Good morning, and welcome to the VYNE Therapeutics conference call to discuss the fourth quarter and full year 2020 financial results and updates. At this time, all participants are in a listen-only mode. Following the company's formal remarks, we will open the call for your questions. Please be advised that this call is being recorded at the company's request. I will now turn the call over to Michael Wood at LifeSci Advisors. Please go ahead.
Good morning, everyone, and thank you for joining us this morning. Before we begin formal remarks, let me remind you that some of the information in the press release issued this morning and on this conference call contain forward-looking statements that involve risks, uncertainties, and assumptions that are difficult to predict, including statements, forecasts, and observations regarding future financial and operating performance, impacts of the COVID-19 pandemic on VYNE, and observations regarding ongoing operating expenses and net revenue.
These statements will include observations associated with the commercialization of AMZEEQ and ZILXI in the United States. They will also include plans and expectations regarding the success, timing, and costs of clinical trials.
Words that express and reflect optimism, satisfaction with current progress, prospects and projections, as well as words such as believe, intend, expect, plan, anticipate, and similar variations identify forward-looking statements, but their absence does not mean that a statement is not forward-looking.
Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those contained in such statements. Several factors that could contribute to such differences are described in detail in VYNE Therapeutics' filings with the SEC.
These forward-looking statements speak only as of the date of today's press release and conference call and t he company undertakes no obligation to publicly update any forward-looking statements or supply new information regarding the circumstances after the date of this call. In addition, the financial portion of this call will include certain non-GAAP financial information.
For additional disclosures regarding to these non-GAAP financial measures, including a reconciliation of the most directly comparable GAAP measures, please see today's press release, which is posted on the investor relations section of the company's website.
Participating in this morning's call are Dave Domzalski, VYNE's President and Chief Executive Officer; Andrew Saik, Chief Financial Officer; Dr. Iain Stuart, Chief Scientific Officer; and Matt Wiley, the company's Chief Commercial Officer. Please note that following the company's prepared remarks on the 2020 financial and operating results, Dr. Stuart will be reviewing the company's pipeline candidate, FMX114.
His review includes a number of slides via the webcast, and these are posted on the investor relations section of the company's website. At this time, I'd like to turn the call over to Dave Domzalski. Dave, please go ahead.
Thank you, Michael, and good morning to everyone. The past few months have been productive for VYNE, and we believe the company is well-positioned to deliver value to our shareholders as we continue to execute on our vision. As we think about our key objectives for the year, there are three areas of focus.
First is commercial execution. The past year has certainly posed challenges that have never been seen before in the commercialization of therapeutics and has been even more challenging for new product launches as companies have faced continued shutdowns and customer access issues globally.
As discussed in past calls, we have faced and continue to address these challenges head-on. Despite the headwinds, we continue to progress trial and utilization of AMZEEQ and ZILXI, driving market share in their respective markets of acne and rosacea.
Matt Wiley, our Chief Commercial Officer, will provide a more detailed update on both product launches. The second is maximizing our operational leverage. The significant overlap that exists between prescribers for acne and rosacea is a key factor in our commercial strategy.
As we add new products in the future, there will be further opportunities to leverage both our sales organization and R&D capabilities to increase revenue and earnings. Importantly, we will continue to prioritize our resources carefully and keep a tight control of expenses.
Andrew Saik, our CFO, will provide a financial update today for you. Our third area of focus is to continue to build a diversified pipeline. For FCD105, which is our minocycline and adapalene combination, we held a successful end-of-phase II meeting with the FDA in November.
The meeting provided clear direction and guidance on the planned phase III clinical and pharmaceutical development for FCD105, and we anticipate initiating this study later this year. Earlier this week, we unveiled a new therapeutic candidate that we believe has tremendous value.
This product candidate, which we refer to as FMX114, is a fixed combination of the pan-JAK inhibitor tofacitinib and a sphingosine 1-phosphate receptor modulator, fingolimod, in a topical gel formulation for the treatment of mild to moderate atopic dermatitis. We believe this has the potential to be the first topical combination JAK inhibitor.
Atopic dermatitis is a substantial market opportunity, with approximately 22 million patients treated in the United States alone. We issued a press release on Monday highlighting the preclinical efficacy and tolerability data. Our Chief Scientific Officer, Dr. Iain Stuart, is joining our call this morning to provide an overview of FMX114.
Iain will walk you through the data and discuss the phase II-A program in AD that we plan to initiate in the third quarter of this year and from which we would anticipate generating top-line results prior to year-end. 2021 has been busy. We executed new PBM contracts for both AMZEEQ and ZILXI in mid-January.
The completion of these agreements is consistent with our goals to achieve broad commercial coverage of AMZEEQ and ZILXI, gives us commercial access to an additional 20-25 million new lives. For AMZEEQ, we received FDA approval to include new information in the product label, referencing the low propensity of P. acnes strains to develop resistance to minocycline, which is the active ingredient in AMZEEQ.
This label update can provide further product differentiation for AMZEEQ, which will be useful to healthcare providers in their treatment selection for patients.
