Good afternoon, and welcome everybody to this first half results virtual meeting, which will start in a moment. This is Javier López-Belmonte, ROVI's Vice President and Chief Financial Officer. Please let me introduce ROVI's attendees today. Juan López-Belmonte, Chairman and CEO, Marta Campos, Head of Investor Relations, and myself. At the end of the presentation, a question and answer session will commence. If you want to ask any questions during the presentation, please do not hesitate to send them through the question button on the platform. Thank you for your presence here today, and let's now start the presentation. I give Mr. Juan López-Belmonte the floor.
Thank you, Javier. Welcome to everybody. I'm happy to present our first half 2022 results. In these exceptional times, ROVI's performance during the period has been above our expectations. Our 31% operating revenue growth was driven by the strength of the CMO business, which grew by 76%, and by the specialty pharmaceutical business, which grew by 9%. According to IQVIA, Spanish innovative product market increased by 5% in the first half of 2022 compared to the same period of the previous year. Nevertheless, ROVI prescription-based pharmaceutical product sales increased 9% in the first half of this year, outperforming the market by four percentage points.
The company forecasts that it will continue to grow at a much higher rate than the Spanish pharmaceutical market expenditure in the first 5 months of 2022, which according to the Ministry of Health, Consumer Affairs and Social Welfare, show a growth rate of 6.9%. In the first half of 2022, ROVI announced two very important milestones for the company. First, the European Commission has authorized the marketing of Okedi for the treatment of schizophrenia in adults for whom tolerability and effectiveness has been established with oral risperidone. The product was launched in Germany in April, contributing to ROVI's revenue line in the second quarter of 2022, and recently in the U.K. in July this year. Second, we expand our long-term collaboration with Moderna for the manufacturing of mRNA medicines over the next 10 years.
This new agreement, which has a term of 10 years, includes a series of investment expected to allow the manufacturing capacity to increase across ROVI's facilities in Madrid. We are delighted to expand our collaboration with Moderna and become a long-term manufacturing partner. At ROVI, we are working to contribute all our experience as a high technological value contract manufacturer of injectables to the solution of this pandemic, and we are confident of our ability to take part in the manufacturing of new mRNA candidates in the future. To comment on the results, regarding the top line of the P&L, operating revenue increased by 31% to an amount of EUR 380.4 million in the first half of 2022.
The main contributors to this growth were enoxaparin biosimilar, which grew 31% to EUR 82.1 million; Neparvis, where sales rose 6% to EUR 18.9 million; Volutsa, sales of which grew by 13%, and the CMO business, where sales increased 76%. Extraordinary increase in sales pushed profitability up by 4.9 percentage points to 30.4% in the first half of 2022. EBITDA increased by 56% to an amount of EUR 115.8 million. Likewise, net profit increased by 58% from EUR 51 million in the first half of last year to EUR 80.6 million in the first half of 2022. Moving to our first pillar of growth, which is our specialty pharma area, prescription-based pharmaceutical specialties grew by 9% in the first half of the year.
They are high strategic value products and contribute to give ROVI a wider scope for the coming years. ROVI considers its heparin franchise as one of its driving forces. Sales of the heparin franchise increased by 8% to EUR 141.6 million in the first half of 2022. Heparin sales represented 37% of operating revenue in the first half of the year, compared to 45% in the first half of 2021. ROVI expects low double-digit sales increase for the heparin franchise in 2022. We aim to become one of the leaders in the low-molecular-weight heparin field worldwide with our two molecules, bemiparin and enoxaparin biosimilar. Bemiparin show a negative performance in the first half of 2022, with sales down 14% to EUR 55.8 million.
Enoxaparin sales increased 30% to EUR 82.1 million in the first half of the year. ROVI expects bemiparin sales to decrease at a low single digit rate in 2022. ROVI continues with internal internationalization plan. Sales outside Spain increased by 48% to EUR 148.4 million in the first half of 2022. 41.2 million euros or 17% of which related to international subsidiaries, mainly due to, first, the increase in low-molecular-weight heparin international sales, and secondly, the increase in the contract manufacturing organization business. Sales outside Spain represented 65% of operating revenues in the first half of this year, compared to 58% in the first half of 2021.
