Ladies and gentlemen, good morning and a warm welcome to our Rovi 2025 Capital Markets Day. Also, a warm welcome to all of you who are joining us online. It's my pleasure to see you all with us today. Let me start by introducing myself. My name is Marta Campos. I'm the Head of Finance at Rovi. Allow me to give a brief overview of today's agenda, which is divided into five sections. First, you will get the chance to hear from Juan López-Belmonte, our Chairman and Chief Executive Officer, on the company's strategy. Then Miguel Ángel Ortega, our Corporate Industrial Director, will present the CDMO business. Afterwards, Miguel Ángel Castillo will present the specialty pharma business and its growth drivers. Iván Gutiérrez, our Corporate R&D Director, will talk about the R&D strategy.
Finally, Javier López-Belmonte, our Deputy Chairman and Chief Financial Officer, will give an update on Rovi's financial situation. At the end of the presentation, 30-minute question and answer session will commence. People attending in person, please raise your hand and someone will come with a microphone. People attending online, don't hesitate to ask your questions through the question button on the platform. Just an additional clarification. In the Q&A, we will answer questions regarding the different business and their strategy, and questions related to the long-term guidance will be answered by the IR team in the coming days. Before we begin, let me add that the entire event will be recorded and a replay will be available later on. Without any further ado, let's get started.
Well, good morning to everybody. I'm Juan López-Belmonte, president and CEO of Rovi. First of all, I would like to thank you for your presence today at our 2025 Capital Markets Day. Just let me kick off right away, trying to give you an overview of Rovi's business model and our vision. Let's see if this works. Yeah. I mean, Rovi is a Spanish pharma company with a current market cap of approximately EUR 2.7 billion. We have been listed on the Madrid Stock Exchange since 2007, and we have managed to deliver a consistent organic growth based mainly on three fundamental pillars: the CDMO business, the specialty pharma, and the ISM Technology platform.
Our CDMO business is a recognized leader in the high-value injectable CDMO services with a focus on highly complex injectable products in multiple dose forms, such as prefilled syringes, vials, or very recently, cartridges. A very attractive business that we believe has a tremendously strong growth story ahead of us. Regarding our specialty pharma business, when I talk about this business, we talk mainly about two different areas of growth: our leading proprietary heparin franchise, our in-licensing business in the Spanish market, and our fastest-growing long-acting injectable specialty pharma, Okedi, which has been developed in-house and is based on ISM technology. Let me end with the third pillar of growth, the ISM platform. This business, I still believe that it will be really the item that will transform our company. ISM is a versatile, long-acting injectable technological platform that is patent-protected.
Our ISM Technology platform has been validated very recently to the approval of Okedi in most of the important by the most important regulatory bodies worldwide. We're also working in two new molecules that we will discuss in depth during today's Capital Markets Day. The Letrozole SIE and a Quarterly Risperidone, for which the phase I has been fully completed. This is going to be basically the content of our Capital Markets Day throughout the day. Just give me a quick overview to say, and that's something I really like repeating, that Rovi is a story of growth. We have a strong track record with a predictable organic growth item.
We have delivered this constant and sustainable annual growth of over 30% over the period 2018 to 2021, and close to 6% over the period from 2021 to 2024. I always like to remark that 2024 has been a transition year. I mean, at the end of the day, it has been a crucial year in terms of investment that will allow us to establish the base for the future growth of the company.
The rationale behind this concept is because we believe that right now we are setting the grounds of what is going to drive our growth and it's going to position the company for the long-term success. If we see Rovi today, we have been extremely successful in developing Rovi to the point in which we have just arrived on the three pillars of growth that I have mentioned before. The CDMO business, Rovi today stands as a premium European end-to-end CDMO platform, and we believe that we have all the ingredients to capitalize and to capture the growth that is out there on the market with our four fully invested manufacturing plants that I would like to remark again that they are mostly approved by all the important regulatory bodies worldwide.
In the specialty pharma business, Rovi has got an unparalleled know-how on the heparin franchise. We are present in more than 60 countries. We have managed to develop and launch 2 really flagship molecules, Bemiparin, coming from our research and development labs, and we have been one of the first companies to market a biosimilar of enoxaparin. Both products last year achieved sales close to EUR 250 million, and we do believe that with what we are going to share with you today will provide further ground of the expectations that we have for this line of growth within the company. We have Okedi, which is currently marketed in Europe to our subsidiaries, and I have to say with pride that it's been a complete success.
With the ISM technology, we have just finished phase I studies of letrozole SIE and our quarterly risperidone, and both, Iván López-Belmonte, we will touch on this performance later on, but we do believe that this is going to be the item that will transform the company. All these items, the investment that we are currently executing on these three pillars of growth definitely are going to set up the foundation and the grounds for the growth that we expect to deliver within the company in the next coming years. If we talk about Rovi in the future, and this is really the reason why we're here today and, it's just to tell you not what we have done so far in the past, but what we expect to deliver in the next coming years.
We believe that all the investment that we have been doing and that we will do during the next coming years will transform and will shape Rovi in what we believe it will be Rovi of 2030. Rovi that will be leader in three major areas. In the CDMO business, we are making a huge effort in terms of investment to increase our current capacities and to adapt to patient and customer needs. We're adding new filling formats like cartridges, assembly lines, direct-to-carton packaging lines, and we believe this is an opportunity that will drive our long-term growth, and we will position Rovi as a global leader in this injectable CDMO manufacturing front. We are also investing in our low molecular weight heparin franchise. We are going to be hopefully in the next coming years, fully vertically integrated.
This is not only going to improve our cost efficiency, but it's really going to improve significantly our gross margins. We'll continue investing in the Okedi's launch. I think we're on the right track to hit our objective in terms of sales between EUR 100 million and EUR 200 million in the future. We are working to include new licensing agreements, both in the Spanish market, but as well now with our European subsidiaries in getting licensing in for our European subsidiaries sales force. We are investing in the next clinical phases of Letrozole SIE and our Quarterly Risperidone.
We really hope that these two new ISM products will expand our portfolio in-house product development, and it will drive what is going to be the growth of the company in the next decade. We're extremely excited about the future, and I hope that you will share with me the high expectations we have as the CEO and the manager of the company once we finish this Capital Markets Day. We really believe that we are prepared, that we really have all the ingredients, and we have make all the investments to really leverage all the opportunities that lies before us.
Before going into detail to the different pillars of growth, let me just give you very briefly a few data regarding our ESG commitment, which I think is important and is one of the major strategies within the company. In December 2024, for the fifth year running, Rovi improved our ESG rating that is awarded by Sustainalytics, achieving 16.1 points compared to 16.4 the previous year. The company was placed 5th in the world ESG risk ranking from among the 424 companies that they are audited by Sustainalytics in the pharmaceutical industry subgroup. Additionally, we are continuing to work in the implementation of our ESG master plan 2023 to 2025 that has been approved by the board of directors in December 2022.
Throughout 2023 and 2024, 65% of the 45 KPIs included in the master plan were completed. Such progress is supervised by the sustainability committee created in mid-2023, which reports annually to the board committee on the progress of the plan. Now, I turn the floor to Miguel Ángel Ortega, that he will give you a much better insight and much deep information regarding ESG activities. Thank you.
Thank you, Juan. Good morning, everyone. Let me begin, as Juan mentioned, providing a brief context and overview about the current CDMO dynamics and how Rovi can be benefit from these opportunities. The first thing that I consider relevant to say is that the outlook of the CDMO market is really promising. The size of the global CDMO market has been estimated in $185 billion in 2024, and the annual growth has outpaced the pharmaceutical sector in recent years, reflecting a clear trend towards outsource manufacturing activities due to several factors.
First, because the strategy of the large biopharmaceutical companies that have focused on reducing operating costs and into allocating the capital expenditures on R&D capabilities, causing obviously a lack of internal capacity and increasing the demand of the outsourcing of manufacturing activities to CDMOs with unexpected penetration of close to 60% by 2031. Second, due to the great number of smaller and emerging biopharmaceutical companies without industrial infrastructure and the expertise to produce this product and to manufacture biological products. Third, thanks to the ability of the CDMO players to mitigate the supply disruptions and the market shortfalls by offering additional sites to pharma companies with multi-site supplier strategies.
