Almirall, S.A. (LBTSF) Q4 2023 Earnings Call Transcript

Almirall, S.A. (OTCPK:LBTSF) Q4 2023 Earnings Conference Call February 19, 2024 4:00 AM ET

Company Participants

Pablo Divasson – Director, IR and Corporate Communications

Carlos Gallardo – Chairman and CEO

Mike McClellan – CFO

Karl Ziegelbauer – Chief Scientific Officer

Paolo Cionini – Chief Commercial Officer, Europe and International

Conference Call Participants

Lucy Codrington – Jefferies

Thibault Boutherin – Morgan Stanley

Alistair Campbell – Royal Bank of Canada

Guilherme Sampaio – CaixaBank

Alvaro Lenze – Alantra Equities

Operator

Good day, and thank you for standing by. Welcome to the Almirall, Full Year 2023 Financial Results and Business Update Webcast and Conference Call. [Operator Instructions] Please be advised that today’s conference is being recorded.

I would now like to hand the conference over to your speaker today, Pablo Divasson. Please go ahead, sir.

Pablo Divasson

Thank you very much, Sharon. Good morning to everyone on the call. Thank you for joining us to review Almirall’s full year 2023 results and business update. As per usual, you can find the slides to this call on the Investors page of our website at almirall.com.

Please move to Slide number 2. I would like to remind you that the information presented in this call contains forward-looking statements which involve known and unknown risks, uncertainties, and other factors that may cause actual results to materially differ.

Please with that advance to Slide number 3. Presenting today, we have Carlos Gallardo, Chairman and Chief Executive Officer; Mike McClellan, Chief Financial Officer; and Karl Ziegelbauer, Chief Scientific Officer. Carlos will start with strategic vision, highlights and guidance, finishing with an update on our biologics growth drivers. Karl will provide you with details on the progress of the pipeline before passing to Mike to review the financials and guidance comments. Carlos will then close and conclude with the comments before opening up for a Q&A session where we will count also with Paolo Cionini, our Chief Commercial Officer.

I would like now to pass this over to Carlos Gallardo, our Chairman and CEO to discuss the strategic vision in Almirall.

Carlos Gallardo

Thank you, Pablo, and good morning, everyone.

In this first call of the year, and given that coincidentally it also marks my first anniversary as CEO of the company, I would like to take a few minutes to share with you some insights and perspectives on where we are as a company in our strategic journey. So, ten years ago, we decided to focus on Medical Dermatology.

And the reasons were, one, we wanted to focus on a therapeutic area and we already had experience in dermatology, as we had a portfolio from Hermal and a portfolio in Dermatology that we acquired from Shire Pharmaceuticals. But also, we saw there was tremendous unmet need in this disease area with a lot of the diseases not having or having sub-adequate therapies.

And also, there had been a number of advances in understanding the biology of these diseases that led us to believe that there was an opportunity to come with novel scientific hypothesis to develop exciting therapies for these indications for this unmet need and to support patients there. And also, it was already a big and growing market.

Today, if we fast forward to — can we come up to the next slide, please. If we fast forward to today, we can say that, Almirall today we are already a leader in Europe in terms of dermatology with a strong product portfolio of 50 products across modalities. So products in topicals, we have systemics, and we have biologics. We have extensive footprint from a commercial perspective. We see almost every single dermatologist that is hospital-based, and we see more than half of the dermatologists that are office-based.

But also importantly, we have a growing pipeline of very exciting assets, and also today, we are very happy to announce our latest addition to our pipeline with anti-IL-21 that we have licensed from Novo Nordisk, and Karl will provide a bit more of color in this deal. But also looking at the market, we would see is that it has grown very nicely in the past few years.

But according to analysts, this market that is today around €48 billion, if you look at Europe and U.S. together is poised for growth for more than double-digit in the next five years, reaching €75 billion. So, a very exciting market to be on.

If we move to the next slide, please. So I just mentioned that we have a strong footprint in Europe, that this is translating into strong commercial capability with a proven track record of executing successful launches of internal and external assets.

If we look at our track record in Europe in the past few years, we have launched five brands, five products, and we can see that we have evolved the company from just a few years ago, from being less than €200 million in Europe to north of almost €400 million in the last year, with a compounding growth rate of 14%. But this growth rate is accelerating. If we look at the growth rate we achieved in dermatology in Europe in 2023, it was closer to 17%.

So, going forward, what can we expect? We will remain focused on Medical Dermatology, on areas of high unmet need such as inflammatory skin diseases such as Atopic Dermatitis, Psoriasis, Hidradenitis Suppurativa, Alopecia Areata, Vitiligo and remember, this is the area where we already have a number of products such as Ilumetri, Wynzora, Skilarence and now more recently Ebglyss.

And we will focus also on two other buckets. One is the non-melanoma skin cancer, where there’s still also high prevalence. Can you go back, please? One sec, yes, where we still have high prevalence, but also on rare dermatology diseases where there are many indications without treatment.