Regarding the enoxaparin biosimilar Becat, it is already present in 38 countries, and we have signed out license agreements to distribute the product in more than 100 countries. We would like to highlight the two most important licensing agreements signed. The first one with Hikma Pharmaceuticals, who has exclusive rights for 17 Middle East and North Africa countries, and the second one with Sandoz for 14 countries or regions. We started the commercialization in Q4 2017, with sales amounted to EUR 1.45 million. Sales have increased quarter by quarter to reach an amount of EUR 124 million euro sales in 2021, and EUR 82.1 million euro sales in the first half of 2022. A 31% rise compared with the same period of the previous year. Let me just summarize the opportunity here.
This is a EUR 2 billion market, EUR 1.3 billion in Europe, and EUR 0.7 billion in emerging countries. With high entry barriers where biosimilars are likely to reach between 50%-70% of market share and with only three other players in the market. The latest launches were again a strong driver of growth in the first half of 2022. Sales of Neparvis, a specialty product from Novartis, launched in December 2020, indicated for the treatment of older patients with symptomatic chronic heart failure and reduced ejection fraction, increased 6% to EUR 18.9 million in the first half of 2022, compared to EUR 17.9 million in the first half of last year. Sales of Volutsa from Astellas Pharma increased by 13% to EUR 8.8 million in the first half of 2022.
Sales of Vytorin, Orta, Orvate and Absorcor, specialty products from Organon, indicated as adjunctive therapy to diet in patients with hypercholesterolemia, increased 19% to EUR 15.9 million in the first half of the year. Sales of Onbrez , Seebri Breezhaler and Ultibro Breezhaler, both inhaled bronchodilators from Novartis for patients with respiratory difficulties due to a pulmonary disease known as chronic obstructive pulmonary disease, launched in Spain in the fourth quarter of 2014, decreased 17% to EUR 4 million in the first half of 2022. Finally, sales of contrast imaging increased by 14% to EUR 20 million in the first half of 2022. This increase shows the strong recovery of the Spanish and Portuguese hospital activity in the first half of the year, after the effects of lockdowns during the pandemic.
ROVI continues to be the market leader in this segment. As I commented before, ROVI has reinforced its long-term collaboration with Moderna to increase capacities for the compounding, aseptic filling, inspection, labeling and packaging of ROVI's facilities in Madrid. In addition to producing Moderna's COVID-19 vaccine, ROVI's platform could also be utilized to service future Moderna mRNA vaccine candidates. To this end, further industrial investments will be made in the ROVI group's facility in Madrid. Regarding CMO, sales increased by 76% to an amount of EUR 166.4 million in the first half of the year.
As a result of the booking of the income related to the production of the COVID-19 vaccines, the booking of the income related to the activities to prepare the plant for the COVID-19 vaccine production under the agreement with Moderna, and finally, the redirection of our CMO activities strategy towards high value-added products. Likewise, in 2022, ROVI expects the CMO business to increase by between 30% and 40%, including production of the COVID-19 vaccine. Regarding our research and development strategy, Okedi is the first ROVI's product based on its leading edge drug delivery technology, ISM. It is a novel investigational antipsychotic for the treatment of schizophrenia with once monthly, every 28 days, injections, which has been developed and patented by ROVI, and which, as of the first injection, provides immediate and sustained plasma drug levels and does not require loading doses or supplementation with oral risperidone.
In January 2020, ROVI announced the commencement of the centralized procedure for registration of Okedi with the European Medicines Agency. On December 16 last year, the CHMP adopted a positive opinion recommending the granting of a marketing authorization for the medicinal product Okedi. Finally, on February 15 this year, the European Commission authorized the marketing of Okedi, Risperidone ISM, for the treatment of schizophrenia in adults for whom tolerability and effectiveness has been established with oral risperidone. It was launched in Germany in April this year and in U.K. in July. Likewise, at this Capital Markets Day, held on November 24, 2020, ROVI announced the filing of an NDA, a registration dossier to obtain marketing authorization in the U.S. with the FDA.