One of the most relevant reasons, as it is the crucial requirement from these global companies in reducing time to market, especially when there is an internal lack of capacity in these companies. Consequently, over the next few years, the great news is that the CDMO market is expected to grow at a CAGR of 7% to more than EUR 360 billion. Let us focus now in the market niche in which Rovi operates, the fill and finish of high-value injectable drugs. Without doubt, the injectable market, which accounts for more than 70% of the total products today under development, is the fastest growing route of administration, thanks to the increasing number of biologics, antibody-drug conjugates, biosimilars, monoclonal antibodies, vaccines that are today in development.
Just to give you a data, the global injectable market is expected to growth at a 9% CAGR from 2021 to 2031. Within this segment, there is increasing demand for injectables fill and finish CDMO services due to the highlighted lack of internal capacity and the required expertise on complex aseptic manufacturing processes and the new regulatory requirements that, as you know, are linked to the Annex 1. In this sense, the injectable fill and finish market is expected to growth even faster at a 10% CAGR on this period. Going deeper into the specific Rovi's niche of injectable expertise, let me talk about pre-filled syringes.
Pre-filled syringes have heavily increased the acceptance over the past years as a route of administration, while it's still one of the most difficult pharmaceutical forms to be manufactured, with high entry barriers and triggering a structural undercapacity in the marketplace and consequently a growth even higher at 12% CAGR in the same period between 2021 and 2031. In summary, huge opportunities for our CDMO business unit and specifically on those products that will drive the CDMO growth in the next decade as you can see in the next slide. All these category products growth are the consequence of a fact that is the increase of chronic diseases globally. The obesity, the diabetes, the cancer, the cardiovascular diseases, the autoimmune disorders, all of them require injectables and PFS as preferred delivery pharmaceutical form.
On the bottom half of the slide, you can see in the graph the evolution of the Western demand in million standard units since 2018 till 2023 and the evolution till 2028. You can see how we increase this PFS total demand from 4.5 billion standard units to 6.3 billion standard units in 2028. There is an unparalleled opportunity for Rovi's, for Rovi Industrial Services, with the capabilities to manufacture all these different category products. GLP-1s, monoclonal antibodies, biosimilar, biotech products, vaccines, heparins, as you can see in this slide. Rovi CDMO business is today totally ready to take advantage of all these market opportunities and has already demonstrated its potential.
Our CDMO business was founded in the mid-1990s, achieving since then an extensive track record in high quality sterile fill and finish services and being integrated in a standalone business unit in 2019 as independent business unit known today as ROIS, Rovi Industrial Services. The sustainable competitive advantage achieved over the years founded in our large capacity, our flexibility, and in our reliability to deliver what we promise address the structural market shortages and allow us to sign transformational contracts. As it is the contract, as you know, we signed with Moderna in 2022 for 10 years to produce the pipeline of the company and meaning a turning point for Rovi. Soon this trajectory enable us to be where we are today and to position ourselves for even greater achievements.
We have been growing in a highly diversified legacy CDMO business with more than 30 blue-chip customers, which provide us a high visibility in terms of revenues, thanks to the long-term contracts. As you know, in April 2024, we signed an agreement to manufacture up to 100 million PFS with a global top five pharmaceutical company, with a dedicated line in our plant in San Sebastián de los Reyes for at least 5 commercial years. Soon, new contracts will be signed involving additional capacity expansions to serve these new partners to a total of 12 aseptic filling lines by 2026. With this, what Rovi Industrial Services is today.
As Juan mentioned, we are proud to say that today ROIS is a premium European end-to-end CDMO platform focused on high value injectables or highly competitive markets, including among others, GLP-1s, vaccines, monoclonal antibodies, heparins, biotech and biosimilar products with European footprint and a large capacity on PFS, vials, and cartridges. Following up with additional bullet points about the ROIS' privileged position, ROIS has an established and growing baseline of more than 30 blue-chip customers considered for us as customers for life, and invested close to EUR 85 million euros since 2020 to expand capacities on our fully compliant and Annex 1 manufacturing sites as a foundation for the highly significant future revenue growth and operating leverage in the coming years. Let me now touch a little bit more in detail the CDMO business strategy.
All the investments done by ROIS pursue it to be vertically integrated throughout the entire pharmaceutical value chain. As you can see, starting off producing complex biological drug substances in our Granada site with expertise in complex technologies like the lipid nanoparticles or the encapsulation of the mRNA drugs. Following up with the capacity to fill and inspect such drugs in our manufacturing sites in Julián Camarillo and San Sebastián de los Reyes in the area of Madrid, where we have currently 11 high-speed filling lines. We will invest also into introduce cartridges as capabilities with the new lines in 2025 and 2026.
Finally, with the capacity to assemble devices and do the secondary packaging in our center of excellence for packaging activities in the Alcalá de Henares site, where we have also invested in two additional lines capable to assemble the cartridges into pens and the PFS into auto-injectors just to follow the shift in market trends.
As many of you know, in addition to the pure manufacturing activities that we can offer as services, Rovi Industrial Services is offering a full service on tech transfer activities, including development, the quality support, the regulatory support, and the quality release to the market in more than 60 countries where we deliver our products, and we are approved by the most important health authorities, as it is FDA in all of our manufacturing sites dedicated to the CDMO business. This is really what makes Rovi Industrial Services pretty unique. Our operational network with highly qualified people focus on top quality and offering to our partners the flexibility, the agility required today with a demonstrated reliability track record to deliver what we promise. We believe that this business model is really hard to copy.
It's our strength, and we believe it's our differentiation factor versus our competitors. Here you can see the specific capabilities of each of our fully invested sites in the Rovi's network, covering, as I said, the complete value chain. I would like to highlight the great development that our CDMO business has achieved over the last three years, not only in capacity, not only in capabilities of new pharmaceutical forms such as cartridges or the assembly of pens and auto-injectors, but also obtaining the FDA approval in all of our sites. This is a clear demonstration of our commitment with the highest quality level and a major turning point for Rovi.
Going deeper now in the evolution of our CDMO growth strategy, you can see on the slide how in 2022 we had eight aseptic filling lines and 11 packaging lines. Between 2022 and 2024, we have been able to install, to qualify, and to obtain the regulatory approval of 3 new highest speed aseptic filling lines and 4 direct to carton packaging lines for injectables. We will continue to make significant investment to expand our capabilities because the market is really hot, we are very well-positioned, and we would like to leverage our competitive advantage. This is the reason why we have also invested today into 2 new highest speed filling lines that can either produce as combo lines, PFS or cartridges. Both will be installed in our facilities in 2025 and 2026.
By 2026, ROIs will be able to offer to our partners 12 highest speed aseptic filling lines. All these investments will significantly increase our total capacity installed. As you can see, in 2022, we had a capacity of 250 million PFS and 80 million vials. In 2026, we will have more than triple, close to 725 million PFS, 100 million cartridges or 160 million vials.
These are really big capacities to grab right now, not in 7 years or in 10 years, but right now, the opportunity of the imbalance between the capacity and the demand of the outsourced manufacturing due to the market shortfall of products like the GLP-1s, the biosimilars, the monoclonal antibodies, and to position in 2026 ROIS's as a global leader in terms of injectables capacity in the CDMO marketplace. As you can imagine, we are really excited for the future to come and also excited to drive this strong long-term growth mainly through our competitiveness, our flexibility, and our cost efficiency.
As a final message to take away, I would say that I'm totally confident that our CDMO business will develop very positively in the coming years and that we will be able to double our turnover, our CDMO sales by 2030 up to EUR 700 million, and doing that confirming our strategy to becoming the top one CDMO in high value added injectables for PFS, cartridges, and vials. Thank you very much, and I would like to hand over now the presentation to our International and Business Development Director, Miguel Ángel Castillo, that will give you an update on our specialty pharma business.
Thank you so much, Miguel Ángel. Extremely interesting and extremely promising for the next eight years. Good morning, everyone. Before taking a closer look to the different products of our portfolio, let me very briefly introduce our specialty pharma business. The specialty pharma business is divided in three units. The first one is our low molecular weight heparin franchise with our two main flagship product, Bemiparin and enoxaparin. Biosimilar, both of them, from a commercial point of view, both of them has been very positive, in the sales performance in Spain and abroad. From a manufacturing point of view, we will keep investing to be fully vertically integrated as a driver of growth of this unit.
