Laboratorios Farmaceuticos Rovi, S.A. (ROVI) Earnings Call Transcript & Summary

Capital Markets Day. Let me introduce myself, my name is Marta Campos, and I'm the Head of Investor Relations at Rovi. This morning, Mr. Juan Lopez-Belmonte, our Chairman and CEO, will be updating the key points of Rovi's strategy and provided an overview of the company's current status. Afterwards, Mr. Ibón Gutierro, our R&D Manager, will talk about the R&D strategy based on our ISM platform. And finally, Mr. Javier Lopez-Belmonte, our Deputy Chairman and CFO, will give you an update on Rovi's financial situation. At the end of the presentation, there will be a 30-minute question-and-answer session. Don't hesitate to send us your questions clicking on the bottom of your screen and people attending the presentation in person just have to raise their hand and someone will come up with a microphone. So you can ask directly. Thank you very much for being here today. And let's now start with the presentation. I give Mr. Juan Lopez-Belmonte the floor.

Thank you, Marta. Thank you, everybody, for being here today in this important Capital's Market Day for the company. My name is Juan Lopez. I'm the CEO of the company. And I'm going to try to give you an overview and update of the company's strategy for the next coming years. I mean, Rovi, as you all may know, it's a Spanish company with a current market cap of around EUR 2.5 billion who have been listed on the Madrid's Stock Exchange in December 2007, and since then, we have multiplied our market cap by slightly over 5x. We like to say that Rovi is a success story. We have delivered a consistent CAGR growth since we went public by 13% until reaching an expected growth in operating revenue close to 20% in 2020. On the slide, you can see a brief overview of our business divisions. We like to structure the company, emphasizing that we have 2 major pillars of growth, the specialty pharma business and the ISM technology platform. The specialty pharma business has 3 lines of business, a leading proprietary franchise heparin, a leading specialty business in Spain with one of the largest salesforces in the country. And thirdly, we have a very important high-added value contract manufacturing operation, specifically focused on low patented injectables in prefilled syringes and finally, we have ISM technology platform. The ISM technology platform is patent protected, a very versatile sustained release injectable platforms that allows to control the delivery of the product once the product is being administered into the patient. There, we have a very attractive and exciting portfolio starting with Okedi and monthly risperidone injection, it has just been approved in Europe and is being filed in the U.S. And hopefully, as a follow-up with Letrozole, which is on -- are sustained release aromatase inhibitor. What I'm going to try to share with you today is what we believe that Rovi has been trying -- as we've been working in the last 10 years to really transform. And that's in the pathway that we are very close to reaching right now. We have, on one end, today, a leading proprietary heparin franchise, as we have shared with you before. That is present today in more than 70 countries. We have 2 products. We have our own proprietary compound Bemiparin that is marketed over 60 countries right now. We're still in the rollout of the biosimilar enoxaparin. And on top of that, we are having today a very important European footprint in which we have established our own subsidiaries across the main countries in Europe. And hopefully, in the next -- as I share with you in the next slides, we're also building up right now on especially salesforce in schizophrenia in the major 7 countries in Europe. In addition, we have as we [indiscernible] of the company, we're one of the leading Spanish specialty pharma business. We have one of the largest salesforce with 250. We are very good at selling. We have shown. We have demonstrated, and we believe that, that part of the business is going to still show a predictable growth item in the next coming years. The CMO activity, the contract manufacturing operations has been really the flagship and the major item of news in the last 2 years because of the COVID-19. And thus, as we have seen in the video, we have 7 fully invested manufacturing operations. I will provide you more information in detail in the next coming minutes. But definitely, the contract manufacturing operation, especially with the COVID-19 front, it has been shown that it's going to be one of the major industry that is going to show a tremendous growth in the next coming years. And finally, we have the ISM technology platform, where we have key products that is already on the market. I think the real important thing regarding Okedi is that it has already been approved by the European -- by the EMEA. That as I have shared with investors many times in different presentations, that works in 2 ways. First, we have a product, which definitely is a fantastic product in a fantastic market. But more important than that, we have managed to validate with the regulatory authorities, the technology behind ISM. And therefore, we have tremendous and exciting products that it would be following up Okedi, hopefully, in the approval pathway of ISM. Before entering into the pure business details, I think it's important just to stop just a couple of minutes to show you this slide. I think this is something that all the company, all the staff of Rovi are very proud of with being audited for a couple of years for one of the worldwide leaders companies regarding ESG and corporate governance. This is sustained analytics. And we have just been recently given the rating for 2022, and we have come with 17.3 that means with a very low risk rating and actually has provided Rovi to be the #1 out of an overall universe of 458 companies within the segment of the pharmaceutical industry. Moreover, if we include in the industry group as well, the laboratories and Sanitary and equipment, we have been ranked as the #22 out of a universe of close to 1,000 companies. And the overall universe of companies being audited by Sustained analytics. I think we have a tremendous good ranking slightly over #2,300. And that, I believe it shows the commitment of the company and the commitment of the every single employee in the company to really not only work to develop the company, but to develop the company in the right way according to the ESG top standards. Well -- as I was going to share as well that we are part of the United Nations Global Compact. We have a strategy in place to reduce the greenhouse emissions and to improve the quality. We have -- we are -- as you've shown -- you've seen in the video, we are neutral in carbon emissions. 100% of all the [indiscernible] the company comes from renewable methods. And that's extremely important and very difficult to achieve when it comes to a company that today, Rovi is the major industrial pharma group in Spain with 7 facilities. So as well, obviously, those greenhouse gases that we cannot eliminate. We are obviously offsetting them with different programs and plans that we're implementing worldwide. So just getting into the business and before entering into detail specifically on the different divisions, I just want to again highlight what is going to be the strategy of the company for the next coming years. On one hand, as I mentioned before, we're extremely focused on specialty pharma products, proprietary compounds. We have evolved the company from a distribution model to a high-end, high-margin proprietary compounds. That means that we are going to have a very well-balanced European specialty pharma with a very important footprint in which we are having now 3 products being commercialized, Bemiparin, Becat, the biosimilar enoxaparin and Okedi. We believe that starting from the heparins, we are -- definitely, we're going to be one of the major players in the midterm in this market that I will give you further information in a couple of minutes. We still believe that we are the leading company to the specialty pharma in Spain. We have one of the largest salesforce, and we have exciting news to share in the next coming months. And as well in terms of the CMO, I think the Moderna agreement on our performance in the last 2 years is self-explanatory of the importance and as well and the competitive edge of the company within this segment. So if we enter now directly into the first pillar of growth, our low molecular weight heparin. Just give me your -- just let me provide you some numbers regarding the market. In terms of volume -- low molecular weight heparin is a global market of EUR 4 billion. Out of this EUR 4 billion, 82% is the European market and emerging markets. So that's basically the market in which Rovi is right now playing. And within this EUR 4 billion market, enoxaparin is by far the major product used worldwide, accounting for 63% of the sales. That means a EUR 2.6 billion opportunity. Bemiparin is also important to highlight that is the fifth molecule more widely used worldwide in the low molecular weight heparin franchise. And I think the COVID-19 as well has put the importance of these drugs in this right place. Low molecular weight heparins has been listed by the World Health Organization as one of the strategic and essential drugs for treatment of almost every disease. Regarding when it came to the COVID-19, the World Health Organization on most of the domestic regulatory agencies listed those drugs that they were essential for any kind of treatments for the population and low molecular weight heparins were within that list. So -- we are talking about a tremendous opportunity in the short term, but you are talking about a product with a tremendous life cycle management in terms of therapeutic importance. So in 10, 15 years' time, Low Molecular Weight Heparins will still be a tremendous market over EUR 4 billion. As you can see, the market is still growing in number of units. So it's delivering growth slightly 5.7% in the last couple of years. So we are seeing that this is really a good franchise and a good business to be. Regarding Bemiparin, as you know, that's our first compound that the company managed to discover and to develop, it's an in-house proprietary compound. And in terms of -- in Spain, really the performance has been tremendously good. We are the #1 market leader with sales in the first 9 months, slightly over EUR 50 million and a market share of 42%. And this we have managed to do it in the last couple of years, thanks basically to our sales capabilities, but as well because we have a wider therapeutic profile and a much more convenient administration dosage especially for the indication of DVT. Actually, Bemiparin is still the only second-generation low molecular weight heparin that provides 24 hours coverage with 1 single dose to all patients' profiles regardless of their risk level. And that's really a tremendous claim that has given us a chance to really position the product as a market leader in Spain and in other countries. We do not only market the product in Spain, as you all know, but we also market the product in another 60 countries worldwide. There, our strategy is slightly different than in Spain. We have always shared with investors that we are a company fully orientated to profitability, and we believe the model of licensing now deployed to third companies which are leading in the domestic markets when it comes to Bemiparin is really the right formula for success. Actually, our sales in -- let's say, international sales of Spain in the first 9 months of this year accounted for slightly over EUR 25 million. When it comes to enoxaparin, Becat and enoxaparin biosimilar, let me remind you the opportunity. It's really -- we were the first company, the first European company to get our registration in Europe. We believe that we have all the items to be one of the market leaders worldwide in the next coming years. This market, as I mentioned before, we are talking about EUR 2.6 billion. The European market is EUR 1.3 billion. We have the capabilities, industrial capabilities and the knowledge to really be able to make the most out of this opportunity. This is a very uncrowded market. Let me remind you that in Europe from a regulatory perspective, and this is something important to highlight biosimilar enoxaparin is a [ bilateral compound. ] It's a biosimilar. Well, in the U.S., it's a generic compound. That makes the regulatory hurdles to get approvals, extremely more difficult than in the U.S. market. And actually, that's the reason why it's still a very uncrowded market. Actually, the biosimilar enoxaparin probably is one of the very few markets, were taking into account that the first biosimilar in our case was launched in 2017. We -- there are only still another 3 players in the market. And actually, none of the big generic firms are still present in the biosimilar enoxaparin. I think that provides a good touch base of how difficult and how do we believe that this is going to be a very uncrowded market for the following in coming years. Regarding Rovi, we're extremely well positioned. Let me remind you that we've been marketing low molecular weight heparins for almost for the last 20 years. It's part of the DNA of the company. So we believe that we have a tremendous leverage in that sense compared to our competitors. Secondly, we have a vertical integration, as I will share with you. Now with the latest agreements, we hopefully in the next coming years will be completely 100% fully integrated, starting from the pig mucosa to the finished product. And finally -- and it is also very important to highlight, this is a product that has been developed from the scratch by the company. So we have tremendous knowledge from a regulatory point of view. And when it comes to biologicals and to manufacturing from an API to finished product to have this sort of in-house knowledge on how to dossier, how the regulatory documents validation has been constructed. It does make a difference when it comes to streamline the industrial processes and obviously, the final gross margin. So on -- just to give you an update, but I'm sure you are all very familiar with our performance in the last coming years. We launched the product in 2017. It was in Italy and Germany. And we have been ramping up the product since then. We have been launching most of the European countries. As I mentioned before, we have a good footprint that it was established for this purpose. The 7 countries where Rovi started operations with their own affiliates. That means Spain, Portugal, U.K., Germany, France, Italy and Poland accounts for 73% of the market in Europe. And that has allowed us that we have had a tremendous ramp-up in terms of sales. In 2017, we made a revenue line of only EUR 1.7 million. Last year, we made global sales slightly over EUR 120 million. In the first 9 months of this year, we have already achieved EUR 119 million in terms of sales. So therefore, we do have still an opportunity in Europe but we have still tremendous ground to keep on growing. Obviously, Europe, as we have always shared, it was our first stage of commercialization that's let put it this way, Europe is like our domestic market. We established our European footprint. But we have already -- we have spent a tremendous effort and amount of time in preparing what we call the second stage of commercialization. That means the rest of the world outside Europe. And we have signed agreements to commercialize the product in more than 80 countries. I think it's important to highlight probably one of those -- 2 of those agreements. One is with Sandoz that is covering 17 countries and regions and Hikma which is going another 14 countries, mostly focused on the Middle East and the North of Africa. And as you can see in the bottom of the slide, you can see what is our expectation in terms of the rolling out in the rest of the world market, which accounts for an opportunity of EUR 0.7 billion and growing fast at the high single digit. So you can see we have already started launching the product in countries like Brazil, Colombia, Bosnia but most of the launches are going to be from 2023 onwards. So definitely, we had a tremendous, and I believe, a very successful performance in the last 5 years. But I think the