ROVI was informed of the delay in the decision on the granting of marketing authorization for Risvan, that's a trademark of Risperidone ISM in the U.S., by the U.S., by the FDA. Furthermore, on September the twenty-fourth, ROVI received a complete response letter from the FDA with outstanding questions on the Risvan dossier. The company has already answered them since. In its letter, the FDA recognizes that it did not review some of the responses submitted during the evaluation process. ROVI expects its response to clarify the outstanding questions.
In the complete response letter, the FDA states that due to the exceptional situation caused by the pandemic, which has prevented the inspection from taking place within the term defined in the filing communication letter, all the responses to outstanding questions will be evaluated in accordance with the timeline described in the 2020 guidelines for industry review timelines for application responses to complete response letters when a facility assessment is needed during the COVID-19 public health emergency, with an estimated review time of six months as of the submission of the response to the questions raised in the complete response letter. The grant of the Marketing Authorization for Risvan by the FDA is also subject to the result of a pre-approval inspection of the plant where the product is manufactured, which is located in Madrid, Spain.
In addition, the company continues with the clinical development of letrozole ISM, which represents the second candidate using ROVI's ISM technology platform. This new investigational medicine is, to the best of ROVI's knowledge, the first long-acting injectable aromatase inhibitor intended for the treatment of hormone-dependent breast cancer. ROVI has obtained positive results that confirm that this ISM formulation provides a prolonged release of letrozole, which produces a sustained suppression of estrogenic hormones. The company has initiated discussions with the FDA to review these results, as well as the next steps for continuing the clinical development of this novel long-acting injectable aromatase inhibitor. Lastly, ROVI's research and development team is progressing in the development of a new formulation of Risperidone ISM for a three-monthly injection, which would complement the current formulation of Risperidone ISM for the maintenance treatment of patients with clinically stable schizophrenia.
This development is currently undergoing regulatory toxicity studies needed to conduct a phase 1 clinical trials in humans, which is planned to start by the fourth quarter of 2022. Finally, we end this part with our guidance for 2022. ROVI expects its operating revenue growth rate to increase between 15% and 20%, including the production of the Moderna's COVID-19 vaccine. We have stayed on the path of sustained growth in the first half of the year. We increased sales by 31%, outperforming the market. We have expanded our heparin franchise to, first, the launch of our enoxaparin biosimilar in 5 new countries in the first half of 2022. Secondly, the increase of our presence in countries where we had already launched the product.
We have consolidated our pharmaceutical specialties area, thanks to the strength of our leading products such as Neparvis, Voluza, and the hypercholesterolemia franchise. We have achieved growth of 76% in our CMO business, mainly thanks to the agreement with Moderna. Likewise, we are making a heavy investment effort in research and development, focused on our ISM technology, which we see as a new avenue for ROVI's future growth. To conclude, we believe we are at a growth inflection point, with a strong growth opportunity driven by the launch of Okedi, our first candidate validating our leading-edge drug delivery technology, ISM, our enoxaparin biosimilar, which will allow us to transform our European footprint, and finally, the agreement with Moderna, which is helping strengthen our manufacturing area and is providing us with a significant growth opportunity in the area.
These growth levers are firmly underpinned by a very solid ongoing business that has delivered year after year based on our leading specialty pharma franchise and our high-value added CMO services. Now I hand you over to Javier, who will run you through the financials in more detail. Thank you very much for your attention and for taking the time to participate in this virtual meeting.
Thanks, Juan. We are extremely happy with our performance for the first half of the year. As Juan already said, our operating revenue increased by 31% in the first half. This growth is driven by the good performance of our CMO business, enoxaparin biosimilar and our leading products such as Neparvis and Volutsa, with which we intend to achieve an advantageous position in the current competitive environment. Sales of prescription-based products increased by 9%, outperforming the innovative product market by four percentage points. Regarding our low-molecular-weight heparin franchise, we achieved an 8% growth. Sales of bemiparin decreased by 14% and enoxaparin biosimilar sales increased 31% to EUR 82.1 million in the first half of 2022.
