those targets that we've just penetrated, their productivity is going to increase. And I think the numbers that I showed previously help support that this market research supports it as well. So finally, next slide. What are we heading, what are we focusing on as we get into 2021? Well, certainly as it relates to our positioning, we want to continue to focus on new patient acquisitions, so NRx generation. We want to more deeply penetrate into the target universe that we've created. We want to mobilize our consumers in a more meaningful way in 'twenty one. So as we're going through our consumer mobilization efforts in Q4, There's a lot of measurement that we will do to ensure that we are focusing on tactics that have meaningful impact on the market and mobilization, and we will amplify those and put more resources behind those in 2021. Obviously, getting to our targets and we're deeply penetrating not just the platinums, but also the golds in 2021 is a top priority. And of course, finalizing the access ambition of having broad access for our patients so we can reduce our reliance on denial conversion and synthetic access programs. With that, I'll turn things back to Dave. Thank you. Thanks, Matt. Really appreciate the updates. As you know, this event is a physician symposia and the focus is really on what our physicians' experience been with Amzik and Wistarview on Zolksy. And as I outlined when we kicked off the event is that we're really fortunate to have 3 physicians from different parts of the country, Texas, Florida and Michigan that are widely published, done a tremendous amount of research, participation in various clinical trials, but equally as important to see a lot of patients and really can speak from their vantage point about how they treat patients for these conditions, what are the products in their armamentarium and then how do our products, AMC and Silksy fit into that, not just today, but their view on it in the future. So with that, I want to turn it over to Doctor. Ted Lane from Austin, Texas. So without further ado, Kathleen, take it away. Thanks. Thanks so much, Dave. And I appreciate being here. I hope I'm not in the silver group of that platinum and gold. I hope there's not a 3rd silver group. We'll talk about that later. So the Amzeq topical foam, 4%. I just wanted to give you the point of view of a dermatologist in the South. I was also luckily involved in the Phase 3 trials. I was a principal investigator in the Phase 3 trials for ANZYK as well as ZILCSI in the Phase II trials for the novel combination product. So I'm well aware of both Amzek and ZILCSI as well as the pipeline for Vine and it's all very exciting. Next slide please. So obviously this is not a CME accredited program. I am a consultant and receiving compensation for this presentation today. I also have been a principal investigator and am a speaker for the company. Julian and Linda would agree with how I approach, they probably have their own approaches. But the first thing I think about with an acne patient is what do they want? Are they wanting to get clear? Of course, all of us want our patients to be 100% clear. We know the psychosocial impacts of acne, even 1 or 2 pimples has a deficit on their quality of life. And so we strive for clear, but are the patients wanting to get to clear and if they are, how much are they willing to do to get to that endpoint? The other thing I think about is how am I going to optimize compliance for this patient? And of course, that varies from a teenage boy to a teenage girl to an adult. And will they tolerate a retinization for example, as we know the retinization is during those first 2 to 4 weeks of using a topical retinoid where you can get that redness, dryness inflammation? Will they tolerate the initial flaring that can accompany the retinization? And then finally, if I think they would benefit from an oral antibiotic, will they take it for the 2 to 3 months that I think may be necessary in order for them to see the full result? So we go through that as well. And then finally, my third goal is what is the reason for their acne? Is there an inherent driver? So for example, is it hormonal if I'm talking to a later teenage girl or an adult woman? Is it primarily hormonal? If I'm looking at an adult male, does he have sebaceous skin? In other words, does he just have genetically oily skin? Or is this truly just a bacterial overload like we're talking about with commonly with the teenage boys where there's a hormonal plus cutie bacterium acnes infection. So really I try and think about what's the main issue that I'm trying to solve for here. Let's go to the next slide please. So when we look at the AAD acne management guidelines, you can see here first line is on the top left, right? And then we have the severity of acne going across on the top, okay? When we look at the first line, you can see the topical combination therapy for mild includes an antibiotic plus BPO. When we go to moderate, antibiotic plus BPO. When we go to severe, antibiotic plus BPO. So that's because the antibiotic that we've had or the antibiotics I should say that we've had to use included clindamycin and erythromycin. But we know that there's so much resistance on the part of cutibacterium acne is the bacteria that causes acne or that's involved in the pathogenesis of acne, I should say, that we've had to combine them with Benzoyl Peroxide, That's what BPO stands for Benzoyl Peroxide in order to reduce the resistance. However, Benzoyl Peroxide can cause irritation. So there's downsides to using Benzoyl Peroxide as well, not to mention bleaching of the clothes, for example. Next slide, please. So when I start thinking about my acne patients, I was forced to think about my prescribing habits, as I put together the slide deck, which was actually quite insightful for me. And I realized the retinoids that I were using were really the new generation retinoids, right? We were I was prescribing quite a bit of Akleif and Auraslo. I still hung my hat on Epidural Forte, which again has the Benzoyl Peroxide in it. Generically, I was using a lot of I still am using quite a bit of tretinoin.05 percent cream. And then of course, for those patients who would benefit and I could perhaps could not substantiate a prescription retinoid, the over the counter different 0.1 per cell at different 0.1 percent gel at $15 to $18 is just quite a bargain for them. The non retinoids of course, Amzinc is at the top of the list. It's replacing a lot of the axon and azelaic acid I was using and then of course we have the Benzoproxide and clindamycin combinations which are also being replaced by the monotherapy MZEEK as well. So systemically the tetracycline class antibiotics continue to dominate. I tend to be transitioning much more to Seysara than from the doxycycline and oral minocycline because of the narrow spectrum and the lack of systemic side effects that we see with Seysara. And then other antibiotics are listed there. Spironolactone for its anti androgen effects, especially in the adult and later age teenage girls and women. And then Accutane as necessary for that severe nodulocystic acne or that acne which does not respond to conventional therapy. And finally, if I have somebody who just really wants to try something different than the topical and oral medications, we'll talk about the unconventional therapies such as sebaceous or blue plus or minus photodynamic therapy and of course we also have peels and facial disease. Okay. Next slide please. So in my algorithm as I've already touched on, definitely replacing the single agent clindamycin. I was moving away from that anyway because of the resistance. It's also replacing Benzoyl Peroxide and clindamycin combination products. Axo and absolutely it's delaying or absolutely replacing oral antibiotics and then it helps to delay isotretinoin use as well and I firmly believe that, especially if I feel like a patient would benefit from isotretinoin, but we're in the middle of summer in Austin. It's really difficult to initiate an isotretinoin course in the middle of summer. So if I can delay that until the fall or winter with a topical antibiotic such as Amzick, I'm definitely going to do that to allow my patients the benefit of taking isotretinoin during the fall and winter months when it's just much easier here. Next slide please. So what are the compelling factors of Amzik? I've tried to think about this both in terms of with my MV as well as the MBA. What are the compelling factors as we talk to this audience? So we know that minocycline taken internally has multiple possible side effects and therefore possible limitations as well and those are listed there. But we also know that tetracycline class antibiotics are anti inflammatory. So their use, especially topically for acne and rosacea makes a lot of sense. We also see why oresia for example, that low dose slow release form of doxycycline has done so well in rosacea because of its anti inflammatory effects at that dose it's not antibacterial. So we also have the AAD, the American Academy of Dermatology kind of pounding on our doors that we need to have antibiotics stewardship. In other words, dermatologists comprise 1% of all physicians that write 5% of all antibiotic prescriptions. So we know that we are overrepresented in terms of the number prescriptions we write. And so if we can reduce our prescription, our systemic antibiotic prescriptions, that would go a long way towards antibiotic stewardship and the goal of our society. Finally, we're looking at the efficacy and tolerability trade off. And historically, when we think about topical medications in particular, there is usually if they have high efficacy, they're going to have poor tolerability. And poor tolerability by that, I mean, it could cause redness, scaling, dryness, thingy, burning, and itching. So if we can have topicals now that don't have this trade off that are not on the teeter totter of efficacy and tolerability, that would solve a lot of issues for dermatologists and patients alike. We tried that with axon 5% BID twice a day and then Axon 7.5% once a day. And the efficacy was okay. It was the tolerability that I think really drove the success of that product. But now, we have pharmaceutical companies such as Vine who are coming out with either novel compounds or novel formulations of existing compounds that allow us to really not sacrifice efficacy for the tolerability. And then the last point, we need to be able to apply the medications to the face and trunk. There's some recent data that's come out showing that 60% to 70% of patients with acne on their face also have acne on their trunk. And dermatologists historically have done a poor job at asking patients about their truncal acne. And yet we know now from research that the truncal acne certainly has an impact on their quality of life. And therefore, it's incumbent upon dermatologists to not only ask, but also examine the chest and back during an acne visit and to treat that. And we just haven't had really good compounds or good data to show that we can treat the face, chest and back. But with a foam formulation such as this with Amzek, we really can now use one medication, therefore one co pay for the patient to treat the face, chest and back. Next slide please. Other compelling factors, you know, we touched on this before. Numerous studies have showed community resistance to clindamycin. And in fact, there was a study that came out in 2019 in the American Journal of Clinical Dermatology showing the resistance of P. Acnes to clindamycin increased from 4% 99% to 90.4% in 2016. And so if we look at, just the number of clindamycin topical clindamycin prescriptions written, I think there is an idea of what the market is for Amzique. And so we'll show that in the next slide. But again, we had to add the Benzoyl Peroxide to the clindamycin to solve this resistance issue. Let's go to the next slide and it's quite illuminating, I think. So 6,900,000 prescriptions written for clindamycin, phosphate and erythromycin, okay, generating over $1,000,000,000 in revenue. So if we think about just the opportunity for MZEEK to capture some of this monotherapy and topical antibiotic. I think it's just huge. And I think the points that Matt made in terms of the number of speaker programs that have been given and the number that will be continued to give are going to be really important because it shows the science behind Amveek in that speaker deck, as well as the efficacy without the tolerability trade off. And so I think that it's just changing behavior in many doctors. Certainly the topical clindamycin prescriptions may not all come from dermatologists. I personally hope they don't and many of them may come from primary care doctors. The primary care doctors will learn about Amzick from the dermatology colleagues and realize that it's a better option in my view than topical clindamycin and erythromycin because of the resistance. So they just may not be aware of. Next slide please. So we think about IgA treatment success. I think when you a topical antibiotic may not reach the IgA treatment success that you think others that we use may. And certainly this has been the case when I've given speaker programs that dermatologists have come in a little bit a little bit skeptic of the IGA success of monotherapy minocycline product. So here we have 3 separate trials. Okay. This is not head to head. These are 3 completely separate trials. 1 is Amzick, of course, the minocycline foam 4%. The other one is Arazo, the cesaretein lotion 0.045% and Akkleaf, which is the triferatine cream, another retinoid focusing on the gamma receptor subside 0.05%. So what I wanted to show here is, of course, we're not comparing, you cannot compare between Phase 3 trials, but I wanted to show each trial individually to see, you know, dermatologists will remember from one speaker deck to the next, from one publication to the next, what that IGA success is. There's a number of, you know, obviously we remember 3 things from every lecture that we hear. Hopefully you remember more than that from mine, but, you remember 3 things. And so, we remember 30% as an IGA success. When you look at, arousal, for example, 30%. You'll see that in some other Phase 3 publications. IGA success. Now what is IGA success? Just to remind you, IGA success means achieving clear or almost clear on the investigator's global assessment. This is the investigator walking into a room, assessing the acne patient at a arm's length and giving a very gestalt, overview of the severity of the acne. Now, every trial that we do has their own IGA training. And so we have been well trained in IGA, especially those of us who have been doing this for a while have been well trained in IGA. And so, you know, IGA baseline also plays a role. It's important to understand this because, you know, the AMZYK trials allowed those with moderate and severe patients. And so if you think about the hurdle that is needed to overcome in order to get clear to almost clear, if you have a substantial number of patients that have an IGA of 4 and they which is a severe acne patient, okay, and they need to get to a 0 or 1, a clear or almost clear, that's a much larger hurdle than for those that are only at an IGA of 3, okay, or at a moderate. So it's important to understand those trials that include those severe patients in those trials that don't when you're when you are looking at the IGA success. So I think here again, not comparing trials, we cannot compare trials unless there's a head to head. What I'm showing here is the data from each trial. And I just wanted to convey that yes, this 30% idea of IGA success rings true with Am Zeek as it does for some of its contemporary competitors. Okay. Next slide, please. Okay. A little bit of an eye chart here. So if I could just walk you through this. So FMX 101 is of course Amzik on the left. That's, the left set of 4 columns and then the vehicle foam is the right set of 4 columns. This is from the pivotal trials and we're looking at the tolerability assessments on the left hand column. Erythema, which is, of course, redness dryness hyperpigmentation, which is brown spots on the skin skin peeling, which is literally, as it says, peeling of the skin and itching as reported by the patient. So what we're showing here is the tolerability what we call the local tolerability assessments of the application of the either FMX101, the MZ or the vehicle foam. And you can see here the vast majority of patients had a rating of none in regards to how well their skin responded to the, to Amzik in the left hand 4 columns and the vehicle in the right hand 4 columns. And you can see actually that in some cases, it looks like Amzik numerically did even a little bit better than just the vehicle by itself. So certainly no safety signals that we see here with AmSeq versus the vehicle and the vast, vast majority of ratings of these adverse events for the local tolerability assessments were either mild or moderate. There's just very few severe, the rating of 3 that you see for FMX101 and the rating of 3 for the vehicle. They're very, very few severe and certainly that number is consistent between FMX and vehicle. So excellent tolerability here. So as I showed before, we have the efficacy of about 30% achieving the IGA of clear almost clear at week 12 and here we have excellent tolerability as showed in the local tolerability assessment. So we