If we move to the next slide please. What we can see here is why are we focusing on these two latter buckets, with non-melanoma skin cancer where we have — what we see is a growing incidence due to increasing sun exposure and aging population. We see an incidence of almost 0.5 in Europe and for BCC and 1% in SCC, a bit less incidence in the United States.

But the unmet need in these diseases is very high. The therapy improvements that we’ve seen over the past year have not occurred as rapidly as in melanoma, that is a better-served market. So still a significant pool of patients that remains medically underserved.

Also in Rare Dermatology, there are more than 1,000 rare Dermatology indications, of which a vast majority they don’t have a single product approved by the FDA or EMA. And many of these diseases are severely debilitating, and impairment for patients and huge impact in patient quality of life. So tremendous opportunity here also in rare dermatology.

If we move to the next slide again, we go here to the immunologically mediated skin diseases. What we can see is that it’s not only we see a high level of unmet need, but also high prevalence. We got a number of patients that will be eligible for advanced therapies. We see in atopic dermatitis almost close to 3 million patients, if we look at U.S. and Europe combined. Look at psoriasis is 2.5 million, and also high prevalence in diseases such as Vitiligo, CSU, Hidradenitis Suppurativa, Alopecia Areata.

And this is why we are heavily focused our efforts in R&D, not only in clinical development, but also in discovery. We have with the announcement of the anti-IL-21 asset that we announced today, we have 13 assets either in discovery or in early clinical development and a number of these assets have potential for multiple indications. So it’s probably we have around 15, 16 potential programs in these diseases.

So many shots on goal on these different diseases that again not only the unmet need is very high but also the prevalence is very high, and still the market can expand dramatically even in indications like psoriasis where the first biologic was launched more than 17 years ago. As you can see, there’s only a penetration of 23% of eligible patients in psoriasis. So with this, let’s move on to the 2023 highlights and guidance for this year, please.

Next slide please. So 2023 has been a good year. The business momentum from our growth drivers remains solid. As expected, we landed around the middle of the EBITDA guidance range and achieved close to our mid-single digit growth guidance which had matched up in our last call the 3Q results in November 2023.

The full year 2023 performance was driven primarily by our European Dermatology business but, as I mentioned before, it grew 17%, underpinned by Ilumetri and our recently launched products Wynzora and Klisyri. This will be discussed in more detail later in the presentation. Nonetheless, let me touch upon a few highlights.

We are pleased to have initiated the first launch of Ebglyss in late December, and we are expecting Ebglyss to gradually start contributing to the European Dermatology performance during this year. We continue to see strong performance of Ilumetri across geographies with solid growth year-on-year in the mid-30s and quarterly performance aligned with expectations.

The launch of Wynzora and Klisyri in Europe is being driven by growth in key new countries as the recent rollouts in Europe continue to progress. In relation to our pipeline, we continue to make good advance with all key assets under development. This includes our Anti-IL-1RAP, and the anti-IL-2 mutein Fc, both of which are now in Phase 1.

Meanwhile, Klisyri large field supplementary indication is expected to launch in the U.S. in the second half of this year. The Seysara approval in China also remains in track for 2024, and with regards to Efinaconazole, the regulatory review remains ongoing, and we now expect the approval by the second half of the year. Karl will soon elaborate a bit more on the pipeline.

Let’s move on to the next slide for the 2024 guidance. In terms of net sales, we expect high single-digit growth and we expect a total EBITDA to be between €175 million and €190 million for the full year. Mike will provide more detailed comments later in the presentation, including some of the key pulls and pushes for the year.

With that, please move to Slide 14 to touch upon the biologics growth drivers. Following the recent launch of Ebglyss, I wanted to share some overall big-picture context around our two big biological drivers, Ebglyss and Ilumetri. Between Ilumetri and Ebglyss, we continue to believe we can achieve potential peak sales of around €700 million by the end of the decade. Of this, Ebglyss should contribute €450 million in atopic dermatitis while Ilumetri will contribute €250 million in psoriasis. This potentially multiplies our current atopic dermatitis and psoriasis sales by 4, driving high double-digit growth in biological sales from 2023 to the end of the decade 2030.

Let’s take a closer look at Ebglyss now in the next slide, please. We truly believe that Ebglyss has the potential to become a best-in-class treatment for atopic dermatitis, thanks to its unique mechanism of action. It binds to IL-13 with high affinity and selectivity with results in early set of action and great efficacy in the long term. As early as in week 16 in these trials, we can see the data supporting greater efficacy.

In fact, we have data collected over two years now where patients who responded well at week 16 continue to demonstrate efficacy throughout the two-year period. Furthermore, we have achieved a unique maintenance dosing schedule with one injection every four weeks, providing long-lasting disease control for patients.

Let’s move to next slide, please. On this slide, we would like to share the estimated timelines of the Ebglyss rollouts across Europe. As you’re aware, last year we received approvals for Ebglyss in Europe and U.K. and have successfully launched in Germany where the initial feedback has been positive. It is too early to share quantitative data about the launch as we need more time to gather the appropriate market data.

