Afternoon. This is the Chorus Call operator. Welcome, and thank you for joining the Recordati conference call. As a reminder, all participants are in listen-only mode. After the presentation, there will be an opportunity to ask questions. Should anyone need assistance during the conference call, they may signal an operator by pressing star and zero on their telephone. At this time, I would like to turn the conference over to Miss Federica De Medici, Investor Relations and Corporate Communications of Recordati. Please go ahead, madam.
Hi. Thank you, Sabrina, and good afternoon or good morning, everyone, and thank you for attending the Recordati conference call today. I'm pleased to be here with our CEO, Rob Koremans, and Luigi La Corte, our CFO, that will be presenting the 2021 preliminary full year results and 2022 targets. We'll be running you through the presentation. As usual, the set of slides is available on our website under the Investors section. After that, we'll be opening up for Q&A. I will now leave the floor to Rob. Please go ahead.
Thank you, Federica, and welcome. Good morning, good afternoon. I'm really proud to have the opportunity to announce another year of very solid results for the group. I'm, of course, aware that I do this in the midst of an evolving human tragedy in Ukraine, where I'm sure you have questions on how this potentially impacts our business going forward. We will address that during the presentation as well. The revenue increased in 2021 by 9.1% versus 2020 or 11.4% at a constant exchange rate. With a progressive recovery in the main reference markets and operating conditions starting to return to near normal, especially in the latter part of the year.
On the rare disease segment, we have seen strong growth of both the metabolic and the Endo portfolio across all regions, resulting in a double-digit growth. SPC has also shown resilient growth, even in tough market conditions, where there were still access restrictions to physicians and medical personnel. In particular, in quarter four of 2021, cough and cold business came back to almost pre-pandemic levels. Also on Eligard, we delivered ahead of expectations with sales of EUR 85.3 million, thanks to an early transition to direct sales and a positive response to our focused promotion. Excluding Eligard, the group organic growth at constant exchange rate was 5.6%, absorbing the loss of exclusivity of silodosin and pitavastatin and the impact of the pandemic.
Overall, financial results are in line with expectations set at the start of the year, with strong continued cash flow generation. EBITDA at EUR 602.3 million, up 5.8% versus 2020 and with a margin at 38.1%. Adjusted net income at EUR 424.6 million, up 3.5% versus 2020. Especially also free cash flow of EUR 469.9 million increased quite markedly by EUR 87.6 million compared to full year 2020. Operating results reflect the impact of EUR 14.4 million non-recurring costs. This mainly relates to a targeted right sizing and optimization of our field force in Germany and Turkey. This reflects an evolution of our portfolio as well as a constant emphasis on commercial access and excellence.
It capitalizes on the learning that we have during this pandemic in the ability to leverage multi-channel instead of just face-to-face visits with sales force. Our net income of EUR 386 million is 8.7% up versus 2020, reflects EUR 5.8 million of FX losses and non-recurring tax benefits of around EUR 27 million recognized in 2021. Another highlight of the last year, 2021, was the EUSA acquisition. We expect to really expand on our rare disease business and accelerate growth. The completion of this acquisition is expected in Q2 of this year. During the year, we have a continued ESG commitment resulting in an MSCI rating improvement to A and an inclusion in the Euronext MIB ESG index from Borsa Italiana.
Let me provide you with some more updates on Eligard and Endo portfolio and as well EUSA acquisition process. On the next slide, you see the strong performance of Eligard. Both Eligard and the Endo franchise made a strong progress during 2021, confirming our expertise as a group in integrating effectively new businesses and launching new assets. Eligard, the transition finalized in a record time, with deal completed in January and the transition of marketing authorizations pretty much finalized by June, in over 20 countries. We were also able to quickly start promoting the products across many markets, with sales stabilizing and in several cases, actually showing a reversal and going into growth.
Very positive sales trends that we could see, particularly in Spain and France. We have completed a regular regulatory filing of the new device and at the end of January of this year in 2022, and we now hope to see approval during the second half of this year for this new device. Which will give a further positive force behind Eligard. On the Endo franchise, we closed the year with revenues of EUR 126.6 million, confirming the guidance range of EUR 120 million-EUR 140 million, with Signifor revenue of EUR 80.5 million and Isturisa at EUR 46.1 million. Both for Signifor and Isturisa, the combination is on track, with Signifor in-market sales growing in the year of over 10% on a like-for-like basis versus 2020.
Isturisa continuing to capture patients across U.S.A. and Europe with strong uptake in U.S., in France and in Germany, and also good progress in Italy with early access and Japan, where we launched in June 2021. The key next catalyst for Isturisa is the agreement of reimbursement across key European countries. Reimbursement price in Germany and Switzerland have been agreed in line with expectations, and we are confident to be able to secure additional ones in the course of 2022. We plan to continue to invest behind this important franchise in 2022 to further drive adoption in EU post reimbursement approvals. Finally, I would like to give you an update on the EUSA Pharma acquisition announced in December 2021, and on the latest stages of the process.
