Almirall SA

MAD:ALM

Earnings Call Transcript 2022-Q4

[Pablo Divasson Fraile, Director of IR and Corporate Communications]

Thank you very much, Sandra. Good morning to everyone on the call. Thank you for joining us to review Almirall's full year 2022 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.

With that, please 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 the highlights and growth drivers, Karl will provide you with details on the progress of the pipeline before passing again to Mike to review the financials. Carlos will then make some closing comments before opening up for a Q&A session.

I would like now to pass it over to Carlos Gallardo to discuss highlights and growth drivers. Please change to the next slide.

[Carlos Gallardo, Chairman & Interim CEO]

Thank you, Pablo, and good morning to everyone on the call. Let's move on to full year 2022 highlights on Slide 5, please. I am pleased to say that we had a strong year for Almirall both from a financial perspective and in terms of pipeline progress.

We saw strong business momentum driven by our growth drivers, and we are pleased to have delivered on our guidance. The performance of the core business was driven primarily by our European Dermatology business, powered by our recently launched products, which I will discuss in detail later in the presentation. Let me highlight the performance of our recent launches.

We continue to see strong performance from Ilumetri, which continued good uptake in Germany and solid contribution from recent country launches. Since the launch of Wynzora and Klisyri in Europe, we have achieved increasing market share in the countries, particularly in Spain and Germany for both products, while making excellent progress with the rollout in other European countries. We also continue to work hard on the pipeline with robust clinical updates on lebrikizumab.

This year, we announced detailed results from the 52-week lebrikizumab Phase III at the EADV Congress in September and submitted the application for regulatory approval in October. Karl will give you additional color on this later on in the presentation. We continued to work with our partners at Eli Lilly towards a targeted late 2023 European approval and launch soon thereafter.

Additionally, in the early-stage pipeline, you will be aware that in 2022, we have entered into a licensing agreement for IL-2muFc with Simcere. We have also initiated the Phase I study of our Anti-IL-1RAP antibody during this past third quarter. And most recently, in February, just a few days ago, we signed an additional deal for an option to license the Isolex 1 [ph] compound. Karl will provide additional details on these two assets later in the presentation.

Let's now move to Slide 6 to comment on the 2022 guidance. With 6.6% growth in 2022, we are pleased to have delivered on our mid-single digit core net sales guidance, and we also hit the mid-range of the EBITDA level. This strong set of financials and solid operation performance were driven by the core business, which continues to perform well, and which is being driven by our recently-launched products and strength in the European Dermatology business.

In the meantime, we are also making good progress on our pipeline. Almirall business started 2023 on a high note, and is ready to keep advancing in its pipeline development and prepared for lebrikizumab's launch. In addition, we have a good penetrating, reflecting our healthy balance sheet which we can use to actively pursue bolt-on acquisitions and in-licensing opportunities that align with our corporate strategy.

Please kindly move to Slide 7 to comment on our most recent European launches. Let me start with Klisyri in Europe, used to treat actinic keratosis. We are pleased with the commercial launch of Klisyri in Europe. The product is doing very well with sales over EUR9 million in 2022, having achieved a strong uptick. In Germany, Klisyri was awarded the Most Innovative Product of 2022. It's gaining solid traction in the different countries where it has been launched.

The product offers a good profile, which represents a significant step forward in the treatment of actinic keratosis due to short treatment protocol, the once-a-day application for five days, proven efficacy and high degree of safety.

Moving on to Wynzora for patients with moderate to severe psoriasis, which we launched in May '22. We are pleased with the progress, having achieved sales of over EUR7 million last year. We have seen excellent traction in the first countries it launched, with double-digit market share achieved in Spain and Germany. The rollout campaign also included the UK, Denmark, Netherlands and Austria. We are confident we can have a very nice uptake in these markets, as well as in additional European countries in the upcoming quarters. Wynzora has strengthened our position in the European psoriasis market as we are the only company to provide a full range of psoriasis products covering the patient journey.

Now let's take a look at the Klisyri and Seysara business in the U.S. on Slide 8 please. In the U.S., Klisyri has recently received a strong recommendation in the AAD guidelines. The product continues to gain penetration in the AK topical market, with around 70,000 prescriptions in its launch in February 2021. It is a good result for a new product launched in a market with numerous generic alternatives.

Furthermore, around 5,000 healthcare professionals have prescribed Klisyri since its launch, and we continue to receive positive feedback with good patient engagement. We have also made progress on patient access, achieving greater than 70% commercial coverage. We continue to differentiate Klisyri for what is already available in the market based on efficacy, tolerability and convenience. While we continue to focus on driving demand and gaining market access in the near term, over the mid-term, we are also working on the large-scale label expansion, which we hope to launch in 2024.