In Q1, we should be able to share the sales data and by July this year, we should have more information. Having said this, let me reiterate that the initial feedback is positive. Regarding the resources that we need to launch Ebglyss, we will keep investing, but we may not necessarily need to double the size of the salesforce considering the competitive nature of Ilumetri, although we believe that it makes sense to add sales reps for Ebglyss. So, we will have to be judicious in how gradually we direct some of the biologic sales force to our Ebglyss without disrupting Ilumetri.

In relation to 2024 rollouts, our current plan calls for a launch in the U.K., Austria, Denmark, and Spain. The rollout in the remaining countries is expected in 2025. We will keep you updated on these timelines as they develop and we get better visibility.

Let’s move to Slide 17. In this slide, we want to show that atopic dermatitis market today is in a very similar position that psoriasis was several years ago and it’s beginning stages. The potential room for growth is substantial. We show psoriasis which grew eightfold over a 12-year program, mostly driven by the launches of novel advanced therapies. In the atopic dermatitis market six years ago, there was only one biologic available to doctors to treat moderate to severe patients.

The available treatment options are still limited in atopic dermatitis and far fewer than psoriasis. Let’s not forget that this is a disease that requires a wide variety of options to serve the patients. In fact, there are still only three mechanisms of action available for moderate to severe atopic dermatitis patients in the market. We believe Ebglyss has a potential to be a first-line treatment for atopic dermatitis.

Let’s move to Slide 18, please. Moving to Ilumetri. Let’s take a closer look at the strong momentum of Ilumetri, our anti-IL-23 biologic for psoriasis. I would like first to highlight that the class itself continues to maintain its leading market share of new patients amongst biologicals. In 2023, we have launched a 200-milligram presentation with the anti-injector and detailed new clinical data.

On the chart on the right, we can see that Ilumetri continues to display strong performance during 2023. It also shows balanced growth as the sales contributions of European countries other than Germany are now at 50% of the total sales, with Germany taking up the other half. This demonstrates good traction of the product in other key European markets. With over six weeks behind us in 2024, we expect to resume momentum in Q1, and we continue to expect 2024 to grow in absolute terms, sales value to be comparable to 2023.

Let’s now move on to Slide 20. Karl will update you on advances in our pipeline, including the recently signed anti-IL-21 deal with Novo Nordisk.

Karl Ziegelbauer

Thank you, Carlos, and good morning from my side.

This slide shows you the progress of our pipeline. We continue to advance both our early and late-stage pipeline. For Klisyri, we have completed the clinical study addressing the expansion to large field in the U.S. and submitted a supplementary NDA in August 2023. We expect launch in the second half of 2024. In addition, we have started a study aimed to enable the label expansion to large field in Europe with an expected launch in 2026.

For Seysara in China, the Phase III clinical study met primary and key secondary endpoint and we submitted a dossier to the Chinese National Medical Products Administration at the end of September 2023. Approval is expected in 2024. For Efinaconazole, we are under regulatory review. We expect approval in the second half of 2024.

The Phase I for our Anti-IL-1RAP monoclonal antibody is ongoing, and we have initiated for our IL-2 mutant Fc fusion protein that we develop in collaboration with Simcere. As you can see, we’re making very good progress with both early and late stage pipeline and we are on track to strengthen our leadership position in Medical Dermatology.

Now, let’s move to Slide 21. With Ebglyss being approved in the EU and U.K., the R&D efforts will shift to how we can maximize the value of Ebglyss and we remain in close contact with our partner Lily to explore various options. In addition, we focus on building a pipeline behind Ebglyss with a mix of in-licensing assets and in-house discoveries. I have already on the last slide, shown two assets, an Anti-IL-1RAP monoclonal antibody and an IL-2 mutant Fc fusion protein, which we in-licensed at preclinical stage and advanced to clinical development.

Now, let me talk about our most recent addition to the pipeline called NN-8828, a monoclonal antibody targeting IL-21 we in-licensed from Novo Nordisk. IL-21 is a cytokine involved in several immune-mediated diseases. Its new and differentiated mechanism makes NN-8828 a promising option for the treatment of inflammatory and autoimmune skin disorder. NN-8828 was developed up to Phase II by Novo Nordisk in non-dermatological indications. Our exclusive global license agreement applies to certain fields including immune inflammatory dermatological diseases in which our development program will focus on. We are very excited about having this antibody now being part of our portfolio.

Now, let’s move to Slide 23. For our in-house discovery efforts we focus internal resources and capability on disease biology, while we work with partners to access state-of-the-art technology platforms in a modality agnostic way, meaning, addressing each disease target with a modality that has the highest chance to work. A number of those collaborations are shown on this slide.

In the area of small molecules, we are working with Evotec, a leading technology provider in that space in a multi-target, multi-indication, multi-year collaboration. In addition, we are working with the University of Dundee on so called PROTAC, a new class of small molecule drugs.

We also employ some of the best-in-class antibody discovery engines, including Absci to generate AI-designed antibodies, AlivaMab’s state-of-the-art transgenic mouse platform, and EpimAb’s bi-specific antibody format. Most recently, we entered a multi-target alliance with Etherna to discover and develop mRNA/LNP-based therapies for severe skin diseases. These partnerships will enable us to select the best modality for a given disease target and bringing innovative products to patients suffering from skin diseases.

