Good morning, ladies and gentlemen. It's a pleasure to have you here today in Dreieich for our first hybrid meeting of the analyst conference. Welcome here in Dreieich, and welcome also the via Teams participants. They are here today from Germany, Spain, U.K., and the U.S. Welcome. Today it will be Michael Ramroth, CEO, to give an update on the ongoing business and an research and development update. It will be Ainhoa Mendizabal, CFO of Biotest, to give you an update on the plasma environment and also on the financials. For this, I'd like to hand over to Michael.
Thank you very much, a warm welcome also from my side, especially to the early birds in the United States, you know. Great that you are following us today. You know, all the long-term followers of you, some of you have been following Biotest since decades almost, you know. You know that we always start with highlights as summary of our presentation. Indeed, I would also start with the highlight. The first and biggest highlight for me personally is that we now have Ainhoa Mendizabal on board and as a new colleague since five weeks here as CEO. Aenor is really great. I'm a little bit proud that I had been able to discover and convince her to join us here at the Biotest team, because I guess she got very.
the early, the connection to Germany. You attended the German school in Bilbao.
In Bilbao.
In Bilbao, yeah. Studied business administration in Spain and Germany. Started her professional career in Düsseldorf. Apologize for all Cologners from Cologne here, but she started in Düsseldorf with Henkel. Switched over to Deloitte and provided financial services, CFO services, and also enterprise application services. Did that for a company who was involved, which was involved in the plasma industry. I guess your first contact with the plasma industry was then in 2007.
This company was the former Bayer plasma protein activities called Talecris, and they had their European headquarters here in Germany. Ainhoa got involved in that and was hired by them and was already with Talecris and active in the plasma protein industry when Talecris then was bought in, I guess, 2011 or something like that.
2011.
by Grifols. Since then, she is, you know, via Talecris, Grifols, now with us. Welcome to you, thank you that you are, you know, that's good. Even after five weeks, I will present the numbers of last year. Don't blame her, blame us, you know. We are responsible for the numbers she is going to present. Yeah. Let me see if that works here. It does work. Here we are with the highlights. As I said, you know, we have new board, new board members on board, not only Ainhoa Mendizabal, but also Jörg Schüttrumpf, who started as Chief Scientific Officer in January of 2022. Peter Janssen joined in September of last year, because Georg Floß then retired beginning of this year. Three of four are pretty new.
You know that I asked Ainhoa to join us, because I could get rid of the CFO functions in early times before I orchestrate the further remaining months, before I then also will leave Biotest and make room for a new chapter of Biotest. What we have done in the last year, we opened new plasma collection centers in Czech Republic. We own and operate 34 centers, Germany, Hungary and Czech Republic. The pipeline is well filled, and the projects are progressing very well, and I will give you some details later on. Sales figures will be presented by Ainhoa. You know, we achieved almost the same sales level as we have achieved in 2021.
The adjusted EBIT number, and this is the EBIT number of the current ongoing existing business, so without any, let's say, call investments in P&L facility or P&L projects. The earnings base for the existing products was EUR 60.7 million in 2022. Now, the, from a business point of view, the most relevant and important event was that we had been able to get the market authorization for Yimmugo. Yimmugo, our new immunoglobulin IgG next gen, as we have called it all the years, which was specially designed and developed for being produced in the new P&L facility. It's produced in a process which ensures that the yield is higher than with our existing Intratect, our existing immunoglobulin Intratect, and is a combination of getting immunoglobulin Yimmugo and later on trimodulin.
That together will lead to a pretty much increase of yield we get out of 1 liter plasma. You all know, as followers of our industry, that plasma is really very valuable because scarce raw material and is needed for produce all our products. Being able to launch Yimmugo still in 2022. In November, we had the first sales with it, and Austria followed with the market authorization and other countries will follow as well. Yimmugo is a state-of-the-art immunoglobulin, polyspecific immunoglobulin. It's well tolerated, especially if you look at the high infusion rates which are possible with Yimmugo and which are, of course, the benefit of patients but also the clinics and physicians who can treat, of course, more people, you know, in the same time period.