In the central part of the slide, you can see that our risperidone ISM, a long-acting injectable of risperidone, based on our proprietary ISM technology to treat schizophrenia. We aim to achieve peak sales between EUR 100 million and EUR 200 million, assuming both organic growth of the countries that the product has been already launched, plus the different launches that we plan in the different countries to cover worldwide. The third is our leading specialty pharma franchise that we have licensed more than 20 products in the last 15 years. We have one of the largest sales force in Spain with more than 200 reps calling specialty doctors. Additionally, recently, we have set up our own direct operations in six countries. In Europe, we have six affiliates, and we count with a headcount above 120 employees.
Now let's move specifically to the low molecular weight heparin products. On this slide, we have laid out all the countries where our low molecular weight heparin are commercialized. Enoxaparin and Bemiparin has been successfully marketed in more than 60 countries worldwide. Enoxaparin has the largest footprint with a commercialization directly in 41 countries and Bemiparin in 35 countries. In 2022, with the goal to enlarge and to complete our integration through all the manufacturing process of heparin, we create a joint venture with Càrniques Celrà and Grupo Costa to be one of the first national structures to become self-sufficient in the production of crude heparin. This JV is called Glicopepton and is expected to be operative next year, 2026.
The JV is right now in an advanced phase of construction, and it's located in Fraga, Huesca. We will be able to transform the intestinal pig mucosa into crude heparin. The crude heparin will be sent to our proprietary site located in Escucha, and we will transform the crude heparin into sodium heparin. Finally, we will end the final process of the manufacturing of low molecular weight heparin in two additional sites, a property of Rovi, one of them in Escucha and the other in Granada, that it will be the last phase to transform the sodium heparin into low molecular weight heparins.
Glicopepton will enable us to take a further step to be totally vertically integrated in our low molecular weight heparin manufacturing, and this will imply a less dependence on suppliers, a reduction in the raw material price fluctuations, also an improved product traceability and obviously an increase in the current gross margins of this unit. We are in a transition phase focusing on the cost efficiency of heparins, and we expect that an improvement of our margins will position ourself in a better competitive position to keep growing in this segment. Now let me talk specifically about our flagship product, Bemiparin. I'm proud to announce that we reached a 31% market share in Spain last year.
It positions ourselves as the market leader in Spain in the low molecular weight heparin market, and we achieve EUR 59 million of sales last year only in Spain. We have a strong competitive position due to our differentiated clinical profile, which provides a wider therapeutic window and a more convenient treatment of DVT. Indeed, Bemiparin, thanks to its superior pharmacological profile, is the only second-generation low molecular weight heparin that warrants an effective 24-hour coverage with a once-daily single administration for all the patients, regardless the patient risk. We are happy with Bemiparin performance. As you know, the product has been on the market for more than 25 years. It is a mature product, but it still keep growing. I know very few product in the pharmaceutical arena that will keep growing after 25 years.
This is what we call the concept of a product for life. It's a product that keep growing after being launched 25 years ago. In 2024, overall, we reach a EUR 96 million revenue for the Bemiparin products that represented a 2% increase versus 2023. The international segment was the main contributor of this increase. Now let's move to Enoxaparin Rovi that was one of the first biosimilar commercialized and launched in Europe. Enoxaparin has been obtained regulatory approval in more than 60 countries worldwide, and it's currently on the market in 41 countries. We sell Bemiparin through two different business models.
The first one is directly through our own affiliates, and the product is on the market in Germany, U.K., Italy, France, Spain, Portugal, and Austria. These countries represent around 75% of the total European market of the low molecular weight heparins. The second, let's say, business model that we have implemented is through partners that in those countries that Rovi doesn't have a direct presence. We signed out-licensing agreements with many domestic companies, and they take care of the commercialization of our products. Regarding the revenues, we are very pleased with the evolution of the product. In the first full year that it was 2018, we reach slightly above EUR 30 million revenue.
Last year we reached slightly above 145, which represents almost 30% of our compounded growth rate versus since 2018. Now let's move to Okedi. I would like to start with a brief overview of the attractiveness of the schizophrenia market. Unfortunately, schizophrenia is a disease that affects 24 million people worldwide. It's a chronic and progressive disease where the long-acting injectable antipsychotics are becoming the gold standard for this treatment.
Europe is the second-largest long-acting injectable market with an estimated market size of EUR 1.5 billion, growing at 7% and with a relatively low competition as has been a few innovation in this field and few product that has been able to reach the market to cover this disease in the last years. The superior value proposition of Okedi compared to other alternatives are related to the following important features. Okedi is the monthly long-acting injectable of risperidone that provides an immediate and sustained efficacy from day one without the need of oral supplementation or loading dosage. The monthly formulation matches with the standard monitoring frequency that the psychiatrists follow patients with schizophrenia and to confirm the adherence to the treatment.
We choose the molecule of risperidone because the consumption is massive worldwide and also the psychiatrists already use to deal with the risk-benefit of this product. Additionally, thanks to its innovative pharmacokinetic pharmacodynamic profile, Okedi provides a superior efficacy preventing patients from relapses, balanced with an outstanding tolerability profile, allowing patients with schizophrenia to also preserve their autonomy and functionality from the day one. I will not devote so much time to this slide that is self-explanatory. What we try is to summarize the uniqueness and advantages that Okedi present compared to the other long-acting injectables approved in Europe. Let me start this final slide regarding Okedi, sharing that our PRISMA-3 clinical trials was designed on purpose to cover a medical need that we identified.
We intended to provide an effective alternative in the management of unstable patients undergoing a relapse. To make it simple, Okedi is the only long-acting injectable approved in Europe to be used in unstable patients with severe to moderate symptoms without the need of oral administration or loading dosage. Please let me guide you through these, the main outcomes observed during our pivotal clinical trials with Okedi. First, our innovative PK/PD profile allows Okedi from day one an optimal dopamine D2 receptor occupancy in the range of 65%-80% in a sustained and predictable manner, which correlate with a high efficacy and with the minimal adverse events.
Second, in the short term, efficacy was demonstrated in severe patients admitted to the hospitals due to a relapse, and Okedi achieves a significant PANSS and CGI-S reduction at day 8. Third, in the long term, efficacy was also demonstrated regardless of the patient's severity, and we obtain a low overall relapse rate of 10.7% and a low rate of rehospitalizations of 4.2%. Last but not least, so the safety of Okedi was also demonstrated in the long term with a low rate of discontinuation caused by treatment-related adverse event of a rate of only 3.3%. That means only seven patients out of 215.
In summary, Okedi has an outstanding efficacy and tolerability balance from the day one, aimed to improve the patient functionality and social reintegration demonstrated through the PRISMA-3 clinical trials. It's a pleasure for me to present where Okedi is already on the market and the rollout of launches that we are planning in the next years. Beside Spain, that is our natural market, we have already launched Okedi directly in Germany, U.K., Spain, Portugal, Italy, and Austria through our own affiliates.
Once we have finalized the launch of through our own affiliate, we have launched through distributors in Greece, Serbia, last year, 2024, in Nordic countries, including Finland, Sweden, Denmark, and Norway, also in Australia and Taiwan. If we consider all these countries plus the new countries that has been recently launched in this first quarter of 2025, Netherlands and Canada, we are now right now acting in a market with a potential market size of around EUR 1 billion.
As you can see, we are expecting to reach our peak sales between EUR 100 million and EUR 200 million, that it will be driven by the organic sales of all the countries that you can see that the product has been launched, plus the additional launches that we are planning for the next years. In the previous slide, I tried to share with you the main outcomes from the clinical trials and how we expect it to contribute positively in the management of the disease of patients with schizophrenia. Now I'm really excited to share. I think that this is the first time that we share with you this information, that this is real data.
They are factual data that reconfirm that Okedi launch has been a great success in all the countries. The uptake curve is as planned, considering a chronic disease. The data demonstrated a steady growth in all the countries, acceptance by patients and caregivers, and also a high adoption by psychiatrists. We have reached a 6% market share in Spain, 9.4% in Portugal, 6.4% in Germany, and 4.5% in Italy and Austria. This data make me very optimistic for the near future, and as you know, and you are totally aware, Okedi has been the first product that we have developed under the ISM Technology.