First of all, this acquisition is clearly in line with our strategy of complementing organic growth with value-accretive M&A, and represents excellent opportunity to further expand and reinforce our rare disease franchise, complementing our existing global footprint and expertise with new capabilities in a platform that will be very important for the future and expanding rare disease in a niche oncology therapeutic area. While the deal hasn't closed, regulatory review process has been progressing according to plan and completion, as I already indicated, is expected in quarter two of this year. Good news is that EUSA has been performing a little bit ahead of expectation in the latter part of 2021, with sales finishing full 2021 just over EUR 150 million.
The step up of this was largely driven by Sylvant, likely from usage in other settings and benefiting from a market shortage of other anti-IL-6 monoclonal antibodies. This is really great news and signals potential additional opportunities for this franchise. At this point, we confirm peak sales of approximately EUR 250 million and a growing EBITDA margin in line with the average of a rare disease segment, which includes potential expansion of Qarziba into the U.S. We will clearly provide a broader update on EUSA post the acquisition close, and once we've had the chance to fully engage with EUSA management. We really look forward to welcoming EUSA into Recordati.
You will recall that we announced that we had secured a EUR 650 million bridge financing to support the acquisition, and I'm happy to say that we have reduced that to EUR 450 million, thanks to a new term loan of EUR 200 million already finalized and will finalize the balance of takeout over the course of 2022, depending on market conditions. Overall, a very strong year with a very solid foundation for further growth in the years ahead. As you know, it's really early days for me in Recordati. I would like to give a little bit of my first impression and my first perspective on the business and share with you the next slide. The first impression I had as CEO after the initial months in Recordati are extremely positive.
We have a strong heritage with a very solid company, with very strong foundations, an incredible commitment to and an ability to deliver. There are people that have a strong focus on performance and excellent track records in delivering on objectives and beyond expectations, with strong discipline in investment and strong discipline in execution and in spending. Our team has a very global footprint. Also in my management team here in Milan, these are really global citizens, often with a different nationality than only Italian. The business is beautifully diversified. There's a good diversification. We have a balanced combination with stable and cash generating SPC business, combined with higher margin, higher growth, rare disease segments. Obviously, there's growth opportunities. The business is growing, and it's very much my aim to accelerate growth with targeted investments, particularly in the rare disease post user.
where I see fantastic opportunities to continue to grow and keep the balance with our SPC footprint. With that, I would for now like to hand to our CFO, Luigi.
Thank you, Rob, and good morning or good afternoon, everyone. As usual, I will take you through our 2021 results in a bit more detail, starting with the sales performance of our main products, which, as you hopefully will see from slide six, you know, really reflects the trend which is consistent with one that we saw at Q3, reflecting, you know, a recovery of cough and cold, gastrointestinal and OTC franchise, continued strong growth of rare diseases and a really good contribution from Eligard. Lercanidipine sales, as you'll see, marginally up versus 2020 at EUR 136.7 million.
This reflects, you know, volume growth across most of our markets and the initial shipments to our new distributor in China, and which more than offset a bit of erosion in Italy and also in Turkey. With Turkey, as we commented in Q3, also accounting for more than half of the decline on Zanipress, which is declining also due to competition of other combinations across various markets. Our metoprolol franchise at EUR 98.1 million declined by 7.2% versus 2020.
Now you will recall, metoprolol, you know, very mature product grew by 7.5% in 2020 on the back also of shortage of some competitive products in the year during the peak of the pandemic. We're effectively seeing the unwind of that, and some erosion in Germany and Poland. We do expect metoprolol to stabilize as we go into 2022. Eligard, as Rob has already mentioned, delivered well. In fact, you will recall, it delivered ahead of expectations that we'd set at the beginning of the year on the back of a very fast transition to direct sales.
Essentially all of the sales in the second part of the year have been through our own organization, and we started to see the benefit of promotion in a number of markets. Silodosin and pitavastatin are both, as expected, reflect the full year impact of the loss of exclusivity in 2020. Both, as also you would have seen, have started to show signs of stabilizing in the second part of the year. Erosion on silodosin was slightly higher than we had set out at the start of the year. You'll recall we'd set around EUR 10 million. It's been closer to EUR 13 million, mainly driven by Italy, but also the effect of currency in Turkey in particular, with erosion in Livazo being exactly in line with expectations.
Other corporate products, EUR 286.1 million, finished on a high. You'll recall this was one of the parts of our portfolio which was most impacted by COVID in 2020. That had started the year with some challenges, particularly in Central and Eastern Europe and Russia. You know, very pleased to see the recovery there in the second part of the year, with cough and cold ending the year still below 2020, but at around 75% of pre-pandemic level for the full year. Again, starting to show signs of returning to normal across many of our markets, not all, but many of our markets in the later part of the year.
We've also saw a very, very strong recovery of the gastrointestinal franchise, continued growth of Reagila, and also strong growth of the corporate OTC products, in particular, proto-Glyvenol, TransAct and Casenlax. Drugs for rare diseases EUR 383.9 million grew by 20.2%. Clearly, that's on the back of significant growth of our Endo franchise, both Signifor and Isturisa. Also thanks to the growth of our legacy metabolic portfolio, with many products in the franchise actually delivering growth. I'll call out Carbaglu, Cystadrops, Ledaga, and also Panhematin, which has managed to rebound after competitor entry in 2020, and deliver growth for the full year.
