Bonesupport Holding AB (publ) ($BONEX)

We're on time. I want to greet you to Bonesupport's Capital Markets Day for 2026. It's been around 2.5 years since we last met in November 2023. So here we are today, a warm welcome. My name is Charlotte Stjerngren. I will be the moderator of today. We have a full agenda with people from the management team, Bonesupport's CEO and also clinicians who are going to talk about the fantastic products of Bonesupport. So we are very many people here in the room and also on the web, so you can ask questions here in the room or you can send them on the web, and we'll post them to management and the clinicians. So without further ado, please, Torbjorn, the floor is yours.

Thank you, Charlotte. Great to see you here. A warm welcome also from me to Bonesupport's Capital Markets Day 2026. It's a privilege for me to kick off the first session. But before I do that, I just wanted to put today's Capital Markets Day into a bit of perspective and into a bit of context. Here, you see the topics of previous Capital Markets Day. And I would like you to take home after today is really these 4 points of the focus that we will go through today. Number one, strategy update. Bonesupport's strategy remains right, remains very strong. What we're doing is that in order to fully unlock the potential of CERAMENT and Bonesupport, we want to become even more segment-specific in foot and ankle, trauma, arthroplasty and spine. We'll talk more about that. Second topic that I want you to take home is that we are making an upward adjustment of the market potential that we see in the U.S. for foot and ankle, trauma and arthroplasty. Third topic that I want you to take home is around clinical evidence. Clinical evidence has been a core part of our strategy ever since 2018. It continues to be. We are announcing that we are continuing to invest in evidence across all 4 platforms, most notably so in spine, where we plan to conduct a multicenter study to introduce and start selling antibiotic-eluting CERAMENT in spine in the U.S. That study, we estimate to cost somewhere around SEK 80 million over 3 years. That is in line with what we have communicated before. We are also announcing that we are going to invest in a study in arthroplasty. That is not to get any market approval. We already have market approval with -- but we're investing in a study to further penetrate the arthroplasty market. That study, we estimate to cost somewhere around SEK 40 million over 3 years. Last topic is that we will talk that I hope you take home with you is that in spine, we see a clear unmet need for antibiotic eluting CERAMENT in spine. And we're going to show you what our research in this field indicates, why we think it's an attractive space to be in and also our plan to not only get regulatory approval, but also start penetrating that market. Those are the 4 topics that I hope that you bring with you home after today's session. So my part will cover 4 areas: strategy, the unmet needs, current standards of care and then the moat being what protects CERAMENT. And if we look at Bonesupport, the company has really transformed over the last couple of years. In the last 5 years, revenue has grown almost sevenfold. Cash flow has gone from negative to actually generate more cash than we actually need. We've stayed focused. We've stayed small. That is in order for us to continue to run very fast. Qualitatively speaking, our evidence has gone from interesting to actually challenging the standard of care. Our brand has gone from actually no brand awareness whatsoever to now actually be a serious market challenger. And our penetration, if we look back 5 years ago, CERAMENT G was not approved for use in the U.S. So we almost had no penetration. Even today, when we look at the market, and we have grown, but still our penetration levels are very, very low. So we're very early on our growth journey. And the strategy that we currently have and that we will continue to apply was really formulated in 2018. It's based on 3 pillars: innovation, which is the core of CERAMENT, this unique technology that focuses on bone healing and infection management. Next pillar in our strategy has been evidence. If you have something innovative in orthopedics and you want it to get traction, you need the evidence, not just to convert the surgeons who use it, but you have to convert the multidisciplinary teams that are around them as well as the payers. Third part of the pillar is around commercial execution. Once you have innovation and once you have evidence for that innovation, it's very simple in orthopedics. The only thing that you have to do is being very, very disciplined and very, very systematic and commercially get that product into the hands of surgeons so that it reaches patients. Those 3 pillars have been the strategy for Bonesupport since 2018. It will continue to be the strategy for us going forward. However, we are taking the strategy and we're making it more segment specific in these 4 segments that I mentioned earlier, foot and ankle, trauma, arthroplasty and spine. Why is that important? Simply because it's different customers, different clinical settings, different needs. So in order for us to fully unlock the potential of CERAMENT it's the same product, but we need to be more segment-specific and cater to the needs that the respective customers have in these 4 segments because the needs are there, there's no doubt about it. And if we look at bone infections, they are among the most complex, costly and consequential complication in orthopedics and the incidence is increasing. In foot and ankle, 1 in 5 diabetic foot infections progress to bone