don't have that trade off, which is what we're all striving for in dermatology and what is great for our patients of efficacy and tolerability. Next slide, please. Okay. Patient selection. So where do I think that AmZek fits in as I look at the patients that I treat? So patient sensitive to side effects. So teenage girls and adult women are notorious for, especially teenage girls, if they get dry, they stop using. They absolutely just stop using products. And even if you walk them through the retinization idea and you tell them to use a moisturizer and you incorporate gentle cleanser and you do everything you possibly can in the room to get them prepared for it, they will stop using it. Now you also have to think about where we are right now with the COVID-nineteen pandemic and all of us wearing masks. I don't know if any of you have experienced any increase in acne or rosacea or any kind of irritation underneath the mask, but certainly if you're experiencing retinization, that redness, dryness, irritation while wearing a mask, it can amplify those symptoms and make it even harder. So that's something that I think about as well. Patients needing combination therapy, again, teenage girls and adult women because we often think about hormonal therapy that we need to deal with either with birth control or spironolactone along with topicals. And then you have the 3rd group of patients who they want to avoid systemic therapy. I mean, I live in Austin, which is an area where many patients have adopted a lifestyle where they where they really try and keep it all natural quote unquote and would like for me to treat everything with essential oils. But really, you know, if I even bring up a systemic antibiotic or systemic therapy, they'll kind of laugh in my face. So I really need to be careful, in, you know, choosing the right patient and giving them the options just to make sure that it fits in with their lifestyle and their choices. Next slide please. Okay. So I wanted to go through 3 patient examples just to give you an idea and make it more real and tangible for you. So this is a 17 year old female. I'm sure Julia and Linda, my colleagues, would agree with this type that we see these patients multiple times every day. Mixed acne, in other words, meaning that she has both pimples as well as blackheads and whiteheads. Very anxious about her skin texture and tone in particular. And as I mentioned before, this is a patient where you've got to be really careful with, dryness because you have most likely stopped using anything that makes her feel her skin feel or look dry. She has anxiety about her acne and she scratches at her acne bumps to get rid of them that could lead to scarring. So we also have to stop this pretty quickly so she doesn't get more scarring as you can see on her forehead she's developing scars on her left, your right. And she wears copious makeup in order to cover the acne. So this is a very typical teenage female patient in our practice. So what will we look at? Well, of course, you know, we're going to think about is does she get worse around her menstrual cycle and we'll target hormonal therapies, if not, maybe an oral antibiotic in order to get things under control very quickly. But otherwise, I'm really focused on what I can do to help alleviate her acne without causing the local tolerability side effects that could lead to her discontinuation and poor compliance. And so this would be a patient where I'd either use MZeq by itself or possibly combine it with Axon in the morning trying to avoid anything that could cause dryness. Now, the nice thing about next slide please. And let me talk about some of the other nice things about MZ. Here's a 32 year old woman, again, an adult female coming in with acne that, you know, she'll come in and say, look, as a teenager, I have beautiful skin and this just started. And I don't understand why and it's on my lower face. And yes, I'm covering it up by the mask, but the mask is making the pimples hurt worse because it rubs on them. I mean, this is a common story that we all hear right now. She's tried multiple over the counter treatment options. She's gone to Sephora. She spent her $500 a month and she just isn't getting anywhere and she comes in quite desperate, wanting a fix now. So this is someone again that we may consider spironolactone or even a birth control pill to work on the hormones because usually in adult woman when the acne comes up, there's a hormonal component. And then I'll talk about using a topical MZEEK either morning or night because again, she won't tolerate dryness either and we have to be very careful with what we use. And if I can make her regimen easy, she'll appreciate that even more. She's a busy 32 year old woman, most likely a young mother. So we have some treatment considerations that we have to think about in terms of the social impact for her, kind of her lifestyle and what she'll be able to use as well. So Enziq fits very nicely into this patient population as well. And the next slide please. And then you've got this guy, right? You've got your average 15 year old male, lots of pimples, lots of pus bumps, lots of open and closed comedones. His mom is there with him. His mom is spreading over his acne and he really couldn't care, right? We've seen these patients as well and many of you have either been this patient or maybe have this patient as your son. I certainly do. So this is a kid that doesn't care, but the mom will not let his skin look like this. And so then I've got to think about, okay, what am I going to do to get this kid clear? Because whatever I do, he's going to want it's got to be easy so that he'll be compliant, but he'll also see results and make them all happy as well. Well, I know I'm going to need a retinoid most likely for this kid because he has a lot of blackheads and whiteheads, okay. And retinoids do a really nice job with that. And plus or minus Benzoyl Peroxide, I don't know, but a retinoid for sure. So as I think about what can I pair with a retinoid to decrease the dryness, certainly I can use the cleansers and the moisturizers, but you know, if we're all being real here, how often will a 15 year old use a moisturizer? And SEEK has in that canister, it's not only got the minocycline 4%, but it's also got coconut oil and soybean oil in it. So it's moisturizing as well. So I know that we'll add some moisturizing components to this patient's regimen by using Amzeq in the morning and it will allow me to better tolerate the retinoid at night. So that again, that's just what goes through my mind as I'm thinking about the treatment options of how I can make sure not only that I get this kid back and better, but that he'll tolerate it, be compliant and see results. All right. Next slide, please. Okay. So here we have a patient in the clinical trial. This is an IGA of 4, severe patient, as I mentioned, remember that the ANZY pivotal trials included IGA of moderate and severe 34. So this is an IgA of 4 patient you can see on the top, getting to a mild, okay. So improvement from IgA4 to IgA2. So this would not be considered a clinical success, right, because we didn't hit clear, almost clear. But if you're talking monotherapy, one treatment, one product, excuse me, that's the MZ, that's all she was on in the pivotal trials, course, with just a gentle cleanser, moisturizer and sunscreen. Getting her from an IGA of 4 to an IGA of 2, that is quite impressive, especially with a foam formulation that is moisturizing as well. So it kind of not only helps with the acne, but it may also help repair some of the barrier defects that we see with acne and moisturize the skin as well. And so we see here as mentioned that the IGA success, which again was clear, almost clear, you can see in that paragraph just underneath the title, was 30.8% with the AMZYK and the percent lesion reduction in terms of inflammatory lesions, which are the pus bumps and the red bumps, the papules and pustules was 43% for vehicle and 54% for AMZY. So we have statistically significant difference there in the reduction of inflammatory lesions as well. All right. Next slide please. Legal requirement here just go over the important safety information or ISI. Of course, this is indicated in children 9 years of age and older as we know that the acne is tending to occur in younger and younger children. So to have that 9 years of age and older indication is excellent. For the treatment of pimples and red bumps, non nodular acne that happen with moderate to severe acne in adults and kids should not be used for the treatment of infections. We talk about that in the speaker deck as well. It is not known if it's safe for children under 9 years of age as well. It shouldn't be used in patients who are allergic, women who are pregnant or who are trying to become pregnant. It is it has flammability because the propellants. And so we talk to patients about not using it around a flame. And of course, they should protect their skin from the sun. And when taken by mouth, minocycline may cause feelings of lightheadedness, dizziness or spinning. We talked about how that is what are the limitations of systemic antibiotics such as minocycline are these systemic side effects and why AmZinc really is such a novel and great compound for us to have. Okay. Next slide. I think that's the end of my presentation. And I thank you very much. Thanks, Doctor. Lane, for that comprehensive overview and your insightful thoughts on how you've been treating patients and how Amzik fits into your armamentariums. So that could get very much and stand by, we'll bring you back in for Q and A in a little bit. So I want to turn over now to Doctor. Moore from Florida down to Miami area that can share his experience and his perspective on how he assesses and treats patients and how Amzeca fits into his treatment regimen. So without further ado, I'll turn it over to Doctor. Moore. Excellent, Dave. Thank you very much. Do you hear me? We can. Excellent. Ted, thank you very much for that very comprehensive overview. So, from the perspective of my presentation, I really want to sort of highlight some of the patients in my practice. I think Doctor. Lane did a fantastic overview of some of the studies and showed some of his clinical patients and I want to do a bit of the same and kind of just drive home some of the salient themes of how I use Amzik and why it's important to me in my practice. So next slide please. So just as some consultant disclosures, this isn't been hosted by Vine. It's not a CME accredited program. I am a consultant speaker for Vine and VINE and receiving compensation for this today's event. And I do get compensated accordingly for lectures that I do with VINE. And all the clinical pictures that I use today are patients that are in my practice. They have been consented for use by these patients. And it's important to note that individual results may vary. Next slide, please. So, Doctor. Lane covered this very thoroughly. The historical, treatment paradigm typically, and this is a very sort of abbreviated view, for the mild patients typically will use topicals and those topicals can be prescription or over the counter. When we move into that moderate patient, the oral medication certainly will be an option, be it antibiotics or spironolactone and some other orals as well as prescription topicals. Now when we move to severe, certainly we're going to use oral medications as well as prescription topicals as well as potentially oral isotretinoin. Next slide please. So relative to the epidemiology of acne in the United States, roughly 50,000,000 people suffer with acne vulgaris. It can affect roughly 85% of teenagers and it can occur at most ages and even persist into adulthood. It's associated with a significant amount of physical as well as psychological morbidity, including permanent scarring of the skin as well as poor self image and self esteem issues as well as depression and anxiety. And we'll talk a little about that as I have one patient who exhibited some of these effects. We'll show that later on. And then relative to its direct impact, relative to cost and indirect costs, totals roughly $3,000,000,000 So folks, we have a captive audience and to have Emsyek, this novel minocycline foam formulation in our therapeutic armamentarium is most certainly beneficial. Next slide, please. Okay. So Doctor. Land again covered this very thoroughly. Relative to efficacy, our Phase III clinical trials showed fantastic results relative to systemic exposure. Kudos to Vine for a very good study looking at maximum use where they essentially compared oral minocycline at 1 mg per kilogram versus topical minocycline at 4 grams, topically daily for 21 days, which is actually 8 times the dose that we use in Amzik. So much more powerful for their maximum use study. And, they assessed the serum concentrations comparatively between the oral administration and the topical. And there was a 750 fold decrease in the topical versus oral. So taking it orally, certainly the systemic absorbent is much more and that sort of plays well into its safety profile. So it's a minimal adverse event profile. And, you know, essentially what we looked at as Doctor. Lane showed up was the redness, the irritation, skin peeling, burning, hyperpigmentation, which are all, I'll tell you real issues in the acne space. So 95% of the skin reactions were considered none or mild in the Phase 3 clinical trials. Relative to the patient experience, which is so important because often when you're dealing with teenagers or even young adults, the cosmetic elegance of the formulary, it bodes and plays so well into you know, whether they're going to use it or not, compliance is a big issue. And if it doesn't feel good going on, if it's irritating, if the patients are just not satisfied with the way it feels going on, they're not going to use it. So patient experience was very positive. A relative results again, the Phase 3 clinical trials showed a significant reduction in inflammatory lesions and a relative accessibility. So eligible patients will pay as low as $35 for the medication. Next slide, please. So, Amzeq, this topical novel foam formulation indicated for the treatment of moderate to severe acne in patients 9 years of older. Okay. Next slide, please. Excellent. You know, I like to the clinical images really, I think, tell a story. And let's start with this first patient. So this first patient was a very sweet and spirited young lady. She represents a very interesting subset of patients in my practice that I think Doctor. Lane and Doctor. Steingold can sort of relate to. She presents to my office and she's the kind of patient that says, okay, Doctor. Moore, I have acne and I need it to be gone tomorrow. And, this particular patient actually was the maid of honor at her sister's wedding. She had a series of events that was coming up in the week in terms of a bridal shower and the wedding was in 4 weeks. So she comes into my office and she says, Doctor. Moore needs to be clear in a week and I need to stay clear. You know? So I think we can all relate to these patients who want to be cleared yesterday. And what was interesting about this young lady was that she had tried over the counter medications. She tried prescription clindamycin with no improvement. And she also clearly said to me that, Doctor. Moore, retinoids make my skin worse. I can't afford to use that right now because I have pictures to take in and make sure she was very adamant about getting clear and no irritation. So I think that again, my colleagues can relate to this patient, wants to be cleared yesterday, can't tolerate anything. So if you look at her baseline presentation, you can see on that right cheek, she had significant redness or what we call erythema. You can see that those inflammatory papules were pretty evident and relatively extensive regarding the right cheek. So we, and it was on both cheeks and the face as well. So we started her on MZEEK and monotherapy and you can see and I'll tell you something. So the little caveat to the story is that we were able to get her relatively clear for that bridal shower and wedding. She sent me some beautiful pictures of the wedding and how well she did. And she was really singing the praises of AMC. So you can see this continued out to week 12. If you look at that digital image there at week 12, you can see a significant reduction of inflammatory lesions. There was less dryness and she achieved and maintained clinical clearance. So these are the success stories that I'd like to sort of highlight. And one point I want to make here with this patient, number 1, is that we were able to achieve clearance with on label use of MZEC monotherapy with this moderately involved patient. And the therapeutic efficacy was clear cut and it was sustainable with excellent tolerability. So she didn't complain of any irritation, no skin peeling. She was able to be that beautiful maid of honor and take great wedding pictures of which she sent to me. So we as clinicians love these success stories. And I'll tell you for me as a dermatologist, it never gets old. In fact, you know, I always tell, I train the residents and I always tell them never be pedestrian or less than enthusiastic about the acting patient. And my colleagues relate, when you're on that 50 or 60th patient of the day and you had already 25 acne patients, You know, sometimes it gets a little easy to be less than enthusiastic