With that, I will hand over to Mike for the financial review.

Mike McClellan

Thank you, Karl.

As Carlos mentioned, 2023 showed solid performance with net sales growth of approximately 4%. We’ve seen strong sales growth in Europe from the dermatology portfolio, which helped drive the overall net sales. Bear in mind when considering the year-on-year comparable for Q4 that in 2022 we had an out-licensing in the fourth quarter of about €19 million.

We also had a minor reclassification this year of healthcare contributions in the fourth quarter with a full year effect to be consistent across countries. This reduced our net sales by €3 million, but also reduced our SG&A with no net profit effect. This impact mainly affected Ilumetri in France.

We achieved a total EBITDA of €174 million in 2023, down from 2022, driven part by the lower contribution of other income due to last year’s AstraZeneca / Covis milestones and we also had higher investment in SG&A and R&D. Our gross margin came in at 65%, which, as we have highlighted in previous quarters was impacted in part by higher energy cost, inflation which affected some of our material purchases, higher royalties as well as sales mix. This is in line with what we anticipated.

SG&A in ’23 was €422 million as we continue to invest in our newly launched products, as well as some pre-marketing ramp up for Ebglyss, which accelerated in the fourth quarter as we executed our first launch in Germany. R&D investments increased to 12.4% of net sales in 2023 compared to 12% in 2022.

We expect the R&D expenses to be a similar percent of net sales for 2024. We finished 2023 at 0.2 times net debt to EBITDA, which remains favorable despite a high level of cash investment such as the recent Prometax acquisition, the Efficib/Tesavel extension deal, the Physiorelax acquisition, Ilumetri and Klisyri milestones, and the Isolex upfront payment. Finally, we renewed our existing undrawn revolving credit facility with our current bank syndicate until February 2028.

Let’s now move on to sales breakdown on Slide 25. As you can see on Slide 25, the dynamics of the net sales. The European dermatology business has had a very strong performance with a 17% increase year-on-year. Our General Medicine & OTC business in Europe decreased very slightly, primarily due to the decline in Efficib/Tesavel following the patent expiration and price decrease experienced in Q4 2022.

Our U.S. business recorded a decrease in fiscal year 2023, and I will provide further details on the next slide. The rest of the world dermatology sales showed a slight decline. General Medicine is growing, mainly driven by a rebound in Imunorix sales in Latin America. Overall, it’s important to reiterate that our portfolio has limited patent expiry risk going forward, in the midterm, especially now that Efficib/Tesavel patent has expired and we are managing that ongoing pricing impact.

Let’s look closer at the dermatology business on the next slides. As you can see on Slide 26, we had a very strong performance in Europe. Dermatology driven by the growth of Ilumetri and other products such as Klisyri and Wynzora which are benefiting in Europe from launches in key markets. Skilarence and Ciclopoli had slightly lower sales due to high competition, particularly in Germany.

Focusing on our U.S. business, Seysara has underperformed, resulting in some impairment losses that I will come back to in the P&L slide. Klisyri keeps growing and we expect this to accelerate after the large field approval in the second half of 2024. As you can see, the legacy business in the U.S. remains under pressure from ongoing generic erosion related to Cordran, Aczone, and Tazorac. In the rest of world sales, the decline is due to a negative performance of Cordran Tape after a bulk sale that took place in 2022 as a plan bridging stock for supply in the Japanese market as we’re changing manufacturers.

Now, moving on to the full financial statements. We’ve seen the net revenue development in the previous slide, so let’s focus on the rest of the P&L. Gross margin was in line with expectations at 65% given the previously highlighted ongoing pressure of energy costs, material cost, inflation, royalties, and mix. Other income was lower in ’22 due to the milestone income recognized last year as previously mentioned, which did not repeat. R&D investments were up significantly from ’22 and reached 12.4% of net sales. The increase is mainly driven by the IL-2 Mutant Fusion, the IL-1RAP, and the lebrikizumab expenses.

SG&A expenses grew 3% compared to 2022 due to the recent and upcoming launches as well as promotions of Physiorelax. We had a slight acceleration in the final quarter as we began to execute the Ebglyss launch. The impairment loss you see here is due to the write-down of our Seysara asset in the U.S. that results from continued pressure on rebates and market access.

While we have taken steps to reduce our cost base in the U.S. to minimize the write-down, we have had to adjust the book value by approximately $50 million in the fourth quarter due to recent trends are below the previous expectations. Financial expenses have been impacted by the interest received from the short-term deposits benefiting from the interest rate increases in 2023, generating a positive impact of €5 million.

I would like to remind you that our effective tax rate is affected by the inability to deduct U.S. losses against the profitable European business. We expect to see this going forward. Our normalized net income differs to net income primarily due to the adjusting for the unusually high impairment loss from Seysara.