Of course, that's only possible if all the other properties of Yimmugo as a new product are pretty much ahead of time, so no thrombogenic activity, a low, very low level of anticomplementary activity and of course it's sugar-free. All those are properties which make Yimmugo a well-tolerated Yimmugo, and we think that with this immunoglobulin, we really have achieved the next generation of immunoglobulins for us. If you look at the name, you know, you have of course new regulations saying that the name has to be somehow artificial. You cannot just name it Immunoglobulin or as was Intratect, you know. Such names are no longer permitted. This is an artificial name and Y, you know, shows a little bit the form of the antibody. Immu is
Immunoglobulin.
Immunoglobulin. Exactly. Then with go, we combine it with a strategy. We call it GoFuture, indicating that with this new product, you know, it's the first product out of BNL, the new facility we have built up here very close to this place here and have now started with actual industrial operations in this new facility with Yimmugo, the first immunoglobulin out of this new plant. First sales in November in Germany, I said that already. Austria followed in December with the market authorization. We have submitted the dossier to get the market authorization in UK beginning of this month. In Hungary, we are lucky we can sell it even with the German packaging material. We have a distributor found in Saudi Arabia who is keen to sell it also in Saudi Arabia. USA BLA.
Biologics License.
Biologics License Application, thank you very much. Is planned to be filed till in the H1 of this year. I will jump to page 9 first because the other big highlight of 2022 was that Grifols has successfully completed the takeover process. Since May of 2022, we are part of the Grifols group. Of course, you know, being part of the Grifols group means that we can also take advantage of the benefits of being part of a bigger group, engaged in the same industry, sharing the same goals of best and optimal treatment of our patients. With that background, of course, we can really accelerate a couple of things which we have already undertaken up to now but are now probably better based in a way to, yeah, as I say, accelerate that.
If you look at the press releases Grifols made, you know, at the time of completing the takeover bit, they stressed very much the importance of our two BNL projects, trimodulin, Fibrinogen. They had probably even a little more fantasy, you know, what we can do with those products as we had because we had very much, especially with regard to Fibrinogen, concentrated on the German, Austrian, Swiss, maybe European market. With Grifols they had a clear idea and vision to also bring Fibrinogen to the US. Therefore, you know, we work very much on that of, you know, getting Fibrinogen but also trimodulin accelerating, in an accelerated way to the markets and not only to the European markets, to the markets worldwide.
Therefore, we are happy that we get the support not only in material way, but also, you know, with really people and a lot of experience because you all know that our experience with the United States, you know, in the history of Biotest is rather mixed, you know, to put it politely and therefore we are really grateful that, you know, we now can rely on the experience. Not only on the experience, but also on the organization Grifols has in the United States. Therefore, you know, always in former times when we said that with the new Yimmugo product we would also like to enter the U.S. market.
We always said that we won't build up our own marketing and sales organization in the United States because it would be just too costly, it would take up too much time to do that. We've always said that we would need a third party there to do that for us. Of course, with Grifols being very well situated in the U.S. market, this is a natural and born partner for us for the expansion of our products in the United States. Therefore, as I said, we have actually accelerated all our efforts, you know, to bring the clinical development to a faster end. I will tell that later on if it's across. As I said, also, we are preparing to enter the U.S. market.
The FDA inspection will be the first FDA inspection for Biotest Next Level. As I said, we will file the Biologics License Application, you know, still probably in the H1 of this year. Probably 3-6 months later, FDA inspectors will show up here in Dreieich and look into the new facility and check if everything is compliant with the US rules and regulations. Same time, together with the Kedrion colleagues, we're preparing the launch for Yimmugo in the United States, but also having some thoughts of how to really bring fibrinogen later on also into the United States. Yimmugo. I said we had the first sales in November and December of the year, but that was, of course, just the beginning.