As you will see on slide seven, rare disease drugs for rare diseases now account for just over 24% of revenue. Of course, we expect this to increase to close to around 30% of revenue post the EUSA acquisition completion. I'll also sort of call out OTC products just under 18% of total revenue growing by 6% versus 2020 with core OTC products actually growing at a higher rate of close to 10% in the year.
On slide eight, in terms of revenue by geography, you know, very obviously pleasing to see all of the lines effectively on this page have shown a progressive improvement over the year. Thanks again to those key drivers of returning to growth of Specialty Primary Care, the contribution of Eligard and the growth of rare disease. In sales in Italy of EUR 258.2 million are down by just over 3%, reflecting the impact in the first part of the year on the cough and cold portfolio.
As I mentioned, some decline of silodosin and also a couple of discontinuation of local products, which more than offset the good growth of the OTC portfolio, in particular, Magnesio Supremo and Grisù. France, great to see returning to growth after a tough 2020. Sales of EUR 151.7 million, up by 5.3%, with growth of both the Endo franchise, the contribution of Eligard, but also good performance of our methadone business and of our Ginkor OTC products, which more than offset slightly lower sales on cough and cold, particularly the Hexaspray line.
Germany, double-digit growth at EUR 162.9 million, with good growth of both specialty primary care and rare diseases, led by Ortoton, lercanidipine, GI portfolio and obviously Eligard. Spain at EUR 120 million, showing a very, very strong growth of over 40%. Obviously Spain being the biggest market for our Eligard. But also the growth reflecting, as mentioned earlier, the strong performance of the gastrointestinal business, which you'll recall was heavily impacted by restriction to elective hospital procedures over the course of last year. Portugal, EUR 45.4 million of sales, up by 6.4%, once again driven by both Rx, OTC portfolio and Eligard.
Portugal is one of our sort of core markets for both Livazo and silodosin, which you know offset in part the growth of the other franchises. Turkey strong performance in market and in local currency with revenue growth of, in local currency terms, of close to 15%. In fact, double-digit growth from both specialty care and rare diseases behind the growth of Livazo, Procto-Glyvenol and Eligard, which more than offset competition or effect of competition from generic products and generic competitors on some of our local products, Cabral and Creval in particular, and also competition on lercanidipine.
Obviously Turkey facing a very significant effects in 2020 of close to EUR 20 million, which reflects the sales on a reported Euro basis. Obviously Paul, one moment for Russia, CIS and Ukraine. Sales of EUR 100 million, EUR 99.6 million are essentially flat versus 2020, recovering significantly in the second part of the year from what was a very slow start, thanks to the recovery of the cough and cold business, and particularly in Russia. And also the growth on the back of the growth of Propranolol, Livazo and the contribution of Eligard, with sales in local currency in Russia slightly down versus last year by 1.9%. Our sales in Ukraine and CIS markets are slightly increasing.
As Rob has mentioned, clearly difficult to predict exactly with, as events unfold, the impact of the escalation of conflict in the region on the business. I would say, pharmaceuticals from what we've seen historically is a more resilient business than many others. It is typically a sector that is protected from sanctions, obviously for the interest of patients. We don't have manufacturing facilities. We're not reliant on those markets for supply into other regions. Of course, the first thought in times like this is towards the people there, our people, and in general, the people in the country. As we said, obviously we're monitoring the situation closely.
We believe we have the right level of stocks in the market both at our level and with distributors. At the moment, we don't see significant disruptions. Of course, the events there are triggering inflation across the globe, which we have, and we will come to guidance for 2022. We have built in some assumptions on that into our financials. At this point in time, while it's difficult to predict with precision, we're not seeing a major disruption to the business in the region.
Sales in the U.S., of which as you know is fully Rare Diseases, EUR 176.9 million, strong growth of 44% and close to 50% actually in local currency. As I've commented already, on the back of the very strong performance of both Endo and the metabolic portfolio. Sales in other Central, Eastern European and Western European countries, which combined account for roughly 14% of our revenue, are growing double digits on the back of the addition of Eligard obviously, and the growth of the Endo franchise and progressive recovery of market conditions on specialty primary care. North Africa sales of EUR 35.9 million, down by 13%.
This really reflects our challenges that we faced during the year in Algeria with imports in the country being restricted and impacting the sales of Hexaspray and vitamin D. Sales of our local business in Tunisia actually continuing to grow double digits, 10% or 12% at constant exchange rates. Finally, other international sales of EUR 24.2 million, up by 1.6% on the back of the growth of lercanidipine across many markets, which more than offsets the impact of silodosin and pitavastatin, which we also sell through our partners in countries outside of our main ones, and the effect of the discontinuation of Kyntheum.
Turning to slide nine, which once again shows that the diversified footprint of the group, which makes the group resilient, has made us resilient over the course of 2020 in the midst of the pandemic. We expect to continue to stay resilient in the context of other challenges that we see emerging. Sales in Italy now represent just under 17% of group revenue. Nice to see U.S. now becoming our second market with close to 12% of our sales coming from that region. Slide 10.
Looking at the P&L, which, as Rob has commented, hopefully you will show very solid financial performance once again for 2021, where we have delivered on the targets we set at the start of the year, despite you know an environment which it was not exactly as COVID free as we all would have hoped. Revenue as we said up 9.1%, and gross profit up 10.6%, with the benefit of the improved mix towards rare diseases more than offsetting very small inflationary pressures that we started to see towards the end of the year.