Please move to the next slide to look at the balance sheet in more detail. On Slide 28, the key point to highlight is the impact of the recent investments in intangible assets aided by the 2023 capital increase proceeds, including €45 million of upfront payment for Prometax acquisition in Q3, Ilumetri and Ebglyss milestones during the year, and this was partially offset by the amortization and impairment charge during the year.

I’d like to highlight that our net debt ratio remains highly favorable at 0.2% times net debt to EBITDA, though we have additional milestones coming in 2024 as well as we plan to invest in R&D assets and potentially bolt-on acquisitions. Let’s take a look at the cash flow statement on the next slide.

On Slide 29, you can see that we delivered operating cash flows of €93.5 million in 2023, which is lower than last year due to the increase in working capital. The negative working capital is attributable mainly to the higher inventories for the launch of Ebglyss, the growth of Ilumetri, and stocking of Klisyri as we had to internalize additional inventory after our partner Athenex declared bankruptcy.

The other adjustments are mainly related to net financial income, including interest received on short-term deposits. Among the investing activities, we made key cash investments in 2023 including the Prometax acquisition, Efficib/Tesavel extension deal, the Physiorelax acquisition, Ebglyss, Ilumetri, and Klisyri milestones as well as the Isolex upfront payment. Bear in mind that as part of the Ebglyss launch milestones will be paid in early 2024. The divestment line refers to milestones and royalties collected from AstraZeneca/Covis. These have been classified under investing activities due to the reduced focus in our operations and are lower than 2022 based on the agreed schedule.

Let’s now move on to Slide 30 for some additional color on the 2024 guidance. As we mentioned earlier in 2024, we expect the net sales growth of mid or — of high single-digit. We expect total EBITDA to be between €175 million and €190 million for the full year. We would like to outline some guidance assumptions we are using for 2024, which includes some pushes and pulls. We anticipate the increase in net sales, mainly coming from the continued expansion of Ilumetri in Europe, the new launches of Ebglyss, and continued growth of Wynzora and Klisyri across Europe.

In addition, we anticipate a positive contribution coming from Klisyri in the U.S., including the large field launch. On another note, we’re also anticipating growth from a full year of the Prometax and Physiorelax products in Spain. On the downside, Almirall U.S. legacy portfolio should still be under pressure and we expect Seysara to grow slightly. We see the gross margin relatively stable near 65% with similar trends to 2023.

For the investment trends in 2024, we expect R&D investment to remain around 12.4% of net sales that we had in 2023. We will keep investing in our early-stage assets, including the Anti-IL-1RAP and the Anti-IL-2 mutein fusion protein given that molecules are now in Phase I. We also intend to invest to support our recent and upcoming launches, which will lead to an increase in SG&A investment in absolute terms. SG&A should be increasing at a percent slightly higher than the net sales, a growth due to the launch investments.

We are also investing in further rollouts as well as additional sales infrastructure for Ebglyss in 2024. In addition, our operating expenses across the P&L are being impacted in 2024 by a significant increase in salaries in Spain due to a CPI catch-up clause in our collective agreement from the past three years, which will require a double-digit minimum increase for the majority of the employees based in Spain with an estimated impact of up to €8 million across the P&L in 2024.

In addition, our operating expense across — we will also continue to see a high effective tax rate in 2024 due to the U.S. effect on the tax position similar to 2023. For cash flow, we expect an improved operating cash flow due to a slightly higher EBITDA, and a much lower working capital investment. Any M&A or additional licensing activity during the year could lead to additional cash outflows in the investing activities. We do not expect major financing activities besides the usual interest payments and dividend payments in 2023.

And with that, let me pass it back to Carlos to conclude the presentation moving to Slide 32.

Carlos Gallardo

Thanks, Mike.

Just to wrap up the presentation. So, after a number of years focusing on Medical Dermatology, we are today a market leader in this market with a strong portfolio of around 50 products across modalities and therapeutic classes. Our newly launched products have north of €700 million peak sales potential, driving double-digit biologics growth until the end of the decade. And in addition, we have a very attractive pipeline in development in areas of great unmet need with internal and external assets. And of course, we continue to explore additional opportunities as we still have firepower to look at more opportunities to fill our pipeline.

We are financially strong, and with all the necessary resources to execute on our ambition. So we have an exciting few years ahead of us in our journey to become leaders in Medical Dermatology.

With this, I will pass back to Pablo to manage the Q&A.

Pablo Divasson

Thank you very much, Carlos. Sharon back to you for the Q&A, please.

Question-and-Answer Session

Operator

[Operator Instructions] And your first question comes from the line of Lucy Codrington from Jefferies. Please go ahead.

Lucy Codrington

Hi there. Thanks for taking my questions. Just starting off and I might be pushing my luck here, but looking at consensus at the moment, it looks like we’ve got about €38 million in for Ebglyss and €37 million for Klisyri of which €20 million are in the U.S. Are you comfortable with those numbers within your current guidance range? And then secondly, if you could expand a bit more on the IL-21 rationale for dermatology, has this been explored by anyone else? And can you go straight to Phase II based on the existing data set? And what are going to be your initial priorities in terms of target indications? Thank you.