It took a lot of time and effort to register, to market, and to launch, but now I'm proud to say that the hard work has been paid off. Also, Okedi is a good example of a product for life in our portfolio. Ending with Okedi, let me move to the specialty pharma franchise, where we have positioned ourselves as the partner of choice for global pharma companies when they are looking for partners in Spain. We have more than 200 reps, and the potential partners will leverage from our leading position in the Spanish market, our portfolio, our experience in the field, regulatory, market access, commercial capabilities. We have a successful track record.
We have licensed more than 20 products over the last 15 years, and we have many success cases, such as launching the second brand of Entresto from Novartis. Also, all the Estatin cell franchise products from Organon, the former MSD. We have many other examples like Astellas or Bracco that have trusted in Rovi as the partner of choice during the last years. Finally, a part of the capabilities in the Spanish market. Seven years ago, we started our internationalization strategy, and today we could say that we have six fully operative affiliates in six countries with more than 120 full-time employees, being enoxaparin and Okedi, our main products sold in most of them.
If you ask me if the strategy finally has been successful, I think that with this data and with the sales that we obtained last year, EUR 97 million, I think that the strategy has been successful. Thank you so much. I will hand over now the presentation to Iván, our R&D corporate director.
Thank you, Miguel. Now I will give you an update on our R&D strategy, and in particular with our three most important R&D projects. Let me start with the tremendous opportunity we have with our quarterly letrozole formulation in breast cancer. We are developing a quarterly formulation of letrozole that is superior to Femara in suppressing estrogens. With the clinical package that we are intending to achieve, we are aiming to get the same indications as Femara, both in the U.S. and in the European market. Letrozole is an aromatase inhibitor like anastrozole, and the only pharmacological effect is the suppression of estrogens by the suppression of the aromatase enzyme. This enzyme converts the precursors into female hormones, which are basically estrogen and estradiol.
Estrogen and estradiol, and in particular estradiol, are the signal for the promotion of the growth of the tumor in those hormone receptor-positive breast cancers. From the epidemiological perspective, about 80%, 79% of all the diagnosed breast cancers have this positive hormone receptor, either luminal A or luminal B, depending on the HER2 receptor. In all of them, the tumor is candidate to be treated with our formulation. Considering the stage of diagnosis, 65% of all of them are localized at the moment of the diagnosis, which means the status of the breast cancer is early breast cancer. Typically, in this situation, the female patients are having endocrine treatment for at least 3-5 years, and aromatase inhibitors represent about 66% of all of the treatments that are prescribed.
When the tumor is locally invasive or has a distant metastasis, it means the tumor is in advanced stage. Typically, in this kind of treatments, an additional treatment is added on top, but the hormone inhibition remains or endocrine treatment remains to be the baseline of the treatment in those patients. Most of the times, at least in Western Europe, CDK4/6 inhibitors are also used as co-medication, and this shows that it will also transfer to our design on the clinical trial. Overall, letrozole remains the most used drug in this field when the tumor is positive to hormone receptors. We are currently in the readout of the phase I results of our phase I single-ascending dose clinical trial in healthy volunteers.
Let me introduce three important, very important takeaways from the results that we have observed in this clinical trial. The first one is that quarterly 225 intramuscular injections of letrozole are superior in suppression of estrogens compared to daily doses of Femara 2.5 milligrams administered orally, and this at perfect adherence. The second is that the formulation is very well-tolerated. Miguel has already introduced the exceptional tolerability that therapy has, and this is related to the sustained plasma levels that are maintained of the hormone suppression and estrogen letrozole levels. Third, thanks to our technology, which is also a characteristic of our formulation, letrozole plasma levels are achieved very fast and are sustained for the whole quarter, and the PK is linear.
This means we can extensively use the PK modeling that is predicting the range of the expected range of plasma concentrations in pivotal clinical trials, therefore giving a lot of visibility and reducing the attrition rate on the success of the clinical trials. These excellent results allows us to progress to phase III efficacy clinical trials in which we have two big objectives. The first one is that aromatase inhibition is the only pharmacological effect of letrozole and anastrozole, in particular letrozole. We want to verify that the superior capacity of this formulation to suppress estrogen has a clinical impact in clinical events of the disease like progression-free survival or overall survival. Let me remind in this moment that the literature also describes that the lack of estrogen suppression in patients that are taking oral medication is significantly large.
About 50% of the patients that are taking the medication are not in suppression, and our predictions and the readout of the results are considering superiority at perfect adherence. The second main objective is to obtain evidence of an improved tolerability profile that is expected for the maintenance of the steady plasma levels. Our pivotal clinical program is going to start in the last quarter of this year, and is intended to consist in two different clinical trials. The first one is a phase III efficacy clinical trial in which we are going to compare our formulation to daily oral doses of Femara, both in combination with CDK4/6 inhibitors, which are the standard of care in the population that we intend to conduct this study, which is female postmenopausal women with locally advanced or metastatic breast cancer.
The primary endpoint will be based on the observation of a surrogate endpoint of efficacy, probably progression-free survival. The specific details of this clinical trial are pending to be reviewed by the regulatory authorities. Rovi anticipates to use also as a standard of care and to be requested to provide the CDK4/6 inhibitor with a significant cost for the clinical trial. The second study will be a PK bioavailability study to compare in a steady state the exposure of quarterly 225 milligrams of our formulation of letrozole to daily doses of Femara in a steady state. Approximately 100 patients will receive oral medication for some days, 2.5 milligrams of Femara, and then will switch to four doses of letrozole 225 milligrams. The potential market of our letrozole formulation is very big.
About 1.1 billion oral daily tablets are being prescribed and used worldwide, which can easily be transformed into 3 million treatments per year. Considering an average price of EUR 600 per treatment, which means EUR 2,400,000, more or less similar to the cost of antipsychotics in the European market, we are talking about a EUR 7 billion market, which is very big. As you know, we have previously explained, there is no other competition in the market. No other company is developing long-acting formulations in this field. The opportunity from the market perspective is very big.
We have an analogy in the prostate cancer in which we can see there are five molecules in the market that account for about 89% of the whole market and total sales of about $2.5 billion. Now let me briefly describe the status of our quarterly risperidone formulation. We are developing a quarterly formulation of risperidone that is very similar in the concept to Okedi. It's capable, thanks to our technology, to provide fast plasma levels and keep them sustained for whole quarter without the need of oral medication, not even additional loading doses or or previous stabilization with a monthly formulation of risperidone long acting.
With the clinical program, we are aiming to obtain the same indication as Okedi in the label, which is treatment of schizophrenia in adults for whom tolerability and effectiveness has been previously established with oral risperidone. The expected clinical package is very similar to the package that we conducted with Okedi and will involve two additional clinical trials. The first one is an efficacy clinical trial in which we are going to compare oral risperidone to our quarterly formulation in patients with unstable disease, so patients with moderate to severe symptoms. The second clinical trial is a PK bioavailability study in which we are going to compare the total exposure of our 300 mg risperidone formulation versus Risperdal 4 mg orally administered. Also, like, with the Okedi formulation, clinical trials are expected to start in the last quarter of this year.
Finally, let me brief as a brief description on Terafront Farmatech. On March 2024, Rovi, Insud Pharma, and Innvierte, which is the capital company, investment company of CDTI, Centro para el Desarrollo Tecnológico Industrial, got into an agreement to create Terafront Farmatech, which is a platform engaged in the development and research of advanced therapies. This agreement favors the development and the deploy of technical and industrial capabilities to support the capabilities to generate a high-performance healthcare system intended to provide health by promoting immediate and flexible responses to healthcare challenges and favoring sustainability. Rovi has a share of 25.5%, and Insud Pharma also has the same share, and Innvierte has 49% of the total share of the company.
The initial contribution that all the companies have conducted is EUR 75 million, and we are expecting to have future investment requirements of EUR 220 million total. Now let me give the floor to our Deputy Chairman and CFO, Mr. Javier López-Belmonte, for the financial update.
Well, thanks, Iván. Good morning, everyone. My name is Javier López-Belmonte, Deputy Chairman and CFO of Rovi. During this last part of the presentation, and before diving into the Q&A session, I will provide an update of the financial performance of the company over the last five years and as well as our future growth prospects. As you can see in the slide, we have been delivering a very robust financial performance since 2020, and we've been able to deliver a CAGR growth rate of 16% from 2020 to 2024, as you could see on the right-hand side of the slide. We have demonstrated a strong operational leverage over time. It's also clear that 2024 has been a transition year for Rovi, crucial for establishing the basis for our future.