and to be a pedestrian in your approach. But I always encourage young residents, get excited about that acne patient because the dividends that you stand to yield in terms of self esteem with that patient, getting that patient clear, getting that patient in that wedding, taking great pictures. I'm going to show you a patient in 2 who also to really, it just, you stand to make some great strides and the acne patient really provides that. Let's go to slide, patient number 2 please. So again, the wonderful opportunity to do some very unique things in these patients' lives, not only in terms of clearing them, but also personally. I'm going to lift that up with this patient number 2. So patient number 2 was a 21 year old African American and Afro Caribbean. Her parents were of Jamaican descent and she presented with a moderate acting for 3 years. She tried over the counter medications. She was on clindamycin. And this patient I consulted actually in my Memorial Hospital West, which is actually it's in a hospital setting. It's a private practice within the hospital setting. So the lion's share of our patients in this practice are our physicians and nurses and healthcare providers. And we see the children of these employees as well. So her mother was a nurse. And when she presented to me, the mom was adamant about no antibiotics. And, you know, the patient was a super, super intelligent young lady. She had to give it a background, she had been dually enrolled in high school. She finished with 2 years of college already under her belt. She majored in biochemistry at the University of Florida, graduated with honors, wound up TAing biochemistry, and she was applying to medical school. So when she presented to me, the first statement she said was, Doctor. Moore, I would love to be just like you, but how am I going to get into medical school with all of this acne on my face? And you could see, and it really resonated with me that her confidence was down, her self esteem was down and she just was down on her luck. So again and this is where I always tell the residents here is a wonderful, wonderful and unique opportunity to do something amazing in said patient's life. So with the caveat in mind that mom did not want antibiotics, you know, we prescribed MZEEK in the morning and we also incorporated retinoid Benzoyl Peroxide at nighttime. And you can see as early as week 6, reduction inflammatory lesions, reduction in the inflammatory and in the hyperpigmentation. You can even see some minimalization in the apparent scarring that was going on before. And again, sustainable results right into week 12, which was fantastic. So she did very, very well. And as an update or caveat to this story, again, why I say these wonderful, unique opportunities never get old for me, she is accepted now to Dartmouth Medical School. She's in her 1st year. Her skin looks amazingly beautiful. Her mom says she's doing amazing. She texts me every now and again to just, you know, just to send me pictures. And again, just a wonderful success story on MSEEK. So next slide, please. Okay. Doctor. Moore, I think we may have lost you. To shape the hyperpigmentation. So this is a patient, if you look at her baseline photos, you can see that she had significant hyperpigmentation, You can see that there were significant dryness as well as significant inflammatory papules. Now, one thing I want to clue everyone into, if you look at her countenance, so look at her at baseline and then you look at her at week 6 and then let's go out to week 12. Let's look at how that sort of I won't call it an angry stare, but she was not happy at baseline. At week 6, you can see somewhat of a half smile and then look at the fantastic smile by week 12. So you can see by week 6, we had a reduction in those inflammatory lesions. You can also see that the hyperpigmentation seemed to be remitting as we had stopped doxycycline orally completely. And, you can see by week 12, again, just tremendous results that were sustainable, reduction of inflammatory lesions, improvement in the overall complexion, less dryness. So this patient did very, very well. Okay. So patient 4, was an Indian patient, Indian American patient who had presented to me who had been using retinoids consistently on and off for about a year. And she said that, you know, when she would use a retinoid, she found some satisfaction in terms of improvement, but she would relay that, when using something in the morning, it would always seem to burn and that sort of would dissuade her from using her retinoid consistently. So, you know, I like this patient presentation because it sort of illustrates how Amzik sort of plays well with some of the other topical agents that we use to treat our patients. We incorporated Amzik into her morning dosing and then she continued to use her retinoid at night. And you can see by week 12 significant reduction inflammatory papules. You can see an overall improvement in the hyperpigmentation and she was doing very well and this was also again very much sustainable. So, you know, I like this case because it illustrates again how this emollient in the vehicle helps to assist that patient using a nighttime regimen, which can sometimes be a little bit irritating, can cause some peeling and dryness, but, and when you couple it with a morning sort of moisturizing agent that also is anti acne in the form of the Amzik Foam, they just work very, very well together. So this patient was able to continue her treatment combination of Amzeq in the day and the retinoid with the Benzoyl Peroxide at night and continue to do quite well. Okay, let's go to the next slide, please. So this next patient, patient number 5, I believe Doctor. Lane had a very similar patient, was on minocycline for several months. And what she had relayed to me was that the minocycline seemed to help with her breakouts, but she was again noticing this sort of grayish or darkest cue or hyperpigmentation that was occurring sort of around her cheeks and a little bit on her jawline. And she said that if she would stop it, she would get a significant flare in her breakouts, primarily on the cheeks and the jawline and even on the forehead as well. So, and a lot, I know that my fellow clinicians on the line can relate to the patient who is on an oral and when they cart blanche stop or just stop it immediately, they get this rebound flare. So this is that patient that we see quite commonly in clinical practice. So when she presented to me, you can see at those baseline pictures of her left and right face, you can see significant involvement of that mandibular line. You can see that there's still some remnant of this hyperpigmentation. She had showed me pictures where it was far worse, but again, she had stopped the minocycline and then she was experiencing this rebound flare. So we clearly kept minocycline orally on hold. I started her in Amzik in the morning and we also introduced spironolactone daily. And I'd like you to take a look at that week 12 picture because, while you can't directly see those cheeks, I have to tell you, the inflammatory lesions cleared very, very nicely and you can also see reduction in that hyper pigmentation that was pretty significant while she was on the oral minocycline. So again, the use here of minocycline and being able to avoid having topical foam, being able to avoid using the oral was very, very poignant here because we were able to gain and achieve clearance that was lasting on out past week 12 with minimalization inflammatory lesions. And you can see from a pigment standpoint, she was doing quite well. Excellent. And then next slide. And then, okay, the next slide, this is the final slide, the ISI, which my colleague Ted Lang went over very thoroughly. We'll bring the rest of the panel in and we can take some questions from the audience before we start our conversation around the rosacea marketplace and Zylchstein. So if we can, let's bring in Doctor. Lane, Doctor. Moore and Doctor. Steingold as well as the rest the team. So, Sarah, do you want to get things going on the question and answer process? Thank you, Dave. So we're now opening up the webinar for questions. If you want to submit a written question, please use the Q and A function. If you prefer to ask your questions out loud, please use the raise your hand feature. We ask that you keep your questions to the topic of Amzik for now. You'll have the opportunity to ask questions regarding Silksy later during the Q and A. So please hold while we pull for questions. Our first question comes from Louise Chen at Cantor. Louise, go ahead and please unmute your line so we can hear you unmute your computer mic. Louise, I think you might be on mute. So go ahead if you can. Okay. Nothing from Louise. Maybe we'll go back to Louise later in the queue. Patrick Doles, are you there? Can you guys hear me okay? Sorry, we have Louise. There we go. Louise, I'm sorry. I was able to unmute myself. Okay. So a couple of questions for the doctors here. First, on Amzeq, the insurance coverage, how has it been for patients? Have there been any barriers to uptake? And then for adolescents, are they treating their acne despite the pandemic? How has that changed the treatment paradigm? And then last question here is in practice, how quickly does Amzik work? How are the results relative to what the clinical study showed? I know you talked about it a bit anyhow in the presentation, but just curious to ask you directly. Thank you. Thanks, Elyse. So why don't we just work around the horn as they say. So we'll take the first question just on access insurance, what's been your experience? So I'll start with Doctor. Lane. Yes. As was mentioned by Matt, there is a PBM that just we don't have great coverage without PBM. So there are certainly a subset of patients that are benefiting from the samples that we've been given as we await full coverage of Amzeq. But in my area, the vast majority of patients that I've prescribed it have been able to get it at very reasonable cost. It hasn't access hasn't been an issue. I think that that has been a surprising that's been very surprising for me as Vine has kind of commercialized this product as a small company, they figured out the access part very quickly. So I have to tell you that was surprising and a good surprise. There were multiple questions there. The onset of efficacy is and I think Doctor. Moore touched on this, I think it's quick. And so what we saw in the trials has been replicated in what we see in clinical practice. In terms of our patients coming in for their appointments, I can tell you, look, we've got 15 practices in our portfolio of practices here. We've got we're at about 95% of where we were pre COVID in terms of number of appointments. We're in Texas and Louisiana. So I can only speak for those 2 states, but certainly growing from month to month. And so we are absolutely getting close to 100% of where we were pre COVID. So hopefully that answers your question. Great. Great. Thanks, Doctor. Lane. Doctor. Moore, how about your experience? You wanna go through each of the questions? Sure. So relative to access, we've had very, very good coverage in access. The line share of my patients do get the medication as prescribed. Some of them who the insurance may not cover it. We do get very good coverage with the reps out in our territory. So we do sample it from time to time. And I'm sure, Doctor. Somewhat been a go between, the patient and the prescription and the insurance. So they've been able to offset things quite nicely. So I'll tell you, we really with those three avenues, either directly through insurance or specialty pharmacy or samples, we're getting patients' medication. So access really has not been a very big issue at all. It's been quite good. And the next question was relative to onset. So I'll tell you my clinical practice clinically, my patients mirror those Phase III clinical trials quite nicely in that, you know, you'll see quite rapid response if I can take you back to my patient number 1, who had to be cleared yesterday. I'll tell you by week 2 or 3 and I'm pretty close with following up with my patients even if it's by text or email to see how they're doing especially when a big event is coming up. And Chi is one of the very classic scenarios of its rapid onset and efficacy that is able to be sustainable throughout time. And then relative to COVID, I'll tell you very interesting, I was humbled that throughout the entire COVID sort of calamity, we were sort of beneficial, Mike. And like you, Doctor. Lane, we have about 25 offices. And we were able to sort of benefit from watching what started as a real collapse in New York. And we really jumped on top of PPE. Entire COVID. Certainly, there was a bit of a off around April, March. But at this juncture, we are back to pre COVID. I'd say about 96%, 97% relative to the general derm patient, so and acne for that matter. Hope that answers your question. Thanks, Doctor. Moore. Let's bring in Doctor. Steingold. And I will hear from you on Zolpi, but let's get your thoughts and perspective on those questions around access and patients coming in through COVID as well as what's been your experience and how quickly Amzik works? So what are your thoughts? Okay. Well, thank you and hello to everybody. So I have very similar experience. I would say the majority of my patients are able to get it. And I do think that sometimes providing a sample upfront when I'm going to write a definitely helped sometimes while they're waiting for their prescription. In terms of time to onset, like the others, I'm fortunate in that I'm an investigator, but I'm also a medical dermatologist. So I get to see how does it act in in the clinic and that is what I found so far. So I think the results are very similar to what we saw in the trials. And then finally, in terms of COVID, we are back to 100%. So my schedule is exactly as it was pre COVID. But what's important to know is that a lot of doctors are practicing telemedicine as we were and acne is one of those diagnoses that is perfect for telemedicine. We can't do full skin exams. It's very difficult to do mole checks, but we sure can treat acne by telemedicine. So I think that that's been a definite advantage for us. Great. Thanks, Doctor. Stagoul. Okay. Michael, Sarah, I think we have other questions. Yes. Our next question, David, is from David Anselm at Piper. David, please unmute your mic in your queue and go ahead. All right. Thanks for taking my questions. So just a couple. I know you alluded to this earlier, but I want to get a sense from you, Doctor. Seingold and Doctor. Lane, how you're thinking about where you slot in systemic tetracyclines versus Amzeq. Systemic tetracyclines have been available for quite some time. You've talked about their limitations. So give us, now that you have a topical tetracycline, give us your view of what kind of patient gets a systemic and what kind of patient gets the topical? Thanks. Then Jose, if I go first. Yes, no, go ahead, Kathleen, by all means. So this is a really good question. And I find myself changing my habits. If you look at the data in regards to lesion count reduction and IgA success for some of the more recent tetracycline class, Again, we see data that the numbers of IGA success are not much different than some of the topicals that we use. And so when you look at it as a data driven decision, topicals can do just as much as the systemics based on the primary efficacy endpoints of the trials. So then again, it's difficult to change provider practices and habits and I've done that even for myself. I know the data and yet I still have been prescribing more antibiotics than I think I should be. And so I find myself kind of really working on switching over to the topical, 2 MZ can put, I mean, this is the only topical minocycline that we have. And so it's, it's, it's really changing my practice because I'm using much more of it. So I think how do I slot it? I think it slots in just like an oral antibiotic and I'm changing towards that because we just don't need the oral antibiotics for the vast majority of patients. Certainly there are some who will benefit from the systemic anti inflammatory effect that you get with the oral tetracycline. But there is a vast majority who will do just fine with the topical in my view. Doctor. Moore, you want to offer your thoughts? Surely. So I agree with Doctor. Lane in that, conventionally, you know, a patient presents and we will you know, you look at the degree of involvement and it sort of will trigger a certain reaction. But with, you know, the advent of this novel formulary, it really calls us to and allows us to be able to sort of look a little bit more closely at antibiotic stewardship from its oral administration versus topically and the upside. And like Doctor. Lane, I have used lot more topicals that have been slow on the trigger when it comes to the oral. And Amzik has done that for me. So again, certainly there are going to be patients that are involved and they are going to need an oral. But I have certainly used MZK a lot more in lieu of the oral administration. Great. And with that, Stagull, your thoughts? Yes. So what's interesting is when we think about the role of the oral antibiotic, they're not necessarily the magic that we give them. For instance, when you take a pill by mouth and you look at the amount of drug that actually gets to the skin, it's very, very, very low. You look