best is yet still to come. The market is there. We are one of the largest players. This is an industrial product. You need an industrial setting to maximize the opportunity, and we are talking about market opportunity globally of EUR 2.6 billion, in which Rovi definitely will want and that's our focus, our goal and that's where the organization is really driven, we don't want to be another player, but we really want to be one of the leading players in 5 to 6 years in this market. Just to give you some data of our performance because obviously, this year, sales are going to be extremely good. But I think that proves what I was mentioning to you about the key competitive advantage of the company within this setting. Our know-how in terms of marketing, our regulatory know-how and a vertical integration and you can see some data from some European countries. In Portugal, when it comes to -- this data accounts for the retail market, in Portugal, we have managed to get a market share of close to 14%. In Italy, which is mainly hospital market, specifically for this country, includes the hospital and retail market, we are close to 20% market share. Spain, 19% market share. And in Germany, close to -- slightly over 40%, 42% in terms of market share. So you can see, we have always shared that this all biosimilar markets by definition, most of the biosimilars in the long run tends to get between 50% to 70% market share of the market. And as you can see, markets like Germany, we are getting close to the figures I mentioned to you. Regarding Spain, with an enoxaparin, we have a market share of 19%. And don't forget that we have a market share of 32% with Bemiparin. The compound market share of enoxaparin and Bemiparin makes Rovi, a clear market leader in Spain with a market share of 52%. So really, the performance has been really good so far. We have to compete our competitors in the most profitable part of the market, which is the retail market. But definitely, there's still a lot of -- still of room to get instead of sales, and definitely, we believe this is going to be a very predictable item growth for the next coming years. This is just to visualize that I'm, again, what I mentioned before, enoxaparin today is in 26 countries. In [indiscernible] Bemiparin in both -- with both products in different countries by 12, globally in 71. Our goal really is in 5 years' time to be in more than 110 countries, either marketing Bemiparin and enoxaparin or both of them. And this is what I mentioned to you. And I think this slide really reflects the strategy that Rovi is working for the long term. We are not so much focused on what is going to happen in the next quarter, but rather we are -- we rather prefer to see as a management, the big picture and where we want to position the company in the next coming years. Our performance with the low molecular weight heparin, I believe has been extremely good, but we're investing heavily to fully integrate in the heparin value chain. As you can see -- and just coming back to the theory, the heparin costs from the pig mucosa. And today, we have a tremendous oil companies without no exception. We need to have a close relationship with China because China host the largest pig herd in the world. And as you can see, and I'm sure I cannot tell you anything that you do not regarding how politics are worldwide nowadays. We've been investing heavily to try to somehow offset that today, the importance that China has got in the supply chain of heparins. So for that purpose, we have signed an agreement with 2 other companies in Spain. We have created a company Glycopepton. These 2 other companies is Grupo Costa, which is the largest breeder of pigs in Spain and Cà rniques Celrà , which is the largest slaughterhouse of pigs in Spain. They kill -- they slaughter 18,000 pigs per day. And we have created a joint venture with the other 2 companies to provide Rovi the fact that we can be fully integrated in the supply chain of low molecular weight heparins. That means that hopefully, in 2025, 2026, we will be able at least 50% of our needs to be self-sufficient coming from this business opportunity that we have created with our partner. The total CapEx involved by the 2 companies will be around EUR 40 million. This manufacturing plant is going to be built in the region of [indiscernible] for very specific reasons because that's extremely close to slaughterhouses which does make a big difference when it comes regarding not losing activity in the new cost package. So again, that's -- I think that's really extremely important. That's something I really want to come across to you guys in the sense that we are really working on the long term. We really want to be a leading player. For that purpose, we thought it was critically necessary to be fully integrated. Don't forget as I would share with you in the next slides, this manufacturing plant that we are building with our 2 partners will allow us to process the mucosa to heparin crude, but we have already 1 facility to process the heparin including to sodium heparin. And as I will show you now in the next few slides, we are building now a second facility to process heparin include to sodium heparin. So Rovi really wants to be fully integrated completely. And that provides some extremely added values. As I was explaining before, we can -- that way would at least 50% of our supplies will come from in-house solutions. But as well, it will allow us to reduce the variability of the price of the sodium heparin. And definitely, which is really much more important in the long run, it will allow us to increase our gross margins, which is something that we are all looking forward to see in our accounts. So moving to the second driver, which is risperidone ISM, the ISM technology. Before getting into much more detail into the product, let me just remind you a few data regarding the schizophrenia market. We are talking about chronic -- unfortunately, a chronic and progressive pathology with an increasing prevalence. Unfortunately, we are talking about 21 million people worldwide that suffers this disease. And long-acting injectables are really becoming more and more important in the prior utilization of the doctors on the pros that they can use to treat the disease. At the end of the day, long-acting injectables, they provide some unique properties that clearly match some still unmet medical needs regarding the treatment of this pathology. On one end, adherence is really key to treat these patients. Unfortunately, after every single relapse, we see a neurological deterioration of the patient. So making sure that they take their drug, making sure that they are fully treated, it becomes mandatory to make sure that the quality of life and to avoid the progression of the pathology on the disease. As I will share with you later, long-acting injectables are really the drivers and the growth in terms of pharmacologicals regarding this pathology. In terms of market size, this is a tremendous opportunity. The market in the U.S., we are talking about a market globally over EUR 4 billion, growing at a rate of 20% in the period 2015, 2019, they grow at a rate of 20%, which is something incredible. Taking into account that the percentage of usage of long-acting injectables in the U.S. is still very poor. We are talking about 5.9%. But likewise, in Europe, the market opportunity, I mean, is huge. We are talking about EUR 1.3 billion in terms of market. Also, the market is still growing fast. We are talking about a high-single digit, 8.9% during the same period. And still the usage in Europe is a little bit more than in the U.S., but it is still very low. We are talking about 8.4% only of usage of long-acting injectables. So there, the opportunity is tremendous. If you see other markets similar to schizophrenia, like prostate cancer, you will see that the usage of long-acting injectables have over 80%, 90%. So there is here a tremendous opportunity. And this is still a very uncrowded market. This is a market with very few players. And that has got some unique properties that -- it makes it very attractive for companies like Rovi on one end, and I think, this is important to highlight. This is a very dynamic market. It's a chronic market, plays a very dynamic market. Patients unfortunately, it takes some time to find for doctors the right drug to treat their specific schizophrenia. And unfortunately, because of their day habits, usually they get very often unstable. So doctors, they have to change continuously their drug medication to make sure that the drug is really fulfilling [ it's effects ] in the right way. So this had tremendous dynamics in changing the medication to patients. Obviously, for a company entering into this market this is something very, very attractive. Secondly, as well, there is a very highly addressable psychiatrist which -- they are the only ones that take care of the schizophrenia pathology. And this is a very reduced number of doctors. So probably in Europe, we are talking to universe doctors between 3,600 and around slightly over 4,000 doctors. That again is a very extremely attractive segment for a company that's entering because it allows you to build specific schizophrenia specialist sales forces that it doesn't have to be tremendous in the number of medical [ reps ] that you have to put on the market. For instance, just to give you an idea in Spain, we are talking about -- we have built and -- a specialty sales force slightly below 40 people. In Germany, we are talking about numbers of around 36%. And this is not market data. This is real data, the way that we have designed our specialty sales forces size according to the number of psychiatrists and the number of calls that we are willing to detail and to visit. And thirdly, which is also very important, as I was mentioning before, long-acting injectables are really become the treatment of choice by psychiatrists. In the old days, they would have never used a long-acting injectable after the fourth relapse. Today, we are seeing that doctors are more and more using the patient in the initial phases of the disease and almost as compulsory after the second relapse of the patient. So I think that's a tremendous opportunity, has some tremendous features. And we believe that the opportunity is there. And we always like to show in the bottom, the right-hand side of the slide, the case of Alkermes, is a real case. It's a company that, to some extent, it could be similar to us. They enter from scratch, brand new on the specialty. And you can see the tremendous performance in terms of sales. And in 2022, they have given a guidance slightly over USD 200 million in terms of revenue line. So again, this a tremendous market. There are very few players and definitely Rovi, we believe we can have a tremendous performance. As I mentioned before, long-acting injectables are really becoming the gold standard when it comes to Europe in the major countries. As you can understand, we have -- obviously, we have the oral schizophrenia drugs, and we have the long-acting injectables. But really, the market -- the part of the market that is really growing is the long-acting injectables. The good thing, and this is obviously is by chance, the largest market in Europe is Spain, which accounts by 23% of the global European market. That's our domestic market as we're as a know-how. So definitely, we do expect a tremendous good performance. But it's also growing fast. It's growing by 7%. But you can see that the growth is -- of long-acting injectables across the top 5 countries is very attractive. You can see Germany is growing by 9%, which is the second market. France, which is the third market is growing by 6% and Italy is the fastest-growing market today with 16% and U.K. growing by 7%. And something that we like tried always to convey to investors is that our product Okedi is the only monthly injection of risperidone. And we decided to choose risperidone because risperidone is the second most widely prescribed oral antipsychotic. The first mostly prescribed antipsychotic drug orally is quetiapine to the best of our knowledge and the market has proven so far there is no way to make a long-acting injectable. And as you can see, risperidone is used by 175 -- well, it's sold 175 million packs in Europe and 117 million packs in the U.S. And that, obviously, it provides a tremendous market advantage because been the second mostly prescribed, that means that the doctor is [ just too many familiar ] with the safety profile and with the efficacy profile of risperidone. So again, quarters will tell, but we definitely -- we see that with Okedi, we're going to have a tremendous success in the market. Regarding Okedi, this is just to remind you, the main properties. When we decide to design Okedi and we decided to design the clinical trials, we really wanted to make sure that we did not only have a good platform with extremely good pharmacokinetics but we also had a good [ gain in this MDC ] that allow us to differentiate Okedi from the rest of the long-acting injectable antipsychotic drugs. And in that sense, the PRISMA-3 was designed in that perspective. And as you may already know, I mean it shows tremendous good results. We are the only long-acting injectable antipsychotics that reduce the [indiscernible] by the #8 day which does a tremendous result. And as well, we decided PRISMA-3 to be able to treat Okedi to unstable patients with -- to moderate to severe antipsychotic symptoms. And that means that we are the only long-acting injectable that we are allowed to treat unstable patients and that provides a tremendous advantage. That allows the company not to position the product only because of its pharmacokinetic profile because we believe the platform ISM provides some unique advantages compared to the other. But as well, we have a unique clinical profile that differentiate the product from the rest out there on the market. We are the only ones that we are approved in Europe to treat unstable patients in the hospital setting with moderate-to-severe symptoms of schizophrenia. And we believe that at the end of the day, we are marketing a medical drug and we are marketing to patients that unfortunately have a chronic and progressive disease. And to be able to market the product, we did kind of data, robust data that we believe it will give -- I mean we'll really put the ground to what we believe it will be a really successful in terms of sales once we are more into the -- marketing the product. So our launch in plant in Europe, it has been extremely successful so far. Obviously, we manage because of an expertise and know how as a company to customary fast into the endorsement process in several countries. So in Germany, we launched the product in April. In the U.K., we launched the product in July. In Spain, we launched the product in September. Portugal, we have already got the reimbursement and they go ahead and we will launch it beginning of the next year. Hopefully, in Q2 next year, we'll be launching the product in Italy. Hopefully, France, Austria, Austria, Poland in the rest of the European countries. I think we have shown already to the market that we do have the know-how to do this properly with Becat in the very recent years. And we do believe that, again, quarter-by-quarter, it would be a real pressure of updating you really the results in terms of sales data. Having said that and coming back to what I mentioned before in the previous slide, our goal today is to market the product to those unstable patients that are in the hospital setting. So obviously, we have to go to the formularies. We have to go to the hospital formulary approvals. So in the case of Germany, we are right now working in making the medical training to doctors regarding the properties of training sales, are still going slow because we're in the process of targeting these hospital psychiatrists, which are much more difficult to visit. But so far, the feedback that we have from the medical training sessions that we are having with doctors in Germany, the feedback is extremely positive. In the U.K., we are right now in the process of introducing the product in the [ trusts, the trusts in the U.K. ] is structured. National Health System are the ones that are just the structure above the hospitals. So now we are now into the process in getting the protein