SG&A expenses are EUR 480.9 million, up by 14%, with selling expenses at 25.1% of sales, with two-thirds of the growth really driven by the addition of Eligard in particular, both the transition costs towards Astellas and the royalty payments to Tolmar. But also behind the targeted incremental investments we made behind the business, alongside the additional investments that we continue to make behind the Endo franchise. G&A costs at 5.3% of sales, growing also on the back of additional resourcing put in place to support those new additions to the portfolio.
R&D expenses of EUR 166.1 million, 10.5% of revenue. The increase versus 2020 reflects additional EUR 4 million of amortization arising from the new product acquisitions. The balance of the increase is once again driven by some of the additional investments made in market access, medical, to support both the Endo business and Eligard, and some of the ongoing trials that we inherited from Novartis behind the Endo portfolio.
As Rob commented at the start, other income and expenses, EUR 15.1 million, mostly reflect provisions made for the targeted rightsizing of some of our primary care lines, particularly in Turkey and Germany, as we adjust our focus to fit with the more specialist nature of the portfolio and leveraging the learnings from the pandemic. Around the EUR 12 million charge, which was relating to that and the residual EUR 3 million of exceptional costs incurred as a result of the pandemic particularly in the first part of the year.
That leads to an operating income of EUR 490.2 million, margin of 31%, and EBITDA of EUR 602.3 million, or margin of 38.1%, which is exactly in line with the target that we had set at the start of the year. Once again, despite some of the pressures that we faced and growing by 5.8% versus 2020. As we've commented throughout the year, the non-operating lines of the P&L reflect on the financial expenses level with cost of EUR 36.8 million that you'll see are almost double what we incurred in 2020.
Actually reflect foreign exchange losses in the year of EUR 5.8 million, which compare to in 2020 exchange gains of EUR 4.3 million. We also had in 2020 EUR 2.6 million gains on cross-currency swaps that we closed and were no longer considered as hedges. That mainly explains the increase versus last year. These are obviously offset by the one-off tax benefits that we had on the tax line relating to the reverse merger transaction, which should be completed in Q2, and also the revaluation of Magnesio Supremo, leading to net income of EUR 386 million, up 8.7% versus 2020, and adjusted net income of EUR 424.6 million, up by 3.5%.
I would say the lower growth rate there due to the fact that we do adjust, we strip out the tax benefit from adjusted net income, but we don't adjust for the FX gains and losses. In slide 11, you will see the sort of usual margins for our two businesses. I will say from my side, both remaining strong. In fact, rare diseases is slightly up by versus 2020 level, and Specialty & Primary Care is still robust, obviously reflecting you know costs related to the Eligard transition.
As we always said, that the progressive return to in-market activity as conditions improved in the second part of the year with rare disease now representing close to 30% or just about 30% of our operating results. On slide 12 and to finish off full year cash flow. Sorry.
Free cash flow in the year was very strong, consistent with a very strong track record of the company, reflecting both the increase in EBITDA, but also with a strong contribution from working capital, which was a bit of a drag in 2020, as we grew stocks during the pandemic, and as we integrated the Novartis business, and we saw both stock levels and payables normalize during this year, which more than offset our increase in debtors linked to the increase in revenue.
Strong benefit from working capital, slightly higher taxes paid on a cash basis, as 2020 benefited from the one-off patent box benefits announced in Italy at the end of 2019. Free cash flow of close to EUR 470 million is EUR 87.6 million improvement versus 2020. In the year, we invested up to EUR 65.5 million in intangibles, being mainly the upfront payment to Tolmar of EUR 35 million for the Eligard rights and EUR 15 million to Almirall for Flatoril. Paid dividends of EUR 217 million and repurchased shares net of proceeds for exercise of options of EUR 59.3 million.
Finally from my side, that leads on slide 13 to a very solid net financial position. As you see, the strong cash flow helped us manage to absorb the dividend buyback and payments related to BD and led to a decline of EUR 129.3 million in our net debt at the end of the year versus end of 2020, with net debt now at around 1.22 x EBITDA. With that, I'll turn back to Rob to talk about projections for 2022.
Yeah. Thank you, Luigi. Turning to 2022 expectations, on slide 14, you'll see the key planning assumptions for this year. Revenue excluding EUSA is expected to grow mid-single digits, reflecting an adverse FX effect of -1%. On our SPC business, we expect low- to mid-single-digit growth, reflecting a progressive return to pre-pandemic conditions, with volumes expected to get back to growth and Eligard to contribute with over EUR 100 million revenues, offsetting limited lercanidipine sales in China. The Rare Diseases [business] to grow double digits driven by Endo's strong performance, expected revenue range of EUR 160 million-EUR 180 million, and further growth of Cystadrops, Ledaga and Juxtapid. Slight erosion of Carbaglu in the U.S. due to generic introduction.