The company is currently undergoing a period of where investment is essential to drive our growth and position the company for the long-term success. In this context, in 2024, operating revenue was EUR 764 million, with a decrease of 7.9% from 2023 sales, mainly due to the performance of the CDMO business. CDMO, as you have in the left-hand side of the slide, CDMO sales fell to EUR 336 million.
Mainly, I would say two reasons: the lower revenues from the manufacture of the COVID-19 vaccine, and second, as you all know, we have lower revenues related to the activities that we carried out to prepare the plant for production of the vaccine and their different agreements. However, we continue to see good performance with our specialty pharma division, where sales were up 2% to EUR 427.5 million in 2024, no? Positively impacted by Okedi, Neparvis, and Bemiparin, and also the contrast agents and other hospital products, no? I will touch on their performance in the following slide. So you'll see on the pie chart on the left-hand side of the slide the breakdown for the division in 2024, no?
87% of the sales of the division corresponds to the prescription products, around EUR 373.4 million, while the remaining 13% were from contrast agents and what we call other hospital products, which are around EUR 54 million. On the right-hand side, you can see the different performance of the main products, starting with Enoxaparin. Enoxaparin, we had a little slowdown of sales last year, which, it was partially recovered by an impressive last quarter of the year. Sales amounted to around in last quarter, EUR 44 million, and in total of the year, EUR 145.2 million, no? Additionally, Bemiparin sales increased by 2% to EUR 96 million also last year, no? Okedi and Neparvis also contributed in a positive way.
Neparvis, you know, is the specialty product that we have from Novartis for chronic heart failure and increased by 13% last year. Meanwhile, Okedi, our flagship product, continued to grow in a very healthy way, and we have sales that double sales of those in 2023. Moving to EBITDA and CapEx, from the left-hand side of the slide, you could see that we've been able to double our EBITDA group level since 2000. In 2024, EBITDA figure was EUR 207.4 million, meaning a slight decrease of 15% compared to 2023, no? That reflects a 2.3 percentage point decrease in EBITDA margin, which again decrease in absolute way 27.2 in 2024.
Moving on to CapEx on the right hand of the slide, you see that we invested EUR 62.2 million last year. Basically out of these, EUR 62 million, EUR 46.6 million related to investment CapEx regarding our facilities, no? As you know, we are adding new filling lines, and we're expanding our operations. We are also investing on the ISM industrialization, and we are adding investment to the JV, to the Glicopepton JV. Lastly, from the CapEx figure, let me remind all of you that we had around EUR 15.5 million with regards to maintenance, which is more or less evolving in the same way next years, no?
Important to highlight is our cash conversion rate, which last year and since 2021, higher than 70%. If we compare side by side the results in 2024 with those results to 2023, we can see, starting again on the left-hand side of the slide with the gross profit, that gross profit decreased 2% to EUR 478.5 million. That means that the gross margin was up by 3.7 percentage points to 62.7% in 2024, no? This increase was due to the contribution of the manufacturing business. You know, the existing customers, excluding Moderna, that has, I would say, a negative gross margin.
The decrease also, for this positive evolution of the gross margin, we have the decrease in the contribution to the CDMO business of the revenue relating to these, what we call activities, no? To prepare the plant to manufacture, drugs under different agreements, which always try to emphasize that has lower margins. For sure, also a positive item for the increase of the gross margin was the increase in sales for Okedi. As we said before, EBITDA, as you have following the slide, has a slight drop of 2% in our EBITDA margins from 2024 to 2023. On the bottom of the slide, we can see the evolution of the G&A, which last year we have an increase by 5.6 percentage points, no?
In the G&A compared to 2023, due to increase of the personnel expenses. This is highly related to the collective agreement that was renewed last year. Also an increase of 13% of what we called other operating expenses, which is mainly linked to the launch of Okedi in Europe and other non-recurring expenses. In fact, if we don't take into account these non-recurring expenses, the other operating expenses only grew by 5% last year. Similar way, R&D expenses slightly grew by 3.3% to EUR 25.8 million. Finally, net profit last year decreased by 18.6% to EUR 136.9 million.
You can see here in this slide the breakdown of the CapEx on our cash flow evolution last year and the debt structure that we have right now in the company. If we started from left to right and from top to bottom, you see the CapEx that we already commented that was 62.2 million euros spent last year. Most of the CapEx was related to the new filling lines and operation expansion, 57%. If you see the evolution of the cash flow on the right hand side, net debt increased to EUR 85.1 million. This, as you could see, is a very small debt, a very conservative net debt to EBITDA ratio.
Only 0.4 times EBITDA, which is very low and highlights our strong balance sheet position. Most of this debt is held with financial institutions, bank borrowings, which accounts for 76% of the total debt. In this total debt, we also include these financial liabilities for leases, the IFRS 16. On the right-hand side, you could check our future debt repayments. Which as you could see, they are very smooth, and they will go away in the next 6 years. I like this slide about our capital allocation because it always comes in our all our investor meetings and face-to-face one-to-one meetings. It's the basics of how Rovi allocates our capital and how we deploy the capital at Rovi.
We first of all always consider the shareholder remuneration. As you know, we believe we have an attractive and recurring dividend policy. Around 35% of our net profit has been distributed to investors since the last years. We have been able also to complete several share buyback programs. In total, above EUR 300 million in the last four years. We are still committed to keep distributing dividends in the future. But we also committed to invest in production capacity.
We have, in the same way, we have invested EUR 180 million in our eight different facilities in the last five years. We are about to keep investing, and we have already highlighted this new important investment for the San Sebastián de los Reyes plant, which includes around EUR 60 million investment, no? As Iván López-Belmonte has been explaining to us today, we have big, also big plans for our R&D capital allocation and investment with these two different programs that we've been showing to you today, the Letrozole and the Quarterly Risperidone. Let me say that all of these capital allocation is always managed with a focus on having a very strong balance sheet, no?
We like to have this strength in our balance sheet with this low net debt to EBITDA ratio. We for sure will keep this conservative balance sheet management in the next coming years, no? Right. starting with the outlook for 2025, there are no big news here today. as you can already check, we haven't changed the outlook for this year. we reiterate this decrease by single mid-digit % versus 2024. you know, we have several times explained about this. It's still difficult for us to forecast the evolution of the CDMO business. You know, we always mention two different factors. I would say the main one is how difficult it is to predict vaccination campaigns these days.
You know, the swing in the vaccination ratios since the pandemic ended. We cannot for sure know how to predict the evolution of the vaccination campaign this year, no? Second, we also, you know, we have thoroughly talked about the expansion of our CDMO business capacities and this is still also difficult, no, to assess how the sales impact for new customers will be this year, no? This is considered, but it's not always easy to estimate, no? As we've been trying to explain to you today, 2024 and 2025 for us are clearly transitional years. I think that's the message.
The company is still making significant investments to lay the foundation of Rovi's future growth, and we try to explain to you in this Capital Market Day which drivers of growth the company will follow for this multi-year growth strategy that we are having in the company. Basically we still rely on our established European footprint, which will continue to deliver growth not only for Okedi, which we believe it will be very successful, but also for our low molecular weight heparin platform. For sure, on top of that, the future avenues of growth that will come from our CDMO business, no? All the efforts that we are deploying to boost and develop the Letrozole and the Quarterly Risperidone program. Right.
We move to the last slide, and the one that I'm sure will attract more attention today, which is the long-term indicative guidance for 2030. Again, starting with our operating revenues, we are estimating the company to grow between 1.5 times-1.8 times compared to 2024 revenues and in 2030. I think it's an impressive growth that will drive the sales of the company to EUR 1.15 billion-EUR 1.3 billion possibly in the year 2030. As we disclosed earlier in the presentation, CDMO is gonna be the main driver of growth, the CDMO business, and we expect this business unit to double, no?
To multiply by two, to double the size of the business, up to the year 2030, meaning sales possibly around the EUR 700 million milestone. With regards to specialty pharma, we are estimating that it will be growing at a low single-digit % growth compared to this, 2024 sales as a base comparator. In terms of EBITDA, I think this is, for me, even more important, no? That our EBITDA pre-R&D level we're about to deliver, we believe that we will be able to deliver a very strong operational leverage that will boost our EBITDA by 2.5 times, and between 2.5 times and 2.8 times the EBITDA pre-R&D levels of 2024, no?