We strengthened our balance sheet, raising a combined $81 million in net proceeds from mid-fourth quarter last year through January of this year. Approximately $46.7 million of this was through a registered direct offering with high-quality investors, $34.3 million of net proceeds were generated from the sale of common stock through our ATM facility, which is now complete and terminated.
In addition to the company's existing cash and investments as of December 31st, 2020, and projected cash flows from revenues, we now expect to have sufficient cash to fund our operating expense and capital requirements through the end of 2022. Finally, we executed a one-for-four reverse stock split on February 12th. We had a large number of shares outstanding following the merger last year, which we felt was disproportionate to the market cap and underlying value of the company.
Our shareholders approved the reverse split, and we look forward to unlocking shareholder value and continuing to drive additional visibility among the important strategics and shareholders in our universe. I will now turn the call over to Matt Wiley, who will give further insight regarding our progress on the commercial front. Matt?
Thank you, Dave. Our sales team remains resilient and continues to perform well despite the pandemic-related obstacles that exist in the marketplace. AMZEEQ prescription volume came in in the fourth quarter at 34,000 new prescriptions and over 44,000 total prescriptions, which represents a 26% and 35% growth over the third quarter, respectively.
We continue to expand our reach and trial of AMZEEQ with the number of unique prescribers of AMZEEQ exceeding 6,700 through the fourth quarter, which represents a 20% increase over the third quarter. To date, we are now over 7,100 unique prescribers of AMZEEQ. Additionally, we've achieved 60% penetration among our target universe, whose productivity has risen to 30 prescriptions per physician launched to date.
We're pleased with the progress we've made over the course of the year and expect the growth of the productivity to continue due to the high volume of patients and prescriptions in these important offices. We continue to be encouraged by our non-personal promotions, specifically on our ability to educate healthcare providers through our peer-to-peer speaker programs.
This platform is allowing us to quickly and efficiently communicate the recent information regarding antibiotic resistance that was added into the AMZEEQ prescribing information. Our online consumer activation efforts have also been fully deployed for AMZEEQ since early January.
With respect to market access for AMZEEQ, we now have all three major PBMs under contract and are working to pull through the underlying plans for the most recent one now. Turning to ZILXI, we are clearly seeing the impact of COVID-19 pandemic on the ZILXI launch.
You may recall we launched ZILXI in October 2020 during the second widespread state shutdowns. The state level and physician office COVID-related protocols have significantly impaired face-to-face interactions between our sales team and doctors over the last few months.
The impact of these constraints is more pronounced in a space like rosacea, where there hasn't been a meaningful launch in nearly five years, and changing these habits requires consistent field efforts and additional education. Despite these headwinds, we've generated over 6,700 new prescriptions and over 7,200 total prescriptions for ZILXI since launch, and prescriptions are gaining momentum month-over-month. Approximately 1,600 healthcare providers have prescribed ZILXI since launch, with approximately 70-80 new writers per week.
As with AMZEEQ, healthcare providers have demonstrated keen interest in the ZILXI peer-to-peer efforts, and we continue to execute these programs with urgency during this COVID-19-impacted period to educate prescribers on our product.
With respect to ZILXI payer access, I'm pleased to share that our conversations with payers have gone faster than we initially anticipated. We now have finalized contracts with the top three PBMs and are focused on pull-through execution similar to AMZEEQ. I will now turn the call over to Andrew Saik to discuss our financials.
Thanks, Matt. I'd like to start with a review of the balance sheet. Our cash and investments as of December 31st totaled $59 million. As Dave mentioned, since the end of the third quarter, we have raised a combined $81 million in net proceeds from the registered direct offering we completed in January and the ATM, which we subsequently terminated. $8 million of the ATM amount was generated in 2020, and therefore was included in the year-end cash of $59 million.
Adding the funds raised in January to the reported $59 million in year-end cash, w e have a pro forma year-end balance of approximately $132 million. We estimate that these amounts, combined with our projected cash flows from revenue, should provide cash runway through the end of 2022.
We are pleased with our fundraising efforts, but we will continue to remain focused on cost control and prudent resource prioritization. Moving to the P&L, I'm going to focus mainly on our quarterly results, as they are more reflective of our operating structure moving forward.
Revenues in Q4 were $4.3 million and consisted of $4.1 million of product sales from AMZEEQ and ZILXI, and $0.2 million of royalty revenues. GAAP net loss in Q4 was $23.2 million or $0.55 per share on a post-split basis. This compares to $37.8 million or $4.17 per share for the comparable period in 2019.
When excluding $3 million of stock-based compensation expense and $2.1 million of non-recurring asset disposal charges related to our completion of our restructuring activities, our fourth quarter 2020 adjusted net loss was $18 million or $0.43 per share, again, on a post-split basis.
Adjusted operating expenses in Q4 were $20.7 million, including adjusted SG&A expenses of $15.8 million and adjusted R&D expenses of $4.9 million. This compares to $32.7 million of adjusted operating expenses for the fourth quarter in 2019, which included adjusted SG&A expenses of $18.9 million and adjusted R&D expense of $13.8 million.