to the different formularies in the hospital setting in the U.K. In Spain, where as in a similar process, just getting the product into the hospital formularies. Obviously, Spain is a domestic market. And for instance, I can share with you that by October, that means last month, we were already in 67% of the formularies in the Spanish market. So the product is going to have a slow ramp-up because of the unique properties of the patients and how the treatment is structured across different countries. But definitely, we'll see -- we are extremely excited and we're very positive on the initial signals that we are receiving from the market already, not only for one market, but already from our different markets. And regarding outside Europe, you have in the bottom of the slide. Our plans to roll out the product in the most important countries worldwide where long-acting injectables, we believe it does have a role. I think it's important to highlight that long-acting injectables because of this price and because of the National Health System structurally it requires to administer these kind of drugs, it's not a product probably for every single country worldwide. So we have chosen the countries where we believe it can have, let's say, important sales in the next coming years. And those are in which we have already -- we're already filing or were prepared the filing, we are making deals to file the product. So you can see on the bottom of the slide, really what is going to be the rollout of the product for the next coming 5 years. When it comes to the specialty division in the Spanish market, really, this is a very predictable growth item within the company. We are really good at selling. I think we have shown it in the last 6, 7 years. We are really the partner of choice for most of the big pharma companies. I don't think you will be able to find a slide similar to this in other companies. And again, we expect in the next quarters to -- I mean to be sharing with the market different agreements. For instance, we also -- we just signed an agreement that is going to be implemented in the first quarter next year with MSD regarding co-marketing of their sitagliptin and sitagliptin-metamorphine product. So again, we are right now in the process of really making sure that we get those partnerships, those agreements that provides synergies and provides really gross margin added value to the company. We have also built a specialty schizophrenia sales force with 40 people. So again, this is something that, as you can see, we expect still every year to -- at least next year, to launch 2 new products, 1 the MSD product, but we have further agreements that have already been -- it's not signed, they are very close to be signed. And we are still -- we believe that we will be able to provide an update and as we have done in the last 10 years to be able to at least to have 2 new products launched per year in the Spanish market. Regarding the CMO activity, again, the only good thing about the COVID-19 probably is that it has put the CMO operations in the place that they've really reserved, has been like a work on the [ desert ] for many years for Rovi, trying to convey that SIM activities can be of high added value margin. We know that CMO as a definition, immediately, mentally, we're aligned to very low margins, big volumes. But at the end of the day, a business which it doesn't provide too much added value to the P&Ls of the companies. I think the COVID-19 has provided to the market, really the reality of how important the CMO operations, not only for a pandemic situation, but really what is for the future. I don't think, I won't be discovering you anything if I say that all the big pharma companies are really restructuring right now. They are divesting their mature markets. They are really orientating themselves to this new innovative or disruptive innovation compounds, which doesn't need such a big probably industrial setting, but they need CMOs like Rovi. In that sense, I think all the data that we have managed to get from the market. It shows that the CMO operations are going to grow on a steady 7% CAGR growth for the next coming years. And more specifically on injectables for a very specific reason. I think everybody will agree with me that probably 10 years ago, injectables was something out of fashion, getting a shot, getting sting by a needle. It was not something that was ideal for any patient. Today, I think everybody understands that probably injectables is the fastest and is the medical device that provides more adherence to treatments. Nobody forgets to get an injection if it requires to get an injection. People may forget to take a pill, but people will -- it does take very seriously when it comes to getting a shot at their Healthcare Centers. And on top of this, if you see the pipeline of most of the big pharma companies, they are today full of anti-TNF compounds, full of biological compounds, full of peptide compounds, DNA compounds, and they all use injectables devices. And when it comes with injectable devices, definitely, the king of the party are the prefilled syringes, is really 1 single dose. It avoids administration mistakes. It's friendly usage and as well for the rest of the world perspective, where they don't have a nursery setting like we do have in Spain or a nursery infrastructure, sorry, we have in most of the European countries, prefilled syringes really does make the difference in that sense. So that's where Rovi today, we are focusing ourselves as I will share you the next few slides, we really want to become -- actually, I do believe that we are one of the top players worldwide, but we really want to become in terms of capacity. One of the most important companies in this setting. So well, probably, this is a slide that you are more familiar than me taking into account of your financial background. But as you can see, CMO, I have been mentioning to you that they are going to deliver a growth -- CAGR growth of 7% in the next coming years. But as what you can see that most of the private equity financial investment has been really very active around the CMO activities in the last coming years. I mean companies like Recipharm, Cambrex, PCI, they are now part of -- or they are owned by private equities funds. And you can see big companies like Lonza, which they were very much focused on API that they are now changing their strategy and moving rather from an API manufacturing to fill and finish of manufacturing. So -- and I think in this sense, well, that's something had been in the newspaper, but I think it's important as well to highlight that Moderna has announced not us, but Moderna has announced an investment plan of EUR 500 million in Spain. And obviously, that's going to be channeled through our company. So again, I think we are -- at least the COVID-19 -- to put it this way, has provided the market a vision that contract-manufacturing operations, if you're in the right segment like Rovi on injectables, it can be a very trendy, I would say, even sexy and as well very profitable segment of business. So this is our footprint today. And I think this slide, it does really work well when it comes to making very visual all our industrial capabilities. On one end, we are going to have 2 crude heparin plants. I mean we're going to have 2 plants to transform crude to sodium heparin. I would say on the left-hand side, will be the joint venture that we treat. On one end, we're going to have 2 crude heparin plants, and we are going to have 2 plants to transform crude to selling heparin. I would say on the left-hand side, will be the joint venture that will treat [mucosa] to crude heparin. Two manufacturing plants from crude to sodium. Two manufacturing plants from 2 -- from sodium heparin to the final product, low molecular weight heparin. We are going -- we have 2 manufacturing plants for fill and finish. And we have a plant, which is the Alcala manufacturing plant that obviously will make a huge amount of other compounds, but as well as our packaging center of excellence, which show you now in the next slide, the number of units that we have bought and that we have built. And finally, we have 2 ISM plants, one for Risperidone and one for Letrozole. And believe me, having those 2 plants is also extremely important because one of the major risk is we carry longer injectables is to make sure that you have industrial capabilities because these are products, which are very difficult in terms -- when it comes to upgrading industrial settings. So this is going to be our capacity. In 2020, we had 4 sites with 5 aseptic filling lines and 11 packaging lines with an overall capacity of 200 million prefilled syringes and 20 million vials capacity. Today, we have 7 sites in place. So I don't think you will find that many companies that have done this kind of CapEx during the pandemic. We have built 2 manufacturing plants during the lockdown. We have today 8 aseptic filling lines, 14 packaging lines and we have upgraded our capacity to 215 million prefilled syringes, and 80 million vials capacity, but in 2024 and probably even before that, we are going to have 10 sites. We are already building. We are already making a second building in the San Sebastián de los Reyes facility. We're making another complete building in Alcala. We're going to have 11 aseptic filling lines. So that means moving from 5 to 11 in a time span of 4 years. 19 packaging lines, and we'll be having a capacity between 450 million and 500 million pre-filled syringes and 120 million units of vials. Again, that 450 million and 500 million is because it depends on the volume. If you do 0.5 mL pre-fill syringes you have 500 million capacities. If it comes to 1 mL standard, 2.25 different volumes. Obviously, your capacity lowers a little bit. But I think that's extremely important to make sure that we do feel that CMO is going to be one of the major drivers of the company. So at least what I have been trying to show you from the very beginning of my presentation, is that we've been growing very fast in the last years, but we still believe that Rovi has got a tremendous growth item for the next years to come. We have Bemiparin, it is still growing. I hope we have everybody has completely erased from their minds the idea of cannibalization between Enoxaparin and Bemiparin. Bemiparin is still growing and it's growing fast. Enoxaparin biosimilar is extremely growing, and we have a lot of ground still to grow. We have Okedi that has just been launched. We have Okedi in the U.S.A. that hopefully we'll get the approval next year. And we have the CMO activities that as you can see, I mean, we don't increase the capacity just for the sake of showing the slide because we do believe that we can fill this capacity, because we do have the capabilities, the knowledge, the people, and Moderna has put us and has shown to the market, something that we knew already and we have been -- and we were in many discussions -- but again, this is a very fancy market, and you can make a lot of money when it comes to CMO activities if you are in the right segment like Rovi's. This 500 million capacity in preferred changes, we are probably in the top 3 worldwide. We don't have data, so we cannot make that claim specifically. But definitely, we are in the global market of Enoxaparin biosimilar. In terms of number of units of shots of Enoxaparin, we are talking about 711 million units per year. So again, I believe this is, again, is another tremendous growth item that I think that we can capitalize in the next coming years. And regarding the COVID-19 because obviously, there is some obvious questions. I have to say a particular in economics, I'm not doctor. But I can at least share with you what people tell us. We do believe that, obviously, the COVID-19, it has come to an end when it comes to a pandemic situation, hopefully. And I think that's something that the whole society worldwide will have to be proud of. But now we're moving into an endemic situation, similar to the flu. I mean, we are now getting familiar, I think everybody now is an expert in strains, a number of strains, everybody reads about what's the next name of the strain coming from Singapore now that is called the nightmare. I mean, we're going to see strains like in the flu coming every quarter. So we do believe that the COVID-19 market in this endemic phase that we are living today, is going to be in the midterm, very similar to the flu vaccine. And as well, something that again, is not something that we can today guarantee, but that's what we believe is going to evolve the COVID-19 market. When you're in a pandemic situation, you need multi-dosing vials because you need to have to get as many doses as possible to the market. A week, if you -- that was something that we discussed in the company, we could win a week in the pandemic situation that meant saving a lot of lives. When it comes to endemic situation, you have to make the product friendly to the patient to make sure that the vaccination rates are still appropriate because people still die from COVID-19 like for flu. So now what we do believe is that we're going to see a transformation and we're going to see that the COVID-19 that today is mostly marketed or fill in multi-dose vials of 10 or 5 doses, we're going to see that transformation into single doses, into one dose per vial or on a pre-filled syringe. And that's where Rovi, we have invested heavily in the last 2 years to really position ourselves with enough capacity to be able as well to get into that market. So we could make 200 million doses in vials of 10 vials, but we have prepared our company to be able to make whatever doses are required on the market, but on a single dose vial. We don't know how the market definitely will evolve. But at least from a market intelligence and our experience from similar products, we do believe there is still a tremendous opportunity for CMO. We don't invoice a product. We only do the fill and finish. We market -- we fill and finish by container. So again, that's something that we will be updating on a quarterly basis. Obviously, the COVID-19 will become as well a seasonal product like it's the flu, but again, we've done our homework and as well I have to thank Moderna because they have supported us incredibly from the beginning to make sure that we have on a seasonal basis, the required capacity to be able to move from multi-dose containers or vials to single-dose devices. I'm just -- to give you very quickly on 2 slides, just to give you, I mean, an update of our Moderna agreements because, obviously, for Rovi, Moderna has been a major milestone in our company's history. We did agreement in 2021, not that far away, and we invested in 3 lines. The third line, the DARA 3 will come to operations by the end of the year. So we're still even implementing the first agreement that we signed with Moderna. And on top of that, and I have to say that Moderna has a tremendous commitment with the country, with Spain. We came to an agreement to install an API new line in Granada, which in terms of capacity, just to give you an idea, when it comes to the booster, we are talking about the capacity of 250 million per year. So again, we do not only have the fill and finish capabilities, but as well, Moderna has some trusted Rovi and Spain as a country to install what is their major API facility outside the United States and Switzerland. And again, I think the relationship is working, obviously, the COVID-19 has been a very demanding market. Any market that you have to update your product on a quarterly basis regarding the strain, and you never know how fast strains can evolve, it's always a very stressful and challenging business. But I think the fact that we signed an agreement -- a 10-year agreement, we never sign that. It's the first -- such a long-term agreement that we, as a company, we have ever managed to sign. I think that it proves as a touch base to put health of the relationship between Rovi and Moderna. And definitely, from this agreement, we want to build the second phase of COVID-19 business that I have shared with you, we kind of moving from multi-dose to one single dose. And I think that's everything from me, and thank you for your patience and for listening to me. And I will leave Ibon to give you an update on the research and development.