infection, which is the leading nontraumatic cause for amputation. In trauma, more than 30% of the fracture-related infections -- or sorry, more than 30% -- the incidence is more than 30% of fracture-related infections after open fracture fixation. And in arthroplasty, periprosthetic joint infections carry a 5-year mortality that rivals many cancers. not only the consequences for the patients, but also for the health care systems. So I think since I joined, I read this quote from late Richard Rothman, a very famous orthopedic surgeon in the U.S. And I think the way that he describes it in this one sentence actually described the potential or the need for our products. telling an orthopedic patient that they have an infection is like giving them a diagnosis of cancer. This quote is 25 years old, more than that. It was recently repeated at the latest International Consensus meeting for bone infection in Istanbul. So bone infection still is a massive clinical unmet need, and CERAMENT has a role to play to deal with that. And if we look at the 3 segments that we focus on now here and now, foot and ankle trauma and arthroplasty, Independent or despite that these segments are different, the patients are different, the clinical settings are different. The failure pattern is the same. You have a bone defect, you have an infection, but there's no single solution that addresses it. CERAMENT is really the first one. And when you don't have a single solution, what happens is that you have multistage care. You have high recurrence of infections. So patients come back. The infections don't go away. And there's a lot of costs. We believe that some of that cost, a lot of that cost, not all of it, but a lot of that cost can be avoided by using CERAMENT because it addresses the unmet need clearly. And if we want to look at the scale of this, how big is this? We will talk about the market adjustment. That's sort of on the micro level. What I'm painting here is the macro level, what's behind the pool of patients that's behind. It's millions of patients. 38 million Americans have type 2 diabetes. In trauma, 54 million Americans have osteoporosis or low bone mass. And that's not the only pool that pushes patients into trauma. And in arthroplasty, 2 million primary hips and knees on average are done every year. So there's -- it's very clear about this cascade. It's almost an inevitability that some of these patients more and more will end up with a bone infection. So what is it then that CERAMENT does? Here, you have a very simplified picture of a femoral fracture. So it's a broken bone. You can get a broken bone or femoral fracture from a car accident, you can get it from tumor. You can get it from many different things. But essentially, the surgeon meets this patient with a bone where they have to fill a void and they are afraid of infection. So that rectangle to the left describes the starting point where you have filled that void with some white stuff with purple dots. The white stuff is CERAMENT BVF, the bone void filler. It's a mix of calcium sulfate and calcium phosphate, hydroxyapatite, which is a subcategory of calcium phosphate. The purple dots is the antibiotics. And what happens when you inject this into the bone, 2 things start simultaneously. First, that white stuff helps the human's own bone to regrow and replace the BVF. So after 6 to 12 months, the body has resorbed the CERAMENT and transformed it into its own bone. The second thing that happens simultaneously is that in the first 30 days, you have these purple dots, which is the antibiotics that elute in a predictable, controllable way to kill bugs. We'll get more into the details of how that works. But that's essentially what CERAMENT does. It heals fractures as effectively as autograft, eliminating the need for bone transplants. Why is it so important with this local or elusion of antibiotics and the local application of antibiotics? Well, you see it on the picture. To the left, you see when you go targeted only to the part where you want to treat -- where we want to manage the infection, you get with CERAMENT, you get a local concentration of around 90 milligrams per liter. Compare that to the standard of care, which is systemic antibiotics. You get a concentration level in soft tissue that is of 15 to 20 milligram. So a large difference. But bone is not soft tissue. It's even worse. It has much worse vascularization. So clearly, you're able to kill the bugs where you want to kill them. There's no problem with patients' compliance when you have local antibiotics like CERAMENT. The patient cannot pull it out. The patient can decide to not take the pills with antibiotics when they do it systemically. Systemically, you can get intravenously or you can take pills. There's no patient compliance risk. You know, the surgeon knows that this will give the patient antibiotics. So very important. And this picture here really shows -- and I would say that you start looking at the graph to the bottom right. This graph really shows this picture that you have a controlled elution curve of antibiotics. So the X axis is time, the Y axis is concentration. It's a lower mix scale. And you can see that it's very predictable over time. That's one thing. But even more importantly, it is above that red line, which is called the minimum inhibitory concentration level. You have to stay above that line for a long period of time to kill the bugs. It's easy to throw in a lot of local antibiotics in the short term, and then it reduces down to 0. That's not what you want because then some of these bugs will actually learn to deal with these antibiotics and become resistant. So this is one crucial