Assuming a closing in quarter 2 of this year, EUSA will contribute in 2022 with a revenue of over EUR 110 million and an EBITDA of around EUR 25 million. We also expect non-recurring costs of about EUR 35 million in 2022, with around EUR 5 million of the further commercial excellence exercise of rightsizing in SPC business in Europe, and around EUR 28 million from the EUSA integration, where mainly the ongoing tech transfer related to Sylvant from Janssen is contributing to this. Financing costs will account for EUR 31 million-EUR 33 million, excluding FX gain or losses. We expect our leverage at closing around 2.4x pro forma, and to return to below 2.2x by the end of 2022.
Tax rate is expected to be around 22%-23%, and we expect an incremental amortization after EUSA transaction completion, plus other non-cash adjustments. These charges will be determined post-acquisition closing since subject to the purchase price allocations. On slide 15, we set our 2022 guidance, which we will fine-tune after the formal EUSA acquisition completion. With the revenue target range between EUR 1,720 million and EUR 1,780 million, resulting in a midpoint growth of 10.8%. With EBITDA expected between EUR 630 million and EUR 660 million, with a margin of 37% and a midpoint growth of 7.1%.
I think we've always made it clear that mid- to short-term margin should and could be affected by deals that relate to the phase of the product and the launch phase. In short-term, it has a slightly dilutive effect, as these are very much still products in launch phase. We will update mid-term plan post-closing, as I already alluded to. Of course, our ambition is to maintain a strong margin with a strong commitment to profit generation. The adjusted net income is forecasted in the range of EUR 450 million-EUR 470 million, with a margin of 26% and a midpoint growth of 8.3%. With that, I would like to give the opportunity for questions and answers.
This is the Chorus Call conference operator. We will now begin the question and answer session. Anyone who wishes to ask a question may press star and one on their touchtone telephone. To remove yourself from the question queue, please press star and two. We kindly ask to use handsets when asking questions. Anyone who has a question may press star and one at this time. The first question is from Brian Balchin of Barclays. Please go ahead, Brian.
Hi, it's Brian from Barclays. Thanks for the question. On 2022 guidance, hoping you can help us understand the extent to which that factors in potential disruption from the Russia-Ukraine conflict, just given that those markets contributed 7% of sales in 2021. How should we think about your ability to achieve 2023 targets given your exposure there? Thank you.
Yeah, thanks, Brian. I'll pass to Luigi to complete, but I mean, the events in Russia and Ukraine are really very recent. So they. Other than that, we have factored in for some inflation to happen in 2022. We do not really expect and anticipate a major disruption of our business, the ability to continue our business. Of course, when all those things started to happen in the last 24 hours, first and foremost concern was with the safety of our people, specifically in Ukraine. But also after that, immediately the continuation of our business. We believe that we should be able to continue our business, relatively short term.
The implications in terms of inflation, we have really good hedging on things like energy, for instance, that should carry us a long, long term into 2022. The full impact of the invasion of Russia and Ukraine was really not foreseen when we gave our guidance. I'll pass to Luigi to complete now.
Yeah, no, Brian, thanks. I'm sure this is a question on many people's mind. I don't know if I can give a lot more color than what I've said in the sense that you know we've seen this. It wasn't quite you know similar kind of shock. Let's not forget what this business has gone through in 2020 in terms of the impact from the whole of Europe being at times in lockdown.
We've seen through that time that, you know, the pharmaceutical sector is resilient, certainly on a bottom line level that, where, you know, if and where you have an impact on sales, you know, that can tend to be offset to a large extent through lower activities and therefore costs. You know, as from what we can gather at the moment, we've been in close touch, as you can imagine, with our people in those markets. We're not seeing to date a disruption. You know, these comments are valid as of 4:44 P.M., Milan time today. I really don't know what will happen tomorrow. We'll see.
I think we are confident once again about the resilience of the sector. The resilience of our business has demonstrated also last year through a pandemic. I think the thing that also is important to emphasize, that we do not have a local manufacturer. We're not reliant in other parts of the business for supplies out of Russia. Beyond that, I just think we'll have to watch and see what happens. I know that's only a partial answer, Brian, but I don't know that we can really give a better one at this point in time.
Okay.
The next question is from Martino De Ambroggi of Equita. Please go ahead.
Good morning. Good afternoon, everybody. The first question is on the guidance, once again. When you talk about EUSA, whose acquisition is finalizing in the second quarter. Are you assuming six months or nine months in your embedded guidance for the EUR 110 million? Because I'm sure you will not provide a guidance for the full year, because it's not in your hands, yet. Just to have an idea of what is your assumption. The second is still on the guidance. The R&D cost, and if you said something, I probably missed it, but just to double-check. Still on Russia. You are presenting a weight on sales, which is 6.5%, including CIS and so on.
Can we say it's 6% Russia, which will become 5%, following user? How much of the sales in Russia are dedicated to rare diseases? Can we say if it's less or more profitable than the average of the group?
Martino, in terms of the 2022 guidance contribution of EUSA. Look, we don't own the business yet, so we're not sort of you know have a sort of detailed sort of phasing for that business. We assume it will be you know based on. It's also difficult for us to predict at this stage when exactly where the closing will be. We've assumed it'll be at some point during Q2.
You can sort of take that as meaning sort of midway through Q2, but it's difficult to be so precise on something that we don't own yet, which is also why, to be fair, I've not given and we don't intend to give sort of guidance by full detail of a P&L line, because we'll have to see once we integrate EUSA what that looks like. I mean, certainly EUSA has a slightly higher sort of, you know, R&D as percent of revenue at the moment. So you should expect the consolidated number to be slightly higher than what we're reporting at the moment. Again, we would say that sort of more fine-tuning and more details on that once we have completed.