We produced 1 batch per week last year for Yimmugo, and of course, in ramping up the new facility means that we would increase the number of batches we are producing per week from 1 last year to 6 to 7 this year or next year. That really, in the end, we can really take advantage of the capacity of fractionating another 1.4 to 1.5 million tons of plasma there and turn it into Yimmugo, Fibrinogen, and trimodulin later on. Challenge for that, and you hear that also from other companies, is to get skilled people on board to operate those facilities and those equipment things. Since we are here in the Rhine-Main area, where a lot of pharmaceutical companies are around, this is risk and challenge same time. The risk and opportunity, same time.
Opportunity, there are a lot of people are in this area, but there are also a lot of competing companies also looking for skilled and trained people at the same time. Ramping up Biotest Next Level facility for Yimmugo is one task. The other task is to get this facility ready to produce Fibrinogen and trimodulin. Both products are still in the clinical development, but at the same time, in parallel, you have to make sure that you, if the clinical development is successful, that you can also produce those products on an industrial scale. We have proven that we can produce such products in our pilot plant, but now have to scale up for the industrial production in Biotest Next Level facility, and we're doing that right now in parallel for Fibrinogen and trimodulin. You know you have to do that, make test runs.
You see that some parameters are changing a little bit because the vessel has now a volume of 4,500 liters. In the pilot plant it was about 200 to 400 liters. Also, you know, the time of heating up or cooling down the material takes maybe a little bit longer in such bigger vessels than in the smaller ones. That needs some kind of parameters being adjusted in the process.
If the process is stable using the big vessels, the industrial scale equipment, then you have to validate the process, you have to produce the product, and then you have to put it on stability to prove to the authorities in the license application phase that the product produced in this large scale facility is as stable and as good as the one which is produced for the clinical trials. You have to prove, you know, the quality of this product produced in the facility in a comparability study.
Doing that, you have to go through this whole process, which take up to 15-18 months, you know, from the beginning of, you know, starting the first test runs in the large scale equipment till you have the stability studies after 6 months and have cleaned the data for then putting those in the submission dossier and then submit such dossier then to the authorities. In parallel, you know always that if you start to fractionate, one liter plasma, you get immunoglobulins, antibodies, you get immunoglobulins, you get trimodulin, you get fibrinogen or clotting factors, and you have albumin. Also, you know, by fractionating more plasma in the new BNL facility, we will get also more human albumin.
We have also to increase our capacity to purify albumin in the last process step, and this will be started also this process of enlarging the last production step for human albumin so that the capacity, you know, is then the right one and matches the capacity we have in BNL for producing the other products as well. With this summary of what we have done, you know, operationally, in the facility and with regard with Yimmugo, our new product, I would then hand over to Ainhoa and would ask her to give us and you a sense of what's going on the raw material side, because as I said, we need plasma for producing our products, so that's essential and a lot of things has happened there also in the past. Please.
Thank you, Michael. Okay, here we go. Well, you know, thank you also for introducing myself. My name's Ainhoa Mendizabal. I know that for some of you, this is going to be a hard name to, you know, to understand. I'm Spanish. I've been spending most of my life in Germany. Besides working in Germany, studying in Germany, also married to a German person. I have two kids that have been born in Germany and now outside of the country. I've been here since five weeks. Bear with me when we go through the numbers. I have an excellent team, most of them sitting in the back there, that are going to help me. Of course, Michael and Monika that are going to accompany with me. I'm very happy to be here.
One of the things, before we go into financials, we will talk a little bit about the plasma market. As Michael has mentioned, I'm not new to the plasma market and also not to plasma collection, I'm more than happy to actually start with this type of things. What has happened, I'm sure that all of you that are interested in Biotest and perhaps also in the plasma industry are probably aware that the pandemic has had an big impact on plasma collection, okay? Before 2020, there was a steady growth in collections, both on the U.S. side with a double-digit growth rate, but also in Europe. The pandemic had a big impact and a significant decrease in collections.