Thank you, Juan. Good morning, everyone. Let me start with a brief description of our ISM technology. So this is a very innovative and flexible technology platform that involves intramuscular injections of already constituted intramuscular suspensions that is delivered in 2 separate syringes. One syringe is contained in the polymer and the API for the injection and the second is contained in the solvent for the reconstitution of the formulation. Our lead candidate for the ISM technology is our monthly Risperidone formulation, which is Okedi that is already registered in Europe and Risvan in the United States that is undergoing the regulatory process for approval. We have also a second candidate, which is our quarterly Risperidone formulation that we are expecting to start clinical trials in the second quarter of the next year. And we have also a long-acting formulation of Letrozole that we think will be a significant breakthrough in the treatment of hormone-dependent breast cancer. That is also expected to start clinical trials on the next year. Our differentiated technology has 5 major advantages that could be found on this slide. First one is predictability. We have this tried many times that we have a formulation, a technology that is very accurate on delivering specific concentrations of drug in the plasma, and we have a lot of population PK and PD model that have been, by the way, validated by our first successful development that is Okedi. That gives us a lot of predictability in terms of how the plasma concentrations evolve and which is the corresponding pharmacodynamic effect or pharmacological effect once the Phase I clinical trial is successfully completed. The second major advantage of this formulation is improved testability because we have a formulation that is stable at room temperature. And in particular, Okedi is stable for 3 years at room temperature. Third one is flexibility. We are capable of adapting the formulation and the release profile to the required medical need. And we'll have the example -- for example, of Okedi that is a monthly injection for the treatment of schizophrenia. We have a quarterly formulation of Risperidone also for the treatment of schizophrenia. I will have a Letrozole formulation that is going to be administered once a year. So a very wide flexibility. The fourth one is the improved clinical management. And this is in particular important for 2 important things. First one is that we are very fast on delivering plasma levels to the central compartment of the drug. As soon as the product is injected, plasma levels rise very fast to the therapeutic window. And secondly, because there is very little accumulation from an injection to the other. And this makes the clinical effect very predictive because there is no accumulation, no evolution of the plasma concentrations along the following injections in the body. So the range of concentrations that is achieved in the first injection is representative of the range of concentrations that are going to be obtained on the following injections. And the fifth one, of course, is the vertical integration as Juan has already commented, we are the owners of our own IP. We have all the know-how on the industrial process, which is very complicated for a product like us. Beyond these 5 advantages, we have 2 additional factors that underpin our confidence in developing newly developed products based on this ISM technology. The first one is that this is a long-acting formulation containing very well-known and frequently a standard of care products. So this gives us access to very fast regulatory pathways, like the 545(b)(2) procedural pathway in the United States for the FDA and the hybrid applications in Europe, which gives us access to expedite clinical trials with a smaller and faster lead times. And secondly, because we have already all the manufacturing in place. Juan has already commented we have 2 manufacturing plants that are given support for the commercial launch of Okedi and for the clinical development of a newly developed candidates. So we have all what we need to continue the development of this product. Now let me give an update on the dossier of Risperidone in the FDA. So as we communicated into the Capital Markets Day in November 2020, we submitted a new dossier for approval for our monthly Risperidone formulation. And the FDA and the acknowledge of receipt communicated that there was going to be a delay in the review process due to pandemic, of course. And in that letter, also mentioned that there were going to be a number of inspections including our own production plant in Madrid, but also to our production plants of suppliers and some clinical settings where the clinical trials were conducted. In September 2021, we received complete response letter with some outstanding questions. And also with the notification that the inspection of course, to Rovi was still pending and the inspection to one of the suppliers was also pending. We provided responses to outstanding questions in January 2022, and the new goal date was established in July 2022. During this period and in particular, 15 days before receiving the complete response letter, so at the end of June, Rovi had the inspection of our own facility in Madrid. And the inspector made some comments that needs to be addressed before the approval of the orders yet. Rovi is currently working on the data to be provided to the inspector for the closure of this observation. And what we are doing now is that the [Indiscernible] plan has already been submitted. And we are providing monthly updates on this. So we have not received objection to that up to date. On the third quarter of this year, Rovi received a second complete response letter which is basically a follow-up questions on the previously addressed questions. No new questions on the dossier review as it is normal in this part of the process because we expect usually cannot make new questions to the dossier. There were also questions to be addressed by a supplier, which is a very experienced supplier with a lot of products in the FDA market. And we also received the notification that the inspection that is pending to a second supplier was still pending. We are providing -- we are expecting to provide the responses to the outstanding questions in January 2023. And therefore, we are expecting to have the new legal date by the end of July 2023. So we are pursuing the same indication as other long-acting products for the schizophrenia market, which is treatment of schizophrenia in adult patients. So which are the next steps in regard to the pending issues. In regard to the questions to be addressed by Rovi, the first important thing that I would like to explain is that Rovi feels in a position to provide adequate responses to the outstanding questions. And none of them has been identified up to now as a potential risk for approval. Most of the responses are very prepared for the data have been generated to provide them. And there is a single one for which Rovi is gathering new data, but preliminary data is suggesting that the -- and response will be successful. So we feel positive and with a high probability of success on the response that is that is pending. Of course, as I have just mentioned, we are expecting to submit the responses in January. So the data will be ready in December of this year, and the response will be submitted in January. This is in parallel with the questions to be provided by a second supplier. The supplier that I have just mentioned is a very experienced supplier, received questions that are not related to our process, but for general processes of the company in which it is manufactured also a number of products that are currently supplying the FDA and the company is continuing to do the supply. So the FDA has not interrupted the supply of the product. And the company also has communicated us that is going to be sending the responses by January 2023. So in parallel with our responses, [Indiscernible] date, as I have previously mentioned, is set or is expected, better to say, by the end of July 2023. And last, there is a company that is awaiting the inspection from the FDA. This inspection is motivated by some deficiencies that the FDA found that are not also related to our product, not even to our process. But -- and the company that also supplies several products to the U.S. market is also authorized to continue the supply of the product. The real issue here is that by regulatory process, the company needs to have it closed before the approval of this share can be done. So no approvals are allowed with pending issues on an inspection. They don't have yet any date for the inspection. So we await and we are optimistic because the FDA, obviously, with the delay of the pandemic has started back with the pending inspections, but the company has not received yet any date for the inspection. Moving to the next slide. Well, we are developing a long-acting formulation of a quarterly formulation of Risperidone. So it is a very well-known product for us. The regulatory pathway will be the 505(b)(2) in the U.S., so very similar to Okedi and the added application in Europe and the reference product will be oral Risperidone, exactly like the same like in Okedi. The design of the clinical trial is shown in this slide. And you can see that up to 3 formulations are going to be tested in schizophrenic patients with a stable medical condition. And after this initial phase or final selection of the formulation, population PK models and PD models will be updated in order to provide accurate predictions on the dose that will establish the bridge between the corresponding doses of 75 and 100 milligrams of Okedi. And the high dose will be tested also in gluteus and deltoid. This clinical trial is expected to initiate in the second quarter of 2023. The good thing of this development is that all the modeling population PK and PD modeling is in place and it's the same for Okedi. So of course, this is a long-acting formulation. And of course, this is a long at formulation of Risperidone. So all the predictive tools that we have managed to develop for Okedi are still value for this product. And this gives us a lot of visibility on the successful development of the product once the Phase I has been completed. Just to give a brief update on the lateral development and for those who are not familiar, we are developing a long-acting formulation of Letrozole which we think will be a significant breakthrough in the treatment of hormone receptor breast cancer. These aromatic inhibitors Letrozole, Anastrozole, have a pharmacological effect and is the only one pharmacological effect that in particular, Letrozole has, which is the Aromatase inhibition that is a sign that is transforming [Indiscernible] into female hormones, Estradiol and Estrone. This hormones and in particular, Estradiol are [Indiscernible] for the growth of the tumors on hormone-dependent breast cancers, which represent 65% of our breast cancers in the world. Now Letrozole and Anastrozole, these aromatase inhibitors are given by daily oral formulations and the need of a continuous hormone suppression and the lack of compliance that is huge in this population makes Letrozole an ideal target for our ISM formulation. We don't have analogs in this field, but we have an analog in the prostate cancer in which we need to suppress masculine hormones, which is up [Indiscernible] and the market is very big. Patient tolerance in these fields are real clinical need. There is a very recent publication by the publication of Ingle in 2020 that describes that only 6 months after initiation of the treatment with aromatase inhibitors, 51% of the patients is not in suppression on Estradiol. 51% is a very big percentage. And the article also demonstrates that the lack of inhibition on Estradiol correlates to a very high -- very big increase on the probability of having a relapse in the disease. So hormone-dependent tumors rely on the inhibition of female hormones. That is for sure. And in the next slides, I will show the superb results that we have obtained with our Letrozole formulation in the LISA-1 study. You can see in this slide, LISA-1 study, by the way was a single ascending dose that was conducted in healthy post-menopausal women. On day 1, patients start receiving oral doses of Femara for 14 days or after -- until a steady-state. And after the last injection, 24-hour PK profile was obtained. You can see the PK profile that is corresponding to the steady-state of Femara on the left side of the slide. After a washout period, a single injection of 50 to 100 milligrams of Letrozole ISM was given to the same volunteers and the PK profile was followed by more than one year. You can see in the right-hand side of the slide, the plasma concentrations of Letrozole that were obtained. The first conclusion of this study is that Letrozole ISM is capable of providing sustained and continuous release of Letrozole for more than one year that is clinically relevant as is shown in the next slide. This slide is representing the percentages of patients that are in suppression on Estradiol, which is the main hormone, is the hormone that is interacting directly with the breast cancer tissue and represents the percentages of patients on a steady-state at perfect tolerance, so 100% tolerance from the oral formulation from our LISA-1 study that are in suppression. And on the right-hand side of the slide, you see the same graph for a total of one year of the percentages of patients that are in suppression with those a single dose of 100 milligrams of Letrozole ISM. Our first important conclusion on this study is that a single dose of Letrozole ISM is capable of providing estrogen suppression, sustained estrogen suppression for more than 1 year, that is in the range or many times even superior to the oral formulation even at 100% adherence. These results have been used to give support to the development of population PK and PD model for the conduction of the adequate dose response studies in order to find the appropriate dose and the appropriate dose in the skin to continue to the efficacy clinical trials. And this gives us to the second conclusion, which is a major conclusion of this study, an initial dose of 100-milligram of Letrozole, followed by a second dose of 100 milligrams of Letrozole, 8 weeks after the initial one, followed by yearly injections of 100-milligram of Letrozole maintenance, one injection of Letrozole every year gives a statistically superior estrogen suppression compared to Femara at 100% compliance. You can see this on this slide, in which on the left side, you see the percentages of patients that is in suppression on treatment with Femara at perfect adherence, so a patient that is not forgetting a single dose, not even missing a single hour over the whole period of treatment in a steady-state. And on the right-hand side of the slide, you see the percentages of patients that is predicted to be in estrogen suppression, Estradiol in particular suppression for the totality of the whole year. This shows that the percentages of patients that is in estrogen suppression with our product is 4x lower, so patients that are not suppressed are 2% in our Letrozole formulation percentages that are not matched with the oral administration in which the probability of being not in suppression after perfect elements with Letrozole is 8%. Let me remind at this point that the fourfold reduction in the probability of not being in suppression is a fourfold reduction in the probability of not being in high risk of developing the cancer and progression of the disease. And it is important also to remind the evidence in real world that is demonstrated by the article of Ingle et al in which only 6 months after the initiation of the treatment with aromatase inhibitors 51 of the patients are not in suppression with Femara and this is easily to -- can be easily comparable to our predicted 2% in our Letrozole. So the difference is big, and we are talking in terms of clinical superiority. This is another way to see the difference that is expected to be between our Letrozole formulation and oral Femara at perfect adherence. This represents the percentage of the patients that achieve and maintain with no introductions, Estradiol and Estrone, both hormones suppressed in parallel for the totality of the period evaluated. And you can see that at the proposed range and dosing for the Letrozole ISM administration, we are talking about superiority versus Femara. This is superior at any time point, but the probability of in superior increases with increasing times. Moving on the next slide. Let me briefly review the conclusions of this study. So a single dose of 100-milligram of Letrozole ISM is capable of providing deep and sustained suppression of hormones, female hormones for more than 1 year. And at the proposed posology, this suppression is superior to Femara in terms of perfect tolerance. The pharmacological effect of Letrozole is inhibition of aromatase. And this is the only pharmacological effect that the Letrozole has. So a superior inhibition on aromatase has to be linked in the efficacy clinical trials to a superior outcome in clinical endpoints as we pretend to demonstrate in our clinical development program. The first injection is given at day 0, the second injection is give 8 weeks later. This represents 2 injections in the first year and a single yearly injection on maintenance, which is a far more convenient treatment compared to the daily oral formulations that have to be given a perfect tolerance on this field. And of course, the amount of Letrozole that we need to provide a superior effect is significantly lower. So in the first year is 4.5x lower, on the second year onwards, is 9x less. So this gives us a lot of optionality on the expected outcomes on tolerability, adverse event rates and effective increase in duration of the treatment due to pure tolerability of the product. We have already conducted 2 meetings with the FDA in order to be [Indiscernible] selection that has been acknowledged by the FDA. So the FDA has reviewed the proposed posology and the rationale for the dosing has accepted that is justified to progress with these 2 efficacy clinical trials. We are also disclosing the clinical end points and the design of the clinical trial, the whole package for the clinical trial program. But the FDA has anticipated us that we are requested to conduct a Phase II efficacy clinical trial in post-menopausal female patients with advanced breast cancer. We are now in the discussion on the design of this clinical trial, but it is expected to start in the second half of 2023. This clinical trial will be supportive to design or to elaborate the treatment effect that is required to define the protocol for the Phase III efficacy clinical trial that will be conducted in the main indication, which is early breast cancer. So we are expecting to continue the discussions with the FDA in the following months. And due to the invention of the project, Rovi is considering to include a partner on the project. So we will provide further updates on the discussion with the FDA along our discussions with FDA. The expected design for this clinical trial will be a multicenter study in 2 parallel groups, comparing efficacy and safety of Letrozole ISM versus Femara as it is in advanced breast cancer, both in combination with cyclin kinase inhibitors, which is the standard care of treatment now for this population, on female post-menopausal women with hormone receptor positive, HER2-negative locally advanced or metastatic breast cancer. This 2 groups will be followed by a totality of 11 and 12 weeks and the primary -- the expected primary efficacy endpoint is progression free survivor. This is a very representative indication for the final design of the Phase III clinical trial program. So in terms of the market, we are talking about medication that is given 1.1 billion units per day -- per year. So this can easily be transforming 2.9 million to 3 million treatments per year. We don't know which is the price of Letrozole formulation that is going to be, but the market is huge. And in terms of opportunity, we also consider that it is huge. We have an analog, which is the prostate cancer, of course. And then you can see our presentation on the right-hand side of the slide, for which there are 5 products in the market. And as Juan has recently mentioned, up to 90% of all the treatments are represented by a long acting, so we are expecting a very high switch and a very high substitution once the product is finally achieved. And let me now give the floor to our Deputy Chairman and CFO, Mr. Javier Lopez-Belmonte.