at the amount that's in the circulation, it's very high. We want to treat the skin. In contrast, when you take minocycline in the foam formulation and you put it directly on the skin, we have magnitudes of more cyclin direct to chronic pain. So I think that we have to take a step back and say, what are we trying to accomplish? We want the drug to be at the site of action. And that's what we're doing with the topical drug. So I think it makes sense. Often people think about it in oral agent when they have a large body surface area and it's difficult to reach all those places. But the foam formulation actually provides a vehicle that spreads very, very nicely. And we don't worry about treating the trunk in terms of bleaching the clothing like we would with Benzoyl Peroxide. So I think this really causes people to take a step back and try to figure out what are we trying to accomplish. If I may sneak in just the second question, just looking further down the line, topical combination products are pretty common in the treatment of acne, as you know. So what I'm asking here is, how big of a deal would it be to have a topical combination of Amzeq with say, a retinoid? And does that sort of change how you're thinking of usage and frequency of usage? Help me understand your thought process there. Dave, why don't you want to address? Myself? Yes, because I mean Yes, sure. I mean, it's we're actually looking to address that. And that's with our combination product FCD105, which is the 3% dose of minocycline in our foam chassis combined with the 0.3% dose of adapalene. We had a very good, very positive Phase 2 results that we announced early in the spring. We believe that we've got an Doctor. Moore and Doctor. Lane and Doctor. Steingold have talked about their experience, which obviously seems to be quite positive. And so we're very excited about the prospects for Amzik. And then our mission as a company is to constantly able to develop new and innovative therapies. And if we're successful in bringing a product such as FCD105 through the process and ultimately to market, that would be the first combination tetracycline with the retinoid. And the data was quite compelling. Our view was that it's potentially best in class. And I think each of the panel members have talked through from their own experience where an antibiotic topically with a retinoid in some combination can help out with some of their patients. So perhaps I'll just turn it back over to the panel for their thoughts on a combination product such as FCD105 and what that could potentially offer. So Linda, why don't I start back with you and we'll work then through Doctor. Moore and Doctor. Lane. I think it makes sense. I mean, we've already talked about the fact that many of us use this as 2 separate times a day. Anytime you can simplify a regimen for a patient and give them one thing to do, and you put the control in the hands of the physician, because you know, every time they apply their medication, they're getting combination therapy. If you simplify it and takes you give a patient too many things to do, they end up doing nothing because it just is too overwhelming. Simplify it down, give them something that they can do, especially one thing once a day is always going to be a win. Great. Thanks. Doctor. Moore? Yes, exactly right. The biggest sort of wall we as clinicians face with our patients is compliance. Okay. So if you can simplify the steps, compliance goes way up. So, you know, without a question, you know, I'm happy to hear Dave that this is already in the pipeline because we know combination products work and they help the patient to have less steps and as efficacy goes up, I mean as compliance goes up, so does efficacy. So I agree. Doctor. Lane? Look, the worst thing Dave did was give me a cell phone number because now I can call him directly and ask him when we're going to start these Phase II trials with a combination product. We were involved with the Phase II and the efficacy as shown in the Phase 2 results that have been announced were seen in my practice. Of course, we were blinded, but there were certainly patients who just did very well. And so I'm very excited about the potential for this combination product. Just to add on to what my colleagues have said, I think ADAPLINK makes a ton of sense because of its work on the comedonal excuse me, the black and white type of acne, as well as we know from some literature that's available regarding the effect of baculary acne scarring. So, I think that it's incumbent upon dermatologists to provide our patients with the best topical that we can give them. And so something that helps both the inflammatory and the non inflammatory as well as the scarring and the overall texture and tone of the face will do very well. It's just going to do very well. Michael, do we have any more calls coming in? I know that we have several we're getting in writing. So Yes, a couple more live, Dave. Next one is from Patrick Dolezal at LifeSci Capital. Patrick, please unmute your computer and go ahead. Hey, thanks for taking the question. So for KOLs, I'm just kind of curious out of all the prescriptions that you're presently writing for acne, roughly if you could ballpark what proportion are for AmSeq presently? And then kind of as we think about the broader launch dynamics, I mean, obviously, you guys are thought leaders in your space and very familiar with Amzeq. But how long does it take for physicians to generally get comfortable with new products? And how does that proportion of patients that they're prescribing to change over time? Thanks. Right. Doctor. Moore, you want to start? Dave, can you, sorry, my interest going in and out, I didn't hear that question. Can you repeat that for me? Dave, can you hear me? Yes. No, I can. So the question was about what percentage in looking at since Amzik has been out in the market, what percentage actually would you sense is Amzik? And then how you actually envision that to be changing over the course of time? You mean percentage what percentage of the therapeutic regimen that I'm prescribing, what percentage of it is the efficacy of Amzik versus something else? Is that the question? No, no. It's a product that actually you're using. So it's I see. Surely, surely. So in terms of my acne patients, I'll tell you, I would say I'm roughly at about 75% of my patients that come in with moderate to severe, maybe an upwards of 80 are getting AmZek. Doctor. Lane? I don't know that I hit 70% or 80% of my patients for AmZek, but certainly it's increasing in terms of the number of patients I'm prescribing it to each month. I really guys, I'm sorry, it would be difficult for me to give a percentage, but it's growing, I can tell you that. And then, there was a what was the second question, I'm sorry. There was a percentage of patients. Oh, the uptake of new yes, it was I think it was the uptake of new prescriptions by community derm. Linda, I'd love to hear your view on this because I find this difficult to answer. Those of us who do research tend to be early adopters because we're so we have experience with the product. But I would say because this is so novel and again because of the clindamycin resistance that's so well known in the community, I would see this as being easily early adopted versus some of its contemporary peers. Ted, I agree with you. First of all, I don't know my percentages either. We see a lot of acne patients and so I would just be guessing. But what used to be Foamix now Vine, what they did was actually really interesting because we started the buzz and we started the conversation well before the drug was FDA approved. And there was some science here that actually caused us, it was a huge just like slap in the face saying a lot of the things that we've been telling you aren't necessarily true anymore. And part of that comes with bacterial resistance. And I think Ted, you touched on this during your talk, but we have levels that are so high with this drug that the risk of developing bacterial resistance is significantly less than what we've seen with other agents in the past. So that is fascinating to do. We're just it's amazing. And so people are thirsty for this kind of knowledge. And they've had great scientists who have really gotten out, gotten this data on the podium. You can't go to a scientific dermatologic meeting without hearing about what we're now starting to understand with topical minocycline. So I think that there's a great buzz about it. I think people are excited about it and that's always great for a new product. Thanks. Michael, any other live questions? Yes. One more live question, Dave. That's from Oren Livnat at A. C. Wainwright. Oren, go ahead please. Hi, can you hear me? Yep, we got you, Oren. All right. Unmuting is harder than it sounds. Okay. So, you just mentioned the buzz on the clinician end. I'm curious about what you're hearing from your patients. Obviously, Vine is just now starting the DTC side of the equation. But given that you've had such early success with your own patients, are you getting people coming in asking about this product just by word-of-mouth already? Doctor. Lane, you want to take a start first? That's a really good question. It's very timely. I have not had any patient come to me asking for Amzik, but I've got a senior in high school. My daughter is a senior in high school and she obviously is very active on Instagram. And she has shown me ads on Instagram or mentions on Instagram for Amzik. She works here in the office with me, part time. So she knows what goes on. And so she has shown me. So definitely there's some uptake and we see some increased awareness in that population. Doctor. Moore. Excellent. Can you hear me? Yes. Excellent. So I got to tell you that while I haven't seen patients who just de novo come in asking for MZ, what I have seen a huge uptick in is, for example, you'll treat a patient for acne and then they'll send you their sister, their cousin. And in that sense, I am seeing patients come back and say, I want you to give me what you gave my sister. I want you to give me what you gave my mom. So from that sense, I will tell you yes, but to say that they're coming in just because they saw commercial or they want to know about MZEEK, No, but intrinsically, patients who I've seen, who tell other family members, they are coming back and asking for it. Like, I want what my cousin had kind of thing. Doctor. Steingold, your thoughts? So to be honest, I don't really care when my patients come in and ask for something and maybe I'm different from I don't care. You can ask for whatever you want. You're going to get what I want you to have. So I'll listen. And I certainly take into consideration their fears and their desires and things like that. But I have I look at them and I develop a plan and they can ask for coconut oil and they can ask for all kinds of stuff from Costco that they've been using. But so I don't know that that matters that much. And I don't know how many physicians are truly swayed when somebody comes in and holding a People Magazine article or something. We're happy to talk about it. But generally, you're going to get what I think will work best for you. Great. Thanks. Michael, any other live questions? No more live these is, since AmSeq has become available, what products do you think that it has replaced most often? Yes. We'll start with Doctor. Moore. Surely. So I will say that, Actone would probably be my number one in terms of replacement. Secondarily, we're going to look at the oral administration of antibiotics, which certainly I have had a downturn in relative to use of Amzik. I think those would be my top 2, Axo number 1 and also 2, let's include in that clindamycin. Those would be my top 3, Axo and Clinda and then perhaps the orals. Okay. Beth Steingold? Just want to make one comment here. So, Amzeq was really comparing itself to oral minocycline, but we have to make reference to the fact that when we looked and evaluated patients who are in the clinical trials, they had both superficial inflammatory as well as comedonal acne. And when we look at the data, we see that it actually worked and was statistically superior in both of those. So it does work for all different types of acne. I certainly think that this would be an immediate substitution if you're looking to substitute an oral antibiotic, but it's also appropriate for potentially any acne patients who has potentially comedonal acne, papules, pustules. So it's something that people would think of top of mind. And Doctor. Lane? Hello. Hello. Okay. It's good. Michael, what else we got? How about take 2 more questions? And then we'll turn it over to talk about Zixi, and then we could pick up any additional questions at the end. So got 2 more Michael? Yes, Dave. We have a question that just came in from Balaji at Barclays. And he'd like to know, are there any clinical settings where the doctors have not seen adequate responses to Amzik? That's why I included in my slide deck the kind of what's the driver for the acne as you think about it. And if there is someone with a strong hormonal driver of their acne, if it's adult female that players around her cycle, for example, a topical any topical, I'm not just referring to Amzik, really this is any topical, I just don't think will give you the kind of results that you need unless you focus on the underlying issues. So I wouldn't again, it's based on patient selection, I would say, where you see a failure of ENZYK as monotherapy versus the product itself. Great. Doctor. Moore? Yes, certainly. So the etiology of acne sometimes can be multifactorial and there are scenarios where like Doctor. Lane said, where there's more of a hormonal component where it might not be as effective. And also too, what I find myself stifling through a lot of times is the level of compliance because I will tell you, I have had patients who've come back and just said it's not working for whatever reason. And you wonder how much of it is a compliance or actually just not efficacious. And I think Doctor. Lane and Doctor. Gold, we all have those patients where you'll talk to the teenager, then the mom is standing behind them shaking their head telling them they're not using it. So compliance certainly will be a factor that will play a role and certainly the physiology or etiology of the acne in said patient it is important to take into consideration when you're looking at whether the AmZinc worked or not. And finally, that's Stinegold. So what's important is, and we learned this from clinical trials, no one drug works in every single acne patient. But when we look at the bar that we use in the trials, it was clear almost clear. So there's a lot of patients that get a little bit better, but not completely better. And in real life, we mix and match medicines to try to get them to that completely clear state. So there will definitely be people who don't get to clear completely clear with monotherapy. There might be some patients who just don't get anything with it, but I think the vast majority at least see improvement and there are many that benefit from having it used with other medications. Thanks Linda. And Michael, why don't we take one more question Yes, just one more here. And this investor would like to know, what do you think the long term potential for AMAZIQ is? And if you were to look at, let's say, 3 or 4 years, how do you see it fitting into the treatment paradigm for acne? Okay. Tatulae, why don't we start with you? I think its uptake will continue to increase. I think as I think about the pipeline of acne products that we have in clinical trials right now in Phase II and Phase III, certainly I don't have all of them at my site, but we've done quite a few. I really don't see anything else overtaking it in terms of the topical monotherapy or combination antibiotic product. There's products that coming through that there's an anti sebum inhibitor, for example, that works in a completely different way. That's a new mechanism of action. There's some combination products coming through, but nothing that would replace or compete with the way that Foamix that excuse me that Amzik works. So I just see it continue to improve in terms of its market share without a competitor coming that would try and steal from it. Thanks. Doctor. Moore? Yes. So there is a reason why I think minocycline was a tried and true Stalford relative to the treatment of acne. So I agree with Doctor. Lane that I think it's here to stay. And again, it fits in very well. We look at the art of treating our patients where in various cases we will use multiple other medications and it plays nicely. So, I do foresee that this will be around for a very long time. And last but not least, Doctor. Steingold, what are your thoughts? Yes, I agree. And Ted really summed it up. When we look at what's coming and what we have right now, I don't see anything that directly competes with it. Great. Well, I want to thank the panel again. These were great questions, fantastic dialogue, excellent exchanges. So why don't we now shift? As I announced in my opening comments, it's an exciting day for us here at Vine. We officially are launching ZILSI, a 1 point 5% topical minocycline foam product for the treatment of rosacea. It is now available for pharmacies effective today, so they can order and bring it in. We actually have our sales force that's in training as we speak. So why don't I turn over to Matt