There was a slight decrease in Europe, but a two-digit decrease, almost 20% in the U.S., going back in 2020. Many factors contributed to the decrease. We've been waiting until 2022 to actually see a recovery. You will see that we have numbers with expecting numbers on 2022 on plasma collections in the U.S. and Europe. This is the numbers we have on the market. They are not published yet. In any case, we envision a big recovery up to numbers of 2019, mainly in the U.S. We see a slower recovery in Europe, but there was also not such a sharp decrease in Europe.
Numbers look good when we look at the plasma volumes available in the world, which is good news for Biotest and for the whole plasma industry, and especially for the patients out there that are in need of our products. What does it mean in terms of prices? Obviously, the volume tensions have had an impact on pricing. We put up there some numbers for you. In blue, you see numbers from the U.S. plasma pricing development, and in gray, you see numbers for the EU plasma pricing development. You will see that the volume tensions we've been seeing, they also have had an impact on the price increase. If we look at 2017 as a base, we are seeing an increase of almost 140% in the prices for plasma procurement.
In the U.S. and in Europe, we see an increase of up to 126%. What does it look for the future? We as Biotest also see the procurement prices for plasma in the market are still high. They've been high in 2022, and they are continued to be high in 2023. This is mainly because donors are being motivated with high compensation fees. There's obviously a higher cost in terms of running the plasma collection center. We envision still higher prices procuring the raw material despite of the fact that there might be more raw material in order to produce our products, okay? Having looked at the plasma market, I would want to look at what Biotest is doing within the plasma market.
As mentioned by Michael Ramroth in the very beginning, the market trend that we are seeing, it confirms the strategy, the Biotest strategy to expand the number of owned plasma collection centers and have access or secure the access to the plasma that we need to produce our materials and be successful in the in the market, but to procure the material with sustainable prices. With the opening of 7 additional plasma centers in the Czech Republic, Biotest has broadened the network that we have up to 34 centers in Europe, as Michael Ramroth has mentioned. Additionally, with a close partnership with Grifols, we are securing access to U.S. plasma in combination with some additional investment in U.S. centers.
If we look at the EU network, some of you might be aware that running plasma collection centers in Europe for private companies is only possible in 4 countries. This is Germany, Austria, Hungary, and the Czech Republic. Biotest is present with a network of the 34 centers in 3 of the countries. We had at the end of 2022, 9 centers in Germany, 11 centers in Hungary, and 14 centers in the Czech Republic with a newly opened 7 centers. For 2023, we are opening an additional expansion and having new centers in some of those countries as well. Let's go into the financials. I would say there's no one to blame. Just as a comment. In 2022, the Biotest group has generated revenue of EUR 516.1 million.
This is at the level of the revenue we had in 2021 of EUR 515.6. There's a slight increase of 0.1%. We will see that we have in the therapy segment, which is the segment for the plasma proteins to the customers, the plasma products, we see revenues in 2022 of EUR 459.5 million, which is a slight decrease versus the prior year. This decrease is mainly coming from lower demand in the coagulation factors, which is probably nothing new to the people in the room and in the call. This has been significantly offset by a continuous high demand for our immunoglobulins. Obviously, we're very happy that we can contribute with a new immunoglobulin product to this market segment.
When we look at the plasma and services segment, this is the segment where we have our total manufacturing services and in some cases also revenue from plasma cells, we see a significantly increase from 7.8% up to EUR 50.3 million, versus last year, EUR 46.7 million. We also see a small decrease of revenue in the other segments. This is mainly the merchandise.
Yep
products that we have in Hungary. All together, we are looking at a significantly improved operating profit, EBIT, of negative EUR 16.6 million, which is a 64.7% improvement versus the negative EBIT result of last year. It was at EUR 47.1 million. When we look at those numbers, we need to consider that this is mainly coming from cost of goods sold, where we had a one-time impairment effect in last year's numbers because of the coagulation factors. Looking at earnings after tax, the Biotest Group could achieve a result of negative EUR 31.7 million, which is also a significant improvement versus the bigger negative number of EUR 67.4 million in last year. What does it mean for our guidance?