As mentioned on our previous calls, we believe that operating costs of approximately $25 million per quarter are sustainable into the future but do not include incremental costs that would be required for the anticipated phase III trials for FCD105 or potentially progressing FMX114 beyond the phase II trial this year, which is built into our current operating plan.
Iain will provide more details regarding this phase II program in a few moments. One note on our previously announced corporate restructuring. Consistent with the overall cost reduction efforts, we significantly reduced our headcount and facility footprint in Israel during 2020.
This caused us to take the aforementioned one-time non-cash charge of $2.1 million in the fourth quarter related to the facility reduction. Additionally, we began liquidation proceedings of our Israeli subsidiary, and as a result, our intellectual property was assigned to our U.S. parent company.
We anticipate this will result in a more efficient tax structure for us long term given our reduced presence in Israel, and we do not anticipate that this will have a material tax expense or cash cost to the company. Moving to a high-level review of our full-year numbers.
Full year 2020 revenue was $21 million and consisted of $10.2 million of product sales from AMZEEQ and ZILXI, $10 million of license revenue, and $0.8 million of royalty revenues. Our fiscal year 2020 GAAP net loss was $255.6 million or $7.88 per share on a post-split basis.
Included in the 2020 GAAP net loss were $159.3 million of non-cash expenses, which predominantly occurred in the first half of the year and were related to the Menlo merger. When including these non-cash items, our 2020 adjusted net loss was $96.3 million or $2.97 per share.
Finally, to share count. Reflecting the one-for-four reverse stock split completed on February 12th, our share count as of December 31st was approximately 43.2 million shares. On a pro forma basis, including the registered direct and ATM, our share count was 51.3 million shares.
Both figures are given on a post-split basis. For further details on our financials, I will refer you to our Form 10-K for the year ended December 31st, 2020, filed with the SEC and available on our website. I will now turn the call over to Iain, who will go through FMX114 program in some detail.
Thank you, Andrew. What I'd like to do over the next few minutes is talk about our new product candidate, FMX114, which we're initially developing for the treatment of mild to moderate atopic dermatitis, or AD. I'll discuss the potential mode of action for the product and review the proof of concept preclinical data we've generated. I'll outline our upcoming planned development activities for this candidate.
Let me begin first with some background on atopic dermatitis. Many of you are familiar with this category. The condition is also known as atopic eczema. It is a chronic pruritic inflammatory skin condition that typically affects the face, neck, arms, and legs. It often starts in early childhood and can persist throughout a patient's lifetime. It can have wide-ranging impact on quality of life, and there is substantial monetary burden from direct and indirect costs to this patient population.
According to published estimates, there are approximately 30 million people in the U.S. with AD. Of these, approximately 22 million are diagnosed and on treatment. The roughly 19 million treated that have mild to moderate disease would be in our target market for FMX114.
According to Symphony Health data, there were over 7 million prescriptions written in 2019 alone for the treatment of AD. Topical steroids are the mainstay for treatment of mild to moderate atopic dermatitis, and in 2019, approximately 2 million, or nearly 30% of prescriptions, were for formulations of triamcinolone acetonide alone.
Steroid use can cause a variety of side effects, which you may know, and raise both dermal and systemic safety concerns, especially with long-term use. These may include rebound or rapid relapse upon steroid withdrawal, as well as damaging impact on skin structure and function.
This is particular concern in AD, where up to a 1/3 of patients affected are children. Topical products we know that are currently in development for AD include JAKs, PDE4 inhibitors, and aryl hydrocarbon receptor agonists primarily affect one component of disease, and that is the reduction of inflammatory cytokine release from activated T- cells in the skin.
It is well known that AD is a multifactorial disease, which is the motivating factor behind our thesis for developing combination therapy that can potentially address multiple aspects of the disease. FMX114 is a fixed combination gel of two approved oral drugs, tofacitinib and fingolimod.
Tofacitinib is a pan-JAK inhibitor that has been shown to reduce inflammation and atopic dermatitis by inhibiting the release of Th2-mediated inflammatory cytokines that promote inflammation in the skin. These cytokines negatively impact both skin barrier integrity and function, which are key components of the disease.
Fingolimod is a sphingosine-1 phosphate receptor modulator that is thought to work by inhibiting the migration of inflammatory cells between the lymph nodes and skin. Fingolimod does this by inactivating sphingosine-1 phosphate receptors that have an important role in managing immune cell trafficking around the body.
In addition, there's evidence that fingolimod can upregulate filaggrin and its byproduct, natural moisturizing factor in skin, which are critical to maintaining skin hydration and restoring overall skin barrier function. We believe FMX114 has the potential to be the first topical combination JAK inhibitor product for the treatment of AD, as well as the first topical product in clinical development that utilizes the sphingosine- 1 phosphate receptor mode of action.
These data reflect our latest safety and efficacy preclinical study for FMX114, which I think will help explain why we're particularly excited by the potential of this combination treatment.
We conducted a study using a common non-clinical mouse model that's typically used to evaluate preclinical efficacy of investigational products in the treatment of AD. The mice were treated with a topical solution of dinitrochlorobenzene, or DNCB, over a 39-day period, which induces a Type II inflammatory response in the skin with similar pathology to AD.