Wiley, again, our Chief Commercial Officer that can take you through how we view the opportunity for rosacea with ZILSI and some of our plants. So Matt, take it away. Thanks, Dave. So we'll start on the next slide and I'll talk about the market size opportunity. So there were 4,400,000 prescriptions written for rosacea in 2019 that is over a 1,000,000,000 in revenue in the same year. So this is a large market. And I've heard previously that the market is not as big as the acne market. But the thing to keep in mind, and hopefully you get this over the course of the presentation, is while this market is not as big, I believe that you'll see that it is underserved and there's a significant unmet need in the market. So as we go to the next slide. First of all, we look at healthcare practitioner perceptions as it relates to different disease states. And so these were live interviews with physicians. And what we tried to assess here is on the X and Y axis, how much time and effort different conditions take up in your practice and then what level of skill is needed for those different conditions. And then the context or the perception of just how many tools you have at your disposal to treat those conditions. And so if you look at acne, for instance, less time and effort is necessary for those patients, perhaps a little bit less skill, a lot of different tools. Conditions like psoriasis, a high level of skill, a lot of time and effort goes into it, a decent set of tools. And in rosacea, it's still on that upper right hand quadrant where it requires a high level of skill, tools that they have to treat the condition are relatively small. So the rosacea patients are more akin to a wedding ring with practices is the analogy I'll use perhaps than acne is and does demand more time from physicians and more attention. Next slide. So let's talk about the patient satisfaction. When asked, and this is a study that was done back in 2019 early on, this is our demand study. We asked consumers if what their likelihood would be to seek a better solution. What we found is over 70% of the patients indicated that they were at least somewhat likely to seek a better solution for the rosacea. And then in another study that was done recently, the awareness trial and usage study, this was just delivered to us in mid September, we found that if a physician were asked for either a switch in therapy or a specific therapy, we found that almost 90% would grant that. Now Doctor. Steingold may be in that 12% quadrant up there. But what we heard is for this condition, they would be amenable to helping the patient, should they ask for a specific medication or to be switched from what they're currently on. Next slide. So these quotes are from an article that was, it's a I'm looking for Self Magazine back in May of 2018. And this is just perspectives of patients about how they feel rosacea is having an impact on their lives. And you can read these, but the hardest part is never knowing what my face is going to look like when I wake up. I was hoping that the medications would work, but they don't. It feels like a permanent sunburn and affects every aspect of my life. So this is a very real condition. These patients are anxious about their rosacea, anxious about their appearance, and they're not necessarily getting what they need from the medications that they've had to date. As we think about the opportunity from a launch surrogate perspective, we note that, yes, Oracea was launched back in 2006 and has the steepest uptake curve here. But if you look at year 1, roughly a quarter of a 1000000 prescriptions, not dissimilar when Solentra launched back in 2015. And the peak year of these surrogates is anywhere between 500 to 750 or so 1,000 prescriptions at peak. Now, the thing I'll note here is that nothing has been done from a market development perspective to actually grow the market. So these drugs have enjoyed these market shares and this growth within a market that is relatively static. And the question that we ask ourselves commercially is, can something be done also down the line to move diagnosis and treatment for patients who may not be under the care of a physician today? Next slide. One of the big opportunities as we think about active competition that's come to market in the last 14 years is that there hasn't been a lot. As mentioned, Eurasia launched back in 2006. Basically, there was no additional direct Type 2 rosacea product launched in between Oracea and Cilantro. But ZILTI is launching at a time when nothing new has been introduced for these type 2 patients in greater than 5 years. So it's a great opportunity for us to really own the discourse in our physician offices and really introduce something with a lot of resonance given the unmet need that we're seeing in the market. Next slide. As it relates to COVID impact, you might think that similar to acne that rosacea would also be climbing back. This market is based on this data anyway, these are Enerex's branded market. And you see that the market is completely healed. The most recent data point is over 10,000 prescriptions in a week. That's similar to what we see back in January, February. So this is certainly a dynamic that gives us confidence that we're launching into a market that is completely back to normal. Next slide. Some of the triggers for rosacea, as I'm sure you're aware, it's the changes in season when patients are overheated or it's very hot outside and when they're stressed. And so one of the things that we've noted as of late is that due to COVID-nineteen, there's an increase in anxiety and increase in stress levels. There's also irritation from masks that need to be worn. And so this has been perhaps a contributor to the healing of the market that I showed in the previous slide. Next slide. This is an interesting slide. It's an interesting market insight that we uncovered early last year that we think is an opportunity for us, especially when we think about our consumer efforts and consumer mobilization. So as you can see in the left side graph, this is rosacea search volume over time, over a 4 year period and a 4.5 year period. You can see that searches for rosacea related searches for rosacea seem to peak in March, April, May of each year. And that's an important finding. So we went back and we looked at diagnosed patients, patients who were diagnosed for the first time between 2015 2018 in our data set. And what we found is that the gating of diagnosis does actually correlate to this finding that we see seasonality. So why does this happen? Well, obviously, the change from winter to spring, especially in the southern states where the heat is exacerbating the symptoms may be driving this behavior. So this is good information for us to have as we think about our digital efforts, how we buy keywords, when we buy keywords, and what may be driving the behavior to get them to a clinician. And with that, we can get them the right information. So as that was asked in the last segment, perhaps we can have them ask for Zildzi by name. So next slide. So our strategy for Zildzi is similar to that of Amzih. We do want to focus on our positioning and our story, which I'm very excited about for this product. Consumer mobilization is a bit different because we're talking about Millennials and Gen X as opposed to Gen Z. So how consumers get information on drugs is a little bit different. And we're going to explore many of those as we get into market at during the right timeframe, of course. Efficient deployment, I will walk you through how we're overlaying the target prescribers on top of our current footprint. And then access is, of course, equally important for ZILTI as it was for ANZYK. Next slide. So I will start with some of that recent awareness trial and usage studies. So we present physicians with a blinded product profile and they get to read through the core attributes and side effect profile of the drug. And then we ask things like what is your intent to prescribe? And what we see here is that there is a high likelihood that are in 75 percent, there's a high interest in the drug to prescribe, which is a good finding from this study. Next slide. And as we think about what ZILCY would then displace in the category, we see things like metrodidazole, doxycycline, etcetera. This is where we believe that we're going to take share in the market. And this is also as it was with Amzik based on demand study is that this is disrupting the market. There is a great appetite for the product. And there is a lot of displacement going on, which shows that it's truly unique and of interest to the physicians in our study. Next slide. So this is our ZILTI campaign. If you go to ziltsy.com, you'll see that that has been launched with similar imagery. This campaign resonated with physicians. The headline was seen as bold, intuitive, drove desire to learn more about the product, the concept itself, the pictures, so to speak, demonstrate a powerful tonality and a nod to known triggers, for instance, exercise and being out in the heat. So, this concept really landed with physicians in our research. And we feel like it's a great concept to represent what we're about to do in market. Next slide. So as we think about the core visual aid in the story, this gets back to our positioning. So we go back to minocycline as a trusted molecule, one that's been on the market for almost 50 years. MST is a cornerstone of the positioning. So this is something that no competitor today or in the future can ever own. And we think that's an important anchor to the rest of the story. And then of course, ZILTZI Redefining Topical Therapy for rosacea. As we go through demonstrated safety of product, the tolerability on already sensitive skin. These are really important attributes to the story. And so as we lay this story out, it really does make an impact. I'm going to show you how in the next slide, while we go there. So as we do our core visual aid testing, one of the things that we wanted to do is to provide a stimulus ahead of the participants seeing the core visual aid. We asked them to evaluate the target product profile, similar to what we saw in the awareness trial and usage study that I showed previously and asked what their intent to prescribe was. And it was 6.9 out of 10 and not dissimilar to the 76% that we saw earlier. Then we went through the full detail, the complete story on ZILCY from start to finish. And after that was complete, we asked again, same prescribers, what is your intent to prescribe? And it went up to 8.5 out of 10. So roughly a 25% improvement when they hear the story. That's important because as we go through our demand study, as we look at other market research we've done, we recognize that the way that our reps are going to go out and communicate the story, the way that they're going to consume the story in other medium is going to be really important in driving the penetration into the market. And so we believe that we have the right story. Obviously, you want to see this separation when you do your testing and we did. Next slide. Let's switch to market access. So the majority of payment type in the branded space is either cash or commercial. I believe that the cash is driven through synthetic access means by competitors. When we look at surrogates in the space, finatia foam, oration and cilantro, we see that the coverage is pretty good that they've been able to secure. And I think that's also a nod to the fact that there aren't a lot of options here and that patients do tend to cycle between the products. Next slide. As we did payer market research, we see that there is based on the product profile that they reviewed, these are 10 payers that represent over 300,000,000 lives, which is most of the United States. These are self reported, of course. But we see the weighted average of unfavorability greater than 5. So there is a favorability metric for the profile for Silksy. And based on the indication, what is the need, the payers believe that there is a need for this product in the market, which is always a good sign when you do your market research. They also indicated that they would expect the net to plan price be somewhere between $200 to $400 not dissimilar to AMZ. In fact, because we price the product at parity to AMZ and because we already have contracts in place with most of the payers, we anticipated that response. Next slide. So I'm very excited to announce on this call that we have now secured a contract with Express Scripts for coverage for their 26,000,000 lives on their preferred, their basic and their flex preferred formularies that brings our coverage right now, up to right around 46% of covered lives. That contract went to effect today. So our contracting efforts are underway. We have also successfully negotiated with a smaller PBM called MCRX that has a couple million covered lives. And we have all of our other negotiations in process and we feel good about the strategy and also the market research feedback that we heard from them. As we think about our field force footprint, so we deployed 51 representatives in territories when we launched AMZ. We always had an eye on rosacea. So we did an overlap analysis back when we did our initial sizing, knowing that we would have to modestly expand some targets. And obviously, we did some refinements on how we targeted physicians in rosacea. But ultimately, we come up with about 4,000 or so targets. So we've expanded the number of called on physicians by about 6% up to 6,700. Still very viable to reach these targets given this universe. Now, 87% of the ZILTZI targets were already in our call deck. So we already have good relationships with almost 90% of the physicians that are going to impact the ZILTZI uptake. And I'm also happy to note here that we have captured with our target universe for ZILTZI 75% of the available diagnosed patients. So this has been a great exercise to go through to make sure that we're leveraging the infrastructure. Our marketing and sales apparatus does not need to expand to bring 2 products to market, which is a great result. Next slide. So in summary, there's a significant unmet need in rosacea for both HCPs and patients. We hear it loud and clear in market research. We believe that we have a very strong promotional story and we expect that we're going to have good demand and the surrogates support that. The surrogates support the fact that brands do get good uptake at launch and we would expect the same here from ZILXY. And with that, I will end and turn it back to Dave. Thanks, Matt. Well done. So let's just move right into the next portion of our discussion here and that's Doctor. Linda Steingold, Director of Clinical Research at the Department of Dermatology at Henry Ford Medical Center in Detroit. Doctor. Steingold, take you through what's new and what's coming in rosacea and review our clinical data as we believe, obviously, it's relevant since we're launching ZILTI effectively effective today. And then obviously, we'll get Doctor. Steigold's thoughts on the zoxie and how she perceives it to be utilized in her treatment armamentarium for the treatment of rosacea, then obviously we'll bring in the rest of the panel to get their thoughts as well. So, Beth Steingold, turn over to you. Thanks. Okay. Well, thanks so much. Really an honor and a privilege to be here and talk about rosacea. One of the things I'd love to talk about and love to treat. So let's go to the next slide. I have been working with Vine Therapeutics really for a long time, kind of from early in the beginning and have gotten to work with both of these products. So it's really been a privilege. I have been a consultant, a speaker as well as an investigator, but I also work with a number of other companies and have done a number of other both acne and rosacea clinical trials. Next slide. So if we want to think about treating rosacea, we have to look at the pathogenesis of the disease. We know that rosacea is an inflammatory skin disease and it basically has an upregulation And We also know that there is neurovascular dysregulation. So we know that the blood vessels, especially on the surface of the skin, dilate or become wide and the skin can then have more blood in the surface and that creates this flushing or this erythema of the skin. We generally need to use an alpha anergic agonist or something that will constrict those blood vessels to get control of that background erythema. Next slide. So when a rosacea patient comes into our office, we have to look at them and decide how we're going to manage them. Next slide. So basically what we do is we look at the signs and the symptoms that are present and we look at every rosacea patient individually. If they have papules and pustules right now, we really have metronidazole, azelaic acid, ivermectin or oral antibiotics including sub antimicrobial dose doxycycline. If they had background erythema, we treat that generally separately with an alpha adrenergic agonist either bromotid or oxymetazoline. If they have telangiectasias, they can cream all day, but they're probably not going to have an impact. So you really need a device to try to get those calm down. And if they have a thymus or a thickening of the skin and the glandular tissue, often they need surgery to really try to get that under control. Next slide. So there is a challenge in treating our rosacea patients because these patients have very, very sensitive moisturizer, even