We believe that the Biotest Group and the board of management has achieved the revenue guideline. We saw last year that there were some downsides that could come from the macroeconomic environment and the socioeconomic or political environment. Despite of those, we could actually achieve a revenue number of EUR 560 million, which is on the higher end of our revenue guidance. When it comes to our EBIT, we have achieved an EBIT number of minus EUR 60 million, and this is significantly higher or more positive of the guidance we provided. You might remember that in November 2022, there was an adjustment of the guidance provided because we could confirm that some of the risks that we were foreseeing at the end of last year.
Yeah, okay.
did not achieve, which is good news for the company. Let's look little bit in more in detail into the sales numbers. We report sales in four regions, which is Central Europe, what we call ESECA, which is East, South Europe, Central Asia, and America, Intercontinental, and Middle East, Africa, and France, MEAF. This is based on the management structure that we have in the company to make sure that we can develop those markets. If you would look at the specific numbers, you will see that we have revenue growth in all sales regions, with the exceptions of the ESECA region. In particular, Central Europe, which includes Germany, has had a significant increase together with the Icon region.
As in 2021, the Central Europe region, again, that includes Germany, made the largest contribution with EUR 205.2 million versus EUR 186.9 in last year. This revenue is coming mainly from additional volumes in the Intratect, the existing immunoglobulin product, and some additional sales from Yimmugo, as we've heard in the past. Michael has been explaining us that the Biotest Group has been expanding the capacity and in the headquarter here at Dreieich since 2013, I believe.
with the Biotest Next Level project, which includes two types of activities, the increase of capacity, but also the investment in additional product portfolios. What we see is that we have spent a total of about EUR 77.3 million in the Biotest Next Level project, and this is leading to an adjusted EBITDA that we've been looking at through the last years of EUR 60.7 million versus EUR 29.4 million in the last year.
This adjusted EBITDA is, in our opinion, it expresses or reflects the core business from Biotest. The significant increase in this number reflects, in our opinion, the improvement of the improvement of business operations in the company and gives a give a positive trend for the future when all our investments have realized. If we look at a glance at the numbers we've been seeing, we are seeing sales staying at the level of 2021 with EUR 560.1 million. We see an improvement in EBIT from - EUR 47.1 to 60.6 million. We see a significant increase in adjusted EBITDA, which is the core business of the company.
This as a glance from our financials, I would like to go a little bit more in depth into our Biotest Next Level cost. Michael has explained in the very beginning that we have been successful in bringing forward the very important project of Biotest Next Level. We have Yimmugo in routine, launched in two countries. We are working in the commissioning of trimodulin and Fibrinogen, we are accelerating all the additional R&D projects. If you look at this has been in fiscal year 2022, it spent EUR 77.3 million, which is allocated to cost of sales with a total of EUR 40.7 million for the facility piece of it, allocated to R&D with a total of EUR 36.6 million, which is the investment in our R&D activities.
Going forward into the balance sheet. The assets of the Biotest group increased from EUR 1,104.2 to 1,203.3 million by EUR 98.8 million. This increase is mainly coming from current assets, where we see current assets amounting to a total of EUR 619.4 million at the end, December 31, 2022. This is an increase of EUR 97 million versus last year numbers. This is mainly coming from increased inventory levels of about EUR 49.2 million in order to be able to supply the market in this year.
When we look at the equity and liability side, we see the equity decreasing by EUR 9.3 million, down to EUR 371.1 million. This is due to the net loss of the fiscal year partially offset by actuarial gains. The debt net rose by altogether EUR 108.1 million in the past fiscal year. The non-current liabilities amounted, at the end of the year, EUR 701.7 million. This is mainly coming from the further tranche that we have taken from the secured loan we had with an external provider in order to finance the operations.