part of CERAMENT combined with the picture that you see up there, which is the bone resorption. So here you have a fracture, it's a picture of the knee. You want to repair that fracture. You use plates and screws that's standard. And then in this case, you also use CERAMENT in the middle picture. And in the picture to the right, you can see that actually CERAMENT has been resorbed and the bone has been reformed. So why doesn't everyone use CERAMENT? Well, the current standard of care has been used for decades and it's largely based on organic bone grafts and systemic antibiotics. And there's a lot of pros with all of those. So if you look at autograft and -- autograft that's the humans own bone. So typically, you cut up here around the hip and you carve out bone from the iliac crest. It's great. It's a standard procedure. It's very biological that knows and recognizes the bone somewhat similar on allograft, but allograft is donated bone from other patients. So biologically works really well, but there are limitations. Part of the limitation is on autograft, there is only so much bone that you can take out if you have a big injury to repair. Also, you get a scar. It's a different surgery. It's another surgery. There's a risk of infection. So clearly, there are limitations with autograft. On allograft, there are other limitations, not as good as autograft. And also, there is an inherent risk of disease spreading from one patient to the other. Clearly, CERAMENT addresses the limitations on both those 2, autografts and allografts. And if you look at systemic antibiotics, why is that good? Well, it's proven, everyone uses it all the time, and you can use a broad spectrum of whatever antibiotics that you want. The limitations you see on the slide, and also what I said earlier, you don't reach the therapeutic level where you want to. It's long treatments, 4, 6, 12 months. You have a toxicity risk, patients that get systemic antibiotics. They're not happy. Just the other week, I was in Denmark. I walked around with the surgeons in the world. And one of the main things that 2 patients said was that, no, I really don't want to continue on the systemic antibiotics. It's awful. It makes me feel really bad. So CERAMENT GMV really addresses that. It regenerates bone and it delivers local antibiotics in a predictable, controllable way. That's the current standard of care when it comes to organic bone graft. Since decades, there are many alternatives, synthetic bone grafts and I grouping them all together. And this is actually a table that I took -- I copied it completely. I didn't change anything. I put those boxes at the bottom below. But this is a picture from the Oxford Bone Infection Conference with Matt Scarborough. He put his overview together. I think it's a brilliant overview. That sort of indicates, so what does the playing field look like? So you have calcium sulfate to the left. Biphasic-s, that's the category where CERAMENT plays. You have calcium sulfate and then you have bioglass and PMMA. All of these solutions have existed on the market for decades. Calcium sulfate was actually clinically documented already in the 1890s in Germany. The great product in many ways. However, it resorbs very fast. So to get that controlled antibiotic elution curve is very challenging for pure calcium sulfate. If we go to the other side of biphasic to calcium phosphate, it's actually on the other extreme. It takes too long. It almost doesn't turn into bone or it's not resorbed. The last, call it, large segment is maybe not to be entirely accurate, but PMMA stands for bone cement. It's typically used when you want to fix primary or implants to the body. The big difference with PMMA and the other categories is that it doesn't resorb. It is in Swedish plexiglass that you put into the body. So if you want it out, you have to have a second surgery to pull it out. Also in terms of the antibiotic elution control as we believe CERAMENT is. So that's really the current standard of care and call it, the competitive landscape. But these technologies have existed for decades. It's nothing new. Now CERAMENT is a biphasic, and we introduced this product in around 2000. So we're in this category. But what is it -- it's unique, but what is it that makes it so difficult to copy and replicate what we've done with CERAMENT? And as with all difficult questions in life, it's not one simple answer, it's multifactorial. And the way that we look at this is that the CERAMENT moat consists of 6 distinct interlocking barriers. We have the patents -- 34 patents valid until 2034. We have the evidence with more than 350 clinical papers and abstracts published. I will go into more details about the secret formula. But essentially, it's a proprietary experience-driven formula that you cannot really figure out just looking at the patterns. It's the know-how that we've built up. I'll go into more details soon. We have the regulatory barriers. We're the only FDA-approved antibiotic eluting bone graft in the market. Reimbursement, I'll also talk about. It's not just the fact that we have IDN, GPO and NTAPs. It's about how the DRGs are assigned. We got some really positive news a couple of weeks ago related to the CMS proposed ruling on that. And then the last barrier is our go-to-market in the U.S. It's a nonexclusive call point-based independent sales rep model. That we started when we split from Zimmer Biomet in 2017, 2018. I would argue that's one key part of the success that we've had and that we plan to continue to have. It makes it better at the market, move fast and focus on this unique technology. So a bit of deep dive into this moat 3, the secret formula. And