Now, let's take up Seysara. We have seen continued volume recovery during the fourth quarter, reaching pre-COVID levels. Seysara continues to make steady gains with commercial lives, with 75% commercial payer coverage. We have achieved a 6% market share in the antibiotic market and continue to focus our efforts on driving demand and improving the gross to net through better payer coverage. With both Klisyri and Seysara, there has been good improvement in 2022 in total prescription volume growth and market shares. We think these are two very good products with growth potential that will help build a more sustainable platform for Almirall in the U.S.

With that, I will cover our biology growth drivers on Slide 10. Let me start with the lebrikizumab. Atopic dermatitis is an underserved and large growth market, estimated to have about 5.5 million moderate to severe patients in the main countries in Europe by 2026. Those patients, almost 4 million are expected to be on treatment at that time. Out of the moderate-severe patient group, we conservatively estimate new systemics will treat around 0.5 million patients.

One similarity with the psoriasis market is that we expect patients and physicians to use a number of different medicines, and we believe biologicals will establish a meaningful share over time. So we believe that the percentage of patients treated by biologicals would likely be higher in time than current market estimates.

Within the biologic share, we remain confident in lebrikizumab's competitive profile. Currently, there are only two biologics approved for moderate to severe atopic dermatitis. We believe that moderate to severe patients have not been well penetrated in AD and that biologics are only just starting to have an uptick, so there is every possibility that lebrikizumab will be targeting a large, unmet opportunity. However, we need to wait and see how all of this develops. We believe that in this field where growth is accelerating and unmet need is very high, lebrikizumab has the opportunity to blossom. We are working diligently on various pre-marketing strategies in Europe and have begun shaping our sales force for this. For obvious reasons, we will not be able to share too much at this stage, but our excitement is strong, and we look forward to providing more information later this year and in 2024.

Now let me talk about our other growth, key growth driver, Ilumetri. Let's now look at the strong momentum of Ilumetri, our anti-IL-23 biologic for psoriasis in Europe. On the left side of the slide, you can see the market dynamics of the class, the anti-IL-23 in Germany, where we can see that the new patient market is clearly driven by the anti-IL-23 class with over 40% market share of new patients within biologics. And this is despite the recent launches in the anti-IL-17 class.

As you can see in the chart on the right, Ilumetri has shown a strong performance year-to-date, recovering from the seasonally flattish quarter 3. We expect a continued strong performance during 2023. Good performance in Germany and new country launches have contributed to the overall strength -- overall growth, sorry, and we are pleased to have achieved net sales of over EUR36 million in quarter 4, 2022. We expect further contribution for new countries in continuing to drive growth.

During 2022, the contribution of the other European countries compared to Germany, increased to around 50%, and we expect this good trend to continue.

With this, I hand over to Karl to provide more details on the pipeline on Slide 13.

[Karl Ziegelbauer, Chief Scientific Officer]

Thank you, Carlos, and good morning from my side. This slide shows the progress of our pipeline. We're advancing our promising late-stage pipeline while building an exciting early pipeline. For lebrikizumab, we have filed a marketing authorization application for atopic dermatitis with the EMA, and we expect approval in Q4 2023. A few more details later.

For Klisyri, we are working on an expansion to large field with a potential launch in late 2024 in the U.S. and 2026 in the EU. In the meantime, the recruitment for the U.S. study has been completed, and we are in an advanced planning stage for the EU state.

For Seysara China, the Phase III clinical study met primary and key secondary endpoints, and we plan to file with the Chinese National Medical Products Administration later this year.

For Efinaconazole, we have submitted regulatory filings with an expected launch late 2023. We have also initiated Phase I for our Anti-IL-1RAP monoclonal antibody. Finally, we have recently entered into a license agreement for an IL-2-mutant Fc fusion protein within this year and aim for a start of Phase I later this year. As you can see, we are making very good progress with both our early and late-stage pipelines, and we are on track to strengthen our leadership position in medical dermatology.

Next slide, please. Let me now explain the next step for lebrikizumab. As mentioned, we submitted the Marketing Authorization Application to EMA in October 2022. This application is currently under review, and we expect approval in Q4 2023. In terms of clinical update, the ADvantage Phase IIIb study is fully recruited. Results from the week 16 readout are expected in the first half of 2023.

As a reminder, the ADvantage trial is a randomized, double-blind, placebo-controlled Phase III clinical trial to assess the efficacy and safety of lebrikizumab in combination with topical corticosteroids in adult and adolescent patients with moderate to severe atopic dermatitis that are not adequately controlled with the cyclosporine A, of whom cyclosporin A is medically not advised.

In addition, a pediatric study was initiated by our partner, Eli Lilly, in October 2022. We're also in advanced planning stage of an extension study to explore long-term benefits of lebrikizumab for up to 5 years. We believe that atopic dermatitis is a chronic disease that requires long-term treatment. We think that lebrikizumab, with the potential as shown in our ADvocate studies to control the disease effectively with every four weeks dosing in the maintenance phase, is suitable to achieve it.

In summary, we are very excited about the progress we are making with lebrikizumab and the totality of the data and the profile that is emerging. Lebrikizumab shows a consistent profile across the clinical development program with more than 2,000 patients. Consistent across geographies, whether in monotherapy or in combination with topical corticosteroids in adults as well in adolescence and across ethnicities. The safety profile is mild and consistent with prior lebrikizumab studies in atopic dermatitis.