Going further into our finance position, cash flow from operating activities decreased significantly year-over-year into 2022 from positive EUR 33.8 million to negative EUR 40.5 million. Cash flow before changes in working capital was at in fiscal year 2022 at EUR 19.8 million. You will see that the cash flow from changes in working capital was, at the end of the year, at negative EUR 45.2 million, which again comes mainly from the increasing inventories needed to supply the market in this year. When we look at the next year, which means this year, 2023, the Grifols management envisions an upper single-digit percentage growth in revenues compared to 2022.
This is due to the rising demand for plasma proteins in the world, which is, in the Biotest case, sustained also by the expansion in our manufacturing capacity. At the same time, we've been hearing that we are going to be further investing in the ramp up of the manufacturing facility and further accelerating our R&D projects to be even faster. We've been hearing about the U.S., the new programs. We envision an EBIT which is going to be still negative of. at the level of about -EUR 20 to 15 million. The general direction of the Biotest group will not change. This is something we've been hearing from Michael, and I think he's going to go into that as well. We will focus on our plasma business. We will focus on the ramp up of the manufacturing facility.
Together with a strong partnership with Grifols, we will focus on accelerating the R&D projects, which are going to be bringing success to the company. Once we have discussed financials, I would like to remember all of us that we are bringing all these performance improvements in a sustainable way. That means not just sustainable in terms of pricing and results, but also sustainable in terms of our contribution to society and to climate. Remembering ourselves that we have a goal that we have put ourselves and communicated openly to be climate neutral at the latest in 2035. What we've been doing in 2022 to achieve this goal or in line of this goal, is to invest in sustainability projects, mainly related to our energy consumption.
We're implementing an installation, a photovoltaic installation, a heat recovery system, and electricity charging stations in our site. That you might see or those of you who are present when you walk around. We've been looking forward to actually decrease our energy consumption. This is just a few slides on our sustainability projects, and we're looking to more of this during 2023. This has been my contribution to financials, and I will just hand it over to Michael.
Actually, you should conclude here, but thank you very much, Aino. I guess I will continue by giving also some ideas of what's going on in our research and development department. If we look at this overview chart here, you see a lot of green signals indicating that clinical development has been successfully completed. IgG Next Generation, Yimmugo, of course, the clinical development has to be completed because otherwise we wouldn't have gotten the market authorization. Here, we can say that's done, that's good, that's great. Also with Fibrinogen, we have the first Phase III study, which is needed for getting the marketing authorization, is successfully completed, and that is in the congenital fibrinogen deficiency area. This is done, submitted, and would be ready to go.
That being said, we would ask for the market authorization if we have also enough successful data available for the acquired fibrinogen deficiency. Not only this deficiency, if it's there by birth, you know, but also if it happens during a huge surgery and all of a sudden fibrinogen is missing, you have a deficiency of fibrinogen, then you replace the missing fibrinogen by giving the new product we are developing. This is really right now tested in a phase three study, and I give details in just a minute. trimodulin, two phase three studies have been initiated, and one is running. The one which is running is the study where we try to prove that trimodulin is also very helpful in treating COVID-19 patients. Come to that.
The main indication as it was designed for and developed for is that for severe community-acquired pneumonia, where we hopefully will see that the first patient will be included in this Phase III trial still this year. On top of that, with our existing products, Cytotect, we have also started a Phase III clinical study to show that we can really efficiently protect newborns if the mother is being infected with the cytomegalovirus during pregnancy. Up to now, the risk is very high that the unborn child could get damaged, and therefore, to prevent that, we have started this clinical trial. Let's look at the details of fibrinogen. As I've said, the first one, congenital fibrinogen deficiency, has been completed.