On sort of further breakout of revenue of sort of Russia, CIS and Ukraine. I think it's appropriate that we give you a little bit more sort of direction. You know, within that, around EUR 75 million would be Russia, EUR 15 million Ukraine. With the balance in the other markets in the area. I think in terms of profitability, we're not gonna go into sort of profitability by market. You have to assume sort of in line with group average at this point in time. Yeah. Let me-
The rare disease is a smaller part.
Yeah.
In the business with again the average profitability for rare disease products. From the history we know that during these challenging times specialty pharmaceuticals tend to really be quite resilient. There is a very short disruption. You can imagine that it's gonna be difficult for any truck to pass into that region and deliver goods. We really have good stock levels on the ground, and we expect to be able to continue this business fairly soon without really big impacts on those two countries.
Yeah. We'll monitor and we'll review that as events unfold.
On R&D?
No, but R&D, as I said, the reason for which we're not giving sort of, you know, breakout of the P&L for 2022, where I think in fairness, we give quite a bit more color on guidance than many companies is that, you know, we have to see once we sort of get our hands on EUSA, you know, how exactly sort of various P&L lines will come together. You know, I would expect our R&D at sort of a percentage of sales to be slightly higher after the completion of EUSA than it has been, if you like, in 2021.
That's simply as a result that, you know, they are incurring a higher level of cash R&D costs than we are at this stage. We're not gonna go into that much more detail in terms of further breakout of the 2022 guidance, Martino.
Okay. Very last on the Endo franchise EUR 160 million-EUR 180 million sales target for the current year. Can we assume roughly EUR 90 million Signifor and the balance could be higher or lower, but is it Isturisa?
Yeah. I would say, we don't tend to give, like, sort of guidance on a per product basis. Of course, most of the growth will come from Isturisa, right? I mean, Signifor we expect will continue to grow. Most of the growth, as we said already, the three-year plan clearly will come from Isturisa. As we said, just to reset expectations, you know, the next important catalyst of that is the progressive reimbursement in Europe. You know, we do expect that to start kicking in as we go into the year, sort of, progressively. Again, most of the growth will be contributed by Isturisa.
Very last. Is there any reason why Isturisa was flat sequentially in Q4, if I'm reading right enough?
No, not of any sort of relevance from our perspective. Patient acquisition has continued to be strong. Sort of, you know, single quarter sales on rare diseases is always a little bit lumpy. I think there was, you know, a small sort of true up of accruals on discounts in Europe in the last quarter. We're talking sort of roundings here, which on a sort of single quarter sales of a single product can distort a little bit the underlying trend, Martino.
Marty, what we've also seen, and that helped a bit in some of the sales numbers before, is that patients didn't really have the access to surgery that you would normally have due to COVID restrictions and specifically also some restrictions in getting into surgery. That has returned to more normal now. In terms of getting patients on the therapy and the ability to grow the numbers there, we are fully on track.
Okay, thank you.
The next question is from Jo Walton of Credit Suisse. Please go ahead.
Thank you. A couple please. AbbVie the other day were talking extremely positively about the opportunity for cariprazine or I can never pronounce it for you, Reagila, in the U.S. Is there any access that you have to any of that data? Is there any chance of effectively reinvigorating that product which now seems to be too small to talk about? Could you also tell us a little bit more about your right-sizing in Turkey and Germany? What's changed in your market environment there? If you're able to do more digital, is that something that you can do in other markets as well? Just give us a little bit more of a flavor for that, please.
You talked for the EUSA business of Sylvant, as I understood it, doing particularly well because there was a shortage of other IL-6s out there. Is this a temporary demand that you're getting, or do you think this is enabling the company to establish the product and that it will therefore grow more strongly from this enhanced base?
Thanks, Jo. A lot of good questions. Let me start with Reagila in the U.S. has a slightly different label, a different indication that unfortunately the bipolar I we will not be able to claim in Europe. Yes, we have a very good collaboration with all the partners behind the product, but there's very little that we can actually really do in Europe, if at all. There might be a small opportunity in Switzerland, for instance, but that's gonna be extremely limited.
But it was the-
Um-
The data they were talking about was major depressive disorder, you know, adding to their bipolar, so adding more depression to it. I thought that was really more of where you had data and, you know, that was more of the positioning in Europe. I wondered if there was any of that incremental non-bipolar data you could access.
No, I think the way we've seen it so far is that this really only works on the basis of bipolar that you can actually sell. It's a very different positioning that they have in the U.S. Clearly, we look at this opportunity, but that's not something that we believe is gonna be really realistic for us in Europe. Unfortunately, I'd love to, but it's not reality. In terms of commercial excellence, what we've really been doing, and it's very much as you hinted to, I mean, it's an ongoing process. This is always a dynamic process, right? If you look at opportunities and with the launches of the new two products, we see that there are opportunities, for instance, in the Nordic countries where we've strengthened our sales force a bit.