Gross profit increased by 47% to EUR 227.2 million in the first half of the year. The gross margin showing an increase of 6.5 percentage points from 53.2% in the first half of 2021 to 59.7% in the first half of 2022. Mainly because the increase in the CMO business contributed higher margins to group sales. This positive impact on the gross margin offset the increase in the low-molecular-weight heparin cost of goods sold in the first half of the year compared to the same period of the previous year. ROVI expects low-molecular-weight heparin raw material prices to decline as a result of the increase in the pig population in China.
Nevertheless, despite the potential decrease in low-molecular-weight heparin raw material prices, the impact on the gross margin will continue to be negative because of the long heparin manufacturing process in which the raw material currently being used, stocked for several months, was purchased at higher prices. ROVI continues to be committed to innovation. R&D expenses amounted to EUR 10.4 million in the first half of 2022. This figure is mainly the result of a focused investment in the ISM projects. Selling, general, and administrative expenses, SG&A, increased 48% to EUR 101.1 million in the first half of the year. Mainly due to an increase in expenses related to the manufacture of the Moderna vaccine and an increase in expenses due to the LKD launch in Europe.
EBITDA increased to EUR 115.8 million in the first half of 2022. A rise of 56% compared to the same period of previous year, reflecting a 4.9 percentage point increase in the EBITDA margin, which was up to 30.4% in the first half of 2022 from 25.5% in the first half of last year. EBIT increased by 65% to EUR 104.5 million in the first half of this year, reflecting a 5.6 percentage point rise in the EBIT margin, which was up to 27.5% in the first half of 2022 from 21.8% in the first half of 2021.
The effective tax rate was 23.5% in the first half of the year, compared to 20.2% in the first half of 2021, mainly due to the increase of the profit before income tax. Net profit increased by 58% from EUR 51 million in the first half of last year to EUR 8.6 million in the first half of the present year. EBITDA pre R&D, calculated excluding R&D expenses in the first half of the year and in the first half of the previous year, increased by 47% from EUR 85.9 million in the first half of 2021 to EUR 126.2 million in the first half of 2022.
Reflecting a 3.6 percentage point rise in the EBITDA margin to 33.2% in the first half of 2022. EBIT pre R&D increased by 53% from EUR 75.3 million in the first half of 2021 to EUR 114.9 million in the first half of 2022. Reflecting a 4.3 percentage point rise in the EBIT margin to 30.2% in the first half of 2022. Net profit pre R&D increased by 46% from EUR 60.5 million in the first half of 2021 to EUR 88.6 million in the first half of the year. ROVI invested EUR 9.9 million in the first half of 2022 compared to EUR 11.4 million in the first half of last year.
Of this amount, EUR 7.2 million relates to investment CapEx regarding our facilities, including important projects such as the ISM industrialization, the building of a second low-molecular-weight heparin facility in Escúzar, Granada, and the new lines for the Moderna vaccine. EUR 2.7 million relates to maintenance and other CapEx. Cash flow from operating activities increased to EUR 169.4 million in the first half of 2022, from EUR 87.3 million in the first half of 2021. This increase was mainly due to the increase of EUR 41.4 million in the profit before income tax.
Also, the booking of EUR 74 million under the proceeds from CMO services captured in the first half of the year relating to payments received, but not yet allocated to the income statement compared to the EUR 12.4 million recognized in the first half of last year. Finally, the increase of EUR 11.8 million in the trade and other receivables captured in the first half of this year, compared to a decrease of EUR 32 million in the first half of 2021. Regarding our debt, as of 30th June 2022, ROVI total debt decreased to EUR 73.1 million from EUR 73.2 million as of 31st December 2021. EUR 44.5 million is debt with banks representing 61% of total debt.
While EUR 11.1 million correspond to debt with the public administration related to the development of R&D projects, which is debt at zero interest rate, representing 15% of total debt. Finally, EUR 17.6 million correspond to financial liabilities for lease, representing 24% of our total debt. In July 2022, ROVI announced that the European Investment Bank had granted a new loan to support its investment in research, development, and innovation. The loan is for EUR 50 million with a repayment period of 10 years, has a three-year grace period, and may be drawn down over a term of 2 years.