We have successfully demonstrated in 175 bleeding events in 36 patients of all age groups that giving fibrinogen as we have developed it in our pilot plant and developed or produced in our pilot plant, is helpful in stopping such bleeding events. We are trying to show the same in the case of acquired fibrinogen deficiency. We started with patients who have to undergo spinal surgery, this, as you can imagine, is a surgery which is pretty complicated and have the risks that a lot of bleeding is taking place while you start with the surgery. Same high blood loss is a risk if you go in this special tumor surgery.
We have added then as a second indication where instead of giving cryoprecipitate, which is standard of care up to now, we would replace this cryoprecipitate by a much safer and more efficient product called fibrinogen. In the meantime, we have 182 patients included in this acquired fibrinogen deficiency study, which we call AdFIrst. We are waiting here for interim analysis, which will be due end of this month, beginning of next month. Due means that we will then see first results. This interim analysis is designed in such a way that we get an impression if those 200 evaluable patients, which we have included in the protocol for the study, are really sufficient, or if we have to increase the numbers.
Please recall that we started with the spinal surgery indication first and added then the tumor surgery as a second indication in the clinical study. The first indication of 200 evaluable patients was the number of patients we had seen as sufficient patients being included in this spinal surgery part of the clinical study. Now, by looking into the development of 120 patients in this interim analysis, we will hopefully see that even with the second indication included in the clinical trial, you know, this 200 patients being included and being evaluated are still sufficient, you know, to get to, of course, in our view, positive and successful result. Please keep crossing the fingers with us so that we don't have to include more patients, because as you can see, we have already 182 patients included.
We need 18 more if the 200 Patient numbers is the right one and is confirmed in the interim analysis, we are pretty fast then also completed with this Phase III study for acquired fibrinogen deficiency. I mentioned in the beginning that the fibrinogen development of Biotest, you know, a couple of years ago was concentrating on serving the European markets, mainly the German-speaking markets here in Europe, because the capacity we have right now installed in BNL would just, you know, be sufficient to supply those core markets here in Europe. I mentioned to you that Grifols has a bigger or a better insight in the U.S. market, we have to say that during the corona times in the United States, the first hospitals made very good experience with fibrinogen instead of cryoprecipitate.
Up to now, they used just either frozen plasma or cryoprecipitated plasma in order to help in the strong bleeding situation. Since plasma wasn't so much available in corona times, they took advantage of fibrinogen, which was authorized or could be marketed for the congenital fibrinogen deficiency. Some surgeon, some physicians took it also for large acute bleeding events, and it was successfully administered. Therefore, you know, we together with the Grifols experts, think that we should really also target the U.S. market. We got in touch with the FDA in the United States and asked them if they would acknowledge the two Phase III studies we have conducted here in Europe. You know, America is special and normally they only accept, you know, products which are produced out of U.S. plasma.
Of course, the fibrinogen we used in those phase III studies have been produced out of European plasma. The question was, would the FDA in the end acknowledge and accept the results in those studies which have been achieved, you know, with fibrinogen produced out of non-U.S. plasma? The FDA, due also to the needs in the U.S. for fibrinogen, said, "Okay. Of course, we have to look into the data." In principle, they would also accept those data of those studies with fibrinogen produced out of European plasma. We would not need, you know, especially U.S. plasma-derived fibrinogen. They said they would only permit it in those very specialized indications as we have done the study in for the acquired fibrinogen deficiency, it would only be then licensed for spinal surgery or tumor surgery.
Here in Europe, it would be then permitted to treat all kinds of acquired fibrinogen deficiency, and we would like to have also the broader label in the US, of course. That's the reason why you see the top of the chart here, that in addition, the broader indication for the US is in discussion, and we are very well advanced in designing together with the experts of Grifols, the design of this US study or study in the US for this broader indication for fibrinogen. Here you see, you know, one of those joint projects we have taken up together with Grifols in order to accelerate the development for fibrinogen, not only for Europe, but for worldwide view, especially for the US market. Trimodulin.