This range is based on a significant gross margin expansion due to the different factors that I believe we have been explaining to you today. The increase of sales of Okedi, the increase of sales of the CDMO business, possibly the contribution of the increase of the heparins too. Also, we are increasing the EBITDA because we are maintaining the operating cost somehow in a moderate way, no? We do believe that our business, and especially our CDMO business, is heavily based on fixed cost, no? I would say that approximately in our facility, we could have around 70%-80% fixed cost, no?
That will imply that once we are able to deliver and to increase the output, we can increase the operational leverage of the company, no? With regards to R&D expenses, you have there the number. We are expecting to increase the annual average expenditure of R&D from 25.8 in 2024 to a range between EUR 40 million-EUR 60 million during the period of the following five years, no? Again, you know, the main driver of cost in this case, and the main driver of investment will be our letrozole program, which we will devote potentially much more money than for the latter for quarterly, and because as Iván explained to you, it's a much more appealing program. That's all. That's all from the financial section.
Thank you very much for your attention today, and we can now move to the Q&A session. Thank you.
Thanks, Javier. We have received a lot of questions. As we only have less than 40 minutes, if any questions remain unsolved, the IR team will answer them. People attending in person, raise their hand and someone will come with a microphone. I'm going to start with an online question just to give time to the person with the microphone to reach the first in-person participant. Javier, the first question is for you and it comes from Nicholas Schmidlin from Prolific Schmidlin. How do you think about capital allocation, in particular once the fill and finish built out has been completed by 2027?
Oh, thank you, Marta. Well, I love capital allocation questions because it comes very often, you know, in our face-to-face meetings or one-on-one, one-to-one meetings. Basically, we tried to disclose this morning, we have different capital allocation criteria. I would say that again, these next years we will allocate good money to increase our operational capacity. We're adding new filling lines. On top of that now, as we have disclosed, we are investing also or increasing the investment on R&D now, so we will devote around EUR 300 million now in the next five years, you know, for R&D. Again, we are always looking for opportunities to keep the growth of the company.
We don't forecast to do any transformational M&A. I think that's important, and that is also a message that I want to reinforce in the sense that the company still believe that our organic growth could deliver much more interesting growth and return to the shareholders rather than transformational M&A. Having said that, we always keep an eye open to what we call cherry-picking opportunities, either in the specialty pharma area, you know, where we have a tremendous opportunity with European footprint now, where we can add products now in that front, or why not to say in other areas of the business where we could add some assets that could spur the growth of the company, you know.
Always in all our capital allocation assessments, also we value if we can, you know, increase the remuneration to the shareholders, which is more accretive for the business. If we can always have the possibility to do share buyback programs if we don't find any other more attractive opportunities in the market.
Good morning. Thank you very much for the presentation. Very useful. I have a couple of questions. Looking at your targets in CDMO, you're expecting EUR 700 million in 2030, which is assuming also 75% utilization ratio, right? Here my question is regarding this is driven by volumes or are you also expecting some price increases? Because obviously with the lack of supply we are seeing in the market, we should expect some probably some price increases. That would be the first question. The second one would be also regarding capital allocation because, well, you have talked about the R&D for the next years and CapEx, but even assuming this, under my numbers, I'm expecting free cash flow of close to EUR 350 million, EUR 400 million by 2030.
What should be the capital allocation after this CapEx and R&D numbers you are talking about? Thank you very much.
Okay. I will take this one. With regards to your first question now about the CDMO evolution, if it's about volumes or about pricing, I think we'll try to show you that it's about both. No, but specifically we are investing on new capacity. We have, Miguel has said that we still have, I wouldn't say low, but a reduced or a big spare capacity, you know, between 40 to 45 to 50% spare capacity. We have a clear avenue of using that spare capacity and try to target a spare capacity of around 30% in 2030 when we achieve that, in a few years' time.
On top of that, it's clear, and I think it's on the market now, the sentiment that there is an imbalance between demand and supply right now in the market about the injectable CDMO and the services around that sector. I believe that also we have an opportunity to increase prices from the legacy customers and also for new customers. I guess it would be a combination of both, as you were saying, but mainly about increasing volumes, which is, I would say, the main direction that we are taking. With regard to your capital allocation, again, I said it before, I think we are investing heavily on CapEx, as you were mentioning, and R&D.
If the free cash flow is there, and if we see that our balance sheet keep growing and keep being more solid, again, as we have done in the past, we wouldn't hesitate to do a share buyback program if is that the right thing to do. I mean, that meaning that we don't find any alternative investment in the market, no? I'm sure that if we achieve, you know, all these milestone and high targets, I'm sure that we will find new opportunities to put the money on and try to deliver more, even more growth in the next cycle of the company now. I'm not that worried about capital allocation. We are focused on executing the strategy of the company and try to deliver all these targets in the next coming years.
Hello. Guillaume Sempé from CaixaBank. One question regarding the phasing of this growth until 2030. On the toll manufacturing business, you've recorded this 336 level of sales in 2024. For 2026, where I have new contracts starting to contribute. There's between what you announced in terms of target and what we know in terms of sales with the building blocks around a EUR 250 million gap that I assume comes from new contracts. This contribution should be seen more post-2026, 2027, so more backloaded, or is something that we could expect already over the short term? And the second question regarding the variability of your guidance.
In the high end and the low end, you have a EUR 230 million difference in terms of sales. This is more attributed to different expectations on the CDMO business or something on the specialty pharma that could come from license agreements or anything? Thank you.
Okay, I will take the first one and Juan will take the second. I mean, with regards to your first question about when we should expect the most important part of the growth, no, for the CDMO business. I mean, firstly, we have already shared the guidance for 2025, no? So we have a slight decrease of the revenue for 2025. So that means that even potentially the sales base that we are comparing 2030 is gonna be a, you know, a bigger growth in the next coming years because we are possibly having a decrease in 2025, no?
I would say that, as we have always reiterated, 2026 we'll see a kickoff or a trigger in new contracts that they start to be paid out to, we will deliver that output, potentially and in a meaningful way. 2027 we'll see a much more important growth. Again, the bad part of our business is that these are very slow-moving business. You know, it takes a lot of time to sign contracts, and then once a contract is signed, it also takes an awful lot of time to start manufacturing on a routine basis, no? In that case, we do believe that the most part of the growth will come from 2027 onwards, no.
Regarding the second question on the gap between or the difference between the lower and the high end of our guidance, I think I just want to reiterate what Javier has mentioned before on the different thing. We are right now in execution phase. Basically what we have had in the last three, four years invested in setting up the ground, the foundation of what is going to be the growth in the next coming years. I think the gap between the lower and the high end of the guidance is going to come from both sides of the business.
On one end, the CDMO, we have invested heavily, not only in expanding the capacity, as Javier has just mentioned, but as well on different formats. Prefilled syringes, cartridges, which is going to be a very interesting and attractive new line of revenue. As well, packaging with new assembly lines that we have mentioned, Miguel, in his presentation. All we see, the more contracts and revenues, they have a, let's say, a timeline of 2 years since initial contract signing. You have to go through regulatory variations, validation batches, so it takes some time to materialize the revenues. As well on the specialty pharma business, we have on one end Okedi. As I mentioned before, we believe the launch has been extremely successful.
We are there on the track to reach the high end of the revenue guidance that we have provided to the market. Having said that, there are uncertainties on how cost containment measures in Europe, and I don't want to extend myself on the geopolitical situation we are living right now, how that can impact on price erosion. As well, we are having right now extensive talks with different pharma companies for potentially licensing agreements, which again, we believe that it can provide as well, a push towards the high end of the guidance. As I mentioned before, and Javier, it's something that we have reiterated throughout the presentation, we are right now in an execution phase.
I mean, what we have been working extremely hard with the team is to setting up the grounds so the growth is there, and it's a question of the team right now to deliver and to be sure that we execute and we leverage the opportunities that lay before us.
Thanks, Juan. I have a question for you, Miguel Ángel, from Sergio Parrado from Brincasa. Congratulations on the Capital Markets Day. You're assuming 70%-75% capacity utilization. How does that compare with traditional capacity utilization in Rovi and normal capacity utilization of other CDMOs? We would like to understand if that is a conservative assumption or utilization could be 80%-90% at some point.
