What I would like to talk to you about today is our tremendous growth opportunity that we have in front of us as a company. I will talk about the two main growth drivers that will drive this growth opportunity for us. And of course, what's next? What's after our two biologics? What are we doing in our R&D side in Sant Feliu de Llobregat in terms of generating the next wave of innovation in medical dermatology? Before jumping into the growth opportunity, for those that are less familiar with us as a company, I'm going to have one slide to tell you about Almirall today and about who we are. So we are a company R&D-based, exclusively focused on medical dermatology. We are the only company today in pharmaceuticals that only does medical dermatology and has capabilities from early research all the way to commercialization.
That makes us a very attractive and credible partner with dermatologists, but also with other stakeholders that want to develop innovation in the field of medical dermatology, and they see us as the partner of choice. We have a long-term ambition to become global leaders in medical dermatology. A proven track record, we have launched six products in the last seven years that has contributed to build extremely strong commercial execution and capabilities both in Europe and in the U.S. Very strong R&D capabilities covering the whole value chain and now an increasing number of very promising assets that I'll spend some time talking about today across different modalities and different indications.
In addition, we have a solid base business that gives us a very nice amount of cash flow to the business that is helping to further this innovation and helping to further the launch of our growth drivers. In terms of sales, this is 2023 data, but last year we closed sales close to EUR 1 billion that already shows the nice growth that we had last year. Our head office is in Barcelona. We are present in 15 countries, commercial presence, 2,000 employees, and a portfolio of products of 140 products, of which 51 of them are in medical dermatology. The first question is, why are we in dermatology? Right? We are in dermatology because it's a great market, sizable, growing very nicely. Already today, it's a $46 billion market between the U.S. and Europe, and it's poised to grow in high single digits for the foreseeable future.
The two diseases that are driving this growth are psoriasis and atopic dermatitis. And those are the two diseases where we have our two most promising assets, Ebglyss in atopic dermatitis and Ilumetri in psoriasis. But if you can see in the slide, we have a number of assets or products or therapies in the different growth categories within dermatology. But it's a great therapeutic area to be, not only because it's growing, but also because it's a great opportunity to innovate. It's an area where there's still tremendous unmet need, great opportunity to come up with novel ideas to develop therapies to continue to support patients that are suffering from many skin diseases where they have no treatments at all, such as many rare diseases, or where there are no adequate treatments, such as many immuno-mediated skin diseases. So very exciting place to be.
Since I became CEO of the company two years ago, we've put a lot of effort on capturing this growth opportunity that I was showing you in the previous slide. So a lot of effort on building commercial capabilities based on the strong base that we had from having launched already five products before we launched the biologics, but also a solid engine in R&D to be able to develop the next wave of innovation in our labs. Today, I'm happy to say that we are already delivering on this growth potential with our biologics, Ilumetri and Ebglyss, and they are both firmly becoming a very credible first-line treatment for the treatment of psoriasis and atopic dermatitis patients, and what we're seeing as a consequence is an accelerating top-line growth, and we're going to see also margin expansion starting this year and accelerating in the coming years.
But also importantly, we are shaping the future. We have already today a very attractive pipeline with disruptive innovation. And when I mean disruptive, it's assets with a potential to be first in class or best in class in not only one indication, but in many of the programs with potentially many indications in medical dermatology and in some cases even beyond dermatology. We have now four programs in Phase 1 that they are going to start POC studies, proof of concept studies in the next 15 months. One bispecific in atopic dermatitis and a number of preclinical development assets in earlier stages of discovery, and I will talk about some of them later on in the presentation.
I'm happy to provide mid-term guidance for the company in the form of sales growth, double-digit net sales, compound annual growth rate between now and the end of the decade, driven mainly by the two biologics, and an expansion of the EBITDA margins reaching 25% by 2028 with further margin expansion beyond 28% as well. How are we going to achieve this tremendous growth rate in the years to come? One of the key assets, of course, is going to be Ebglyss in atopic dermatitis. Let me spend a few minutes talking about the tremendous opportunity in the treatment of moderate-to-severe atopic dermatitis patients.