a sunscreen, they say, oh, it stings, it burns, I can't tolerate it. The other issue is compliance with any chronic skin disease. They have to treat it usually over the long term and it's always best to simplify the regimen. If we can give them one thing to do once a day, more likely that they'll find a way to incorporate it into their daily regimen. Next slide. So we've used minocycline in both acne and rosacea for many, many years. We know that it's bacteriostatic, but it also has potent anti inflammatory properties. The problem is it's been very difficult to formulate a topical agent. We have to make a vehicle that allows this drug to be stable, but we also have to have a cosmetically acceptable vehicle. Slide. So as we know next slide. Topical minocycline foam in the 1.5% concentration has been FDA approved and as Dave mentioned is now being marketed. And we had the results of 2 Phase 3 clinical trials that were published in one of our major journals, the American Academy of Dermatology, just this year. Next slide. And when we look at the way these studies were designed, they were designed the way we see Phase III studies. There's always 2 sister studies that are done simultaneously with different investigators, different patients. And we want to make sure there's reproducibility of the data. We want to make sure that the data we see in one study is similar to what we see in the second study. The way these studies were designed, for every 2 patients who received the topical minocycline foam, one received the vehicle foam. These patients were treated once a day, every day for 12 weeks. And then these patients had the opportunity to go into an open label study for an additional 40 weeks. It was mainly a safety study, but we also gathered some efficacy data as well. Next slide. So when we look at the demographics, this is always important, because we want to make sure that the patients who came into these studies really mirror the type of patients we see when we're treating rosacea. And we really see that here, the mean age is around 50. The majority of these patients were female, the majority are white, but we have to mention that you can see this in any race, especially we see it in African American patients, Hispanic patients, Asian patients, we can see it in anybody, but it is more common in Caucasian patients. Now, I want you to notice the inflammatory lesion count at baseline. It's around 30 lesions at baseline. This is important because most studies, when they're done, have a much, much lower inflammatory lesion count. This is very similar to what we saw with the ivermectin studies, but higher than what we saw with the METRO or Azelaic acid or even Auracea. And when we look at the IGA score or in the investigator's global assessment, and again, this is an arm length assessment, we look at the patient at baseline, we just get an overall feeling how bad is their rosacea. And we had about 85% of the patients who had moderate disease, about 15% who had severe disease. What's important is the severe patients are difficult because we have to get them all the way down to clear, almost clear, and that's a 3 or a 4 grade improvement using just monotherapy. Next slide. So, how did they do? Well, we had 2 co primary endpoints. The first one is the absolute change in the inflammatory lesions. And first thing I want you to notice is when you look at the studies, they are very similar. So the studies performed fairly similarly. That means there's good reproducibility of the data. The second thing I want you to note is that both studies had a statistically significant improvement in the active drug as compared to the vehicle. The next thing I want you to note is that there is some vehicle effect. When we talk about topical therapy, we have to understand that the topical agent is a marriage of the active ingredient and the vehicle. And this is very, very important, especially for rosacea. We need to have a vehicle that actually carries some weight on its own. It's not placebo, it's vehicle. And here, this vehicle was formulated to be very well tolerated. We also feel that this vehicle has kind of a healing process for the barrier. It hydrates the skin, it helps to heal the skin barrier, which will also help to improve the rosacea. So we should expect that there will be some efficacy with the vehicle by itself. But we also want to see that the active drug is statistically superior to the vehicle and that is what we see. Next slide. The other co primary endpoint is looking to see how many patients got to clear or almost clear. And again, we're taking patients who have moderate to severe rosacea at baseline, giving them one thing to do once a day and asking them to get all the way to clear or almost clear. And again, we see about 50% of patients who had this severity of disease at baseline got all the way to clear, almost clear at the end of 12 weeks. Again, we see there is some efficacy with the vehicle, but there is a statistically significant difference between the active and the vehicle. And this was seen in both studies. A 50% result of getting half of those patients to clear, almost clear, is really quite a milestone for a monotherapy. Next slide. So, let's take a look at the percent change of inflammatory lesions over time. Here we see, again, the studies were fairly similar. We see a statistically significant decrease as early as week 4, and that difference from the vehicle is maintained over the course of the 12 weeks in both studies. Next slide. When we look at the difference in IGA success, we start to see a separation from vehicle at week 4, which is statistically significant. At week 8, only one of the studies actually reached statistical significance. The other one missed it by a little bit. And then by week 12, both studies were statistically superior to the vehicle. Next slide. So you might say, okay, well, we put moderate patients, we put severe patients into this study. Is there a difference or does it work for both the moderate patients as well as the severe patients? So here, we separated out by baseline IgA. And in the graph on the left, we look at the inflammatory lesion count in the overall population, and then in the moderate as well as the severe. It was statistically significant in terms of the reduction of inflammatory lesions, no matter how we slice the data. But notice that those patients who had a lot of capiols, the severe patients, had a very nice reduction with the active drug. And here's where you absolutely see the benefit of having this active drug in those patients who have more significant disease. Again, when we look at the IgA by baseline severity, statistically significant, whether it's moderate or whether it's severe. And you see with those severe patients, it's very difficult for the vehicle by itself to get a severe patient all the way to clear or almost clear. So we have a nice delta or difference, especially in the severe population. Next slide. Okay, so it looks like the drug works. But as I mentioned, with our rosacea patients, we worry a lot about tolerability. We have to give them something that they're going to be able to use and use it for long enough that they're going to start to see an efficacy result. So what's interesting here is when we look at the overall summary of adverse events, we see the active drug and then we see the phone vehicle. Notice then when we look at the number of subjects with any AE, it's actually higher in the vehicle than it is in the active. Treatment emergent adverse events, again, higher in the vehicle than it is with the active. Notice that there were 9 patients who discontinued due to an adverse event, 7 in the active group and 2 in the vehicle group, and only one patient who discontinued was thought to have an adverse event, which was moderate itching that was related to the drug. And actually, none of the serious adverse events were thought to be related to the drug. Next slide. Okay. So, what about the other things that are not skin related? Well, viral infection is very similar. Upper respiratory tract infection, greater in the vehicle. Headaches, notice that it's greater in the vehicle than in the active. And minocycline, you might worry because taking systemically, we worry about headaches. We did not see that in the active group. Diarrhea slightly higher in the minocycline group than in the phone group, but only 1% of the total population. Next slide. When we look at the skin related the skin treatment emergent adverse events, we see the numbers are very, very low here. Overall, they were very similar between the active minocycline group and the vehicle group. And just looking, all of these individually are less than 1%. So there's no red flag. I do want you to note that there was one case of skin hyperpigmentation. And we haven't really talked about this. But one of the side effects of taking systemic minocycline is that you can see hyperpigmentation of the skin. And so we worry if we're putting large doses of minocycline on the skin topically, are we going to see minocycline induced hyperpigmentation? The answer is no. We didn't see it in the ACNE trials and we didn't see it in the rosacea trials. Here, there was one case of skin hyperpigmentation, but this was thought to be post inflammatory hyperpigmentation and not related to the minocycline. Next slide. Okay, so what about dermal tolerability? So again, this is a rosacea patient. They're sensitive to begin with. How do you know they're sensitive to begin with? Well, we looked at dermal tolerability. We looked at telangiectasias. We asked about stinging and burning, flushing, dryness, itching, peeling, hyperpigmentation, and then we looked at erythema. Notice and then the first grouping, the green line is none, the blue is mild, the gray is moderate, and the dark blue is severe. So notice at baseline, most people had at least some stinging and burning just at baseline. When we look at how they did it 12 weeks, the vast majority of them had no stinging or burning after 12 weeks. Same thing with flushing, with dryness, with itching. Notice at the end of 12 weeks, they didn't get more itching, they got less itching. Peeling and desquamation, again. Also hyperpigmentation, you worry about using a topical minocycline, you might get hyperpigmentation over the course of 12 weeks. They saw a decrease, More patients are clear or none as compared with the baseline. Then we separated out erythema and looked at that separately. And here we have a 5 point scale, clear, almost clear, mild, moderate and severe. And at baseline, very few people were clear or almost clear in terms of their erythema. But notice that at the end of 12 weeks, about 45% of patients were clear or almost clear in terms of their erythema. Next slide. So, it's also important to ask patients, you know, what do you think about your treatment? And what we found was overall patients were satisfied with their treatment. We found that 72% were satisfied or very satisfied with the minocycline foam, 90% thought it was easy to use or satisfied with the ease of use, 63% were satisfied or very satisfied with the feel of it, and 70% said they were satisfied or very satisfied with how this drug compared with other drugs that they've used for the rosacea in the past. Next slide. So pictures, you know, we're dermatologists. We love to see pictures. So, here's a patient who had moderate disease at baseline. You can see a number of inflammatory lesions. Look how red her nose is, especially with the paralegional erythema. Look at her at week 12. She has a beautiful clearing that you can appreciate both from the side. She still has a little bit of TL injectation on the nose. This other patient at baseline had moderate disease. At week 12, she went down to a mild. Now when we look at her, she had an obvious improvement in her skin. She's obviously better. Relative looking at her might say, wow, you look good. But she is a treatment failure because she went from a moderate to a mild. So she didn't achieve that too great improvement to a clear or almost clear. So in real life, she might be a study treatment failure, but in real life, she might be a disease at baseline in a gentleman, went down to an almost clear. And this patient at baseline had severe disease. So she had to have a 3 at least a 3 grade improvement. She had that by week 12, going all the way down to an almost clear. And these pictures are typical of what I saw when we were doing our clinical trial as well. Next slide. Okay, so as I mentioned, those patients who completed the Phase III clinical trial were, eligible to go into the open label long term safety study. And here, everybody gets the drug, they apply it once a day for an additional 40 weeks. So patients who started on the active drug had a 52 week access to the drug. Next slide. So of those patients who entered into the study, what's interesting to see is about 80% of them completed the long term open label study. For a long term study, that number is very, very good, because you can lose people for any reason. When we look at why people discontinue this study, the bulk of them lost a follow-up subject request. Very few, only 5 out of all of them stopped due to an adverse event. Next slide. Okay. So the real goal of doing these long term studies is safety. What we want to understand is, is there a new red flag that's going to come up over having access to this drug over the course of an entire year that we didn't quite tease out in the 12 week Phase III trials. And the bottom line was the majority of the treatment emergent adverse events were mild and moderate. No serious adverse events were related to treatment. And when we look at it, basically, very similar whether they were started on the active drug or started on the vehicle and then transitioned over, no new red flag was bound during this part. Next slide. And then again, looking at some of these other adverse events that occurred in the open label, upper respiratory tract infections, nothing really new, sinusitis, bronchitis. Again, looking at the headache, this remains low, vascular disease, hypertension. So there is no callout that would cause us to have any cause for alarm that showed up when patients had access to this drug over the course of the entire additional 40 weeks. Next slide. So what about tolerability? When we look at patients who use this drug for a full 52 weeks and look at where they were when they came in, and where are they when they end up, telangiectasia is tough to treat unless you're going to use a device, as we talked about. But looking at stinging and burning, notice that the vast majority of these people, when they finish the study, 97% of them have no stinging or burning. Flushing, 57% have none. Dryness, 80% have absolutely no dryness. Another 18% have just a little they're considered almost clear in their dryness. Itching, almost no itching remaining. The vast majority of people are clear or almost clear. And again, hyperpigmentation, these patients have access now to minocycline for up to 52 weeks and notice that the hyperpigmentation again goes down. So we don't see a flag that tells us that we're having any type of minocycline hyperpigmentation. Any of the hyperpigmentation that developed was deemed to be post inflammatory or as a result of the inflammatory lesions. And then also when we look at erythema, at baseline, the clear almost clear was only at about 4%. When we look at the end of 52 weeks, we see that almost 60% of patients are clear, almost clear in terms of their erythema. Next slide. We did also monitor the efficacy of the drug. And what we find is when we look to see how many patients got clear or almost clear in those patients who remained in the trial, we see those numbers continuing to go up. And by the end of the 52 weeks in those people who started on drug, who remained on drug, who continued through 52 weeks, almost 82% got to clear, almost clear, And more than 75% of the ones who started on vehicle and then transitioned over to active drug and remained in this study got to clear or almost clear. Next slide. So, in terms of patient satisfaction at the end of the open label study, we asked patients again, how are you feeling? How happy are you with the drug? And overall, there was a high level of satisfaction. You notice the green is the very satisfied and the gray is the satisfied. Overall satisfaction with the product is about 85%. Comparing it to other products, again, about 80% or so, hard to count in my head. And the vast majority of them would recommend this product to a friend. Next slide. So Ted went over the important safety information. For acne, it's very similar for rosacea. It's FDA approved for adults for the papules and pimples and bumps caused by rosacea. It's by prescription only. It has not been studied in children. It's to be used on the skin only. It shouldn't be used by people who are allergic to it and not to be used by pregnant women and it is flammable. And then other side effects very similar to what we saw with the acne drug. So that concludes my formal part of the presentation on rosacea. And we'll turn it back over to Dave. Hi, Saba Stangold. So I want to turn it over to Sarah and Michael to see if we have any questions from the audience. We're actually making a pretty nice time here. So we've got some availability for any additional questions on rosacea, on Zolksy or also continued questions for Amzik. So, Darren, Michael, I'll