here, what we mean here is that this is stuff that you cannot really read it in the patterns. So it comes separately. And essentially, it is a combination of advanced material science, years of bone biology research, manufacturing and production experience at scale. And I say at scale because one thing is to manufacture and produce this in small batches a couple of times, but to do it at scale at the volumes that we've done, you don't want to know the production yields that Bonesupport had a couple of years ago. Most of the stuff that we produced just had to be scrapped. Now we don't have that issue anymore. And of course, it's a combination of all those things plus the clinical evidence, both from a theoretical point of view and a practical point of view. So it is -- this secret formula is part of the moat, and it's not so easy to copy. Another one is the regulatory barriers. And I would argue that this barrier or moat is probably the least understood or least appreciated by the investor community. And essentially, it goes to the fact that, as I said earlier, CERAMENT G is the only FDA-approved antibiotic eluting product in the market. If you look at the category of bone graft, calcium, I think the we didn't have the wording here. But synthetic bone void failures and resorbable calcium salt bone void fillers, it falls in this category. Since 1996, there are around 400 to 500 product indication combinations approved. That means between 10 to 20 approvals every year in this category. CERAMENT BVF is in that category. New products all the time. We created the category together with FDA, of course, that is called resorbable calcium salt bone void failure containing a single approved aminoglycoside antibacterial. Gentamycin is an aminoglycoside. We were the first one in that category in 2022. It's been open for everyone to use it as a predicate device for 4 years. No one has done that. No one has done that. Is that because the space that we're in with CERAMENT G is not very attractive and not commercially viable? We don't really think so. So by setting the standards, you see that in the box below, we set the standard in terms of the clinical settings and special controls that all future products will need to live up to, to enter this space. And it's not only what you see here on the slide, but there's a lot of different things that future products will need to live up to. I'm sure they will. I'm not saying that it's impossible, but it's part of the barrier. I think this is my second last slide and it relates to the last part of the mode, which is around reimbursement. As I said, reimbursement is not only on, IDN approvals. Those are important. As part of running the business, you have to get them in order to grow. We've grown. So we've got them, and we continue to work on them all the time. But this example relates to DRG assignments. And the CMS came recently with a full year 27 IPPS proposed rule. And if you simplify it, you can say that this proposed rule increases the payments to support the standard use of CERAMENT G in the U.S. It's a long document. It's a long document I think it's 1,600 pages. Of course, not all related to CERAMENT, but there's quite a few pages that relate to CERAMENT G. But if we simplify it and we do our calculations based on the data that is in this proposed ruling, we see that the payments that we interpret is for CERAMENT G DRG codes, meaning codes where CERAMENT G can be used, will increase somewhere between USD 5,000 per procedure to $11,000. It's not just one simple list, and it's not very easy to sort of draw simple conclusions on what this means. But we took an example here and looked at fracture-related infections, you see 3 DRG codes, 492, 493, 494. They exist already, so there's nothing new in that. What is new is what we've marked in blue. That's top level. That's the most complicated. MCC stands for major complications and core morbidities, I think. So that's the most complicated. And that category remains the same, but the proposal is that they change the wording of it or the title to include or insertion of antibiotic eluting bone void filler. There's only one antibiotic eluting bone void failure approved in the U.S. market. So essentially, that DRG code can only be approved or used when CERAMENT G is used. What happens, well, there's not a lot of extra money from $26,700 to $27,700. So yes, it's an improvement. But the key thing here is that it's a proxy or instead of using the lower codes, whenever CERAMENT G is used, they can code it fully with this 492 code. And in this specific step that relates to fracture-related infections, the average payment increase for the hospital would be $7,900. Now of course, what you all ask is, well, what does this mean this quarter, nothing this quarter because it doesn't have any impact this quarter. The -- this is a proposed ruling. We expect the ruling to be announced firmly beginning of August and come into effect starting October, but how fast and how much this will impact us, we don't really know. What we know is that it's very positive. And what we focus now more on is to prepare ourselves and prepare our customers to take advantage of this. This clearly reduces one of the barriers that we have. Sorry, I ran over a bit, but we're okay. So that concludes my presentation. So I have taken you through the strategy, the unmet needs on a more of a macro level. I went through current standard of care and competition. And then lastly, we went through what are the components that protect CERAMENT. Now I'm happy to hand over to Emily, that will talk more in detail about what does it mean to take a more segment-based approach with CERAMENT.