You all remember that this IGM concentrate activity has been developed for treating patients which have or are suffering under severe community-acquired pneumonia, not a pneumonia acquired in hospitals, but outside, you know, the hospital's normal life. We have very good phase 2 data, and we had an agreement of the authorities that we should take the same design as in the phase 2 study and start a phase 3 study, which we call ESsCAPE study. This ESsCAPE study has been submitted. You know, we got the permission to start in Europe, and also the FDA is granting us a permission to open sites in the United States. The first sites will be opened in the next weeks.
As I said in the beginning, we hope that also in 2023, we can also recruit the first patients and include the first patients in this ESCAPE study. Already running is a phase III study with COVID-19 patients, because here again, we had very good data out of a phase II study, and now we have designed and agreed with the authorities to start a phase III study with planned 334 patients. Thank God, we all know that, you know, the COVID-19 situation, even if the numbers right now are going up again, but the overall situation is no longer so imminent and bad as it was before. You see here the last line of this chart that up to now we have just 7 patients, or actually today are 8 patients enrolled in this study.
Unfortunately for us, I guess we won't see, you know, in a reasonable timeframe that we can reach the 334 patients which would be needed in this COVID study. Good point is here, we have been able to get governmental funds for doing this TRICOVID study. Even if we were to discontinue the study because we don't get enough patients here anymore, there would be no fiscal burden on Biotest because, you know, we got already EUR 14 million for this TRICOVID development and this study. As I said, even if we, from our perspective, are not successful in finishing and completing this trial, it would be no financial harm for us, for Biotest. I mentioned also that with Cytotect already hyperimmune globulin, which is marketed already against the cytomegalovirus.
Currently, we would like to show in this Phase III study and get further on a label on that treatment for treating or protecting the unborn child if during pregnancy, the mother is infected with the cytomegalovirus. Here you see that out of 80 patients which are necessary in this Phase III study, we have 29 already included. Again, we hope that also this study will prove and confirm what we see already in situations when physicians, you know, prescribe Cytotec in off-label use in very seldom circumstances to pregnant women in order to protect the unborn child, and that we can show that also in the clinical Phase III study and get officially then also the label for it.
Having said that, you see, you can expect this year that the ESCAPE trial study initiation and even the first inclusion recruiting of the first patient will be seen in 2023. As I mentioned a couple of times already, we will see the first step into marketing immunoglobulin in the United States by submitting the Biologics License Application with the FDA in June of this year. We should end up, hopefully, keep my fingers crossed, with the AdFIrst trial completed and get top-line results till end of the year. If the interim analysis confirms that the 200 evaluable patients are enough for showing statistically significant results in this AdFIrst study.
Cytotect PreCyssion with 29 patients included, we expect that we can also recruit the remaining 40 or less than 40 patients in during this year so that also we can then later on get to hopefully very positive data with regard to Cytotect being able to protect the unborn child. Yeah. With that, let me summarize it. R&D, fibrinogen and trimodulin projects are progressing very, very well. You will see, and I've outlined you what kind of clinical development activities we are continuing or even starting this year. Therefore, the EBIT will still be negative in 2023 despite a almost 2-digit increase. No double-digit increase. Upper. Yeah, we say upper single. Upper single-digit increase. Let me be a little bit more ambitious.
Maybe we can cut to a double-digit number here that despite the increase due to the higher R&D investments, you know, the EBIT number will still be negative. The further integration towards Grifols is progressing very well. I have really big hopes that we really can contribute quite a lot to the future, good and successful future of both company being Biotest being part of the Grifols group. Personally, you know, I've been responsible here for Biotest Next Level, BNL, and would be very, very happy if I could also contribute to GNL, to Grifols Next Level.
I think we have a lot of it in our pipeline. Maybe we can convince, you know, our colleagues in Barcelona that really also with our products, there's even a broader possibility for those products in the bigger Grifols group, so that, you know, BNL can grow into GNL. Yeah. With that, thank you very much.