Atopic dermatitis is an IL-13 dominant disease, and we believe lebrikizumab is the best antibody targeting IL-13. For the maintenance of patients that responded at week 16, every four weeks dosing show strong results that are like every two weeks option. Those data demonstrate the potential benefit that lebrikizumab could bring to both HCPs and patients.

Next slide. This slide summarizes the progress we are making in building an early pipeline, starting with ALM27134, which is an anti-IL-1RAP monoclonal antibody that we recently in-licensed from Ichnos. ALM27134 blocks signaling of 6 members of the IL-1 cytokine family. Phase I is ongoing. We believe this is an opportunity to address unmet needs in several autoimmune dermatology indications.

Let me continue with ALM223. ALM223 is an IL-2-mutant Fc fusion protein that activates regulatory T cells that we recently in-licensed from Simcere. Pre-clinically ALM223 exhibits an improved PK profile and the potential to restore immune balance. Start of Phase I is expected in the second half of 2023.

Finally, we announced the research collaboration with Isolex, the U.K.-based biotechnology company, with a novel approaches for IgE-mediated diseases. Pre-clinically, the lead molecule shows potential as a differentiated approach to treat IgE-mediated diseases such as chronic spontaneous urticaria.

In summary, we are making good progress in advancing novel approaches to treat skin diseases. With that, I hand over to Mike.

[Mike McClellan, CFO]

Thanks, Karl. And now, on to Slide 17. As Karl has mentioned in the introduction, we have seen a good performance in 2022 with core net sales growth of 6.6%, and we have successfully met our 2022 guidance. We've seen strong sales growth in Europe from the Dermatology portfolio, which helped drive the overall core net sales increase.

We achieved total EBITDA of EUR198.3 million in 2022, which compared to 2021 is impacted by a significant increase in our launch and R&D investments as well as the absence of deferred income, partially offset by an increase in other income due to AstraZeneca/COVID milestones. In 2022, our gross margin came in at 66.4%, which was impacted by higher energy costs and inflation, which affected some of our material purchases. This is in line with what we have mentioned in previous quarters.

SG&A for 2022 was EUR409.7 million as we continue to invest heavily in our newly-launched products, which we will discuss in more depth later in the presentation. R&D investments increased 40% and came in at 12% of core net sales, which is in line with our guidance. As we've previously outlined this year, we will have to pay for the Phase IIIb reimbursement with studies for lebrikizumab, the Klisyri large-scale studies as well as an increased investment in earlier-stage assets such as the anti-IL-1RAP and the IL-2. We will also discuss this in more depth in another slide.

We recognized an out-licensing income of EUR18.5 million in Q4 from the Motilex transaction, which is consistent with our strategy to manage our mature product portfolio and is an amount similar to previous transactions in 2021 and 2022. A typical level of out-licensing was included in our '22 guidance range, and this transaction helped us to partially offset the unanticipated negative impact, which we had inflation and energy costs throughout the year.

Our strategy for mature, non-focused products is to out-license when we can generate more value than by managing them ourselves. We are also looking to in-license assets aligned with our strategy of driving growth, with bolt-on assets such as the recent acquisition of the consumer care dermatology product, Physiorelax in Spain. We expect to continue to opportunistically manage our mature non-focused portfolio in the coming years.

We finished 2022 at 0.8 times net-debt-to EBITDA thanks to the good cash flow generation and the reduction in the pension plan liability.

For the detail on core net sales, let's move to the next slide. You can see on Slide 18 the dynamics of the core net sales. The European Dermatology business recorded a very strong performance, with an 18.4% increase year-on-year. We also had a solid performance in many of our general medicine and OTC brands driven mainly by Spain due to good seasonality and sales force efforts.

In our U.S. business, there's been an improvement in TRx growth in the fourth quarter, however, the full year net sales is down versus 2021. I will provide further details of that on the next slide.

Overall, it's important to reiterate that the portfolio has limited patent expiry risk going forward. And in the midterm, aside from Efficib in Spain in 2023, where we are managing the pricing impact. We also had some downward pressure in the U.S. legacy business, which we will see on the next slide.

Rest of World Dermatology sales showed good growth year-on-year, while General Medicine has seen a small decline year-on-year, mainly driven by Imunorix in LATAM, which had very high demand during the pandemic and winter months of 2021.

Let's take a closer look at Dermatology business on the next slide. On Slide 19, as you can see, we had a very strong performance in Europe, driven by the growth in Ilumetri, as well as good trends for our Decoderm franchise and Solaraze. Other EU dermatology is also benefiting from the initial launches of Klisyri and Wynzora in key markets.