Well, good morning, everybody. Thanks, Ibon. We're running a bit late. So I'm going to make this quick, don't worry. So we would like to explain or to talk to you about our robust financial policy that we have followed -- we have for the last years. You have in the slide that we have a tremendous growth, the last 4 years in terms of revenue line with a growth over 29% CAGR growth rate that help us to increase the profitability of the company with an adjusted EBITDA over EUR 220 million without R&D clearly. And as we've been showing to you good cash conversion north of 80%. All these investments related to the ISM platform has meant that the company has invested around close to EUR 30 million in the last 4 years. And on the right-hand side, you see that with the impact of the R&D expenditure, we've been able even to deliver a great operational leverage with EBITDA margins above a 30% figure last year. CapEx was historically around EUR 20 million figure. Last couple of years, as Juan explained thanks to our expansion of the facilities. We have been devoting around EUR 40 million and around EUR 12 million to EUR 14 million of that are related to maintenance CapEx. So the year so far has been extraordinary. I think everybody will agree with us that this has been a historical year for Rovi, 24th growth in the top line and all business of the company performing really well. The CMO growing by 49%, but also the specialty pharma business increasing by 9% the revenue line. Our heparin franchise business grew by 11%, and that represents the sale of the sales at that moment of the year, the heparin franchise was around 35% of the total sales of the company. And Enoxaparin was leading that growth with a growth over 33% and Bemiparin, as we have explained many times, this year has a small drop of sales, due especially to increase of use for COVID in the previous year and some extraordinary drop of exports that we are suffering during the year. Again, this incredible increase in sales boost our profitability. As I said before, we have a 25% increase in the EBITDA number, 30.2% margin and our net profit growing likewise, around 23% with a great profitability margin. Also gross margin grew from 57.6% to 59.9%. And that's thanks to a contribution of the contract manufacturing business. But as you know, it's accretive to the company. And we could offset the increase on the high cost of the -- cost of goods of the raw material, of the material of the API of the low molecular weight heparin business. SG&A expenditure also increased in an important way. That's mainly due to the increase of the operations, the manufacturing operations also because we launched Okedi in some countries already, like Germany, U.K. and Spain and also because we are suffering, I guess, it's the same as the rest of the companies, a tremendous increase of the energy cost. Somehow we were able to maintain or to even reduce the R&D expenditure this year, around 15%. And that makes this incredible profitability for the year, as I said. In terms of cash flow, it's been a fantastic year again. Cash flow from operating activities increased by EUR 170 million. The main reasons you know the increase of EUR 33.6 million in profits, the booking of EUR 55.3 million under the proceeds from CMO services and basically the increase of EUR 2.6 million in the trade and other receivables item line that is very well under control. As you know, we have around EUR 73 million of total debt, which that means that we hold net cash position of EUR 25.9 million. And that means that we've been able to finance all these tremendous growth with our own internal resources. And now we have a very comfortable cash position now that the macroeconomic cycle is changing. This year, I think this is something that we would like to highlight is that we've been very focused on increasing the remuneration to our shareholders. We -- as you know, we've been able to proceed with 2 different rounds of buyback programs. On total, we have been able to buy -- to purchase over 2 million shares, those shares has already been delisted and amortized, and we've been able to increase the dividend payment also to a figure of EUR 0.9556 per share, which represents an increase 151%, sorry, compared to the last year, and that represents a 35% payout ratio. On total, we have spent EUR 186 million already this year to remunerate our shareholders. And everything has been done with internal resources. And again, maintaining positive cash position. Well, next year, as you know, we have already forecasted our guidance for the year. This year, we consider the year very difficult to forecast, by the way. We have said with all of you a low double-digit negative growth versus the end of this year's sales, 2022, but a positive growth compared -- positive growth between 5% to 10% compared to 2021. As Juan was clearly explaining during his presentation, we believe that next year is going to be the first year of this new phase of the COVID-19 disease, which makes it much more difficult to predict the change of the -- well on the forecast of the manufacturing business for us. And as you know, and as we've been trying to explain to you, we are investing heavily and expanding our operations and those operations will not be fully implemented until 2024. So we do believe that this 2023 could be an interim year. And according to all the information that we have, this guidance could be considered a conservative scenario, again, with the current information that we have right now. And what we have to expect for the next coming months, I think we're trying to tell you that in terms of the Specialty Pharma division, we expect to keep announcing new countries where we are going to announce the launch of our biosimilar Enoxaparin. Again, we have already shared with you today that we are going to launch additional programs for 2023 as this agreement with Merck for these new products. And probably, as Juan has mentioned, we could announce more products coming to us in the next coming months. We will also be expecting to keep you a posted with the different launches of Okedi and that's very relevant to us in the different European markets. Also, we will, for sure, update on the evolution, as Ibon was explained to us today for Risperidone ISM in -- the approval of Risperidone ISM in the U.S. for this one. And we will update with news with these talks with the FDA and this efficacy clinical trial of Letrozole ISM. For sure, and everybody will be waiting news for our agreement with Moderna for next year. Our outlook for the vaccines and the rest of the portfolio of our CMO business that we will expect to manufacture next year. Well, thanks for being with us today. We are about to end the presentation, and now I can turn the floor to Marta, and we can finally start the Q&A session.