As of June 13th this year, ROVI had a gross cash position of EUR 160.5 million compared to EUR 100.5 million as of December 31st last year, and a net cash of EUR 31.3 million compared to EUR 27.4 million as of December 31st, 2021. Regarding the dividend, ROVI general shareholders meeting on 14th June 2022 approved the payment of a gross dividend of EUR 0.9556 per share on 2021 earnings. It means an increase of 151% compared to the dividend on 2020 earnings and represents a 35% payout. This dividend, by the way, was already paid on the 7th of July this year.
Regarding news flow for the remaining part of the year, we will monitor the evolution of the manufacturing of the Moderna vaccine. We also expect to announce Okedi launch in some European countries. The product has already been launched in Germany and in the U.K., and it's expected to be launched in Spain, the largest LAI market, in this September. In addition, we expect to inform on new national marketing approvals for the enoxaparin biosimilar outside Europe. With regards to R&D, we expect to obtain the marketing authorization for Risperidone ISM in the United States in 2022. Regarding Letrozole ISM, we have already initiated discussions with the FDA to review phase one results, as well as the next steps for continuing the clinical development of this novel long-acting injectable aromatase inhibitor. We expect to have feedback from the FDA this same year. That's all.
We can now start the Q&A session.
If you want to ask any questions, please do not hesitate to send them through the question button on the platform.
Thank you very much for your participation. The first question comes from Patricia Cifuentes from Bestinver. Juan, how has been the reception of Okedi? Maybe the contribution to sales is still minor, but you can give us some color on the impact of the marketing activity on the feedback from doctors.
Hello, Patricia. Thank you for your question. So far we have only launched the product in Germany in April this year and very recently, in the last couple of weeks, in the UK. So the feedback that we have is still very limited, but I have to say that so far, so good. I mean, the feedback coming from the sales force is extremely positive. I have to say that we are very excited of the reception of this product. We cannot forget that this is the first long monthly long-acting injectable of risperidone, which is one of the most widely used products to treat schizophrenia. Specifically in Germany, the feedback is extremely positive. We've already been marketing the product for the last three months.
At least the reception from the doctors is aligned with all our pre-marketing surveys that we performed before launching. We do expect that Okedi is definitely going to fulfill our expectations in the near future.
Thank you, Juan. Javier, Patricia also asks, the third fill and finish line for the Moderna was due to start producing batches for regulatory approval during this summer. Are operations going on track with the initial plan, or you have delayed works in the third line given the lower than expected production of the second quarter?
Well, actually, the news are very positive on this side. Like, we can confirm to all of you that the new line is already set up in our facility, and we expected to start manufacturing activities, probably at the end of the third quarter of this year, no? Everything is going according to plan, and I think that's, again, fantastic news for us and for our collaboration with Moderna, as we are always hitting on all our deadlines.
Okay. Juan, Álvaro Lenze from Alantra asks, Neparvis has shown some slower growth than the previous quarters. Is it approaching normalized revenue levels, or do you think that it can continue growing at double-digit rates going forward? Also, on specialty pharma, any new in-licensing that could fuel sales growth in 2022 or 2023?
Hello, Álvaro. Thank you for your questions. Regarding Neparvis, the product is almost on its sixth year of commercialization. We still believe that it has got still growth to deliver. Having said that, we have to take into account that this, for the same indication of Neparvis for heart failure, there has been some other product recently approved, especially the DPP-4s, that they are currently being used to treat diabetes. We believe Neparvis has got some unique characteristics, and we do believe that at least we should be able to grow at a single digit in the next coming years. There's a clear need for products to treat heart failure.
I think Neparvis was the first to come, and it has provided to the market and to the specialists some unique features. That's the reason why we believe after the sixth year of commercialization, there's still growth within the product. We do feel that the growth it might be moderate in the next coming years, but still we're going to enjoy a continuous growth of the product. Regarding potentially licensing products, we're still working on having new agreements in place, and I believe that we might have news before the year end. Having said that, we are right now mainly focused on the launch of Okedi.