Focusing on our U.S. business, we see good progress in TRx in market share of Klisyri and Seysara, although we still need to improve the gross-to-net results as we work to create a strong customer base for the brand. You can see the legacy business in the U.S. remains under pressure related to Aczone and including additional competition with Tazorac, which was seen in the second half of 2022. In Rest of World, we've seen a significant growth related mainly to the stocking of Cordran Tape in Japan, driven by a change of contract manufacturers.

Now moving on to SG&A and R&D details in the next slides. On Slide 20, we want to highlight the details of SG&A evolution to better explain the current and future drivers of costs within SG&A. A significant driver of SG&A development is related to our newly-launched products in Europe. This is mostly focused on the ongoing rollout of Klisyri and Wynzora as well as support for the high levels of growth of Ilumetri and the pre-marketing expenses of lebrikizumab, totaling an amount of EUR34 million in the year. We've seen around EUR12 million of FX impact mainly related to the U.S., which saw a slight decline in local currency.

Finally, we have optimized our portfolio by reducing investment in the mature and non-core products. Overall, we've cut expenses in the base business by EUR29 million. For 2023, we will increase our investments in lebrikizumab as we get closer to launch, and we will keep investing in our growth drivers.

At the same time, there will be more limited scope to further reduce costs in the rest of the portfolio, and we will have some added labor cost pressure from inflation.

Now let's move on to the next slide for R&D cost evolution. As you can see on Slide 21, R&D cost growth in 2022 reflects the investment to advance both our late-stage and early-stage pipeline. We have the lebrikizumab cost mainly related to the Phase IIIb studies, amounting to a total of EUR8 million incremental increase compared to what we already invested in 2021.

For Klisyri, we've had a seven day increase including the large field study in the U.S. We've also been quite active during 2022 in relation to our early-stage pipeline, including the Phase I study of the anti-IL-1RAP and other pre-clinical projects amounting to approximately EUR9 million incremental in total. Finally, we have had other minor items such as energy cost, inflation and an increase in personnel related, amounting to EUR6 million.

In 2023, we will keep investing in R&D on mostly the same items and expect to be in the similar range of around 12% of net sales. Bear in mind that 2021 was unusually a low spending year as we discontinued part of the previous early-stage portfolio.

Now let's move on to the next slide, with an overview of the rest of the P&L. On Slide 22, we can see that this successfully met our guidance by achieving mid-single-digit core net sales growth of 6.6% and a total EBITDA of EUR198.3 million, considering our target of EUR190 million to EUR210 million.

I've already highlighted the key factors on sales performance, so let me continue with our focus on the core business by running you through the rest of the P&L. Year-to-date, we achieved a gross margin of 66.4%, which was impacted by higher energy costs inflation affecting our material purchases, as we had mentioned in previous quarters. I will not go into detail on SG&A and R&D as we've already dealt with that in previous slides.

The reconciliation at the end of the P&L reflects the deferred income in previous year, which was fully amortized in 2021. Total EBITDA of EUR198.3 million includes EUR12 million of other income due mainly to milestones following the AstraZeneca/Covis Pharma agreement.

Let's now continue down the P&L. Turning to Slide 23, there are not too many items to go through. However, I'd like to remind you that our effective tax rate is affected by our inability to deduct U.S. tax losses against the profitable European business. We expect this to continue going forward. Early in 2022, we discontinued the sale of certain products of the legacy portfolio in the U.S. as our contract manufacturer discontinued production and alternative suppliers were too expensive, thus triggering an impairment.

We continue to focus on keeping the U.S. business sustainable through the growth of Seysara and Klisyri. Financial expenses have been impacted by the lower share price connected to the equity swap on the balance sheet. The impact of 2022 is close to EUR6 million, with the remaining expense being the ongoing interest impact following our refinancing in 2021.

Additionally, I'd like to highlight that we finished '22 with a normalized net income of EUR33.5 million, which resulted in a normalized earnings per share of EUR0.18.

Please move to the next slide to look at the balance sheet in more detail. On Slide 24, you can see there are quite a few comments provided on the slide, so I'll just highlight some of the most important factors. Some financial assets have been reclassified to accounts receivable following the agreement with Covis to advance certain milestone payments related to the China respiratory business. There was also a slight decrease in financial debt related to a reduction in our pension plans due to the increasing interest rates.

We finished '22 at a leverage of 0.8 times EBITDA-to-net debt and a healthy cash position, which gives us flexibility in the current environment for additional licensing and M&A activity.

Let's take a look at the cash flow statement on the next slide. On Slide 25, you can see we delivered operating cash flows of EUR155 million in 2022. We've seen normalization is expected from the change in working capital following the timing impact on accounts payable and receivable balances earlier in the year.

Tax cash flow turned to a net outflow due to a change in the phasing of net refund of corporate taxes in Spain. In 2021, we received refunds for two years during the first and fourth quarter instead of a single refund that year, as we had seen in previous years. We see this as a phasing effect from the change in how the Spanish government refunds taxes. We made key investments in '22, including the upfront of the anti-IL-1RAP, from Ichnos, the IL-12 mutant protein from Simcere and other regulatory and launch milestones for lebrikizumab, Wynzora and Ilumetri.