Thank you. So good afternoon, everyone. So today, I will cover 3 areas. I will go more into detail around how we apply this segment specific strategy and the value proposition. I will also take you through the market opportunity and how we have updated our market model since the last time that we met. And finally, I will also provide some more insight to market research we have done in arthroplasty and spine. Need to be a little bit more firm there. Yes, so the CERAMENT strategy applied. At the core of our strategy is a very straightforward and powerful idea. And as Torbjorn talked about before, we have the same core technology, but we apply it in different types of segments. As Torbjorn also said, CERAMENT combines 2 essential capabilities, the bone healing and also trying to control infection. As you can see on the picture here, we are there trying -- there you basically have the recipe for how we work. We start with early adopters. We start to make clinical evidence in forms of first case [Audio Gap]. We expand to clinical data and more longer studies. Driving adoption and further on coming up with standardized techniques, which helps also for hospital protocols and finally, guidelines. That is what we also aim for. Importantly, we are also expanding from surgical treatments into prevention, and we look for adjacent market segments to move into and muih later here, arthroplastics. So if we look at the different values Yes, basically, it's the same value all over, heal bone, repair bone and protect from infection. But there are some different surgeons to work with, and there are some different -- the basic problem is a bit different. So when it comes to foot and ankle and diabetic foot, the most important thing is there to save the limb. And it's to secure that the patient can stay mobile and preserve the function of the body. That really helps to prevent amputation. An amputation is really disaster for patients where the survival rates are really, really bad. So within 5 years, there is a horrible situation for patients with larger amputations. We are also translating, if we can do that, we can translate the value into health economic value with fewer surgeries, lower complication rates. And in the reduced hospital stays and which also positively impact costs. Looking at trauma. The most important thing there is to protect from fracture related infections or reinfections, which leads to -- sorry, sorry, which helps to faster recovery and shorter hospital stays as well. Trauma is a large underpenetrated market. I didn't touch anything, I think, yes. So trauma is a large underpenetrated market, and you will see that also when we come to the market model. In arthroplasty, which is the latest segment where we have really made a big strong foothold in. We see here a strong growth driver and preventing prosthetic joint infection will really be a benefit. And we have the opportunity to also listen to Dr. Meller here, who have done the [indiscernible] study later on, and he will give you a much more deeper insight to how it is for these patients. Lastly, but not least, spine, here, we see a future big growth opportunity. We have just stepped our toes into this segment. And right now, we're focusing on some [Audio Gap]. As I said in the beginning here of our recipe, standardizing procedures is super important for this. And here, you see some examples of different types of surgical procedures and application techniques that have been developed by our surgeon community serving around the globe and which also have been published and that is what we aim for. And that really helps to expand into new segments and subsegments. [Audio Gap] picture and maybe also when you have been meeting H kan, Torbjorn at other different types of meetings. There, the data was triangulated by multiple data sources, including market reports, [Audio Gap] data, CMS codes and primary research. Data coverage was relatively strong there for synthetic bone grafts and allografts while the data we had on autograph was less transparent and often excluded from available data sets. This is important, as Torbjorn earlier talked about, CERAMENT covers all areas, both synthetic in allo organic, both autograft and allograft -- and therefore, we need to have the whole full picture. Since then, more comprehensive and higher quality data has become available, enabling us to refine the underlying assumptions and improve the accuracy of our market segmentation and total addressable market. And in here, I will just give you a brief update on what is the most significant updates we have done. So when it comes to the bigger changes we have done, revision arthroplasty is larger than we modeled earlier. Our earlier work underestimated proceeded volumes, but new data shows that it was bigger, and it also had grown over the years since we were last here. Second, local [indiscernible] yes, I will go back to that also. So at the time -- at the same time, infection has emerged [Audio Gap]. Second, local antibiotics are already widely used in clinical practice. This was also under estimated [Audio Gap] updates, which you will see. And [Audio Gap] our strategic focus. So