We've seen in the past few years how the creation of this market, thanks to the advanced therapies, and already with a growth rate of around 85% in the past few years, already today with 81,000 patients being treated in the top five countries. With the projections that there will be five million patients in Europe that could be eligible for advanced therapies such as Ebglyss. What we are predicting is there will be around 400,000 patients treated with advanced biologics or advanced treatments by 2031. Tremendous growth opportunity, market expansion opportunity that's in front of us. How are we going to capture this opportunity? We plan to capture this opportunity with Ebglyss that we believe is the best product out there to treat moderate to severe atopic dermatitis patients.
The best product because of the efficacy profile that we've seen in terms of skin clearance, in terms of itch control, in terms of tolerability of the product and safety, and the convenient posology of the product. Very recently, a few months ago, we announced or we published our three-year efficacy results with Ebglyss. And what we've seen of the patients that achieve response by week 16 or week 24, after three years, 80% of these patients maintain clear or almost clear skin with one injection per month. 80% of patients after three years maintain clear or almost clear skin with one injection per month. For us, it's the best value proposition for patients and for healthcare providers out there. And we are delighted to be commercializing this product in Europe. We've launched last year in Germany, and since then, we have launched in six additional countries.
The feedback that we're getting from HCPs is very positive, very consistent with the results that we have seen across the different studies that we've done until today. It's been the best launch in the class since Dupixent was launched in the previous decade. In the first three quarters of last year, we did EUR 20 million. I think that's a testimony of the strong commercial capabilities that we have in Europe. I'm extremely pleased, proud of my team, not only for these results, but also for achieving the prices and the market access in the different countries in a difficult environment.
We have been able to hit the plan in these dimensions in all countries, and in some countries, even exceeding by a number of months, such as in Spain, where we have been able to achieve reimbursement nine months ahead of what typically takes to get reimbursement in Spain. We're going to be launching in 12 new countries this year, so extremely exciting time for us. And brand awareness of a level of anticipation of HCPs for this product is very high. Finally, we are not alone. We are not alone. There's two companies behind Ebglyss. It's us, and it's Eli Lilly. And we are delighted to have a strong partner also supporting Ebglyss.
We have a joint program to generate additional evidence to make sure we continue to build on the body of evidence that positions Ebglyss as the best product out there to treat naive patients in atopic dermatitis, but also beyond atopic dermatitis, as the product is also being developed for perennial allergic rhinitis and for chronic rhinosinusitis with nasal polyps, and we continue to evaluate additional indications in which we believe that Ebglyss can help patients that are suffering in additional skin diseases. I will not go through all the list of studies, but very exciting coming soon is a pediatric study in atopic dermatitis and other data points that we believe will be a great addition to the body of evidence that is supporting Ebglyss as the first-line treatment for atopic dermatitis, so atopic dermatitis [is a] great opportunity.
We believe we have the best therapy out there to capture this tremendous opportunity. Let's move on to psoriasis and Ilumetri. A quick look at the market. Also, the market has been, as we are anticipating atopic dermatitis, we've seen it happening already in psoriasis. The number of treated patients in Europe is close to 400,000 already, and it's being driven by the number of new classes and new treatments that have been launched that instead of cannibalizing, what they are doing is expanding the market. Now, the number of eligible patients is very high. This 400,000 only represents 20% of these eligible patients. So psoriasis is yet a market that can continue to expand significantly. We are capturing an important part of this opportunity with Ilumetri. Ilumetri today, anti-IL-23, is already today our best-selling product with achieving EUR 150 million in the first three quarters of last year.
It grew 25%, and it's a product within what we call the winning class. It's the preferred class, the anti-IL-23, to treat moderate-to-severe patients, and within the class, we are gaining market share, so we're gaining market share to Skyrizi, to Tremfya, to formidable competitors, but again, that's another testimony of the great work that we're doing in the commercial front, but it's also based on the experience that HCPs are getting in dermatologists, in the personal experience in treating patients and the good results that they are achieving.