That's really our major driver of growth, and it has to be our catalyst in the Spanish market. Hopefully, Okedi should be on the market in the next just after summer. That's where I have to say that all our efforts and all our energies are right now focused on the Spanish market. As we have delivered in the past, we are one of the largest and more efficient sales organization in Spain, and we are currently working on trying to secure new licensing agreements. I'm extremely positive that we will have additional products to be launched next year besides Okedi.
Okay. Juan, Álvaro Lenze from Alantra also ask, we have seen European Union member states agreeing with Moderna's delays in the delivery of vaccines. Do you think that volumes could fall further or be canceled? Are the orders firm?
Well, Álvaro, that's a difficult question for me to answer because I don't really have the information. That's the information that I've shown. Moderna have not, let's say, shared with us. At least from the information that we have got and our perception, which is mainly related to market data and to internal forecasts, we do believe that we are going to have a year according to our initial forecast. Unfortunately, the COVID-19 is still provoking contagions, and unfortunately, the newer strains coming from different regions of the world, the latest being the famous Centaurus from India.
Unfortunately, I said before, we do believe that in terms of usage of the vaccine, still there's going to be a very important need in Europe during 2022 and probably as well during the 2023. Beyond that, we don't really have more information and it wouldn't be an objective feedback that I could provide. When it comes to ROVI, we do believe that forecasts are really being fulfilled. As Javier has mentioned before, I mean, we do feel that Moderna is a very important part of our business.
We will fulfill our guidance, this year, and the growth of the company will be according to the figures that we have shared with you before.
Thanks, Juan. Francisco Ruiz from Exane has three questions. The first one is, can you give us an update on the situation of Letrozole discussions with the FDA?
Hi, Francisco. Regarding Letrozole, I cannot share much more than what we did in our previous statements. We're expecting to finalize our discussions in Q3 this year with the different regulatory authorities. We are very positive and very excited with the phase one results, and we are really looking forward to have a defined pathway of how to follow on our clinical development. I believe that by our next call, by the end of third quarter, we should be able to provide you more granularity and color of how this clinical development has been agreed with the regulatory authorities. So far, the discussions are going. They are going in the right pathway, and we are very positive on the.
Really on a successful development of Letrozole.
Okay. The second one is, do you have already any visibility on Moderna vaccine for 2023?
No, unfortunately not. I think everybody, governments, Moderna, ourselves, everybody's focused on making sure that the vaccine is delivered according to time this year. All our efforts of everybody right now is just focusing on making sure that we hit the right strain and that we deliver the right volumes to countries on time to make sure that the population is fully vaccinated. We don't have really any color or any guidance on what could be the 2023 pandemic forecast.
The last one is, any clue about how you will commercialize Risvan in the U.S.?
No. Unfortunately, I know this is a recurring question and again, that's one of the, if I may say, hottest topics within the company. We are right now just very much focused on the registration process, which is ongoing, and it's taking more time than we would have desired. Right now all our efforts are focused on trying to secure the registration. COVID-19 has brought many good things to the company. Unfortunately, COVID-19 has provoked a tremendous backlog in all regulatory bodies when it comes to approvals and inspections. Right now, all the organization is focused on making sure that we get successful positive registration of the product in the U.S.
We are still having plenty of ongoing discussions to try to decide which is the best value proposition to market Risvan in the U.S. So far, unfortunately, I cannot share with you any further information.
Juan, Antoine Pilo from Arbevel asks, after using capacities for Moderna, what will you fill up the rest of capacities with?
I mean, as we mentioned in our presentation, I think this is a message that we have been delivering in the last 18 months. We changed really the strategy of our CMO activities to really high added value products. Moderna definitely has been the golden star of this strategy. As well, a collateral positive effect of Moderna is that has put ROVI really on the news of a major contract manufacturing organization for injectable compounds. Definitely, we do believe that we have a tremendously good future in this field. I think the market has already acknowledged that injectables and CMO activities can be a very profitable and a very successful business.