The divestment line here refers to milestones and royalty collections from AstraZeneca and Covis that have been classified as investing activities due to the reduced focus in our operations. And finally, there was a decrease in debt related to the regular loan repayments with the European Investment Bank. Free cash flow in the fourth quarter was flat due to the investments in milestone payments related to lebrikizumab, Wynzora, Ilumetri and others.

Let's now move to 2023 guidance on Slide 26. In 2023, we expect net sales growth of low to mid-single digit. In terms of total EBITDA, we expect to be between EUR165 million and EUR185 million for the full year. And I want to outline the guidance assumptions that we're using for 2023, which includes some pushes and pulls. We anticipate the increase in net sales mainly coming from the continued expansion of Ilumetri in Europe and the new launches of Klisyri and Wynzora across Europe.

In addition, we anticipate a positive contribution from Seysara and Klisyri in the U.S. On the downside for sales, the patent expiry of Efficib and Tesavel in Spain will have a full impact in 2023, and some products in the U.S. like Tazorac will see further deterioration due to additional generics. Additionally, we are taking into account some price pressure in Europe across our portfolio. We expect the other income line will normalize to the underlying royalty of single-digit millions.

On spending trends, we intend to invest to support our recent and upcoming launches, which will lead to an increase in SG&A spending in the mid to high single-digit range in 2023. We'll be preparing for the launch of lebrikizumab, and additionally, we will continue to invest in the launch of Wynzora and rollout of Ilumetri and Klisyri in Europe.

In 2023, we expect R&D spending to be around 12% of net sales, and these are the three factors driving the sustained level of high R&D. First, the Phase IIIb studies for lebri, where we will have to pay the cost for the reimbursement studies in Europe. Secondly, the spending on Klisyri large field, and finally, we will increase spending on earlier-stage assets such as the Anti-IL-1RAP and the anti-IL-2 mutein we mentioned before, as well as other early-stage projects. We will also continue to see a high effective tax rate in '23 due to the U.S. effect on the tax loss position.

For the cash flow, we expect lower operating cash flow in 2022 due to lower EBITDA and potentially higher outflow impact of tax payments. Investing activities will increase slightly due to lower divestment inflows following the positive impact of Covis-AstraZeneca deal in 2022. Any M&A or additional licensing activity during the year could lead to additional cash outflows in investing equity.

With that, let me pass it back to Carlos to conclude the presentation.

[Carlos Gallardo, Chairman & Interim CEO]

Thank you, Mike.

Please let me give you a quick reminder of the news flow that we expect going forward. As previously mentioned by Karl, EMA accepted our marketing authorization application for lebrikizumab in quarter 4 2022.

The anti-IL-1RAP compound has started Phase I in the first half of 2022. It is a first-in-class, fully human, high-affinity monoclonal antibody against human IL-1RAP, which can be applied across different autoimmune skin diseases. Klisyri's large field expansion will be potentially launched in late 2024 in the U.S. and 2026 in Europe, with significant upside in treating actinic keratosis. Seysara clinical drive in China is ongoing Phase III to [indiscernible], and the recruitment has been completed.

We signed a licensing agreement for IL-2 mutein with Simcere, further development of which can potentially address various unmet needs in autoimmune dermatology indications. Phase I is expected to start in the second half of 2023. We expect lebrikizumab to be approved in Europe in the final quarter of 2023. The regulatory filings for efinaconazole have been submitted, and we're expecting to launch this year to enable on onychomycosis.

Now let's please turn to Slide 29 to discuss Almirall's priorities in the capital allocation for creating long-term shareholder value. Let me remind you that we are fully committed to creating long term shareholder value, with growth expected to accelerate in the coming years with recent and future launches. Our capital allocation is focused on four main principles: First, invest in current and future product launches in dermatology to drive significant midterm revenue acceleration.

Second, innovation, by strengthening the pipeline both by proprietary research and in-licensing assets. Third, maintaining a secure stable dividend to our shareholders. And fourth, thanks to an prudent approach, we have a healthy debt profile, allowing for inorganic growth while maintaining a solid liquidity position. A good example of this is the recently acquisition of Physiorelax in Spain. This is a product that complements our Consumer Healthcare business and has the potential to generate further synergies.

Let's move to Page 30 to conclude the presentation. To wrap up, we have delivered a good operational performance in 2022, achieving our guidance. Our focused strategy in the medical dermatology space positions us well for the midterm. We continue to execute on the transformation of the company by preparing the business for the launch of lebrikizumab, with pre-launch activities advancing in key markets in Europe. We are confident that Almirall growth driver will continue their trajectory during 2023 as we continue to support key products.

Ilumetri has had a very strong performance, and we expect increasing contribution from new country launches to continue the growth during the year. We also expect the positive trends of the rollout of Klisyri and Wynzora to continue during the year. Furthermore, as detailed by Karl, we are progressing well with our exciting, innovative late-stage pipeline while at the same time, we are strengthening our early stage timeline with exciting new assets. Almira is well positioned for long-term growth. This growth will come from both current and future growth drivers, and also continue to explore inorganic growth options as we have the opportunity to leverage our strong balance sheet and flexible capital structure.