On days 32 to 39, we applied each treatment once daily and evaluated efficacy using a modified Atopic Dermatitis Index, or mADI, which is a composite measure of the severity of skin erythema, excoriation erosion, and dryness and peeling. If you look at the line plot, you can see the upper line represents the control group, which received DNCB alone.
These animals clearly had worsening disease over the seven-day treatment period. We evaluated tofacitinib and fingolimod monotherapy gels as well, and these were also successful in independently reducing mADI scores.
The most profound reduction in scores were observed in the two groups that received the FMX114 combinations. These combinations represent two different dose levels containing different concentrations of tofacitinib and fingolimod. The magnitude of improvement is obvious here. By day seven, there was an 89% reduction in mADI for the 0.6% tofacitinib, 0.01% fingolimod dose relative to the DNCB control group.
Also of note, both fixed combinations had comparable efficacy to triamcinolone 0.1% cream. The safety results from the study are presented here on this slide. We recorded changes in animal weight throughout the treatment period, as change in weight is a common surrogate as to how well a particular treatment is tolerated in preclinical studies.
You can see here that the body weight gains for both FMX114 groups continued to develop during treatment and were comparable to both DNCB negative control group and the healthy control group that only received the FMX114 vehicle.
In contrast, the group which received triamcinolone 0.1% cream lost a significant amount of weight throughout the treatment course. These animals lost approximately 1/5 of their weight at treatment day seven compared to FMX114, likely as a result of steroid's systemic effect on altering metabolic rate.
The clinical images here, taken on day seven, show the different outcomes for the three treatment groups. The animal on the left was in the DNCB control group, where significant presence of erythema, erosion, and dryness scaling are evident. The middle image shows the FMX114 combination with almost no evidence of lesional skin.
In addition, good skin tone and structure have been demonstrated at the end of treatment. We see similar efficacy effect on lesional skin with the triamcinolone-treated animal. However, there is preliminary evidence of skin thinning, which is indicative of a deleterious impact the steroid has on skin.
We are pleased with the preclinical results. Next, we plan to initiate a phase II-A proof-of-concept study in patients with mild to moderate AD that will evaluate a single fixed combination of FMX114.
Our proposed design for the phase II-A study is outlined here on this slide, including the efficacy and safety assessments that will be conducted during the trial. This will be a randomized, double-blinded trial designed to compare the safety and efficacy of FMX114 gel to vehicle gel. We intend to enroll 25 subjects, where each subject will serve as their own control.
Enrolling criteria specifies that subjects must have two comparable target AD lesions for treatment upon entry. Participants will have FMX114 gel applied to one of these lesions and vehicle gel applied to the other by clinical site staff in order to limit dosing errors and/or omissions.
The treatment will be applied twice daily for four weeks in a double-blinded initial phase of the study. After completion of this phase, subjects will continue into a two-week open label treatment phase and will then be able to apply the active drug to both lesions.
We plan to initiate a study in Q3 after we have completed requisite IND-enabling nonclinical safety work and anticipate reporting top-line results before the end of this year. We look forward to provide further updates on our progress. I will now return the call back to Dave.
Thanks, Iain, for providing an update on our exciting new product. I believe the future is very bright for VYNE. We are eager to get beyond the impediments caused by this pandemic the past year and leverage the potential of our products and commercial operations. We have worked hard to deliver on our vision of creating a fully integrated pharmaceutical company with commercial products and a growing pipeline.
We now have two approved products that have been launched within the past year alone in AMZEEQ and ZILXI. We have a phase III-ready asset in FCD105 and now a phase II-ready asset in FMX114. Our balance sheet is strong, with cash expected through the end of 2022.
We are completely focused on delivering against our key objectives of commercial execution, maximizing operational leverage, and continuing to build a diversified pipeline, all with the singular aim of creating long-term value for our shareholders. That now concludes our prepared remarks. We are happy to open up the call for questions, I will turn the call back over to our operator. Thank you.
Thank you. At this time we begin our question and answer session. If you would like to ask a question please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participatory speaker equipment it may be necessary to pick up the handset before pressing the star key. In the interest of time we request you keep to one question.
Our first question comes from the line of Louise Chen with Cantor Fitzgerald. Please proceed with your question.
Hi. Good morning, everybody. This is Carvey in for Louise. A couple of questions from us on FMX114. In the preclinical studies, did you observe additive or synergistic pharmaceutical benefits when a JAK is added to a S1PR modulator? Also during preclinical, how did your team arrive at the two combination dosages? That is, one more JAK-based, and the other is more evenly split. Which dosage are you going to be using in phase II? Thank you.
Hi there, Carvey. It's Iain. Yeah, we saw an additive benefit. I think you can see that from the slide. We did obviously evaluate the monad therapies individually. Both performed well at the concentrations we evaluated to date. Obviously, when we added combination, they both contribute meaningful additional efficacy to the overall.