And also, what is helping a lot now is the launch of the new dose, the 200 milligram, that is providing dose flexibility for HCPs to treat those patients that prove difficult to treat with the 100 milligram, and in particular, those patients that are overweight, that are obese, or patients that have a high level of burden of disease. The dose is once a quarter as well. And also, we have recently generated a wealth of new data with real-world studies, but also with a POSITIVE study. The POSITIVE study is the first time in dermatology that a study is done with a wellness endpoint. In many skin diseases such as psoriasis, patients have a number of comorbidities that severely impair quality of life, including depression and anxiety. And we've done this study with the WHO-5 endpoints looking at well-being.
We have demonstrated that patients treated with Ilumetri, we are able to restore the level of well-being back to normal, back to the level of a healthy patient, which is an extraordinary result. It's also a very innovative study because it's the first time that a study is done with this innovative endpoint. Again, this contributes to the wealth of evidence that supports Ilumetri as a very credible treatment for first-line treatment of patients suffering from psoriasis. Together with Ebglyss and Ilumetri, we have a tremendous growth opportunity in front of us. We expect that our biologic franchise will multiply by more than five between now and the end of the decade. Combined, they have a combined peak sales estimate of north of EUR 800 million, what makes an extremely exciting opportunity for us in terms of organic growth.
And that's what's going to be driving the nice growth rate that I announced before. By the way, I forgot to mention that this double-digit growth rate that we are announcing between now and the end of the decade is only accounting, taking into consideration the existing portfolio that we have today. There's no placeholder for M&A or other inorganic deals. It's only organic growth based on the existing commercial portfolio that we have in our hands today. But of course, we are not stopping here, although we have exclusivity for these two assets to well beyond 2030. We are working very hard, and we started working a number of years ago on building a first-in-class portfolio pipeline of products in R&D. And we are very excited to share some news today.
We have four programs in Phase 1, but they are about to enter proof-of-concept studies in the next 15 months. All these four assets have potential, not only one indication, but most of them in more than one indication, and in some cases, even beyond dermatology, so very exciting opportunities, and again, all four of them have the potential to be first-in-class or best-in-class. We have also a very attractive asset, bi specific for atopic dermatitis. We're very excited about it. We have a number of early discovery programs, and again, this is not an exhaustive list ranging across different modalities, so the way we work is that we are very close to customers, to dermatologists, to understand where the unmet need is.
Then we have a very strong, and we've been building this capability in the past few years, extremely strong disease biology group to turn these ideas or these ideas of unmet need into ideas to develop scientific hypotheses that can convert into programs and eventually into new therapies. And then we think about, okay, what's the best modality? Should we target this mechanism with a small molecule, with a biologic, with mRNA? And then we go out there and look for the right partners to partner in the modality and in the technology. So that's our approach to modality. Innovation, of course, we are developing programs from scratch in-house. But also, we have a creative licensing group that has been very successful in the past few years. Both Ebglyss and Ilumetri are in -licensed products. So we continue to source for external innovation.
So of course, if you are a company looking to partner your ideas, your developments in medical dermatology, we are open for business. This is an example just illustrative of some of the partnerships that we have across modalities, whether it's mRNA and lipid nanoparticles, small molecules, biologics, bispecifics. All this collaboration is working extremely well for us. And that's a testimony of the strong evidence that we have in working with other companies at different stages of development of the molecule and up to commercialization. So overall, and that's the last slide, one, we think we got it right when we decided 10 years ago to focus solely on medical dermatology. It's a great market in terms of size and where is it going, but also a great market to innovate. There's still tremendous opportunity to help patients in need in many diseases that there are not adequate treatments.
We have been building in these past few years an extremely robust platform so we can capture this nice opportunity, right? Of course, commercially, building the right marketing and sales capabilities in the different countries, but also in our labs in Sant Feliu so we can generate the next wave of innovation, and after these years of investment, we are starting to reap the rewards. We are seeing how our sales are coming in nicely. They are accelerating and how the pipeline is evolving, maturing, and we have now very promising assets, so I am personally extremely excited to be leading this company and to take Almirall into the next stage in this journey to become leaders in medical dermatology, and hopefully, you will be witnessing from the sides our growth in this space and hopefully towards leadership in medical dermatology, so thank you very much.