Carlos Gallardo

Thank you, Lucy for the question. So, we are not providing detailed estimates for our sales this year with Ebglyss and Ilumetri. As I mentioned, we are quite bullish with Ebglyss. We do think it has potential to become first-line product. The initial feedback from customers in Germany is very strong. But at this point, we are not prepared to provide more details about expectations for year one. With Ilumetri as I mentioned, we expect that this year will show a similar growth in absolute numbers than we saw last year. In terms of the IL-21 rationale, I think that Karl is much better equipped than me to answer this question. So, Karl?

Karl Ziegelbauer

Yes. Thank you, Carlos. So thank you, Lucy for the question. As mentioned, we are now very excited to have this asset on board. IL-21 is a very interesting cytokine affecting T-cells as well as B-cells, and to our knowledge has been underexplored in dermatology. This asset is basically ready to start Phase II, and we will do so after we have produced the necessary clinical material. In terms of indication, that is a bit premature to discuss today, but we will keep you posted as we go along.

Lucy Codrington

Thank you.

Operator

Thank you. We will now go to the next question. And your next question comes from the line of Thibault Boutherin from Morgan Stanley. Please go ahead.

Thibault Boutherin

Thank you. Three questions, please. The first one on the Ebglyss peak sales. You maintained it has €450 million. Are you maintaining these peak sales following an assessment, or are you still in the process of reassessing the market and the opportunity? And what do you need to see in order to potentially update this target?

Then one question on Ilumetri. The quarterly sales have plateaued a little bit. Right now it’s annualizing around €180 million. So if you could just tell us, what the drivers are in order to push the sale to the next level and reach your €450 million peak sales.

And then last one on the pipeline, you highlighted three launches this year. So Klisyri large field in the U.S., Seysara in China, Efinaconazole in Europe. Please, if you could contextually say a little bit these launches, and maybe give us an idea of which one do you think is the most important contributor? And overall how material these launches can be for your topline growth? Thank you.

Carlos Gallardo

Sure. Thanks, Thibault for the question. So, in terms of the update then, if you look back at what I presented in slide 9, while we see that atopic dermatitis was like psoriasis was ten years ago in terms of market development. So there’s only 9% of patients that will be eligible for advanced therapies or treated with advanced therapies.

So one of the key assumptions, or one of the key drivers of Ebglyss and other therapies in this class will be how quickly this 9% evolves to be 15%, 20%, 25%, and that’s something that is probably not within our control, right? So the other assumption, of course, that is more within our control is market share.

And again, that’s what we’ve been working on to have with our commercial organization to push strongly, and we’re aiming for first-line for this product. And I think that, again, things so far are looking good. But I guess, in market expansion, how quickly we can expand from this 9% of penetration to higher penetrations, will largely determine whether we can go north of €450 million.

So at this point, your — it’s difficult to say when and how this market is going to evolve. So I think we have to play it a little bit by year. So hopefully maybe in terms — sometime down the road this year we’re able to provide a revisited estimate. But again, it’s largely defined — determined by how quickly the penetration this market evolves.

Second question was about Ilumetri and again, we have Paolo in the room, so maybe Paolo can touch upon this. But again, we had strong performance this past year from Ilumetri. We expect similar growth in absolute terms for 2024, main drivers being, again, we have backwinds from the class in Europe, the Anti-IL-23 class is the winning class and there are three products in this category. We have launched a new anti-injector, we have launched a 200-milligram dose that provides a lot of flexibility in terms of treating different patient populations.

So, probably long-term efficacy, flexibility in terms of dosing convenience, again, our product is dosed only once a quarter, or also it’s seen as extremely helpful for, in terms of convenience for patients.

So this is largely the main advantages of Ilumetri. But Paolo is here, and but before passing the word to Paolo, your last question about the new launches. Of the three that you mentioned, the one that is more important to us is the launch of the large field in the U.S.

As Mike said, we have underperforming compared to expectations in the U.S. We think that Klisyri large field will bring an approach to the market that will be well received and that can bring the U.S. operation back to growth, back to profitability. So, to us Klisyri large field in U.S. launching this year, later this year is fundamental to see the shape of the U.S. organization going forward.

Paolo, you want to add anything about the question about Ilumetri?

Paolo Cionini

Hi everybody. So well, I can add just a couple of things. Maybe to consider, first is the fact that IL-23 class is the dominant class in psoriasis biologics, and is going to continue to grow like this. And again, referring back to slide number 9, you can see that there’s still a lot of potential, untapped potential in — even in psoriasis biologics. We have launched Ilumetri also in new market in the Nordics and in CE. So we are really confident about confirming an absolute growth in the same range of 2023, also in 2024.

Mike McClellan

Yes. And Thibault, I would add, just remember what I mentioned in the financials. We had a reclass of net sales in SG&A, so there’s €2 million less in Q4 that would have been more allocated throughout the year. That was just a technical adjustment because there were some healthcare contributions that previously were in SG&A and in order to make it consistent, we reduced sales. So, that’s why you see maybe a little slower Q4 on standalone than you would have. If you add €2 million back to that, you see that the pattern remains in a very similar shape that we’ve seen in the last couple of years.