With this, we conclude the presentation. Pablo, I hand back to you for instructions on Q&A.

[Pablo Divasson Fraile, Director of IR and Corporate Communications]

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

[Operator]

Thank you. [Operator Instructions] We will now take the first question. It comes from the line of Harry Sephton from Credit Suisse. Please go ahead. Your line is open.

[Harry Sephton, Credit Suisse]

Thank you. Three questions from me, please. Firstly, can you comment on how you expect recent changes in the German AMNOG pricing to affect your portfolio? And maybe more specifically on lebri, it looks like you'll have to take a 10% discount to Dupixent unless you do a head-to-head study. Is it fair to assume that you are comfortable in taking that 10% discount at this time, given time is running out to actually run a head-to-head and have it submitted to Almirall in time?

My second question is on the Klisyri large field European launch. It looks like your expectation here has been pushed back from 2025 to 2026. Is there any specific reason for the delay there? And my third question is that given the ongoing losses you have in the U.S. and the unfavorable tax treatment, does it strategically make sense for you to remain in the U.S. market? Thank you.

[Mike McClellan, CFO]

Thanks, Harry. Let me take the first one, and then I'll pass it over to Karl. So you're right with the German, AMNOG, we anticipate that in our launch in Germany. We will probably need to take some discount versus Dupixent, because of the timing of the process. But we still think we will have a very good value proposition. We think we will get off to a very good start. We're still in the filing process. We do think we have a very, very solid asset, which could have some very good upside versus Dupi in many ways. So yes, that is an impact we need to take into consideration, but it is part of our plans. Karl, do you want to take the second one?

[Karl Ziegelbauer, Chief Scientific Officer]

Yes. Thank you. Mike. So thanks for the question, Harry. I mean, when we look at Klisyri large field, it's important to acknowledge that there are differences in the way regulators look at this between the FDA and the EMA. In the U.S., we have basically an agreement with FDA for the expansion to large field to do a PK and a safety tolerability study with about 100 patients that has been fully recruited. We expect readout this year, and then a potential approval in 2024.

Now in the EU, the situation is slightly different here. Regulators as part of the approval offer to do the safety study, that is a large study of about 540 patients where we compare Klisyri against [indiscernible] in terms of incidents of biopsy-proven squamous cell carcinoma. We expect this study runs roughly until 2026. Now again that's a different background, a study for the large field expansion yearly more likely includes, in addition to safety and tolerability, also efficacy endpoint. And as said, we're in advanced planning stage and given all the considerations, it's now more likely that we then look at an approval date in 2026 rather than 2025.

And Carlos, over to you for the last question.

[Carlos Gallardo, Chairman & Interim CEO]

Yes. Yes. Harry. So on question number three about the U.S., the answer is yes. We will continue to be in the U.S. Our ambition is to become a global leader in medical dermatology, and the U.S. is the largest and most important market. And if you look at our efforts to build an exciting pipeline, all the products that we are in licensing has U.S. rights. And of course, the proprietary process as well, right? So we need to continue to have an operation there to prepare for future launches.

Additionally, in the short term, we're expecting Klisyri and Seysara to continue to grow in terms of demand generation in terms of prescriptions, and also we have a number of initiatives in place to improve the gross to net.

[Harry Sephton, Credit Suisse]

Brilliant. Thanks very much.

[Operator]

Thank you. We will now take the next question. It comes from the line of Alistair Campbell from Royal Bank of Canada. Please go ahead. Your line is open.

[Alastair Campbell, Royal Bank of Canada]

Thanks very much for taking the question. I wonder if you could just press a bit more on the U.S. losses and the tax situation. Can you maybe give an indication if the U.S. was to get to breakeven, what you would expect the corporate tax broadly to look like? And can you give an indication of any kind of accumulated tax losses that you might be able to offset against future profits in the U.S. if and when you reach that point? And then just as a broader point on the EBITDA margin.

Obviously, you have further investments this year ahead of your launches. It's going to take EBITDA margin down to sort of probably a nudge below 20%, but historically, you've had sort of high 20% range for the EBITDA margin. So just a question that once the company is established, Ilumetri and lebrikizumab, is there any reason why the margin shouldn't get back to those levels over time? Or structurally is it going to be a different organization? Thank you.

[Mike McClellan, CFO]

Thanks. Alistair, I can take these two. So the U.S. is in a tax loss position, mainly from the amortization of the intangibles of the previous acquisitions. If we were to strip out the U.S., our tax rate would be more normalized in the low 20s. So very, very normal with a Spanish company. We are accumulating tax losses at this point. Until we have clarity as to when the U.S. will be profitable, we are not booking those as deferred tax assets. So when we do get the profitability in the U.S., we could have a swing the other way helping us out quite a bit on the tax line.