Thank you, Marta. I would say I think that in the presentation we have shown the evolution of this utilization rate in our operational network. Taking out the pandemic times that are distorting obviously the level of operations, we our way of working is to have utilization rates around minimum 75%. You can see in the presentation before 2020 that we have this level of utilization rate and the execution phase, as Juan said, is to turn again to this high value of utilization rate after filling the capacity that we have heavily invested on these years.
The consequence of the investments is that now our utilization rate is lower, 50-55%, and the only thing that we need to do is to fill this capacity thanks to the imbalance in the market regarding the outsourcing capacity. We will reach the 70-75% thanks to these increasing volumes that we mentioned before, thanks to the new contracts. Regarding the second part of the questions about the ideal level of utilization rate, we think that 70-75% is a realistic conservative target, and beyond 85% could be a risk.
Sorry, I just had one quick question linking to that one. The gap that you gave on the PFS from 610 to or 625 to 810 seems. Why is that so large a gap between the two estimates in capacity?
I can take this one.
Sorry, just to add to that, it does seem like you're embedding some price appreciation as you evolve on the business, which, given, I guess, the presumed capacity coming into the market, why do you, I guess, have some confidence that you will be able to keep prices or even increase prices for the CDMO? Thanks.
Thank you. Yeah, it's not always easy to assess your full capacity because obviously there are different scenarios based on multi-product strategy in your operational lines. It always depends, this capacity, about the complexity of the product, about the volumes that you will introduce from the same products. This is the reason why there is a range in the capacity considering different scenarios. In any case, what we can say is that this range of capacity is based on our historical overall efficiency equipment, that means that our realistic capacities increase.
The difference to be in the high part of the range or not, it depends of the future contract, future products and depending of the complexity of the processes. Regarding the second part of the question, I think that was mentioned before, we expect due to this imbalance between the demand and the capacity today that can be offered in the CDMO marketplace, that even can have some increase in prices in the future. This is part of our scenarios of growth linked to additionally to the increase in volumes and utilization rates.
Hi. Álvaro Lenze from Alantra. My question is on if you could provide some additional detail on your process of having new clients jumping on board to the CDMO business. Because we had the announcement last year, maybe that was a one-off thing because it was so large that you had to disclose. But we, I think, don't get the sense of whether you're
Continuously signing new clients that are just too small to be made public? Or is it that the negotiations are taking longer than we expected? Just to get the sense of how much of the guidance can you achieve with the clients you already have and the contracts you have already signed, and how much requires new clients jumping on board. My second question would be on the development of letrozole. So if I understand correctly, you're no longer looking for a non-inferiority trial, you're looking for superiority. I think that was the original design, and I have thought that you have changed to non-inferiority. So why the change? Is it just because of the phase I results that you now have? I don't know if you are getting into higher risk pursuing a superiority trial.
Thanks.
Okay, I'll take the first one. I think we have tried to explain that. I mean, asking your question about new customers, how we onboard customers and how we do sign contracts, you know, with them. First of all, I think I can say very bluntly that customers normally will not allow CDMO to make anything public. We are just suppliers, we're just providers, but we are manufacturing the products for big pharma companies. So they, on general basis, they don't want anyone to know or they don't want the public to know, to acknowledge that they are not manufacturing the drugs they are selling. I think that's a basic rule that applies to all CDMOs and to all large pharma companies, you know.
In the case of the April contract, you were right, you know. I mean, it was so material to us that we needed to negotiate with the customer that in order to abide with the CNMV rules, we needed to make some statement, you know. Because the info was well-known within a big number of people within the company and within the customer and suppliers, that we need to make sure that we comply with the CNMV rules. Normally we cannot make disclosures, you know. Unfortunately, we cannot tell you if we are adding more customers or not, unless there's something very material. Coming to the question about how we have...
How do you foresee, you know, the evolution of the business, if it's with the existing customer or we would need to sign new ones? For sure it's a combination of both, you know. When we are forecasting these big numbers, which is doubling our existing sales, on the one hand we have the already signed customers, ones that we are already manufacturing on a routine basis, and others that we are still not manufacturing on a day-to-day basis.
On top of that, you know, we are assessing our pipeline, we are assessing the contracts and the contacts, you know, that we are having and the evolution of the market, and we are estimating that some percentage of those will become real, will become signed, or we'll get those signed, and some even in the next coming years. You know, it's. We're talking about 5 years, so we expect some other customers to be signed and being fulfilled. I can tell you that we've been conservative, you know, that these figures are not something unrealistic or something that made out of nothing. You know, it's been a good assessment of the pipeline, of you know the sum of the contracts already signed.
I think we haven't commented this yet, we believe there is a great opportunity in the market because one of possibly the main player in the field is being taken over by a large pharma company now, which is the case of Catalent, and is no longer being in the market or is gonna be supposedly no longer to be in the CDMO environment, you know. It's another big opportunity for the rest of the CDMO players, and they can capture, why not to say, this current business, which is above possibly 80 or 90 customers, you know.
Yeah.
It's a great opportunity for the rest of the CDMO players, you know, to host the current companies that are being manufactured by Catalent.
Just let me to add that, as Javier mentioned, our industrial development team is working at full speed. As we mentioned previously also, to sign a contract with a top pharma company is a lengthy process for mainly two reasons. Because as we explained during the presentation, we are talking about really complex products. We are talking about biological drug substances that should be filled in aseptic conditions, in a very strict quality conditions. On top of that, we always talk about long-term agreements. Our business model is long-term partnership, and to sign a contract for 5-10 years is a lengthy process.
Considering the response to the second question, we have not changed our approach on the basis of a difference in the superior capacity of our formulation to suppress estrogens. That can be linked, as I have previously explained also, that we want to evidence that there is an impact in clinical endpoints that are recognizable by the regulatory authorities, like progression-free survival, overall response rate, or maybe overall survival. That approach does not change. The statistical approach to the clinical trial that can contain either a non-inferiority design or a superiority design is something that is a matter of discussion with the regulatory authorities, so we are now in the readout. This is a 505(b)(2) approach. Of course, somehow different to our previous letrozole formulation because we are now matching the exposure to the API.
This is why we are intending to get one single efficacy clinical trial to achieve all the indications. The specifics on the statistical approach are pending to be reviewed by the FDA, in particular, and probably with the regulatory authorities in Europe. We have not changed our approach. The concept of risk, considering that we are developing model-based products, once we demonstrate the superiority in the suppression of the hormones relates to sample size, cost, and probability of success. We have already demonstrated with Okedi that our approach is very powerful predicting efficacy. This is how we did in the past, and this is how we intend to approach also the letrozole and also the quarterly risperidone formulation developments.
Iván, I have another question for you from Joaquín García-Quirós from JB Capital. How long will it take to complete letrozole phase III? When could we expect some readout news?
Well, the letrozole phase III duration also depends on the specific requests of the FDA. We're anticipating the clinical program to be finished by the end of 2029, but of course, this is our first approach. There are a number of things that have to be considered on that. One is the requirements of the FDA about the alpha and beta on the final readout of the data that are transformed into the sample size and duration of recruitment and of course, the follow-up period, no? That gives a wide variety of possible variables that have to be managed and discussed with the regulatory authorities.
In principle, as far as we are understanding the previous requirements in our previous meeting with the FDA, we are anticipating that the clinical readout of the results of phase III will be by the end of 2029, maybe beginning of the following year.
Hi there, thank you for taking my question and for the great CMD. I have two questions. One on the CDMO. How big do you think is the execution risk to start production properly in 2026? You signed a contract about a year ago, so is it according to the timeline you set out back then? Do you see any problems coming up there? Maybe you can elaborate a little bit on that. The other one is on risperidone and letrozole, launching to the phase III trials, and you already said something about the timeline. Will the cost for that be covered by the increase in R&D you already alluded to, or will you be partnering on the research side?
Second to that, when you wanted to go to the U.S. with risperidone, it was difficult to do that without a partner. How do you think about both going forward, to launch into the U.S., possibly? Thank you.
Yeah. Regarding the first part of the questions, at this moment, we don't see any risk regarding the production of commercial phases for the agreement that we sign. As we explained before, after signing a contract, there is a lot of activities to reach the market, starting with all the engineering runs in our own lines. Later on, it's necessary to do all the PPQ batches or the validation batches and to obtain the data for the stability before the regulatory submission. This is the standard process. We are fully aligned in the timelines with these steps, and so I cannot see any risk in reaching the commercial phase with our agreement.