I'm going to give priority to people who have attended the Capital Markets Day in person. And I'm going also to insert questions from our online audience. Don't hesitate to send your questions by clicking on the bottom of your screen. I'm going to start with an online question in order to give the person with the microphone time to reach the first in person participant. So the first question comes from [indiscernible]. Ibon, Juan. A few weeks ago, Teva announced that it had once again applied to the FDA for approval of its non-acting injectable for schizophrenia and that it is expected to be approved in the first half of 2023. Thus, this possibility of both launches considering in time, change your view of Risvan's potential in the U.S. market.

I will let Ibon answer more the technical part regarding this cutaneous modular injection of Teva. Regarding the marketing perspective, although it may sound [Indiscernible], I think is something positive. I mentioned before that really the longer change to our penetration in the U.S. is still very low. We're talking about 5.8%. So I think something that works in pharmaceutical business like you know their businesses is really the concept of awareness. At the end of the day, I think it's important that this penetration of a skin injectables, it does increase significantly. I think Teva is an important company that it will bring even more light into the use of Risperidone. The 2 products are different, and Ibon can further explain why we do believe that our product is superior compared to Teva. And as well, we are taking for granted that the product is going to be approved in the time line that has been communicated by Teva. But even it takes also, we don't see it really as a threat, we see it more as an opportunity in terms of bringing more awareness to long-acting injectables and more specifically providing more awareness into the use of long-acting injectable Risperidone.

Well, in regard to the product of Teva, of course, one would expect that is focused on maintenance to be very efficacious in preventing relapses. And the rate of Teva has not been published yet. So the pharma publication of the efficacy clinical trial, for whatever reason is not public, but you can go on a couple of major course that have been published in the Congress. And if you go to the data, you can see that the 1 year after the treatments of Teva-included patients on a stable condition of schizophrenia, and it was a study of relapse prevention versus placebo. One would expect a very efficacious relapse prevention in terms of a product that is focused on maintenance, as I have said. But if you go to the data after 1 year, the proportion of patients that were not having a relapse was 85% for the monthly formulation and the proportions of patients that we're not having a relapse was 77% on the bi-monthly formulation. So if you translate on percentages of patients that have suffered a relapse that is 15% a monthly formulation and a 22% to 23% for the bi-monthly formulation. So 1 out of 4 on the bi-monthly formulation have a relapse on the following year. We have a superb efficacy study that is focused on what we understand is the real market need with these -- in patients with unstable condition with moderate to severe, but we have also an open-label extension of that study. And if you go to the open-label study, and I'm sure I'm not missing the data, we have a 10% relapse on the following 12 months. So our data look better compared to the Teva even if the product is not focused on maintenance treatment of patients in a stable condition. Why is this? Well, as Juan has mentioned, we will consider that the subcutaneous tissue is not the better target for the long-acting injections. The subcutaneous tissue has very low water content or fluid content for the release. So greater variability is expected in conditions of water restriction for drug release. And secondly, because -- and this is extremely important for the subcutaneous tissue. The tissue has a far more variability or range of variability in terms of temperature. So the tissue -- subcutaneous tissue becomes colder and hotter depending on the condition of the patient and also on external conditions, exercise, et cetera. And we know, from our own development, how big the changes are even in the small changes on body temperatures. So this leads to variability. And if you go to the population PK model, that is the article that Teva has already published, you will notice that -- and in particular, for the bi-monthly formulation, that the concentrations on a steady state tends to go lower than the concentrations on the steady state for the corresponding doses of the oral Risperidone. Meanwhile, we have demonstrated in our more recent study that our concentrations are equivalent to the oral formulation. And in particular, we are above the range of the minimum plasma concentrations for the Risperidone ISM treatment, Okedi or Risvan the United States compared oral Risperidone. Meanwhile, Teva product goes, and in particular, with the bi-monthly formulation, several weeks lower. And this -- based on this PK risen because at the end, this is a long-acting that relates to PK profile because the API is well known. So predictability, what we always mention of our formulation that is the strength of our technology is behind every result on efficacy. And of course, we will monitor, very carefully, the data from the Teva clinical trial, but the preliminary results do not seem comparable to what we have with Okedi.

Please Guilherme.

Guilherme Macedo Sampaio from CaixaBank BPI. So 2 on Risperidone ISM and 1 on Moderna agreement, if possible. So on Risperidone ISM, you already commented that the drug progression was going to be slow in terms of market penetration. Could you comment on the details on the lower progression in Germany versus your expectations and the main steps that you might undertake to overcame this headwind? And second, considering the limited sales force requirements, could you provide some color on the materiality of the expected launching costs for Risperidone ISM development in Europe? And on Moderna, just to understand that 2023 should be a transition year, but looking over the long term, so Moderna has talked about EUR 0.5 billion to EUR 0.6 billion market in terms of flu. What's the level of volumes that you can -- or volume declines that you can withstand maintaining the same level of revenues, considering that the prices of prefilled syringes could be materially higher than the prices of multi-dose vials on a per dose basis?

Regarding Germany, really, the products is -- I mean, it's evolving as we expected. We, as a company, we always approach the launch and the marketing of our compounds looking in the mid-long term. There are 2 different ways to approach a long-acting injectable business or to any chronic condition. One is to try to make a patient switch when they go to see their regular doctors. Another way is to try to get the initiation of the treatment when the patient needs to be changed for therapeutic reasons. We believe, as I mentioned in my presentation that, Okedi has got some unique properties that is being specified as the MPC of the product. And that's what we want to make leverage of. And that's the reason why we are targeting right now only the psychiatrists within the hospital setting, which are the specialists that they receive the patient when they are unstable, when they're having a relapse. And with, by definition, at least, the product needs to be sterilized. And secondly, it needs to be -- or -- continue with the same treatment or probably, as it mostly happened, to be changed to another medication that probably responds better to their new condition. We believe that, that's the right way to do it, really instead of trying to make gross detail to primary care psychiatrist or to health care psychiatrists, one -- to try to switch because of a superior conditions of a stable patient. We feel that at this stage of commercialization, really at the launch, where we need to go is really to the basics where when the patient is stable. Okedi has proven clinically that we can stable the patient after 8 days of the injection. We have a reduction of the bands. We get plasma levels from the brief first day. And I think that's the way that we can build a good franchise from the future. The other way would be probably a faster ramp-up in terms of sales. Probably we will plateau very soon. And I think the approach that we have decided to follow, we are going to have a slow initial outcome in terms of sales because we need to build a reputation. Obviously, this is a chronic condition and although this is very dynamic market, we are targeting only the market of unstable patients initially. We are going to build a reputation. And we believe that in the long term, that's really going to pay off and it's going to provide a steady and continuous growth of the product. Regarding the SG&A related to…

Yes, I think the -- our forecast for next year, I think it's not changed in terms of SG&A cost related to the Okedi launch in Europe. We are progressing as expected. We launched in Germany in April, in U.K. in June, and Spain in September. As Juan said this morning, we expect to launch in Italy, France and Portugal next year. So that will mean more countries to be launched. And for sure, more additional SG&A to be expanded. And that's the strategy of the company. Again, the good thing is that we are having our most profitable results so far in our history. At the same time that we are launching Okedi, which is a landmark in our history. So the total expenditure, we have shared sometimes, it will be around EUR 30 million figure annually. We keep to that firmly. I mean, we keep the figures, and we do believe that this -- one of the goodness also about this product that targeted -- the target of doctors that we are calling is very narrow and limited. The expenditure is also very small if you take into account that we are launching in the whole Europe.