This has also been a learning phase, not just for doctors, but also for us, in what are the best way of getting your message across and interacting with your customers. Using multi-channel is something we've been doing. We will definitely take the best practices to other markets. In Germany and in Turkey specifically, it's also reflecting the focus on specialists rather than on general practitioners, which is really a slightly smaller target audience, so that we can actually work with fewer people as well. To the extent that that is true in other markets, we'll continue to drive it. We do not foresee as significant impact as we've seen in 2021, also in 2022.
Whereas in 2021, this is, in terms of actual reduction, you're talking about a 175 positions that we were able to reduce without, in any way, bringing down our commercial impact. In fact, probably we're better now than we were ever before.
The last question was related to. Okay.
Who's the other users of Sylvant?
What we've seen is that on the back of some shortage of the anti-IL-6, Sylvant has been able to probably increase. We don't own that business yet. It's very difficult to really comment on, but that's one of the very first things we'll definitely do once this is approved by the authorities, is sit down with EUSA management and look at opportunities. Theoretically, there are some, but I don't really wanna speculate, and I wanna really save that for the update we'll give after we've had the time to look into that and have been able to close the acquisition.
Maybe I'll just add, Jo, I think. Are we looking at sort of potentially other countries in terms of right sizing? I think we mentioned we have foreseen you know part of the non-recurring costs that we've foreseen for 2022 reflect that mostly voluntary sort of programs that again in a very sort of targeted way we're looking at you know across some of our other established markets.
I'll ask just a final question if I can. I assume that you are fully occupied with your EUSA acquisition, but what is your sort of pipeline for more product, given that you've had a history of growing 50% organically, 50% by acquisition? You know, how is the pipeline for new opportunities coming along?
Well, I'm not gonna, of course, mention anything concrete, but the pipeline is as good as ever, if not better. There are plenty of interesting things to look at and, yes, we are very busy with interacting with our future colleagues and cannot wait to get them on board. Fantastic people, but there are some other interesting opportunities as well. I mean, I don't think you expected that we would give anything concrete, but it looks promising.
Thank you.
It's very much part of our strategy.
The next question is from Rajan Sharma of Deutsche Bank. Please go ahead.
Hi, thanks for the question. I've got a couple on just the research thing. Rob Koremans, could you just give us an update on the regulatory path for the asset in Cushing's syndrome in the U.S.? Have you begun discussions with the FDA yet on that one? And then secondly, how are you tracking on your target of 500 patients on Isturisa therapy by 2023 in the U.S.?
We're on track, is the short answer, for the target that we set of achieving over 500 patients on Isturisa in the U.S. We think the sort of sales sort of guidance that we provided for next year or for 2022 should confirm that.
Nothing has changed in terms of the expectation in terms of engagement with the FDA in the early part of this year to discuss the pathway that we see for the potential expansion of the Cushing's label for Isturisa in the U.S. So nothing has changed there. We expect we're gonna pull together a dossier which sort of draws from previous studies and real world evidence that we're gonna be collecting and plan to engage with the FDA in the early part of this year.
Take it from there, right? Because it's difficult to comment on how the FDA will react. We think we have a good dossier, so.
Okay. Thank you.
The next question is from Niccolò Storer of Kepler. Please go ahead.
Yes, good afternoon, everybody. I was wondering if you could provide us with some more detail on your margin guidance for 2022 and maybe how all the moving parts contribute to it. You talked about inflation, so maybe if you can detail a bit on which kind of inflation, on which items are you talking about. You talked about launch phase of EUSA. That also I guess all your right sizing carried out in 2021 could bring about some benefits.
If you can make a kind of bridge between 2021 and 2022 and also give us an indication on whether this scenario you have projected for 2022 could some way be carried also in 2023, putting at risk your business plan target. Thank you.
Niccolò, as I said, we're not gonna sort of try and unpick too much the guidance because as you said, there's a lot of moving parts. To just give sort of some really high level sort of direction and trying to sort of keep it simple. You're asking sort of for a bridge between 2021 and 2022. You know, we're guiding to 1 percentage point lower in terms of margin target, which as we said, you know, comes from a combination of integrating the EUSA business which is running at a sort of lower margin level and inflation pressures.
You know, if I was to put sort of tentative numbers to it, I would say half a point of margin from gross profit and the impact that we'd expect inflation to have. Despite which sort of, you know, more than offsetting the benefit of mix, and half a percentage point on R&D on the back of the higher investment that the EUSA is incurring. Also the investment that we plan to do because, you know, as I said, there's some work that we want to do on Isturisa, as we prepare for sort of getting the full benefit of reimbursement in Europe.
If I mean that in terms of sort of particularly investing in medical and sort of small observational studies in Europe. I think that's to give you just a general direction. In terms of, does that sort of put pressures on 2023? Well, we're not sort of updating today any sort of 2023 numbers. You know, inflation kind of depends on you know how quickly that subsides. We'll see.
Again, I think we'll be in a better position to provide guidance both on top line potential and bottom line once we get our hands on EUSA and can more sort of fully articulate the plan for that.
But-
Sorry, and about
Sorry, just to add. What doesn't change is our commitment to good margins and affordable development, right? That is not new, and nothing has changed in that respect.
Thanks. Maybe a follow-up on that. On no mention of savings from right sizing of your sales force, because 175 people is quite a lot.