ROVI is one of the major global market leaders, and what we are right now doing is marketing our spare capacity to the right players and to the right products, which may provide a future continuous growth of contract manufacturing operations. On the same side, we're also investing to increase our capacity. Definitely, contract manufacturing operation is a core business of the company. Again, we believe it's going to be a part of our business that is going to deliver plenty of growth and EBITDA to the company in the next coming years.
Thanks, Juan. Javier, James Vane-Tempest from Jefferies has three questions. The first one is, you reiterated 15%-20% growth and also 30%-40% for CMO business, but you've qualified, you don't know how pandemic will pan out, so why do you still have confidence in the 30%-40% for CMO, and how much visibility do you have?
Well, thank you, James, for your question. I think we are very positive on the visibility that we have in the remaining quarters of the year. It's clear that, as Juan was saying, you know, that the pandemic is still very unknown how it's gonna be developed in the next coming quarters. According to public Moderna information and also Pfizer, no, it seems that both companies are gonna be delivering all the doses requested for the year or most of the year in this end of 2022, no. According to the info that we managed with Moderna, that seems that the third quarter and fourth quarter is gonna be strong, no, on the manufacturing side and on the Moderna vaccine side, no, of the business, no. We are very confident.
We know that the guidance is quite aggressive, no? Take into account that last year we grew by 57%, and this year we are growing on top of those, on this growth. We are optimistic, no. We want to see how the months evolve, but I would say that we have more visibility today than when we set up the guidance, no. I think that's very reassuring from our side, no. This applies for both the contract manufacturing activities and also the guidance for the whole company.
Javier, the second question from James is, can you give us a steer on the weight, on the weighting of the year and direction of profitability in the second half of the year versus, the first half of the year?
Well, I strongly believe that if the company is able to achieve the operating revenue guidance both in for the total operating revenue guidance of the company and also for the contract manufacturing business, I think this year is gonna be very positive on the profit side, too. We don't provide guidance on the profitability of the company, but again, if we see and we assume that the contract manufacturing business is growing as expected and also the company, I think we can expect that the profitability of the company will increase in a substantial way also. Again, let's see how the quarters evolve, but we remain very optimistic at how the year is gonna end up for ROVI.
Javier, the last question from James is, net cash has increased from EUR 27 million - EUR 87 million. How do you view the optimal capital structure, and what are your priorities for cash?
Well, I think the one of the most satisfying parts, no, of these first half results are that we've been able to transform the profitability into cash and we are piling cash. We have to take into account that we've been buying shares during the first part of the year with our share buyback program. I think these are fantastic news for the company, no, that we are able to increase the cash position of the company. Again, I think we have reiterated several times that ROVI is a growing company, and we will try to focus and to use the cash to keep growing the company, possibly, from an organic growth, as we are doing right now, but also take into account a potential inorganic acquisitions, no.
I think that's something that we are still looking at, and we are trying to fuel the M&A part strategy of the company. We would love to make use of the cash through acquisitions and eventually, if this is the case, why not to have some leverage also on the capital structure? We would love also to add some leverage, not that much, although. I mean, we are a conservative company, and we want to maintain that profile from a financial perspective. If we find the right target, we would love to add some leverage on the company and to boost the growth of the company with a potential transaction adding some inorganic growth to the company.
Thanks, Javier. Roberto Casoni from Otus Capital asks. Hi, do you have visibility for 2023 on any other vaccine production for Moderna apart from COVID?
Hello, Roberto. No, so far, we don't have any visibility. Again, I don't think that in any way, as I mentioned before, right now we are only focused on the 2022 vaccine program, making sure that we deliver the product to countries and making sure that we get the
The right of stream. That's something that I guess if it comes to the moment of discussion, it would happen probably in the first quarter next year.
Juan, Patricia Cifuentes from Bestinver asks, sales of bemiparin are now expected to fall this year. Aside from the demanding comparable, is there any other reason to explain this? Should sales recover in 2023, or this is the beginning of a declining trend?
No, I think the bemiparin obviously will have two major segments that we have to differentiate. On one side we have the Spain sales, which they have decreased by 4%. Probably this decrease is basically due to the comparator. 2021 was a very strong year because of the COVID-19. We cannot forget that COVID-19, one of the therapeutic tools used to prevent the clots was a low-molecular-weight heparin. Bemiparin, because of its market share in Spain, was widely used. As well, we have a really high rate, unfortunately, of hospitalization of patients. There was an increased use of low-molecular-weight heparins in 2021 from previous years. I don't think in regarding Spain, I don't think that we see further declines in the future.