Thibault Boutherin

Thank you.

Operator

Thank you. We’ll now take the next question. And your next question comes from the line of Alistair Campbell from Royal Bank of Canada. Please go ahead.

Alistair Campbell

Good morning, everyone. Thanks for taking the questions. Just a couple. On the IL-21 project, just looking at that, obviously, Novo seemed to have done quite a bit of work in Crohn’s, RA, lupus, but put it back on the shelf about ten years ago. So it’s quite some time ago. So I was wondering what the IP situation is on this product, or is this probably going to rely much more on kind of exclusivities and necessarily patent protection? And then just for a bit of sort of a — just getting numbers right this year. Can you give me an indication of the upfront you’ll be paying to Novo? And also the launch milestone you expect to pay on the Ebglyss approval? Thank you.

Carlos Gallardo

Yes, thanks. Thanks for the question. I mean, as you rightly pointed out, this antibody has been developed by Novo in a number of indications already. They saw activity, but maybe not the level of activity they had liked to continue. If you look across the autoimmune space, this is not uncommon, because a lot of those mechanisms have their sweet spot in terms of indication, and we believe there is a strong rationale to explore these mechanisms in autoimmune skin diseases.

With respect to exclusivities, you’re right. This antibody has been in development for quite some time, and part of the exclusivity will rely on regulatory data protection, which depending on the geographies is up to 12 years. In terms of financials, we will not disclose detailed numbers, but this is a standard deal with an upfront typical for this kind of stage of development, then milestones according to progress in development, regulatory and commercial, and then tiered royalties.

Mike McClellan

Yes. And in terms of the Ebglyss launch, we will pay a $45 million milestone in Q1 of 2024. It was triggered in December upon the launch with payment terms that will push that payment into Q1.

Alistair Campbell

Thanks very much.

Operator

Thank you. We will now go to the next question. And your next question comes from the line of Guilherme Sampaio from CaixaBank. Please go ahead.

Guilherme Sampaio

Hello? Thank you for taking my questions. So, three if I may. The first one regarding our guidance. If you could provide us some thoughts on what could drive performance more towards the high end or the low end of the guidance in your view at this stage? Second topic on Lebrikizumab. You mentioned that you are in conversations with Lily to discuss the next steps in terms of R&D. If you could share some thoughts here as well, that would be good. And third, if the impairment of Seysara could come with some peak sales updates? Yes. And this will be for the day. Thank you.

Carlos Gallardo

Sorry, Guilherme, can you repeat the question number three, please?

Karl Ziegelbauer

It’s Seysara and Klisyri.

Guilherme Sampaio

Yes, on Seysara, my question if you could provide some details as well, that would be good.

Mike McClellan

Okay.

Carlos Gallardo

So. Again, in terms of reaching the high end of our guidance, I think that there’s a number of factors. Again, we have quite a comprehensive portfolio with many products. So it will be the addition of push and pulls. One of them, of course, will be Ebglyss performance. Again, we are expecting a strong uptake, but it could be even stronger. Of course, same thing with Ilumetri, and the other key drivers that we have on — in terms of net sales right? In terms of cost, maybe Mike can comment on that as well if there’s any element that you can see that could influence this. Mike?

Mike McClellan

Yes, I think the two things to keep in mind will be product mix. So how that will affect gross margin, we do expect to be somewhere near 65%, but depending on the mix of the products, that could change up and down a little bit. And in terms of the overall investment, we are very ambitious in terms of our investment plans in SG&A and R&D. So if there’s any slowdown there, there could be some pluses and minuses. But we think we can manage fairly well within the guidance. And in terms of the lebri additional R&D, we’ll pass that one to Karl.

Karl Ziegelbauer

Yes, thank you. I mean, as already mentioned, we are very excited about Ebglyss. We believe this is potentially the best antibody targeting IL-13, which is a key cytokine driving the pathophysiology of atopic dermatitis. And we see a very good benefit-risk profile and a convenient every four weeks maintenance dosing. So with such an asset in hand, we’re, of course, exploring further value consideration opportunities, together with our partner Eli Lilly, for example, additional indication, but also whether we could even further extend and reduce the maintenance dosing frequency.

Mike McClellan

Yes. And in terms of the peak sales, Seysara and Klisyri. Well, Seysara, clearly, with the impairment we have in the U.S., I think in the U.S., we’re probably going to end up more with an asset between $30 million to $40 million peak sale. We don’t know yet with China. China is still something we haven’t launched into, so there could be additional sales there. But we’ll give you an update at some point once we have a little clearer view of China.

In terms of Klisyri, it’s too early to say. The large field in the U.S. will be the real key. It will unlock our ability to compete against the other field therapies instead of just going against the cryotherapy, which is used on the spot basis. So we’re really looking forward to it. We expect to launch that in the second half of 2024. I don’t think it’s going to have a meaningful impact in 2024, but it will put us on a trajectory to accelerate the sales of Klisyri and hopefully to really stabilize the U.S. business.