Regarding Moderna, I mean, we're actually very excited for different -- not only by the situation. Firstly, because virus pandemic has been -- I mean, has become something that people has to understand that without a good public health, you don't have economy. I think with the lockdown, it has been shown, the association between public health policies and economic outcome. And something that we're going to see in the next coming years is that vaccination rates, they have to be improved and they have to be upgraded. So with COVID-19, we believe in 1 front, it’s going to happen in that way. I think no other questions today that the population tier of over 80 years old, they should be fully vaccinated and even the tier of people over 60 and 65 years old. And on top of that, any patient, we may have a comorbidity, I mean to have another pathology, EPOC, diabetes, I mean, certain pathologies that we know COVID-19 --specifically on those patients, it might be a more aggravated pathology. So we have on that end, the COVID-19 that, again, 2023, as Javier has mentioned, is going to be an interim transition year that we don't really know how population is going to respond because there is a certain level of, let's put it this way, of fatigue-ation regarding vaccination. So we are going to see how vaccination rates evolve in 2022 and 2023. We believe that as CMO, we won't suffer that much because at the end of the day, the market is going to move from multi-dose to single dose, whether on vials or prefilled syringes. So when it comes to our revenue line, we are talking about number of units rather than a number of doses. But in addition to this, we have what you have mentioned, the flu. You know that Moderna and Pfizer, this is public information. They are, right now, developing a combo product. So in order to avoid the fatigue-ation of people to get 1 shot of flu, 1 shot of COVID-19, probably another shot of pneumonia, they are making a combo. So to some extent, in 2024, that apparently are the days where these companies are planning to these products to the market. In terms of units, which that doesn't mean in terms of prices, probably the COVID-19 will move to similar figures that the flu is having today. Again, I'm talking not in terms of volumes, but in terms of prices because I'm sure that you are familiar with the policy prices of COVID-19 for the new companies. And on top of that, you have the pipeline that both Moderna and Pfizer, because I'm talking as what --regarding Pfizer because this is not something unique to Moderna. This is something that markets that are going to be created. You're talking about the respiratory syndrome virus, the RSV, which there are programs that they will come to the market pretty soon as well and it's a tremendous thing. And I think we will see huge quantities on that field. And obviously, the whole pipeline regarding orphan talks, rare diseases and oncological compounds. Very recently, Merck, the American company, has renewed its development agreement with Moderna regarding the oncological compounds and it has been made public. So we believe that as well mRNA is going to be a platform that is going to provide, I think, a lot of good news in the next coming years. This mRNA platform, it has -- is an injectable compound. It will be a single dose and Rovi, today, I believe we’re one of the very few companies that will have a license to fill and finish mRNA compounds. In addition that, we have a privileged situation because we have an API facility that we counter manufacture for Moderna, their mRNA compound. So I think we do have the combination and synergies. But globally, I don't know how it will evolve, but definitely, '24, '25, '26 and even next year, it has to be very, very good years for the company, both because of our expertise and the image that we have generated to the market in the mRNA front, which, believe me, is a very difficult product to fill and finish. This is not something like filling water for injection. And globally, obviously, it has positioned Rovi as one of the top leaders on CMO, and we have never had so many requests for information, requests for proposal programs as we are, right now, tackling. So that's the reason why behind we have decided to make such an important CapEx on this business. So globally, we are extremely optimistic and excited, because we believe the CMO is going to be a very successful story in the next coming years.

Please, Paco. Go ahead.

Paco Ruiz from BNP Paribas Exane. I have 3 questions. One is a follow-up from Guilherme. So you always show the evolution of Aristada on your presentations. But listen to you, do we -- or shall we be able to think that your product in Europe will have a similar evolution that Aristada? Or probably it's going to be a lower pattern than what we have seen in this chart. The second is on Letrozole. So could you give us an indication of the cost of the Phase II assay versus Femara and the schedule of this development? And why do you need a partner there if you have such a solid financial situation? Is it because of the knowledge? Is it because of the -- what is the reason for that? And the last question is on the CDMO business, not on the Moderna but on the other one. I mean, you have commented that this is a business which will grow 7%. I don't know if this data is including, I mean, the baseline or not. And taking into account the big amount of new projects that are coming to the market, do you think that it could be an oversupply situation and a problem for many of the competitors there?

Regarding the Okedi sales evolution and its comparison to Alkermes, to Aristada, definitely in terms of units, we do expect even to improve that ramp-up in terms of sales. You have to take into account the price in the U.S. are 3x prices in Europe in terms of manufacturing and selling prices. But definitely in Europe, in Europe, we are much more -- I mean, we are ambitious. I mean this is our domestic market, our domestic region. We have a tremendous MPC . I think we're investing heavily, knowing that we are going to have a slow ramp up, as I mentioned to you because we believe that we -- what we want really is to build up an important franchise. And we want to build the reputation of the product. But definitely in Europe, we're ambitious, and we do expect to have a performance that in terms of units should improve even the Aristada performance in the U.S. I will leave Ibón regarding the Phase II, but regarding the panel of Letrozole. Again, we -- what we are really looking is to try to find the best formula that provides the best business case scenario for the company. Obviously, Letrozole, from the data that Ibón has shared to you is really an extremely exciting and it can be a game changer in the treatment of the breast cancer. So again, what we were trying to say that we were going to looking for partners that -- we won't be shy to try to strike a deal if a partner comes to us with an interesting proposal. We have always been very transparent to investors and to the market that in Okedi, we're a follower. I mean, we are coming -- we are not the first long-acting injectable in the schizophrenia market. We are the first Risperidone in Europe because to the best of our knowledge, Teva is not planning to launch in Europe. But we are a follower in terms of a long-acting injectable to treat schizophrenia. When it comes to Letrozole, we are the first -- that we are developing a long-acting injectable for an oncological pathology. So that explains as well probably why we have been required to make a Phase II, but this product could be a game changer. This product could be -- like, a prostate cancer just to make an analog. I mean, this product can be a potential that it can completely change the paradigm of our company. And again, we know that, again, the sooner to the market the better. So when it comes -- if a big pharma company approaches that regarding Letrozole with an interesting proposal, what we were trying, with that headline, to share with you is that in this case, we -- probably we will not be shy to enter into a partnership with the big pharma companies if we believe that it really does provide a tremendous advantage. Because this is a game changer. I mean, this is something that we are not talking -- we are talking some things, too many significant that it will change the company. It's a tremendous market. The adherence of oral Letrozole is poor. You are talking about, unfortunately, a very serious pathology. And again, something that has been completely controlled in the case of prostate cancer, unfortunately, it’s not fully controlled with the aromatase inhibitors. And 1 injection per year, that's not friendly. This is more than friendly. This is going -- you can forget for a whole year that you are sick. So that's -- again, the Phase I has been so good in terms of results. The feedback from the FDA has been so positive that what we’re just trying to share is that if it comes to the case, in this case, we won't be shy in making an agreement with a third company.

Yes. And in terms of design of the clinical trial, of course, we are still under discussions with the FDA, so we cannot provide our guidance now for the discussion, meanwhile with discussions are ongoing. Talking about patients in advanced breast cancer, we know which is the median time to progression. And of course, we can estimate a size effect or treatment effect for that based on our experience on our observations on the superior or expected superior outcome on estradiol and strong suppression. So we can provide guidance on duration on the follow-up of the treatment, like I have previously explained, in the population and the use of concomitant medication like cyclin kinase inhibitors. But we cannot provide now our guidance for the size of the cohorts, so the number of patients that are going to be included. And the size of the cohort relates to duration of the recruitment and of course, the cost because it's highly related to the number of patients that are going to be included. And as far as we are with ongoing discussions with the FDA, of course, as soon as we have this fixed, we will communicate to the market.

And regarding the CMO activities, we had just provided a market figure of CAGR growth of 7%. Obviously, that's an average across the whole contract manufacturing operations franchise, globally speaking. But definitely, I mean, we do believe that injectables is really going to be the fuel of the CMO activities. That's why people are investing like lumpsum. The good thing about injectables for companies like us is that it takes a lot of years to build a manufacturing plant [ for ] injectables, globally around 5 years. And it takes, on average, a couple of years to other regulatory approvals if you get customers that fast. So I don't believe there's going to be an oversupply. I think injectables, by their definition, is going to be always under supply and more in terms of prefilled syringes, because one of the negative side effects of the COVID-19, and I'm pretty sure you are all familiar, is that the supply chain and the delivery dates of new equipment, unfortunately, is -- now are extremely long. So we have done all these orders and everything. We did it in the '21, 2020 and 2021 and there, we are going also as well to have a competitive advantage. And as well, it's not something -- I mean, sometimes we tend to take everything given, okay? They start like a lumpsum, invest so much money, as a consequence in 4 or 5 years, well, the pharmaceuticals, unfortunately, it's not mathematics. And probably, we have a competitive advantage of being 20 years on the market. We have different sites. We have FDA, GMPs and [ BISA ], the Arab countries, Japan, Korea. I mean, that's something it takes a lot of years. And that's the main competitive advantage as well with the training of our people. So definitely I believe the market is going to be, for the next 10, 15 years, undersupplied in terms of capacity. And what is -- we believe we have this unique feature that we have a very good reputation in the market and the market trend of the big blockbusters, they are moving to injectables. Just last example, the lost-weight, rather, there is now on everybody’s -- on the newspapers, because that is another injectable compound. Probably that would be inconceivable 15 years ago. But today, injectables are really becoming the standard of the market.

Patricia, please go ahead.

I have several questions on the -- sorry about that. Okay. So it would be about the -- okay, so about the Phase II trial. Sorry. So the Phase II trial seems relevant enough that it suggests that you could get a conditional approval with the Phase II and maybe go for this small indication and launch the product and then contract a Phase III for the larger indication. Is that correct?

Well, we can see examples in the market of these cyclin kinase inhibitors, for example, what, accelerated approval based on the superb results, because their results were very good after the Phase II efficacy clinical trial in advanced breast cancer. Of course, the FDA will never commit to that before we win the data of the Phase II. So we prefer to keep it as optionality. And of course, not in the proper plan, which is the Phase II and then the preparation of the Phase III study. But of course, we aim to provide a superior clinical effect. And the market is in real need of a product that is saving lives. So I mean it could be -- we have examples on the market that is showing now.

And regarding the agreement, you are looking to sign if somebody approaches you. Would it be only for the development? Or you could consider a joint commercialization in the U.S., because you were thinking about going into the U.S. by yourselves? But if you do the development with a big pharma, maybe it would make sense to do everything with them.

Again, Patricia, this -- what we are only trying to say in this specific case, we wouldn't be against signing an agreement in this stage of development. I cannot -- honestly, I wouldn't know what would be the scope or the terms of the agreement because we don't have anything material right now. I mean, not even -- we were just trying to send the message that because we believe that with the data of Phase I, it has really exceeded our expectations, and we do believe this could be a market game changer, that if a big pharma company approaches us or any potential partner, in this case, we would be willing, positive to try to find a potential agreement. Again, going beyond this point, honestly, we don't have anything material. We don't have anything that we can even think about it. So that's something that -- the moment that we have something really material the end of time, we will update the market in saying and give signal that we will be moving into that pathway. But right now, it was only to provide -- to keep the information that we believe this product has exceeded our expectations. And definitely, we know that it's creating some positive awareness among different companies. And in case that we -- finally, they approach us or we approach them and something could end up in a potential agreement, in this case, we wouldn't be against it. We do think that, therefore, what we really to speed up the process to registration. And definitely, in terms of sales capabilities, probably to partner with a big pharma company, we provided a much faster ramp-up in terms of sales.

Just 1 more. Thinking about the opportunity. I wonder if there are other long-acting injectables under development, either with Letrozole or with the other 2 relevant molecules? I also wonder what's the size of the market in the advanced patients, which would be the first indication.

Yes. In regard to the first one, to our knowledge, there is no other competitor that is developing long-acting for aromatase inhibitors. So we understand that it is extremely complex, by the way, to develop a product like this because the regulatory is very sensitive to variabilities and the probability of keeping patients not in suppression. As you can imagine, this is a medication that is saving lives. So the approach has to be very conservative, and you really need to be very sure on your expected PK profile. So no other competitors as far as we have detected in the market. I don't know if -- yes, the indication. Yes, I thought you were going to answer. But I mean, the market size for this, of course, the big market size that represents 70% of all the sales in a number of patients on treatment is early breast cancer, which is the main indication. The indication of advanced breast cancer could be around 15% of all the treatments.

Please, Álvaro. Go ahead.