turn it to you. Yes. Dave, it looks like we have a live question from Tim Chang at Northland Capital Markets. I had a question just about duration of treatment with Amzik. You guys have all highlighted the treatment success you've had, but sort of wanted to get your thoughts on how many administrations or how many canisters do you think a typical patient would use for MZK? And also maybe the same question on ZILCY, given the fact that today is the 1st day it's commercially available? Thanks. Thanks, Tim. Linda, do you want to start? So it's really going to be variable depending on the patients. For Amzik, people potentially might treat their face as well as their chest, shoulders, back, they're probably going to use more. In rosacea, generally, the rosacea just involves the face, so you're going to use less. I don't know if we've calculated how many pumps there are or how much you get out of H2, but generally each prescription should last at least a month. One of the issues is, how will patients really use this in real life? We don't have long term maintenance data at this point. In real life, people probably get themselves clear and then many doctors will recommend that they go to maybe 3 times a week or every other day or something like that as maintenance, but it's not approved that way and we don't have data that way. Doctor. Lane? Yes. I don't know that I have much to add to Doctor. Steingold. I think patients will also just take themselves off the drug if they get cleared just like we've seen with psoriasis and AD, so and eczema. So look, we're not curing acne. We're treating it and controlling it. So there's it's not like we're getting to a cure here. So I don't know that we have an endpoint necessarily unless patients age out of their acne. So it's difficult to say. Doctor. Moore, any additional thoughts or comments? I don't know if we got Doctor. Moore there. Looks like Doctor. Moore is on mute. You can unmute yourself, please. Can you hear me now? Yes, we got you. Thanks. Okay. Excellent. Yes, I agree with Linda and Ted in that. It's very variable and would be very, very difficult to ascribe a number to how many cancers that the patient would go through. I mean, the variability of its face, chest and back only involving the face. Then it's the ZILT C, which typically will only be face. So I think there's tremendous variability there and to describe a number would be very difficult to do with any true consistency? Yes. And I think just from a company perspective, it's early for us. I mean, as Matt alluded to earlier in his discussions, we're seeing now that 20% of the prescription volume coming in is a repeat prescription. And obviously, that's encouraging, that obviously patients seem to be satisfied and will continue to take the product itself. Trying to get a really clear view as to how many prescriptions or canisters that a patient will go through during the course of the year is really just it's not an exact science as Linda outlined. The unit itself is set up as a month of therapy that could be a little more, a little less, just depends on how widespread the disease is, much less of an exact science as what you see with oral dose solids where it's bottles of 30. But we certainly are encouraged by what we're seeing in the underlying repeat usage data. And I think that does align with certainly what we saw earlier in the market research on levels of satisfaction. We'll continue to do our analytics and put our analysts around this as we work through this year and into 2021. So hopefully that helps Tim. Yes. No, that helps. I just had a follow-up question. I know that you've talked a lot about payer access. And I wanted to sort of ask that to the physicians. I mean, have you ever come across patients who haven't been able to get access to Amzate because of inadequate insurance and how big of an issue is that? Sure. Chad, do you want to go first? Sure. There are patients who don't have access to Amzik. I mean, it happens. I think as Doctor. Moore alluded to, we have specialty pharmacies, which are these pharmacies that help us figure out a best way to get the prescription to the patient and they do a great job. As I alluded to, it's not a majority of the patients, that's for sure. It's a minority of patients. I couldn't put a number to it. But I could certainly kind of ask around to our primary medical assistants who deal with some of the callbacks and the issues with that more than I do to give you a better idea. But I know it's a minority as I just don't hear about it very much. Yes, that's Steingold. Doctor. Moore, I don't know if you have any additional thoughts. No, I agree 100%. And I think our commercial team, Matt and the team have done a very nice job of trying to offset and to support patients. That's obviously our mission. Our goal is to make sure patients can get access to our product and physicians can prescribe a product without a lot of burden. To support the patients, while we're working with payers. And we have the tools in place to support the patients, while we're working to get our products on contracting the various formularies. And so our coupon programs we believe have been helpful. In that regard, it helps patients that may not have access to the drug yet because we're still in negotiations with various insurance payers. They still get the product and that physicians obviously can continue to prescribe it and we want that to happen. So that's always been part of our strategy and we believe that we're it's a sound strategy and that we're executing. Michael, any additional questions from the audience? Yes. Live question from Stacy Ku at Cowen and Company. Stacy, please go ahead. Right. I think this is Ken coming in under Stacy's line. Can't catch Tore if you can hear me okay. Hi, Ken. We got you. Hi, thanks. Doctor. Steingold, thanks for the presentation. Just wondering, we did see a slide where you had where the company listed out all the different treatment options. Can you just talk about what is your go to for rosacea? Just your standard of care and the process that you would work through and then obviously where Zolksy might fit itself in? And then wondering just about response rates, obviously there seems like a need. Can you try to quantify that need? How many patients are actually satisfied? And you didn't talk about topical steroids at all, but how many patients are actually satisfied or get resolution? And then would maybe not need to bring us to ZILTI versus is it a very is it almost all would end up progressing to ZILTI? Then also wondering from your perspective, what went wrong with RHOFADE? And maybe the company could talk about that as well. So that launched with, good expectations, but clearly did not go well. So maybe get your perspective and the company's perspective on RHOFADE and how we'll do this differently. Thank you. Okay. So, there was a time when people used to talk about rosacea as kind of a made up disease that Galderma made up to sell metronidazole or topical metrogel. And when we look at the efficacy that we used to have, it wasn't very good. You know, some people call it used to call it like a branded placebo because it wasn't working well. We have and it works some. Azelaic acid is an acceptable alternative. It can be very irritating and we have other formulations that work, but it's fine. But for a rosacea patient who has a tolerability issue, it can be quite a challenge. The oral agents, or ratio, for some patients that does well, but when you actually look at the efficacy, the efficacy is not that outstanding. So, cilantro was really the first of the newer drugs that really made a difference. They took patients who had moderate to severe disease. They studied it as monotherapy. They went head to head with branded metronidazole and showed superiority. You're coming Vine is coming in now with the drug and when we look at the clear or almost clear data, they're getting to about 50% at the end of 12 weeks, which is higher than anything we've seen in those very rigorous clinical tolerability, which is something that has to be there, your tolerability was great. And then when you have side effects and the vehicle is higher than the active, you say, wow, that doesn't usually happen. And that really goes to the fact that the drug has anti inflammatory properties. So it's calming the skin down even better than just using a vehicle. And Ted mentioned when he was talking about, using minocycline for acne, there's a lot of, ingredients that were formulated into the vehicle to make it very well tolerated. So hopefully I answered your question as to where we are right now and where I think this will fit in. I think this will fit in quite well. A lot of patients who don't have the newer drugs are not satisfied because the drugs that we've had in the past really just don't work. Yes. I think if I could just offer a quick thought just on metronidazole since Doctor. Steingold brought it up. It's despite the fact that it has its challenges in terms of effectiveness, There's still a 1,000,000 plus prescriptions a year prescribed for rosacea. I think it goes to what Matt outlined earlier in his discussions. There really just hasn't been a lot of innovation in the space. And we're obviously very encouraged by the safety and efficacy data of mine. And I think the research shows it could have the potential to be very disruptive for the space. And I think it just goes to the points that Doctor. Steingold, Doctor. Lane and Doctor. Moore have made that there's just not a lot of all terms out there. And in the absence of that, you're just going to continue to go to what's available. And we think we've got something that has the potential to address those unmet needs, not just for the reduction of the inflammatory lesions associated with rosacea, but obviously the erythema data, which is a hallmark for patients that present with rosacea. Doctor. Steinfeld talked about it. We were very encouraged by the improvement in erythema. And that, Ken, goes to your question about RHOFADE. I'll offer our thoughts because obviously we've spent a lot of time looking at it. RHOFADE is a vasoconstrictor. It is indicated for erythema associated with patients that have rosacea. The data shows it does not seem to have any impact on reduction of the lesions. And so if you have patients, if a large number of patients, if not the majority of the patients that have rosacea have both the lesions that they're trying to address as well, darothema associated with it, Then that goes to the notion of having multiple products perhaps that you have to prescribe, multiple co pays, etcetera. We're encouraged by what we've seen in our clinical trials with ZILTI in the efficacy reducing lesion counts and getting clearance rates of almost one out of every 2 patients. But also the, what seems to be rather profound impact on your curtailing erythema and improving erythema over the course of time, not just in the 12 week studies, but obviously taking it out for 52 weeks at all endpoints. So I'll turn it over to Doctor. Steingold, Doctor. Lee and Doctor. Moore for any additional color around that. So Doctor. Steingold, you want to go first? So I think one of the problems with the launch was there really wasn't a launch. And I believe that this drug came out in a transition period. So I'm not sure that it ever got the attention that it truly deserved. But Dave, as you mentioned, this is a drug that is strictly for the background erythema in rosacea. There are some studies that say that alpha adrenergic agonists like brimonidine and oxymetazoline when used in combination with a topical anti inflammatory might make the condition even better. But as a monotherapy, it's really just going to be for the pink face. Yes. What I'm learning from this is that analysts like to ask 4 part questions. You guys are amazing with the number of questions you have. So if I could just touch on this, just the opportunity for topical minocycline for rosacea. So Linda, I'm sure you have as well. There have been 3 different topical minocycline products that have gone through development. Vine has the only one that's come through to commercialization, but each one of them, I have been so impressed with the efficacy. Of course, again, I'm blinded in the trials. But the topical minocycline, mark my word, that will be a home run for rosacea. It will be a home run for rosacea, because everything that we've had just doesn't work as well. Okay. And we've seen the reduction in erythema as well as the reduction in lesion count. Now we when we look at RHOFADE, I'm a big RHOFADE believer. I still prescribe it just about in combination with everything because I agree with Doctor. Steingold that it works the best when it's used in conjunction with another product. It is a cosmetic product for many and it's priced that way. I think their price right now is $50 a tube and they'll last for 1 to 2 months. And I don't know what the kind of recidivism is on the prescriptions that I write, but I think it's quite high because patients get hooked on it. And the nice thing is I remember from the trials, from the trials, I believe we have them use it daily for 28 days and then we have them come back either 14 or 2 weeks or 4 weeks later after stopping and many of those patients didn't have redness that recurred at that point. So there's a physiologic and or anatomic change that occurs with the use of oxymetazoline in my view. So I'm a big believer in RHOFADE. I think as Linda said that the launch was hampered by issues with the company. It has been relaunched a couple of times. And for those of us that are believers and are users of it, I think we still believe in and are lucky that we still are able to prescribe it honestly. So those are my 2¢. Thanks. That's fine. Doctor. Moore? Can you hear me there? Yes. Now we got you. Excellent. Excellent. So my vantage point being from South Florida, rosacea is just a tremendous issue and I have a large number of patients that I treat for rosacea. And I will tell you that the sentiments and okay, it's a chronic condition, so we're going to be treating for a while. But the sentiments that I want to echo Linda and Ted's in that patients, they don't seem to be overwhelmingly overjoyed with their therapeutic options. So from a standpoint of ZILT this should be a game changer. And again, a welcome one because the landscape and space that it stands now for rosacea just I don't find it wow factor. I can help control and relative to RHOFADE, I've always had to use that in combination with other things to really get decent efficacy monotherapy. I just didn't see Wow factor with it. And again, we know based on its mechanism of action that it will help with the redness, which is a significant component of most patients with rosacea. But being in South Florida, again, there's such a chronicity with rosacea, my rosacea patients that they're constantly seeking options that are going to be more efficacious. So I really cannot wait to get my hands on ZILXC from geographically. I really I struggle with that one in terms of getting my patients to be not that I can't control them, but I want to see that overwhelmingly ecstatic outcome and happiness from my patients like I do with MZXYK. So I'm really looking forward to seeing again relative virofade. It has its efficacy in terms of minimizing the erythema or redness component, but it was always with additional many additional things too. I just have to more. Michael, any additional questions? Yes, we have a live follow-up from Louise Chen. Great. So what percentage of your rosacea patients would you prescribe ZILSI to or what are you expecting from that perspective? And then for Vine Management, what are the synergies of the ZILSI launch plus Amzeq? How is your sales force positioned? Or will you need to add additional reps here? Thank you. Great. So, why don't Matt, if, why don't you address the second question on the commercial synergies and then turn it back over to the panel on their expectations around usage and percent usage and how it will fit into your armamentarium. But Matt, why don't you take the first one on the synergies, which we obviously believe we've got excellent synergies, why we built the field force the way we did from the stock. The line stake. So hi, Luis. So the overlap so just to kind of put things in perspective, on our current called on universe for AMZ, 87% of those called on targets are also ZILTZI targets. So it is it's a really important point that our overlap with Amzik is quite good. We had to add roughly 500 to 600 targets into our call universe. We do cover now 75% of the total patient volume in rosacea. And as a synergy, it's a nice complement to talk about the acne patients and the Gen Z component and the acne component and then also transition over to rosacea or vice versa depending on the target. But these are synergistic call points we can anchor around the positioning of minocycline as a molecule and molecule stabilizing technology, as an anchor for both. And then talk about the different patient populations and the stories, as I mentioned. I think it's also helping us out, Luis, in our discussions with the payers. This is we've spent a lot of time with payers, both on the business side, but obviously on the clinical side, taking them through the drug itself. So this is the 1st topical tetracycline, topical minocycline product available. And so we've already gone through that hurdle in large part