In relation to the clinical doses, the study is still ongoing. We still have additional data to collect and analyze, and once we'll be in a better position then to determine what concentration we'll be taking into the phase II-A. As you can see from the slide, the 0.6% tofacitinib and the 0.01% fingolimod, again, appears to be performing slightly better than the other dose. What was your other question again, Karvi? There was a middle one. Apologies.
Yeah. I was just wondering, your team has two combinations during preclinical. One is more JAK, and the other one is a little bit more evenly split. I remember it's like 0.3 plus 0.2, if I remember correctly. Why did you end up with the one that is a lot more JAK-based?
We've conducted a series of experiments leading up to the one we're presenting today. We've done significant dose-finding, both on tofacitinib and on fingolimod. The two combinations we're presenting today show effectively a low-dose tofacitinib effect and a high-dose fingolimod and obviously vice versa.
We've kind of focused in on those particular doses to date. As I say, once we've completed the analysis of the study, as I say, we have additional data to come, then we'll be able to make a selection for the phase II-A study.
Got it. All right. Super helpful. Thank you so much.
Thank you. Our next question comes from line of David Amsellem with Piper Sandler. Please proceed with your question.
Hey, thanks. On the payer landscape for both AMZEEQ and ZILXI, can you just talk about the nature of utilization management to the extent you're seeing that for both products, and maybe delve into specifics on what kind of step-throughs patients are going through and the extent to which they're onerous? Secondly, can you just provide a roadmap of sorts for how we should think about net realized price for both products this year with all the contracting that's now in place for both products? Thanks.
Good morning, David, this is Matt. The utilization management prior to the most recent major PBM contract represented roughly a third of all commercial lives. The primary utilization management is a prior authorization either for the diagnosis and treatment of acne, rosacea, and/or a step therapy.
Some of these are electronically adjudicated, so there's an electronic look back for a period of time. They don't seem to be all that onerous. The physicians are able to get through these and certainly the more recent work that we've done with specialty pharmacies is intended to help that process along. We've heard pretty good feedback.
In fact, just got an email last night from one of our representatives who conducted a speaker program. He was asked specifically about the access for AMZEEQ and whether he felt that he was able to easily get the product for patients. He said he had not experienced any major issues.
For those that did have prior authorization, they were pretty easy to handle. We feel pretty good about the overall strategy for our payer approach. The idea of having broad access for our patients is paying off, and we would expect that as we are pulling through the remainder of the lives over the course of the month that that will continue on both brands.
Yeah. David, this is Andrew Saik. I'll take the second part of your question. We've indicated in the past that we think that a $200-$250 after discount net realizable value is what we expect, and nothing's changed on that. As to the timing, this was always around getting coverage of commercial lives above 80% so that we could get rid of our denied conversion card.
We've indicated in the past that we have a goal of getting rid of that early in Q2 as early as April 1st. That's still the goal. Obviously, we announced that we signed the Caremark contract early this year. That was a great milestone. Gives us access to a number of commercial lives and certainly is helping us along our way to reaching our goal of over 80%. We need to give those time to come up on formulary.
We always indicated that it was sort of a two to three-month lag. We're monitoring that. Assuming that happens in sort of the normal course, we should be able to get rid of the coupon card, at least the denied conversion card by early April.
What that means is that you won't see a huge step up in Q1. Just to be clear. You'll see that start to improve, hopefully significantly in Q2, and then by mid-year we should be there. We should be at our net realizable price of what our target is of kind of between $200 and $250. Does that answer your question, David?
Yeah, no, that's very helpful, particularly in terms of the cadence for the year. Thanks for that.
Sure.
Thank you. Our next question comes from line of Balaji Prasad with Barclays. Please proceed with your question.
Hi. Good morning. Thanks. Two questions. Just a question each on FCD105 and ZILXI. With ZILXI, if I look at your deck that you published a couple of days ago and spoke about 250,000 prescriptions the first full year for launch drugs.
If I triangulate that with where you are currently with your December run rate and double it, I still end with around 40,000-45,000 prescriptions for the year. How do I bridge the two? Secondly, on FCD105, can you help us understand if there's any variation in the Molecule Stabilizing Technology you have between AMZEEQ, ZILXI, and FCD105, and if there's any incremental differentiation of clinical benefit? Also why would it not cannibalize AMZEEQ? It seems to cover both the nodular and non-nodular version, why would it not cannibalize AMZEEQ? Thank you.
Well, let me speak to the surrogates first. It's Matt. Thanks for the questions. It's hard to view the surrogates in the first year given the fact that we launched ZILXI during a pandemic. The surrogates all are based on launches that did not launch in this type of environment. I would keep an eye more so on the outer years of what the peak potential is of these brands.
Certainly the feedback that we've gotten in market research on ZILXI indicates that there's a clear unmet need. There's a clear switching behavior between patients from a first therapeutic to something else or discontinuation altogether. We know that that need in the market exists, and we've heard that from our physicians as well.
We would expect that as this market heals and as we get into a normal ability to launch our product, that these surrogates are a good tool to help define what the peak potential is for a brand like ZILXI.