No, of course. We always also said that we would notice when I sort of talked about the margin progression, I talked about cost of goods and I talked about R&D because, and we did always say that we would progressively reinvest in the business as and when sort of market conditions improved. We've done a little bit of that in 2021. Of course, conditions did remain in market somewhat restricted for part of the year.
We'll do a bit more of that in 2022, which will be offset by the savings, which are generated by the right sizing that we talked about, where we expect, you know, the return to be quite short.
Cool. Thank you.
The next question is from Isacco Brambilla of Mediobanca. Please go ahead.
Hi. Good afternoon, everybody. Thanks for taking my question. I have just a quick one on Eligard. Can you elaborate a little bit more on the missing steps for having the product green-lighted and launched on the market and also on which is the potential in terms of contribution from the new device to the midterm prospects you unveil with this year business plan? Thanks.
Isacco, I'm not fully sure we fully understood the question. I think it was around sort of expectations from the new device. We've been filed. We expect, we hope to see the approval in the second half.
First quarter of this year. Just to be sure, Eligard is on the market, right? This product was taken over with a negative trend we've been able to reverse and stop the negative trend and in some countries grow. We believe the device will help to improve handling by patients and management of the therapy. Of course, it's gonna create a positive momentum in terms of plan. That was very much part of our initial plan when we acquired the products and so things are going as planned on track and we're happy with it.
The next question is from Giorgio Tavolini of Intermonte. Please go ahead.
Hi. Good evening. Thanks for taking my questions. I was wondering if you can elaborate more on the cough and cold expectations for this year, since we are seeing a faster recovery from a COVID pandemic and a progressive lifting of the restrictions. I was wondering if you are projecting a faster recovery on that front. The second one is on inflation. Do you have the pricing power to transfer part of the inflationary pressure to the final clients in terms of retail pricing? The third one is on the guidance for 2023. You didn't mention targets, and I was wondering if there is any adjustment to consider after the EUSA Pharma acquisition or not. Thank you.
Giorgio, thanks for your questions with me. Yeah, but I think probably on inflation, Luigi, you want to-
No. Well, I'd just reiterate what I said before. Do we have pricing power? Yes, we do. We do sort of regularly take those opportunities. It's not on the whole of the portfolio, and it's not in every country. It is limited, but that's how we are in part also able to contain the impact to, you know, I'd like to think a sort of relatively sort of low number when I say sort of around a sort of half a percentage point of margin. So
Cough and Cold, like Luigi already indicated during his presentation, that we've seen a return over the entire year of 2021. We're at almost 75% of pre-pandemic. Towards the end of last year, we were getting close to 85%, and we expect actually going into this year that we will be not completely on pre-pandemic level, but more or less around 90% of the pre-pandemic Cough and Cold market.
On your third question on sort of 2023 guidance, you know, do we update it post-EUSA? Well, no, we don't because, well, one, we're just not updating guidance for mid-term today. We'll do that later this year once we complete the acquisition. Don't forget that our 2023 targets already included a contribution from BD as they've always done. We're not gonna do that. The one thing, and I know that in sort of talking guidance that maybe we haven't touched on, just a big one thing to mention.
You know, obviously the guidance that we provide and as we have, sort of done, sort of consistently over the last couple of years, is for results, on an adjusted basis, both in terms of EBITDA and adjusted net income. Of course, with an acquisition, particularly one of the size of EUSA, there will be non-cash, IFRS 3 acquisition accounting adjustments that we'll have to factor in terms of additional amortization and, other charges, you know, particularly arising from the step up to the value of inventory, that we will acquire, from the acquisition. You know, we can't sort of determine those, until post-close. We'll have to go through the sort of full purchase price allocation exercise.
Just thought I'd mention that obviously as a reminder.
Thank you. Just a follow-up, if I may. Could you clarify what you are expecting a limited decline of the lercanidipine sales in the year due to the adverse impact of tenders in China? Is that something that was expected or how should we consider this element? Thank you.
It was not expected, but I'd consider it just to give a sort of round figure, sort of less than EUR 10 million. We mention it because it will show a little bit, particularly in the first part of the year. We had initial shipments in 2021, and I think we commented during the year, initial shipments to a new distributor out there. Lercanidipine, to be fair, a little bit surprisingly was included, albeit being a relatively small molecule in the country into the fifth round of sort of volume-based tenders in the country.
I think that will compress sort of in the short term revenues and therefore will result in our distributor probably not ordering very much over the course of 2022. We remain positive about the outlook for China. It's a big market. I think we see this more as a sort of you know a one-year effect rather than anything.
A very committed distributor.
Yeah.
That really works along with us really very constructively. We believe we should be able to overcome this, like Luigi said, beyond the short term.
Many thanks.
For any further questions, please press star and one on your telephone. Mr. Koremans, there are no more questions registered at this time.
Thank you. I'd like to thank you all for your participation. I look forward to interact with you soon. As Luigi indicated, we will be interacting as soon as we have the closure of the EUSA and the chance to really interact and digest that business. I think also in the same timeframe, we'll be giving a more long-term outlook as well as we've typically done. Thanks for the interaction and the questions, and have a very good day.
Ladies and gentlemen, thank you for joining. The conference is now over. You may disconnect your telephones. Thank you.