Thank you, Carlos. Now we'll open up the floor for questions. In addition to Carlos, we also have with us Mike McClellan, CFO, and Karl Ziegelbauer, CSO. So any questions? If not, I can get the ball going. Carlos, you mentioned about long-term guidance and also about driving double-digit growth. Can you talk a little bit more about that and also what your vision would be for 2028?
Say again, sorry. Talk about the growth end?
Yes. And what the vision 2028 would look like?
Well, as I mentioned, we've been investing for the past few years in building the right capability to maximize the sales potential of our growth drivers. We believe that now we are entering into a new era of rapid sales acceleration. So that's why we are announcing and providing this midterm guidance of double-digit sales growth until the end of the decade. As we have already built the capability, the cost base will not grow as quickly as the top line, and therefore it's going to be margin expansion. Therefore, the guidance that we have provided of EBITDA levels of 25% in 2028, and we'll continue to expand beyond that as well.
Okay, great. If no additional questions, then moving on to Ebglyss. Congratulations on the great product and the amazing launch. Could you please give us an update on how the performance has been so far versus what your internal expectations were earlier in the year or towards the end of last year?
It's going very well. Particularly in the market where we have more experience, that is Germany, we're getting great feedback from dermatologists in all sorts of patients. Atopic dermatitis is quite an heterogeneous disease with different types of manifestations of the disease.
And I think what we've seen in the clinical trials that we are seeing now in real-life experience to the dermatologist is that Ebglyss works in all patients, so in all types of patients, right? And therefore, that help contributes to the body of evidence to support that Ebglyss is the best treatment out there and should be used on all patients that are naive to the product. Although we've seen as well that works well, for example, in Dupixent failures. So we shared recently a study done by Lilly that was done with Dupixent-exposed patients, including failures, but also patients that had dropped out of Dupixent for other reasons. And we have achieved very good efficacy results as well in this patient population.
Great. So in terms of the patient mix right now, how many would you say would be the patients who have switched from other products versus how many would be, or what percentage would be naive patients, and how do you see the market dynamic or the market share evolving over time?
The mix today is 60-40, so 60% naive patients, 40% second line or switch. And that's normal at that stage that we're getting this amount of switch patients because there's a pool of patients that they are not adequately controlled with existing therapies, and therefore, physicians are expecting for new treatments. And when a new treatment comes out, automatically, they prescribe it for this pool of patients, and then that's fine. Our positioning is in naive patients, and I think that's working, and that's where we see the 60% of patients. The opportunity, most of the market of new prescription opportunities is driven by naive patients.
Got it. Then going back to the guidance and how the performance was in 2024, would you say that you are comfortable with the current consensus of approximately EUR 30 million-EUR 35 million for 2024?
We will provide full year results and more granularity after our board in February. We will provide guidance for 2025 as well in February. I would say that we are comfortable with this range.
Great. Then in terms of peak sales, has your view changed since the launch now that you have more visibility on the market?
We provided some time ago a peak sales estimate of EUR 450 million. We most probably will revise this estimate once we have all the data points that we need. In some countries where we're still negotiating the price, such as in France, that is a key market for us. So I think we need to have the final prices and then probably start seeing a little bit the sales trend, the launch trend in other important markets such as Italy and Spain. And in a few months, probably we'll be in a good position to revise our peak sales estimates.
Great. Okay. So then moving on to more exciting things, which would be pipeline and R&D investment. You have some amazing products in the pipeline. How do you think the investment into that would look like in the coming years? And when do you expect your current preclinical assets to be entering into Phase 1?
I'm going to pass the word to Karl, and I'm sure it will be a good job answering this question.
Very happy to talk about that. So we're very excited about the early pipeline. As Karl said, we have four assets in Phase 1 and bispecific antibody preclinical development that will enter the Phase 1 in about a year or so.