Hey, I'll just cover off on the phase II. Yeah, FMX105 does utilize our MST technology, o bviously, we're adjusting for different components and concentrations of the two APIs. In relation to your question on efficacy, as you can see in our IR deck, we show that approximately 36% of patients in our phase II study were clear or almost clear.
That's class-leading potential there with respect to efficacy. As you know, there's two sides to that coin. It's not just about efficacy, it's about safety as well. As you know, FCD105 contains a retinoid adapalene at the prescription strength of 0.3%. We can see in our data that that's particularly well-tolerated in the skin, particularly important to support compliance to therapy and obviously ultimately clinical outcomes.
How it compares to AMZEEQ, again, you can see on our IR deck, we actually had a monad arm of 3% minocycline in our MST technology. That's actually quite a good surrogate for AMZEEQ, which is 4% minocycline. There we had approximately 30% treatment success. You certainly see an additional benefit of adding adapalene in there. As you showed, nice consistency between the 3% arm and AMZEEQ itself.
Yeah, this is Dave. Our objective obviously is to continue to develop new and improved products, and that's our ambition for FCD105. We obviously are combining what's viewed as the gold standard for inflammatory acne, which is minocycline. It's been the gold standard and was the driver behind AMZEEQ, and we know adapalene is one of the, if not the most widely used retinoid and very effective for comedonal acne.
As Iain alluded to, these retinoids or retinoid combination products, often of which include benzoyl peroxide, could be quite irritating to the skin. When you take a look at our technology, our MST, our Molecule Stabilizing Technology, our thesis has always been, could our chassis that we have for our product, could it help mitigate some of the cutaneous adverse events that you see with these retinoid-based products?
In our phase II study, it certainly appears that that may be the case. We've seen substantial efficacy, we've seen a very strong safety profile, very low cutaneous adverse events. When we just compare versus just in literature comparison, it's quite profound. Obviously, we need to take this into the pivotal program, which we anticipate doing later this year.
Assuming we get results anywhere in the same general arena that we've seen in phase II, as Iain outlined, we think it could be a best-in-class product. We've done a fair amount of market research, I'll turn to Matt to comment on. We think that this product could be the biggest of the three that we have in the tetracycline class between AMZEEQ, ZILXI, and FCD105.
The initial feedback that we're getting in the market research is that this is clearly additive, not so much a cannibalization play for sure. There's obviously going to be some cannibalization anytime that you launch a new product, but it seems to be much more additive in terms of the potential for the brand. I'll turn to Matt for some additional color on that.
Yeah. A couple things about this market research. This is a demand study with hundreds of physicians. We do a pre- and post-utilization, and we look at impact based on a product profile for FCD105 and others that may be entering the market. What we found in the study is that FCD105, we never disclosed what our peak share was in previous studies for FMX101 or AMZEEQ, but I can tell you that the implied share for FCD105 is about double what we saw in the AMZEEQ study, which is really encouraging.
The other thing that's encouraging out of this study is that clearly you want to understand what the impact is to your in-line brand, what is the cannibalization opportunity on AMZEEQ? What is that ultimately gonna be at peak when this enters the market?
What we found in the study is that the cannibalization of AMZEEQ is going to be less than 20%. Now, again, this is in a vacuum with product profiles, but we're encouraged by that because we feel that AMZEEQ is oftentimes either used alone or in combination that is bespoke to the patient.
AMZEEQ will still offer that opportunity for clinicians to treat their patients the way that they want to but FCD105 offers new patients that come into the practice or others that aren't satisfied a clearly beneficial alternative.
Thank you. Very helpful.
You got it, Balaji.
Thank you. Our next question comes from line of Patrick Dolezal with LifeSci Capital. Please proceed with your question.
Hi, thanks for taking the question. Congrats on the new program in atopic derm. Starting there, I guess we've seen the moderate to severe market become a blockbuster opportunity in a rather rapid fashion, and the mild to moderate market has lagged a little bit despite some really great potential there.
Can you just help us think about some of the relevant factors at play here and maybe provide in a general sense what a successful therapy might look like in the mild to moderate setting? Perhaps speak to why you ultimately chose to pursue this topical therapy in mild to moderate. Thank you.
Sure. I'll offer this to Dave again. I'll offer a few comments up front, then turn over to Iain. As Iain outlined in his initial commentary, the mild to moderate space is a big space, right? There's 22 million patients treated for atopic dermatitis in the U.S., and around 19 million of that 22 million are mild to moderate.
We know a lot of [inaudible] did a lot of work in recent times, it's been around moderate to severe patients. Obviously the big opportunity in terms of patient volume to be addressed is in the mild to moderate category. In thinking through as we were developing this product, what are the needs for patients in treating the disease, as Iain outlined, it's a multifactorial disease. Our belief is that the best way to address a multifactorial disease is to have a multimodal product.
Hence why we developed FMX114, which combines tofacitinib with the sphingosine 1, fingolimod. We think there's two, and Iain outlined this, clear different modes of action that can help address the condition. I think a key component is the potential for this product to improve skin barrier function, which is a key lever, we believe, for patients that have atopic dermatitis, especially when you're dealing with such a large number of patients being in the pediatric range. Yeah, that's the thesis behind this.