This is Alvaro from [indiscernible]. First question would be going back to Risvan. And first of all, how confident are you on the new deadline from the -- for the approval from the FDA? And also, if you could update us on the marketing approach to the United States. You said you've been open to partnering in Letrozole. What's the situation with Risvan if the delays in the approval process have implied any changes to any potential partnerships? The second question would be on Glicopeptón? And what's your long-term view on this approach? I understand that this is mostly to secure product sourcing even in the context of geopolitical conflict. Does this mean that once the vehicle is in place, would you be willing to consolidate it in pool and buy it from your partners? Or would you be working to selling your stake and just making a long-term agreement in order to secure procurement but have no involvement in the ownership of the vehicle? And the last question would be on capital allocation and whether you will be looking to make any additional buybacks, especially considering the decline in the share price or whether you would be more interested in M&A. Or are you saving your cash for a potential R&D expenses mostly related to Letrozole?

Shall I start with the responses to Risvan. Well, of course, as I have previously said, we have pending questions from our side and from a supplier, which has a big, big experience with the FDA. In regard to our own questions, we feel very optimistic on the successful resolution on the whole date. What we cannot control is the deadline for the inspection that is pending by the FDA, because the FDA decides its own calendar and does not provide guidance. So we cannot even have an opinion on that. We -- of course, we feel optimistic that the ramp-up of the inspections will give us the opportunity to have the inspection in this their manufacturer within the time frame of the call date, but we have no information on that.

Regarding Risvan and potential agreements. Obviously, everything will be very much related to the finance MPC that we get in the FDA. We are having open channels, and we're having discussions, and I would say even advanced discussions with different companies, working on different scenarios from virtual JV, a pure standard licensing agreement. But again, everything is very much related to the finance MPC. So we do believe that we will be able to finalize whatever is the strategy that we've already decided by the first quarter next year, even before getting the approval because as Ibón has mentioned before, we feel very optimistic. A positive thing about the COVID-19 for ROVI has been the Moderna agreement, a negative side effect of the COVID-19 is the backlog that all regulatory authorities have got on their audits and inspections, so it’s normal. What we are suffering, we are not the only company that were suffering in these sort of delays. And again, once we got -- we are very close to get the clarity of what is going to be the finance MPC, then we will take a decision. The good thing is that we do have, how can I say, companies that they are interested in either licensing agreement, either joining forces with us. And again, we will take the final decision whether we do it by ourselves or whether we join forces or now potential virtual JV or a pure standard licensing out agreement once we get the clarity of this MPC. Because at the end, how this MPC is worded, how do you get your claims for pharmaceutical companies is really our marketing tools, and that's how defined -- the SG&A that you must dedicate to penetrate the market, what it’s going to be, slightly higher or lower. So hopefully, I believe that by the end of first quarter next year, we should have clarity on that. With regards to your last question on the capital allocation policy for the next coming months, I guess, in the future. I think we have always highlighted that Rovi's company of growth. The last 4 years, we've been growing at close to 30% CAGR growth rate. This year, we are growing around up to 9 months at 24%. And I believe that's the main objective of the company. So in the meantime, for sure, we have done -- we have increased the remuneration of the shareholders because we haven't found any alternative to keep growing in a faster way. I believe that right now, we are very comfortable with our cash position. I think it's a nice position that we have, taking into account the macroeconomic environment. And for sure, we're going to use the money to finance Letrozole. That, I think, is very clear to us. On top of that, again, we'll try to find opportunities to fuel that growth. Potentially, we keep growing our cash position. And eventually, we don't find any M&A alternative. We could repeat the buyback programs. But I believe that -- I would love to say Rovi is a company of growth, so we prefer to use the money and our funds to fuel the growth of the company. We will not change our conservative financial policy items. So that means that we will be very happy to be always on the safe side of the financials. But again, eventually, if we keep growing our cash position, and we don't find alternatives. We would probably repeat any -- or increase any shareholder remuneration.

Regarding Glicopeptón sorry that I -- our idea initially is to remain having the majority on that joint venture. And what we are really looking is to push those margins on the low-molecular-weight heparin franchise. Obviously, we want to secure the supply chain. We want to be more self-sufficient. We wanted to reduce the variability of prices. But having said that, the final ending is boost the gross margin. So what we are building the strategy on the company, if you make compartments on the supply chain of heparins, you have the mucosa, you have the heparin crude, the sodium heparin. So what Rovi is trying is to build enough capacity to buy whatever interim raw material at the best price possible. So for instance, if we see, all of a sudden -- it has happened the past that it’s crude heparin is more cheap to buy than sodium heparin or even to manufacture ourselves, we will go to the market to buy crude heparin. And we will sell our own manufacturing to the market. Because in general and by definition, a bilateral compound, unfortunately, there are going to be very little scenarios where there is an oversupply of product. Unfortunately, and that has been the case for the last 10 years. And I don't think it will change in the next 10 to 15 years. We’ll always be in a scenario of undersupply because as well, it's not very popular to build big farms worldwide because of the [indiscernible] right now. So what we just try to make sure is that as well with Glicopeptón that I mentioned that before, the fact that you control the supply chain you can as well tailor major crude heparin to boost the yield. You can adapt all the manufacturing process to make a better raw material to boost the final manufacturing output of the low-molecular-weight heparin. So I would say that what the company is trying to do is to secure the supply chain and most over any other thing, to boost our gross margins. And we believe that’s the strategy to follow and it would pay off in the midterm.

Please, Javier, go ahead.

Just a question on the CMO business. So you said that is -- you think it's going to be an undersupply market for the long term. So considering that you are targeting to have, like, EUR 400 million to EUR 500 million capacity, we can assume that you will be using that capacity or the majority of that capacity beyond 2025? Is that a right assumption?

Yes. I mean, that capacity would be available for 2024. In injectables and CMO, it’s pretty normal that you start even making agreements before you have the capacity available because you can use other lines to run the stability batches, that those batches can be later -- be submitted with a regulatory dossier. And then you can to a variation with whatever new lines you are studying and implementing. But yes, 2025, 2024, '25 and '26 should be where we see the ramp-up in terms of potential units being manufactured by our CMO operations.

Ibón, we have a question from [ Samir Devani ] with ISM Letrozole as it's a yearly product, if you needed to reverse its effects following injection, how would you do so?

Well, Letrozole ISM will never be a medication to start a treatment. So the patients, of course, most of the lack of tolerability that is related to the Letrozole treatment is observed during the first few months of treatment. So discomfort in this kind of adverse events. So our product is expected to be given once the tolerability has been demonstrated. A person in advanced breast cancer usually has also received previous aromatase inhibition treatment. So we are talking about patients that are having tolerability or an adverse events on that. On top of this, and it is an important thing, we are talking about a significant reduction in the amount of Letrozole that is being given to the patient for maintenance statement. We are talking about a product that is going to be given 9x less dose compared to the oral formulation at 100% of compliance, so you're right. And of course, this has to relate to a better tolerability profile or this is our understanding. And of course, this will be a matter of revision on the clinical efficacy program of course.

We have another question from Ignacio [ Ortiz ] Mendivil. “Looking at the successful results of ISM, aren't you considering the licensing of the platform for new treatments that are not currently in your pipeline that would certainly unlock value for the company?”

As I mentioned before, I mean, for us, the approval in Europe of Okedi, it worked out in 2 ways because we have a product, but second, it has validated our platform. When it comes to Okedi, we are looking into our long-acting injectable that we need to get certain plasma levels to get efficacy required. When it comes to Letrozole, we are talking to the inhibition of the release of -- and in this case, of hormones. So both ways of acting. Definitely, we do believe that we will see in the very short future, opportunities of potential partnerships with other companies. The reality and the theme today and in this case, I want to be transparent and honest, is that we are 100% so much focused on Letrozole and Okedi with the Risvan potential approval in the U.S. that we have little free time really to open discussions with all the other companies. We do believe that once we get the approval of Okedi and we have the Phase II already running or whatever clinical trial design has been agreed with the FDA, we will have the time and the focus to start marketing the goodness of our platform to third companies. We have already identified certain products that we believe would be ideal for the life cycle management, our platform. But again, the moment that you want to start those discussions, you really need to have the people, the facility ready to be able to accommodate our customer requirements. And we don't believe that we are still at that stage right now because we are focused on the Risvan approval on Letrozole. But hopefully, once the Phase II is undergoing and we get the approval of that Risvan, that would be the moment that we’d start with those conversations.

A very quick 1 about the 2 products that you have signed to co-market with MSD. Can you give us an indication of what could be the contribution to sales from these products?

As we are saying before, I mean -- and I think that's most important to convey is that we are, right now, focusing on our proprietary compounds, basically because of margin-wide. What we are trying to find right now is agreements in the market, which can complement perfectly our product pipeline and that can provide additional profitability to the company. But we are not looking today into the market in terms of in-licensing with the exception of Europe that we are having discussions for -- with certain companies to accommodating a schizophrenia-specialist line, probably additional products. When it comes to Spain, we are looking for a product profile that can complement our proprietary compounds and can allow us to maintain the focus in which I think is material to the company today, which is the growth of the heparin franchise and the growth of Okedi. In that scenario, that's what it suits perfectly, products like the one we are talking about with Merck, which it goes to primary care, or it can really be retail in second position and it can provide tremendous leverage to a sales force that you have already in place and it can provide additional profitability to the company. I cannot disclose exactly the economics of the agreement because of the CDAs and the contract itself. But I can say that the percentage that we have agreed in terms of sales that goes to Rovi, almost 95% goes directly to the bottom line because it's playing on the leverage of the 16 sales forces. And that's the sort of deals that we are, right now, looking into the Spanish market as all the focus, as I mentioned before, today is really making the heparin franchise business, growing over that 52% market share that we have and as well as making sure that the ramp-up of Okedi fulfills our expectations.

We are largely out of time. I'm going to ask the last question to Javier. It's a question from Renta 4 Gestora. How should we think about gross margin progression in the medium term?

Thank you, Marta. Thank you, Javier. Next year. In terms of gross margin, we believe that probably as the CMO business is reducing a little bit compared to this year, we will have a little exposure on the gross margin. So probably we'll have a little erosion, but happily, we believe that in the medium term, long term, we could offset that -- probably coming from different factors. As we've been discussing today, Okedi, we would love to think that Okedi will be 1 of the main contributors to the company in the midterm, maybe in the long term with higher margins than the group. Second, as we've been discussing thoroughly today, we expect the CMO business want to expand. That's why we're investing, and that's why enlarging our capabilities and hopefully, we’d like to think that new potential business coming to that part of the CMO will be accretive again. And hopefully, as we are working and discussing about the low-molecular-weight heparins and the cost of the APIs, we believe that we could have good tailwinds also with regards to heparins. So in a mid-,long-term outlook, I believe that our gross margin would expand or at least that's what we initially think.

Thank you very much for your high participation. The IR team will answer all the pending questions as soon as possible. I give Mr. Juan Lopez-Belmonte the floor for the closure of the presentation.

Well, thank you. Well, thank you very much indeed for being here today and for having the patience. And we have beyond the time allocation that we perceived and now we'll just have a small cocktail if you would like to join us. Thank you very much.