with a lot of the P and T groups. So as we're for AmSeq and so as we're now having the discussions and negotiations with ZILCY, that's been helpful for us because it's not reeducate it's not educating them on a completely different product. It's different concentrations, different prevalence rates. But that's been helpful to us. And I think that's evident that we got Silksy on formulary for Express Scripts before we actually launched the drug. So that was helpful for us. Why don't I turn it to Doctor. Lane and Doctor. Moore and Doctor. Steingold just on I know these are always tough questions to ask about percentages, but maybe in broad strokes how you envision ZILXVI to fit into your armamentarium. So Daphne, you want to go first? Yes. I think it's going to quickly become first line for me. I mean, this is a drug that I've been excited about for a long time. So, I see it kind of very quickly becoming first line. As I said, I tend to combine things with RHOFADE, so I see a combination therapy approach happening. But it may even take away from my ORACHA requirement as well because usually there a combination therapy approach that we use for rosacea where it's oracea. Oracea and cilantro together have been the kind of the primary combination that I've used, but with Bilksi now available, I can see that overtaking it. So I'm not going to back down from my original statement. I think it will be first line of perhaps monotherapy most likely combined with rafine. Thanks. Doctor. Moore? Doctor. Moore, please unmute your line. Can you hear me now? Yes, there we go. Yes. All right. So I'm very excited to get my hands on it. I'll tell you, the lines here of my rosacea patients will receive ZILT C because I want to see the mirroring of those clinical trials. And again, being in South Florida and having so many patients with rosacea that just are controlled and relatively happy, we want to see tremendous success. I want to see patients overjoyed. So I can't wait to get my hands on it to try it. And I'll tell you, I will be trying it with most of my rosacea patients as they follow-up and certainly getting a sense for clinically how they're doing with the current regimen that typically will include an Orescia with SOLANTRA, maybe RHOFADE or even metronidazole in certain cases. And again, just because of the fact that I don't have what I want to consider to be overwhelmingly clinical success with these patients, certainly control. ZILC is going to be my go to to really see if I can get some home runs with my patients as opposed to single or double. So I'm really looking to get my hands on and try it. So I will be trying with most of my patients right off the bat. Thanks. And Doctor. Steigle? I agree. I can't see a reason why it wouldn't be first line for pachycardiaularization. I would use it as monotherapy in these patients. Thanks. Michael, any additional questions? Yes. Follow-up from David Amsellem at Piper. David, please go ahead. Sure. So you may have covered this, and this is for the featured speakers, the KOLs. You may have covered this in terms of how you're going to use ZILTI in practice. But I wanted to sort of dig a little deeper. I mean, you have bimonidine, you have ivermectin, you have these older products that are used with relative frequencies. So do you envision a role for ZILTI? Sorry, if I mispronounce it. Do you envision a role for it primarily as mono therapy? Or do you envision some type of paradigm that's similar to Oracea where you're combining it with an anti redness product like bimonidine or Rophate. Help us understand how you think about it and is there going to be sort of an individualization and in terms of how ZILTI is used in practice? Linda, why don't you start first this time? So you asked 10 dermatologists, you'll get 10 different answers. It's the art of medicine and everybody's going to use it how they want to and it's going to start them on combination therapy to try to get them clear yesterday. Somebody comes in, just a regular patient, they have a busy life, monotherapy is okay for them. There's not a reason for me not to use this as monotherapy because we saw that it kicked in quickly. And in half of the patients, they got to clear almost clear in 3 months. If somebody has excessive background erythema, I might add in an alpha adrenergic agonist, probably oxymetazoline because remonidine has a risk of some rebound erythema associated with it. So everybody's going to do it differently. And the beauty of it is there's not a treatment regimen that it wouldn't fit in with. There's not something that you'd say you can't use these together. That's Doctor. Seidl. Doctor. Moore? Yes. So I agree. Given the said patient, there are going to be different variables that will play a role in terms of how they present and what their expectations will be based on their personal life. For me as a clinician, I do foresee it again based on the trials and what Doctor. Sanghol presented today that monotherapy should be where it should fit in. However, again, we practice medicine as an art form and we're going to see as we go through. I will be very interested to see it monotherapy, how it works and that doesn't mean that I'm not going to try it in combination with some other products. But I think that it will, as time goes on, peter out and we'll see because this is how it works on the clinical side. Medications are released and we look at the trials and then there's going to be the real world application where we'll see what happens and it usually will kind of dictate prescribing habits and again said clinician and said patient, there will be those variables. But my plan will be to try monotherapy. And if I have to combine it with other things, certainly not an option. It is an option. And then finally, Doctor. O'Neill? Yes. I think, I mean, look, monotherapy rosacea, but a lot of our rosacea patients have an overlap syndrome with seborrheic dermatitis. It's not uncommon for us to see bumps along with dryness. And that's the overlap syndrome that I'm discussing that I'm talking about. And we haven't really had a great monotherapy knockout drug for both conditions. So I'm really excited to use this in our overlap patients because I think this will really help us to treat both with 1 and maybe avoid some of the other either higher cost medications, topicals that we use that are anti inflammatory or even topical steroids that we sometimes have to use to get the seborrheic dermatitis under control. So and systemic antibiotics. So I'm excited to get started with zolksy not only for monotherapy for rosacea, as I mentioned, in combination with oxy, but also for our overlap patients. Great. Thanks, Doctor. Mike. Michael, coming to the home stretch, any additional questions for the panel? Yes. There's one more live question from Oren at H. C. Wainwright and then we have a couple of written questions we'll take from the web. Okay. Thanks. So I have a couple of questions. Just on the cost side, all of you have spoken to at least on the Amzik front having really good access, only a minority of patients not having not being able to get the product. And I'm just curious what your perception is of cost sensitivity in general amongst your patients, especially when we're talking about more chronic patients in the rosacea side of the equation. Are you hearing back saying, look, can you prescribe something that's cheaper for me? I can get a generic drug for $5 This other thing, even with the coupons, costing me $40 And I do have a follow-up. Thanks. If you want to answer that first. Dwayne, you want to start? Yes. Okay. So, I think the price sensitivity is an issue. I think with the advent of these direct to consumer website based compounding pharmaceuticals such as HIMS and HERS and Apostrophe and Curology where patients are paying $75 let's say for them to be seen by a physician's assistant and get some something compounded that we don't even know the stability of. They're willing to pay $75 there all day every day. And so when they come in and they see a dermatologist and they're given something which we know is manufactured correctly and has the studies to prove it. I don't see a lot of pushback in the $40 to $50 range. A lot of our adult females, for example, the retinoids aren't covered for them and so it's $75 and we don't get pushback. So I think that the price sensitivity is really not huge issue in the patients that I see. Of course, this could be very personal. But in my patient population, I just don't see a huge issue with that at all. Okay. Scott Stagull? So, there's a difference between treating patients who have an acute condition and treating somebody who has a chronic disease. If somebody comes in and they have poison IV, it's going to go away. I'll be a hero whether I give them a branded steroid or generic steroid or if they need oral steroids, it's going to go away, it's fine, it doesn't matter. If I give them a generic drug and the consistency is a little bit gloppy and heavy and they don't like it, it's okay because you know what, you use it for a week and then it's done. When somebody has a chronic condition like rosacea or acne, they're more sensitive to the type of medication that we give them. They want somebody something that's cosmetically elegant. They want something that's going to work. They've tried other things. So that's why if I'm going to write a branded drug, the samples are important because that does help the patient to understand what you're giving them. And usually I'll say to them, I'm giving you this drug, which is a brand name drug for these reasons. I want you to have it because I know your skin is going to be able to tolerate it. And I know that it's going to work well for you. And I think that kind of an educated consumer is great. So with a chronic condition like rosacea, I don't think if the coupon card was $75 that's okay. They'd spend that over the counter at Target anyways. And Doctor. Moore? Yes. So I agree. When you educate a patient that they're going to be getting a preparation that's been studied extensively and undergone several sort of hoops to get to where it is to market in terms of its safety and efficacy and tolerability. The patients are very astute. And I agree with my fellow colleagues that that sweet spot between 3575 is usually okay for them. And again, I think that's where patient education comes in. And once you explain and a lot of these patients, again, because of the chronicity of the condition have been on other medications. So they have a point of reference to compare vehicle, to compare the tolerability and even efficacy. So I don't really get a lot of pushback, I'll tell you, with the branded meds and when the efficacy is there, absolutely not. So it's not a big issue, but you do have some patients who'll bring it up, but it's not the biggest issue that I face with it. Okay. And this might be related, but maybe for the company more specifically. All of the docs here today have talked about mineralization in particular, the combo of drugs they're using. And I don't think they brought up metronidazole too often, right? Yet upfront, we can see in the script data and you highlighted, Dave, that there's a 1,000,000 prescriptions a year of that. So I'm just curious, is that a cost issue and that there's X number of patients out there that can only get the old cheap stuff or is that because that's primary care docs prescribing that stuff and not you guys? And so what would it take long term with your targeted 50, 60 reps, how does that eventually translate to this drug being used much more broadly? Yes. I'll offer some initial thoughts and turn it over to Matt. Indeed, there are lots of prescriptions for metronidazole that are written every year. We do believe that that's an product that can be very helpful for physicians and for patients and to address the various unmet needs and challenges that Doctor. Steingold, Doctor. Lane and Doctor. Moore have spoken about. So sure, when you take a look at it, you can look we can look at it to set up a finite market of just the branded products, which is robust. But we think of it in terms of the product itself. I think in part there hasn't been a lot of new innovative products to the category. And as we are having discussions with payers that seems to be resonating with them that our product can fit into the into the obviously the benefit plans, but also be meaningful for physicians in our armamentarium. So we certainly view the entire category as an opportunity for us to bring a new and innovative product like as folks eat the market. So Matt, perhaps you can offer some additional thoughts. Yes. So as we look at the surrogates in the market access paradigm, we see that some have either prior authorization or step therapy as a requirement. And so it makes me wonder how much of that metronidazole is required for step therapy before getting to a brand. And maybe I'll kick it over to the physician panel to see if my assumption is Yes. So there's a number of reasons why metronidazole is written and none of them are that you think that this is a superior drug. It's written because a patient has Medicare or Medicaid and that's the only thing that's covered. It's written because maybe it's a dermatologist who doesn't know the newer drugs or hasn't seen the data with the newer drugs and that's all that they know. And I don't think it's going to necessarily be on the shoulders of the reps to get this out. I mean, some of it is, but we have so many meetings. And our meetings, given our COVID environment where everything's virtual, we have thousands of people signed up for these meetings. And you guys are getting a lot of play in acne symposium, rosacea. So there's a lot talk. So even if your rep doesn't touch somebody, they're going to hear about it. If they get any CME at all, they're going to hear about it. That's great. Doctor. Lane? I have nothing to add. I totally agree with Linda. Doctor. Morgetto, I guess. That is correct. She summed it up very nicely. Great. Michael, I think we're down to about the last minute or 2. So not sure if we have any other questions, but maybe we got time for one more and then probably good for us to wrap it up. Yes. David, a couple of related questions that came in from the web that I think would be interesting to get the answers to. I think first of all, how has telemedicine been for the treatment of acne and rosacea in clinical practice? And then do the doctors anticipate using telemedicine going forward once the pandemic is over? Good. It's a good way to wrap it up. So why don't we just go around the horn with the panel. Doctor. Moore, why don't we start with you? Absolutely. So telemedicine essentially revolutionized our ability to get to our patients during this COVID environment. There was a tremendous amount of trepidation for patients coming into offices. There were recommendations by the CDC. So I'll tell you, telemedicine was heaven sent and truly a lifesaver because you can very accurately analyze a patient with acne and rosacea via telemedicine. So in short, telemedicine has been fantastic throughout the COVID environment. I'll tell you, I have the patients have now returned. They are coming in for live visits, but there are some who still enjoy telemedicine. So I'm still doing telemedicine as well, even though the COVID has sort of tied it down in a sense in certain locations. I still do telemedicine. I still have live visits. So I think it's been fantastic and really helpful. Great. Doctor. Lane? Yes. I mean, lifesaver during the shut down. Since then, the number of telemedicine visits have waned to the point of maybe 1 a day at this point. So really not kind of back to where it was previously, level of in office visits in the future. But great to have now, nice to have. I don't know that it's revolutionizing anything as we get back to normal. And Doctor. Stinegold? Absolutely agree. I did all telemedicine at one point, then maybe half. Now I do none. And it's everything is going to depend on reimbursement. Once it stops getting reimbursed, it will shut down completely. So, you know, but for now, it works. Okay. Thanks. Okay. Well, first of all, I want to thank everyone for attending and joining this conference. It's been a great event. I've had a chance to watch a number of participants. I can see it on the screen. And we've actually gone for a full 3 hours and there's been it's almost the same level of participation since Minute 1. So I think that's a credit to obviously our physician attendees, fantastic job providing a great comprehensive reviews of the markets, of the treatment algorithms, the regimens that are available and obviously on the data for our product Samsik and Silksy. I want to thank each of you, Doctor. Steinhold, Doctor. Moore, Doctor. Lane for doing a fantastic job and also sharing your personal experiences. And so thanks again. Thanks to the team at LifeSci for putting this event together. Logistically, it was a lot of work. And then last but not least, I want to thank the audience that have spent time, 3 hours of your day to join in on this call. Hopefully, you found it to be helpful and productive. And we look forward to as a company providing you updates as we continue to grow our progressive business. Again, exciting times for us here with VINE and we're excited to be launching Zolksy today. Thanks again everyone for joining. Thank you. Have a great rest of the week. Thank you very much.

• Slides