We're very much focused on the treatment segment, where we are by far now the market leaders. I would rather say that we probably will start seeing next year some growth in the Spanish market compared to 2022 sales once the COVID-19 use of low-molecular-weight heparins has been consolidated. On the international arena, there has been two effects. One is Turkey. Turkey was one of our most important markets. Unfortunately, the depreciation of the local currency has provoked really that it's no longer sustainable to market a product coming from Europe in that market. A good portion of that decline is related to the Turkish market. The second one, and it's, I think it's affecting throughout our industry, is really the Ukraine-Russia war.
Russia was also an important market for us. Again, that's something that is beyond our control. Having said that, I believe, as you've mentioned, that 2021 was a very strong year for different reasons. I think the COVID-19 use has to be consolidated. I believe that 2023, definitely we are positive that sales will stabilize if probably we also may see again some growth on the bemiparin franchise.
Thanks, Juan. Javier, Patricia has two more questions. The first one is, how much was inflation in cost of goods of low-molecular-weight heparin in the second quarter of 2022 or the first half of 2022, if you prefer?
Well, actually, we wanted to keep informing our investors and analysts how the cost of goods of the heparin was evolving. That's why we said that we have a small increase on the cost of goods of the heparin. I think the good news of the company is that we've been able to increase the gross profit and the gross margin, even though the cost of the raw material is not helping at all for us. I would say that the increase has been a small one this first half compared to last year, no?
If it's related to inflation or not is something that in the heparin, on the heparin field is difficult to assess as we're trying to teach our investors and is more related to the peak prices and the peak population. Again, it's a small increase on the cost side. The good news is that even though that heparin part of the business is not helping on the cost of goods side, we have been able to increase the gross margin once again in this quarter.
Thanks, Javier. The second question is, considering the commercial efforts required by Okedi and the sharp inflation in the economy, what level of SG&A costs do you expect for 2022 and 2023? Thank you.
For us, I mean, inflation is affecting everybody, all the companies in, I would say Spain and Europe and around the world. It's a big issue for everyone. In our case, anyhow, I think it's more of the companies expanding, no, as we commented today. Last year we grew by 57%. This year we're growing again in a very strong way. We need to expand our production, our manufacturing sites. We need to hire more people. And as Patricia was saying, we need to launch Okedi in different parts of the world, or at least of Europe, no. It's affecting us, the inflation, that's for sure. But it's more related to these drivers of growth of the company, that in the case of the SG&A, it's also growing up, no, and it's normal and reasonable.
How much it will be next year related to inflation or to these drivers is still difficult for us to assess, but we can expect that the SG&A will be similar.
To this level.
Thanks, Javier. Isabel Carballo from Oddo has two questions. The first one is: could you please provide any indications for R&D for 2022 and 2023?
Hello, Isabel. For this year, although we have a small decline in the expenditure on R&D up to the first half of the year, I think this is something that will be offset in the second part, and we expect a small growth on the R&D line of expenditure at the end of the year, no? Next year, it's still early for us to predict, as we are waiting for the Letrozole feedback also, as you know. Once we have the full visibility about what we have to do with Letrozole, is, I think, the moment that we can provide more a good update on the evolution and on the cost of the R&D line for the next year.
Okay. The last question, Javier, is from Isabel. Which is the tax rate expected for 2022?
Well, basically this year as things that the profit before income tax is growing so much, we are close to the 24% that we are having at this first half. My best guess is at the end of the year we'll be in a similar situation to we are right now.
Okay, there are no more questions, so thank you very much for your high participation. Let me now turn the call over to our Vice President and CFO, Mr. Javier López-Belmonte, for the closure of the presentation.
Well, thank you. Thank you, Marta. It seems that there are no more questions at this time, so thank you very much for all of you for participating in this first half virtual results call. Hope you have a great summer break and have a good day.