Far, again, we're very encouraged with the preclinical data that we've just provided earlier this morning. We're quite encouraged by it. We're eager to get into a phase II-A study later this year with the aim to have the top-line readouts before the end of the year. Turn it to Iain for any additional thoughts or color around it.
Yeah, I think, Patrick, you kind of hit the nail on the head. The moderate to severe space is a very busy space in development with a lot of high-value therapeutics in development, such as biologics. As Dave covered off on, the biggest unmet need is in the mild to moderate space. Steroids work, but they have specific challenges, and therefore we still see a huge unmet need there in mild to moderate.
As I say, there are up to 90 million patients in the U.S. that are in that category, that are using steroids on and off that have to be managed long term. We see this as a potential replacement for steroids. Also in the mild and moderate to severe category, you'll also see a lot of companion drug use with steroids as well.
Such as DUPIXENT and other products that are coming through tend to run studies where steroids are used either as a run-in phase or concomitantly used to get control of flares. Again, we can also see opportunities for FMX114 there as well.
Thank you. Our next question comes from the line of Oren Livnat with H.C. Wainwright. Please proceed with your question.
Hi, I have a few. Just to go back to the commercial business. You highlighted in rosacea that there's a lot of evidence of drug switching, which makes a lot of sense because this is a chronic condition. I'm trying to get your sense on how AMZEEQ and acne compares to that. It's a little more of an acute condition, right?
Assuming that people are having to step through other therapies or at least have to date to get to your product, how do you get new patients on your drug if it's not first-line therapy? Does it have to be failures on other therapies, or are you just hoping that docs have enough experience in patient profiling and they know this isn't going to be a good candidate for X, Y, and Z existing therapies? I want to start them on AMZEEQ, and I'm willing to go through the hassle of PAs to get there.
It's a great question, and I can speak to the avenues by which AMZEEQ is used today. Roughly half of our patients have not been on any previous Rx therapy, which I think speaks to some of the open access that we have in specifically the ESI contract, where we're on the national preferred formularies.
Those patients can easily get AMZEEQ out of the gate. Roughly half of our prescriptions are coming from those that are stepping through something else or have tried and failed something else and would otherwise satisfy step therapy or prior authorization. Look, as we examine share shifting between AMZEEQ and others in the category, we're seeing some additive opportunities.
For instance, if a patient's on a retinoid and they need additional therapeutic advantages of AMZEEQ, then we see AMZEEQ added to those types of drugs.
We see a lot more switching between oral antibiotics and AMZEEQ, and I think that's an important point to make as well. We're seeing it both ways, and I'm pleased with the way that this is shaking out because this has been consistent really since we first launched. We've seen roughly the same amount of de novo patients and the same amount of switching patients over time. That seems to have some durability, and I think it also speaks to the point you're making about maybe some dissatisfaction in the market, especially as it relates to oral antibiotics.
All right. Thank you. Just regarding script trends, things have obviously, you've had a lot of weather and other factors, I'm sure, late in the year and into January and February. I'm just wondering, big picture, can you remind us what sort of seasonality is there in the respective acne and rosacea spaces, both from an actual season weather perspective, but also the typical New Year insurance resetting factors? I guess, how much should we be adjusting in our minds the earlier script volume we're seeing now for a normalized run rate?
Yeah. I think you're talking about seasonality of deductibles and out-of-pocket versus seasonality.
Plus actual seasonality, I guess maybe in rosacea.
Yeah. We definitely see the deductible seasonality in both markets. It's fairly pronounced in acne. Usually you start to see an emergence from that in the March, April timeframe. We would expect to see that ease over time. As it relates to disease state seasonality, we do see very clear seasonal patterns in rosacea, both in how those patients search for symptoms online and also what we see in diagnosis rates.
We see the diagnosis of rosacea patients start to increase in late March, April, May, June. That's typically when the weather changes. That's when the symptoms become more pronounced and more patients come into the system. We're just on the tip of that happening now, and we would expect the course of the next two to three months to see additional flow of the patients.
By the way, we do take advantage of that as we think about our consumer paid search buying and advertising for rosacea. We typically press that into those peak months. We're ramping up those efforts now as well.
Yeah. I would say too, there's a bit of a bolus of patients going into dermatology offices for AMZEEQ, for acne treatment as you move to the end of the summer into the beginning of the fall, which coincides obviously with kids going back to school. We didn't see that typical trend this past year, obviously for COVID reasons.
We would anticipate that we should see back to a more normalized environment this year as more and more patients are getting vaccinated against COVID and as the economy continues to open up. All the modeling suggests that.
I think between the inherent seasonality that Matt was outlining for rosacea and what we would anticipate to be kids getting back to school and getting back into the classrooms in the high school and college settings as we move through the summer months into the fall, that should all align quite nicely with, as Andrew's outlined and as we've talked about, us starting to get to that more appropriate realized net price per prescription, which we should start seeing that as we move into the midpoint of this year.