In terms of EBITDA margin, you're right, we will be in the high teens, low 20s. Our goal, our aspiration is five years from now to be back in that mid-to-upper 20s range. So that, of course, requires us to do very well with Ilumetri, to launch lebrikizumab very well, and continue to move forward the rest of the portfolio.

[Alastair Campbell, Royal Bank of Canada]

Great, thanks Mike.

[Operator]

Thank you. We will now take the next question. It comes from the line of Peter Welford from Jefferies. Please go ahead. Your line is open.

[Peter Welford, Jefferies]

Hi, thanks. Just a few follow-ups really. Firstly, just with regards to -- you said your outlook assumes in Europe some pricing impact this year. I wonder if you can just talk a little bit about what it is you've assumed and sort of which countries are key to that? And secondly, in the sort of low to mid-single-digit range of the outlook for sales, perhaps a bit broader than you've given in the past. Can you just talk a little bit about what are the pushes and pulls to give you that perhaps slightly wider sales guidance than you have done?

And then just secondly, a few sort of housekeeping issues. Firstly, you said the divestment income would be sort of normal given your optimization of the portfolio over time. Can you just talk a little bit about that? What should we assume in terms of your assumption within the outlook for this year with regards to divestment income within the P&L?

And then also you rattled through a few of the pushes and pulls for the P&L during this year. Can we just go back to -- did you give an outlook for SG&A growth at all this year? And then did I hear correctly, you also gave an outlook for royalties income. What we should assume for that this year and going forward?

[Mike McClellan, CFO]

Okay. All right. Looks like some stuff for me. So in the outlook, we do have some pricing impacts. There are some changes in healthcare contributions in countries like Germany and a few others. I would say, in total, around the EUR10 million range, but we'll see. We're keeping a very close eye on things. That's something that could develop in that range that we have, is if there are more pressure in some of the markets, we could see more. But we've anticipated at least what we see on the horizon.

I think that flows into the second one. The reason we're giving a wider range is exactly that. We're going into a year where we just don't know if there's going to be further pressure on the healthcare systems in Europe. So we would like to be towards the upper end of what we've guided, but we need to be a little cautious. We just don't know what's going to happen in Europe.

In terms of divestments, I would assume that we will have a normal amount. We've had small divestments in the last four years. I would assume just a similar amount there in 2023. Nothing particular at this point, but we do see those things come up throughout the year. This is part of our portfolio rejuvenation, if you want to call it that.

When people come and offer us amounts for some of these small non-core assets, we look at them. And if we can get more than our NPV, then we transact. At the same time, we are looking, as Carlos said, to do bolt-on acquisitions. We've done a very small one in Spain for an OTC product. But if there's other things in Dermatology or in our General Medicines business in Spain, we will look at those very actively.

In terms of SG&A, I think I said mid-to-single digit growth, mid to upper single-digit growth. So that's what we would expect. It's really focused on the pre-launch of lebrikizumab, continuing to drive Ilumetri and rolling out Klisyri and Wynzora in some additional European countries. Investments in the U.S. will be flat, so we're not increasing investment there but we are looking to rebound in the key products.

In terms of the other income, we had a nice little one-time bump in '22 from the designing of the deal with Covis and AstraZeneca to advance some of the milestones in China. Next year will just be the typical single digit royalties in that line. So I think I've covered everything.

[Peter Welford, Jefferies]

That's right. Thank you.

[Operator]

Thank you. We will now take the next question. It comes from the line of Jaime Escribano from Banco Santander. Please go ahead. Your line is open.

[Jaime Escribano, Banco Santander]

Hi, good morning. So a few questions from my side. So although you have given guidance in terms of gross margin in 2023, what should we expect? So something in between 65% to 66%, would that make sense?

Second question would be regarding new products, the one for onychomycosis, efinaconazole. Can you remind us what is the peak sales of this in combination? I don't know if there is some cannibalization with it globally or just to -- how should we think about this product in combination with your current portfolio in terms of big sales? And final question regarding -- can you remind us the milestones you have to pay in 2023 for housekeeping purposes? Thank you very much.

[Mike McClellan, CFO]

Yes, so I'll take these three as well. Jaime. So in terms of gross margin, I think your range is fairly okay, 65% to 66%. I would expect from the 66.5% roughly we had this year to see potentially pressure of 50 to 75 basis points. It really depends on the mix, but we are continuing to see inflation. We're seeing the pass-through in our suppliers of additional cost increases as they hit inflation and material costs. So I think that's a relatively good number.

In terms of the new products, we've never really given peak sales for efinaconazole because it's additive to the portfolio. There will be a slight amount of cannibalization, but we also see it as a nice way to expand that, but it's really tough for us to give a concrete number. So I would say, after we have a little bit of experience with it, we'll give a little bit more of a feel for what we think.