Guilherme Sampaio

Thank you.

Operator

[Operator Instructions] We’ll now take the next question. And your next question comes from the line of Alvaro Lenze from Alantra Equities. Please go ahead.

Alvaro Lenze

Hi, thanks for taking my questions. I wanted to discuss on the strategy that you’ve mentioned in the beginning in dermatology. So you mentioned entering into non-melanoma skin cancer and rare dermatology diseases. Just wanted to know on the oncology side, how different is to approach that market as I don’t know to what extent that is covered by dermatologists or by oncologists, and how is your commercial approach to that? Then on rare diseases, I see here, just as an anecdote that you mentioned here, Ichthyosis I believe that you have had products in the pipeline for Ichthyosis in the past, but you didn’t go through. What does it make you want to go back to this group of therapeutic areas?

And then on this topic, what is your approach? Do you expect to develop drugs here internally, or some of the maybe the proceeds from the capital increase could be dedicated to bolt-on acquisitions in these areas? And then just another question, if you could just comment or give us more color on the pricing for Ebglyss in Germany? And what do you expect for the other countries in Europe? Thank you.

Carlos Gallardo

Thank you. Thank you, Alvaro. So, very good question. So, in terms of Oncodermatology; Oncodermatology, particularly if you go to non-melanoma skin cancer from a vast majority is treated by onco-dermatologist. So let’s say that the dermatologist, particularly the hospital dermatologist is still has a significant, if not a protagonist role in the treatment of these patients. And that’s why we have included this area within our focus area.

And I think also it builds very well on our presence already in AK, that, as you know, Actinic Keratosis, there is a precursor of skin cancer with Solaraze and Actikerall. So, Almirall is already known by these customers as being there in the field. So I think it makes a lot of sense to move in the continuum and go already to a — override cancer with BCC and SCC in particular.

And I think that’s from a commercial perspective, but also from an unmet need perspective, there’s still unmet need in these diseases, so still a lot of work to do. So room for new therapies, but also the incidence of the diseases continues to increase because again, it was because of the very high sun exposure without adequate protection in the 80s and the 90s and in the early 2000s, now we’re seeing how this is translated into more — higher number of skin cancer incidence. And then of course from a science perspective, and maybe Karl can talk to that, now, we have a much better understanding of these diseases. So we can come with novel ideas on how to start programs that will hopefully evolve into therapies.

And a great example is the agreement we have done with Etherna recently, in which now we have access to their mRNA technology, and we can encapsulate polypharmacy in these lipid nanoparticles, that we think, we believe, at least this is our scientific assumption that we can really have a significant impact on the treatment of this disease.

Karl, anything to add with — no it’s okay. And in case of rare disease, I think from two angles. The first angle is that of course the tremendous unmet need. There are north of 1,000 diseases here, a number of them are very debilitating. They have a huge impact on the quality of life of patients. And because of the increased understanding of the disease biology of these diseases now also we can come up with novel ideas on how to treat these diseases. And again, because of the high impact on the quality of life of these patients, how debilitating some of them are, we do believe that payers will pay for these therapies. And that’s one angle. So unmet need is an opportunity to come with scientific hypothesis.

The other angle is of course, as I mentioned before, some of our assets that we have today in our pipeline, particularly the ones that are in the area of immunology, we do believe that has potential for more than one indication and some of these indications are rare diseases. So we do believe that opportunistically with internal assets, we can also have internal programs.

So to your question, we’ll be tackling this opportunity both from external opportunities driven by unmet need, but also internally opportunistically when we look at our assets that we believe they might have a potential in — as a second or third indication in some of these rare diseases.

Karl Ziegelbauer

Maybe to add on, you mentioned, yes, in the past, we had a collaboration with a small company called Tyris, on a novel gene therapy for a rare dermatological diseases. However, as in the research stage, we had a high attrition. This program did not go forward and we terminated that at an early stage.

Carlos Gallardo

And I think that Alvaro your last question was about Ebglyss pricing. So if you look at Germany, we’re aiming to price Ebglyss on parity with DUPIXENT. We have a different dosing scheme on year one. So if you look into Germany, we are a bit more expensive on year one, around 15%. But also in year two, once we get to the maintenance phase, we are not as expensive as DUPIXENT, in a similar range.

So if you get year one and year two combined together, and that’s a way that payers typically look at this in Germany, and they look at price comparisons. We are similar on par with DUPIXENT. Of course, when you start looking at longer periods of time, three, four, five years, Ebglyss will provide a saving to the health system. So that’s another level we have to provide additional attractive profile of the product to payers.

Alvaro Lenze

Thank you. That’s all very helpful.

Operator

Thank you. That concludes the Q&A. I will now hand the call back to Pablo.

Pablo Divasson

Thank you very much, Sharon. We are now going to close our Q&A session, and with this, we will conclude our conference today. We want to thank you for your participation. You may now disconnect.

Operator

Thank you. This concludes today’s conference call. Thank you for participating.