I think all that really works nicely with us if we're seeing the type of price per Rx that we anticipate in that $2-$250 range, and we're in a steady state by the time we move into the mid-year, beginning of the third quarter.
That ticks and ties quite nicely with the seasonality and the bolus of patients we would anticipate to see into the clinic for rosacea seeking treatment, as well as kids going back to school at the end of the summer and beginning of the fall months.
All right. Appreciate the help. Thanks.
You got it, Oren.
Thank you. Ladies and gentlemen, our final question this morning comes from the line of Tim Chiang with Northland Securities. Please proceed with your question.
Hi. Thanks. David, could you just comment on where you see out-of-pocket costs for AMZEEQ, ZILXI, once all the major PBMs and the coupons come out? Where's the normalized out-of-pocket cost going to be for both of your products, let's say by the time we get to around May, June?
Yeah, sure, Tim. I'd say probably an average out-of-pocket cost is somewhere around the $50 range, probably capped at about $75, which is what we have for our coupon program. If you just think through a Tier 3 formulary status, what's an average out-of-pocket cost, it's going to be somewhere around that $50 range.
Again, we have a coupon program, and we'll continue to have it in place that the patient would pay $35. If an out-of-pocket was $50 for that particular patient, and they leveraged the coupon that we have, they pay $35, we pay the difference, the other $15.
We think that based on all the research we've done, that's a good number that mitigates abandonment of prescriptions. Matt and the team has done a lot of research on it. We've obviously put a lot of thought into this.
It goes with our total strategy on payer access and reimbursement but, g enerally speaking, patients that have insurance coverage, a out-of-pocket Tier 3 formulary position is going to put you at around a $50 or so copay.
Okay, great. Maybe just one follow-up. Obviously, COVID's having an impact on AMZEEQ and ZILXI, but just in terms of the typical patient, what is the typical patient that's getting AMZEEQ? Is it mostly middle-aged women or more adolescents that are getting AMZEEQ at this point? I'm sort of wondering if the age stratification will change some once we get to the other side of the pandemic.
Yeah. We obviously take a look at two things. One is the age range of diagnosed acne patients generally. What we found when we did that exercise through claims analysis is that the majority of the patients diagnosed are between the ages of 12 and 24. That's what we see with AMZEEQ as well. We see the majority of our patients are actually between the ages of 10 and 20 now.
The way that we analyze in real-time, we have bracketed age ranges that are a little bit different than the claims analysis that we did about a year and a half ago. The age range for AMZEEQ prescriptions is typically in that 10- 20-year-old range, with some falling outside of that. It's what we would expect, and it's kind of falling in line with what we saw initially with diagnosed patients. We would expect that to continue.
Yeah, Tim, I think one thing that shouldn't get lost, and it's probably a good way to kind of wrap up the call here, unless you have other questions, is for last year, despite all the headwinds, despite all the challenges with COVID, which we've all talked about many times over, is we generated over 100,000 prescriptions for AMZEEQ. Over 100,000.
Despite all the challenges, despite the fact that our sales force was basically shut down for about four months. We had the first quarter of the launch of AMZEEQ, last year, which we were quite thrilled with the uptake for the brand. Then, as we all know, we were all in shutdown mode, locked down. Sales force was locked out for about four months. Then ratably started to see things bounce back through the summer and into the fall.
By the end of the year, again, we generated over 100,000 prescriptions for AMZEEQ, which is no small accomplishment. We're certainly very encouraged by the potential for this brand. For ZILXI, we're just getting started. We haven't even had that chance of having unfettered access. We at least got a quarter of that last year for AMZEEQ, and we haven't even had that opportunity yet for ZILXI.
We're quite bullish about the potential for both these brands. I think in terms of the age range that you're asking regarding AMZEEQ, it's in that early teens, older adolescents through teens into your early 20s. As we've often said, ZILXI picks up where AMZEEQ leaves off. Prevalence for ZILXI is at 30 years- 50 years, 60 years range. We know we've got two great products.
We know that the feedback that we've received from patients, once they get a chance to try it, has been excellent. For ZILXI, it's just a function of us being able to get access to physicians, communicate the features and benefits of the product, let them try it. Those that we've been able to get access to, those that have been educated on ZILXI that have tried the product, the response has been really good.
We're certainly encouraged by all the underlying metrics. We're certainly encouraged by what's happening on a broader basis globally with vaccinations continuing to increase. We're certainly anticipating that the markets and the offices will begin to continue to open up as we move through the spring and into the summer months and as you get to that steady state, hopefully by mid-year or so.
Okay, great. Thanks, David.
You got it.
Thank you. Ladies and gentlemen, this concludes our question and answer session. I'll turn the floor back to Mr. Domzalski for any final comments.
Thank you, operator, and thanks to everyone who's participated on the call today. We're obviously very excited about how our business has continued to progress, the prospects for our in-line products, AMZEEQ and ZILXI, as well as our pipeline of products, including FCD105 and FMX114. We look forward to providing you further updates as we move and progress through the upcoming quarters. Thanks. Be well and stay safe. We look forward to talking with you soon.
Thank you. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.