Regarding the second question, the cost of the clinical trials are included in the research and development cost that we have guided today. Regarding the second part of the question, quarterly risperidone, we are only going to develop the product for the European market and the system markets. Regarding letrozole, we have really high expectations. I mean, the main difference between risperidone ISM and letrozole is that in risperidone, we were really followers. We were just coming with a product, obviously unique with a monthly injection in Europe, but we were not the first ones to launch a monthly injection of risperidone in the US. On the other hand, letrozole, we are really being the first ones to develop such a concept in breast cancer.
Actually, following the question before that Iván López-Belmonte has answered, we are going to have a significant advisory meeting with the FDA later this year. Actually, the final design is going to be dependent on the feedback from the FDA, because we do believe that for letrozole the FDA opportunity is immense, is very attractive, and definitely our expectations regarding letrozole are maximum in that sense. The good thing in terms of predictability, risperidone has been a tremendous learning lesson. I mean, not only in terms of clinical development, in terms of knowledge of the technology, but as well in terms of FDA inspection of the industrial setting of ISM.
Again, the harder sort of uncertainties regarding letrozole for the U.S. are going to be. I wouldn't say minor, but I mean, less unpredictable than we had with risperidone.
Yep. Juan Ros-Padilla from Oddo BHF. I have a question regarding the CDMO. Sorry to insist. I don't know, maybe you can give us a sense of how many potential new clients are you currently in talks? Maybe elaborate a little more on what are the main friction points. Is it price? Is it, I don't know, some kind of technicalities or adapting your production to that specific client? Maybe you can give us some more detail there. Thank you.
Well, I would say that we are talking to many, many partners as a consequence of this imbalance in terms of capacity to be offered. As we mentioned during the presentation, the great advantage of Rovi Industrial Services is that this capacity can be offered today. This is the spare capacity that we mentioned regarding the utilization rate. The difficulty for us is just to see if the number of clients will be 3, 5, 4 or 10, depending on the volumes and the length of the contract that we will establish with them.
I mean, we can just obtain in a contract as in the previous agreement 100 million PFS, or we can just reach agreements with a couple of companies with half of these volumes. What is clear is that we have already this capacity, that we have the expertise in the most important category products that are driving the CDMO, the market, the pharmaceutical growth. We will return to this utilization rate by filling this capacity in the coming years.
If I may add something, I think Javier has mentioned before, but I really need—we need to reemphasize on the CDMO. We have two avenues of growth there. The first one is the injectable market is just booming. So you have plenty of therapeutic areas where new launches of injectable compounds, not to mention GLP-1s, not to mention ADCs, biosimilars. I think we have provided some data how the market is just on a therapeutic usage, is just growing probably as the fastest growth we have ever seen. But the second avenue of growth, which is something that we need to reiterate and put it on the table, is that at least 80 customers are looking for housing after the Catalent acquisition. So we have here two trends.
The first one is the market itself that is growing in terms of units, and I think we have provided you plenty of information in that slide. Secondly, and it's something that we also need to put it, and to give it the importance that it deserves, is that the number one market leader has been acquired by a top pharmaceutical company. Those 70-80 companies, which they are right now manufacturing on their facilities, they will need to find somewhere else. Really, the CDMO is right now. I don't know if it's a hot topic, but really the imbalance is in two ways.
The first, the market itself is growing in units, and secondly, because all of a sudden, I don't know the market share of Catalent off the top of my head, but that market share will disappear in the next 3-4 years. That's why we do believe that by 2030, I mean, we have all the ingredients to really make ROIS the market leader worldwide because we have the people, we have the capabilities, and we have the expertise, and we have the capacity now. I mean, we can discuss with customers today about factual and actual capacity, and that's what really makes a difference, and that's why we are so positive on the revenue guidance that we have provided today on the CDMO front.
Paco.
Okay. This is Paco Ruiz from BNP Paribas. I have three questions very quick. The first one is on the calendar of your R&D expenditure. I mean, if it's gonna be front-loaded and we will spend more of this EUR 40-60 per annum in the coming 2 years, or it's gonna be equally shared in the following years. The second one is on slide 19 when you talk about the capacity utilization. You said 50%-55% at the end of last year. Does it include the contract that you won on April or is without it? Last but not least is on your guidance.
On excluding the CDMO business, guidance, on especially pharma, you expect a mid-single digit growth, that if we exclude Okedi. That means that the sales are not growing more or less. I mean, is this because you expect decrease on Neparvis or what's the reason for that?
Just let me answer your last question. I will let the rest of the team answer the other ones. Regarding the guidance on revenue on the specialty pharma, you have to bear in mind that our major product Neparvis, I mean, the patent expires sometime next year. That is going to mean that out of sales of slightly over EUR 50 million, EUR 50 million-EUR 60 million, they will have a sharp decline in terms of price, easily between 40%-60%. The low single-digit growth that we have guided on the specialty pharma business includes this price erosion and these sales erosions that Neparvis is going to suffer.
On the other hand, we are forecasting growth on the rest of the franchise in order to offset that decline because of price erosion, because it's, I mean, the patent expires, I mean, the regulatory environment works that way. Generics will enter into the market and at least 40%-60%, probably even more of the sales will be gone. On that guidance is included as well that price erosion that can also suffer to some extent Orbera from 2027 onwards and probably Volutsa as well.
We do expect certain growth on the rest of the products and actually the rationale behind investing on Glicopepton is not only cost efficiency, gross margins, but if we manage to obtain those CapEx, obviously it will have some effect as well in our revenue line on the Neparvis. I mean, we do foresee growth in specialty pharma, but we have all those sales to compensate because of the patent expirations.
Yeah.
Regarding the second part of the question about the product related to the agreement that we signed in 2024, as I mentioned before, we are totally on time with the milestones of the chronogram in order to introduce the product, but we are still in the tech transfer phase. The commercial routine of the product is not included in the utilization rate of 2024.
This 50% is without the EUR 100 million?
Correct.
EUR 100 million.
100 million syringes. Yeah, correct.
Finally, your first question about the R&D expenditure and the evolution during the next 5 years. Let me answer you that, in our forecast, the cost is not as balanced as the average, so we are expecting having a bigger cost from 2025 to 2028, and maybe Iván López-Belmonte can explain the reasons for that, no?
Yeah, sure. Of course, we are starting for clinical trials, both PK studies, multiple dose in a steady state will finish before the efficacy studies. That means that there is part that is dedicated to the cost of those clinical trials that are more concentrated in the previous years, no? On top of this, the efficacy clinical trials also have a higher cost at the beginning. Setup of the clinical trial, purchase of the medication, initiation of the centers. We are talking about a big number of hospitals to be opened, so there is a significant startup cost that logically is transferred, no? On top of this, there is a higher pay per patient by the beginning of the participation of the patients in the clinical trials and then the follow-up. Slowly the visits are more with more duration, no?
Of course, the last year of the readout of the results is just the preparation of the review of the data cleaning, importing and everything, and the cost reduces significantly, you know? As Javier has mentioned, maximum expenditure is expected on the first two years.
We are out of time, sorry. The pending questions will be solved by the Q&A team in the coming days. Let me now turn the floor over to Juan López-Belmonte Encina, our President, Chairman and CEO for the closure of the presentation. Thank you.
Well, thank you to everybody. We are at the end of the presentation. I think it has been a very exciting day. I don't think we ever had so many investors and analysts in our Capital Markets Day we have today. First of all, I really want to thank you for taking the time and your commitment to be here with us. I think Rovi's management team, Miguel, Angel, Javier, Iván, you know, Angel Castillo, and the rest of our team will be more than willing to answer any additional question or additional info that you may require for any of the topics that we have discussed today. I do believe and I think that's something that we have reiterated today, that we believe the future holds great for Rovi. We have all the ingredients.
We have been investing heavily to have all these levers of growth ready to deliver. We hope to see you again on our next Capital Markets Day just to check out if we have managed to deliver the milestones that we have shared with you today. Now just as a practical remark, I believe we are going to have a wine and a Coke and a snack right here, so we can just keep on talking. If you have any other question or information, we are more than willing to discuss it with you. Thank you so much. Thank you.