Let me answer the next one real quick and perhaps I'll pass it over to Karl to talk a little bit more about the process for efinaconazole. In terms of milestones, and I'd say that in total investment outflow will be the same, if not just a touch more in 2023 than we saw in 2022 because we will have some milestones related to the approval of lebrikizumab we're expecting. We'll have some sales-related milestones on some of our other deals, and we do continue to see some investment in early-stage assets.

[Karl Ziegelbauer, Chief Scientific Officer]

Just a quick update on efinaconazole, we'll meet it with basically existing data in a decentralized procedure in Europe, in Germany and in Italy, with Germany as a reference member state. And just to remind that efinaconazole will be a prescription product where we cycle prescribed [ph] and OTC products, so we think that this is rather complementary.

And what makes efinaconazole attractive from our point of view is that it has property, molecular property that results in a very low binding to keratin, the main component of [indiscernible]. And with that, it has a strong penetration, and therefore, can deal with this maybe more severe and deeper infections, yes, wherein an OTC potentially, those product goes potentially more for the kind of milder infection.

[Jaime Escribano, Banco Santander]

Okay, thank you very much.

[Operator]

We will now take the next question. This comes from Guilherme Sampaio from CaixaBank. Please go ahead. Your line is open.

[Guilherme Sampaio, CaixaBank]

Hello. Thank you for taking my question. So three, if I may. Two on lebrikizumab. So the first one, if you have any additional details on the need for further studies beyond the ones already disclosed on lebri? Second question, if you have any additional conclusion on the extremely high Phase III efficacy data of the placebo arm in leverage as much two weeks results?

And the third question, if you could talk a bit more on your initiatives to improve revenue? Thanks.

[Karl Ziegelbauer, Chief Scientific Officer]

Yes. Thank you, Guilherme. Maybe I'll start with the lebrikizumab. So I think, first of all, when we look at lebrikizumab, we are looking from the clinical trials where we already have read out to a very strong data package. And I think this will be now complemented by the data of the ADvantage trials I mentioned earlier. We expect the readout in the first half of 2023. But also in addition by studies Eli Lily has initiated. I mentioned the pediatric studies, which is in children older than six months and up to 18 months.

But also they're studying lebrikizumab in Dupixent fully exposed patients. And also, they're studying lebrikizumab in patients with skin off-color, again, complementing the already very exciting data package we have.

[Carlos Gallardo, Chairman & Interim CEO]

With the gross-to-net, I think, Mike, can you take that of this question, please?

[Mike McClellan, CFO]

Yes. So we've got a lot of things going on in the U.S. First of all, we've expanded coverage last year, but now we're needing to continue to refine our methodology of getting past the step edits and the prior authorization. So a lot of work is going into our pharmacy network to turn more and more of the potentially covered scripts into covered and to reduce the amount that we put into consignment.

We're also fine-tuning our targeting of physicians in areas that have better coverage versus areas that have less coverage, and many other initiatives that we can reveal a little bit later when we see how they're working. But a lot of effort is going into capitalizing on the very good TRx momentum we have. We've gotten the market share of Seysara up about 6%. We've got the market share of Klisyri up above 5%.

So we're continuing to grow the prescriber base. We are getting more depth, but we need to continue to push in their way to capitalize on the coverage expansion that we've had last year. So a lot of efforts are going on, and hopefully we'll be able to come back to you later in the year with some success stories.

[Guilherme Sampaio, CaixaBank]

If I can just a follow-up on the placebo data that I think you did not answer?

[Mike McClellan, CFO]

Yes. The placebo data. Can you answer that one, Karl --?

[Karl Ziegelbauer, Chief Scientific Officer]

Maybe I didn't hear. Can you please repeat your question?

[Guilherme Sampaio, CaixaBank]

Yes, it's possible. So we've seen extremely high Phase III efficacy data on the placebo arm in lebrikizumab, 52 weeks. If you have any further conclusion on why is that, and how should we read this?

[Karl Ziegelbauer, Chief Scientific Officer]

Yes. So when you look at this side, I think it's important to keep in mind that the patients after 16 weeks that were then re-randomized for the maintenance phase, they're already very well controlled. We started on average with an easy score that is a score from 0 to 72 of about 30, yes. And then the patients were treated for 16 weeks and then those patients that were re-randomized had an easy score, easy for about 2 to 3. Based on that, they were randomized to every four-week lebrikizumab every week and to receiving no treatment. Now, as lebrikizumab is an antibody with a very high potency and affinity in the picomolar range and a very long half-life of about 25 days, we believe that those different factors are well controlled, but also the excellent properties of lebrikizumab have contributed to this high maintenance of disease controls even in patients that didn't receive any further treatment between week 16 and week 52 when there was the result.

[Guilherme Sampaio, CaixaBank]

Okay, thank you very much.

[Karl Ziegelbauer, Chief Scientific Officer]

You're welcome.

[Operator]

Thank you. There are no further questions at this time. I would like to hand back over to Pablo Divasson for final remarks.

[Pablo Divasson Fraile, Director of IR and Corporate Communications]

Thank you very much, Sandra. 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. Thank you very much.