Okay, great. So then moving on to some guidance which was provided during Q3 update. You had mentioned that the gross margin guidance would still be approximately around 65%. How do you see that changing in the coming years? Do you think it would decrease given the higher percentage or just the higher amount of royalties that you might have to pay out in the coming years?
I think what we're going to see is definitely growth on the top line. The gross margin will probably not expand from the 65%. If anything, there may be a tiny bit of price pressure on that coming from the older portfolio.
But where we're going to see leverage, as Karl said earlier, is that once we get past the investments in 2025 to launch Ebglyss in the final markets, we should see that rate of growth of SG&A slow down. And the percentage of SG&A over sales will decrease as we rapidly grow the sales. So the real margin expansion getting us to 25% in 2028 and further expansion after that is going to come more from the SG&A line. We are, of course, going to invest in R&D. Right now, we're at about 12%. We think that's a good benchmark for the next couple of years. But as sales grow, that means we're going to be investing more in R&D. And you saw the exciting pipeline we have. But gross margin, because we have licensed-in products, biologics tend to have a higher cost of goods and significant royalties.
We're not really going to see the expansion on the gross margin line.
Okay. Maybe in that vein, could you give some color on what you expect 2025 performance to be?
Yeah, we'll give our full guidance in February. But we already said at our nine-month call that we expect sales to accelerate. So we will see a little bit higher growth than we'll see in 2024. We do aim to have a slight bit of margin expansion. For us, we appreciate that the investors have been patient. We've really invested in the last three or four years to build the commercial capabilities, to start building the pipeline. 2024 was the first year we saw EBITDA growth in the last couple of years. Next year should be the first year we see a little bit of margin expansion. So sales will accelerate. EBITDA should accelerate a slight bit more.
Okay. Then in terms of M&A, do you expect anything in the foreseeable future? And how much firepower would you want to allocate for any upcoming investments?
We see that the opportunity for value creation in the short term is through organic growth, as I mentioned during the presentation. We don't want to risk being distracted by a transformational kind of M&A, right? That's not in one of our priorities now. We are looking at M&A, but more from a maybe product acquisition perspective. If we can find a nice bolt-on opportunity for the U.S. or even in some markets in Europe, we will definitely try to action this. Again, the great opportunity for our value creation is organic growth, and we will limit M&A in the short term to product acquisition opportunities, probably in areas of rare disease.
Okay. Since you mentioned U.S., what is the plan for the U.S. business?
So now we have our operation there that is a bit less than 10% of our revenues is cash flow positive. We have recently launched the large field presentation of Klisyri. With this launch, our projection is that the U.S. affiliate will go back to top-line growth. And in addition to that, now we are looking for opportunities to bring additional products through M&A, as I mentioned before. And this is while we wait for our internal pipeline to deliver. In all our assets that we have in our pipeline, whether they are coming from our labs from scratch or they have been licensed, we have global rights, of course. And the U.S. remains an extremely attractive market in medical dermatology and the largest market. So definitely, the U.S. remains important for us.
We are working on this plan to become, to maintain and enlarge the presence whilst we wait for our pipeline to deliver.
Okay, great. Since you have so many amazing products, do you want to maybe provide an update on Ilumetri, Klisyri, and Wynzora in terms of if there have been any updates from your side in terms of peak sales opportunity and maybe in terms of any changes in volume and pricing?
Well, Ilumetri, I've talked already a little bit about Ilumetri. It remains a key product for us. We have exclusivity until 2033, and we hope we plan that we'll continue to contribute strongly to our top line.
About Klisyri and Wynzora, probably highlighting the launch of the large field of Klisyri in the U.S., that the good news that we're seeing, the large field is not cannibalizing into the small field, but it's providing an additive effect into the franchise. So it's great news. We are developing the large field also in Europe, so we plan to launch it in the foreseeable future. So very excited about enlarging the Klisyri franchise. Wynzora grew last year around 50%. So also a strong growth driver for us in Europe.
Amazing. Do you have any questions from the audience? If not.