in the previous picture, you saw 4 segments, now we focus mainly on 3 segments in extremities. So this slide shows our updated U.S. market view for 2025, covering the 3 core segments [Audio Gap] foot and ankle [Audio Gap], trauma and revision arthroplasty. And the biggest update there is in revision autoplasty but all have been upgraded due to growth over the years. In the total number of 460,000 will also include tumor and [Audio Gap] but we are not focusing on that area. The infection incidents before we also try to differentiate between prevention and infective cases. And here, we now take a more overarching view on it. And the use of local antibiotics is quite high. And you will also see some number in the market researches that I will show that this is the case. [Audio Gap] Spine, we have not done so much. We have upgraded the number a bit, and the total estimates are quite in the similar situation as in 2023, but we will do more research on those moving forward. At the bottom, you see how we expect our market share to be within the different segments. And as you can see, we are -- although we think that we are very successful in -- on the U.S. market, we are still just scratching the surface. So in diabetic foot and foot and ankle, is where we have the highest market share, while in trauma is still very modest. And there, we have a big opportunity for future growth as well as in revision arthroplasty. And spine, we have just, as I said before, just put or toe in. Torbjorn was talking also about that this is not -- this is the current serviceable market that we are addressing. But there is a lot of other factors that will continuously increase the market size. We talked about diabetic patients. They get diabetic foot ulcers. These results in that bone also get infected where CERAMENT has a good -- good place hold. Surgical trauma, we see a growing amount of people with osteoporosis, which will also eventually increase the number in our -- in the CERAMENT segment. Primary arthroplasty [indiscernible] is also growing. It's also increasing the number of primary ultra plastic procedures and -- so that will also give a lot of more revision auto plastic in the future, which will also come and help increase the market size. So market dynamics is there. We estimate the biggest growth of the market between now and 2030 to be in foot and ankle, diabetic foot and in revision arthroplasty, while a bit -- very much in the foot and ankle will be the diabetic foot, and we hope to be able to prove that earlier intervention can help even more patients in the future, which will grow that segment quite drastically. And we believe that it can reach around 100,000 procedures per year. Today, around 40,000. We calculate that around 40,000 of the 80,000 is the [Audio Gap] now I will go into a bit more of our segment deep dives, and we will start with arthroplasty. And we are continuously doing market research stay alert and to stay informed about how the market situation looks like. So this is the latest study we did for arthroplasty and here, we were looking at revision arthroplasty, and also a bit into prevention of also in primaries, how do this [Audio Gap] do. And I previously showed that there are around 120,000 revision arthroplasties made in the U.S. each year where bone grafts are used. Our quantitative research shows that 96% of the surgeon consider infection prevention challenging. Recent separate data from the structured registries from 2025 shows that the most common reason for revision of a primary arthroplasty is infection. The use of local antibiotics in septic revisions is very easy to understand. But what we saw also in this research is that the surgeons are applying local antibiotics already in revision surge, 54% in hip and 60% in e PMMA and antibiotic powder were most -- the most common application forms. And when telling about the technology that we had without not mentioning our -- the name of CERAMENT, 82% found the concept compelling to very appealing. And this is a very high number for [Audio Gap]. So on the next slide here, it's also from the same -- the top the top section there is from the same research, and that was primary arthroplasties. And in this survey, they -- it showed that antibiotic local antibiotics is used in 40% of the cases already which, for the future, leaves a possible segment for us as well. We believe that this is primarily in high-risk patients and reflects the growing burden of comorbid disease as diabetes and obesity. In the bottom section, it's from an earlier study we did in Europe and U.S., and it was specifically looking into prosthetic joint infection [Audio Gap] local antibiotics is critically important. And the current administration is through either PMMA and in space of [Audio Gap] for antibiotic powder or also [Audio Gap] So one other thing that was also seen was that [Audio Gap] were also worried about micro defects in bone, and that is something that can occur in routine surgeries, fractures, primaries and revisions. And this also opens up a significant use of CERAMENT with the possibility of its injectable form. So not just for larger defects, but also for small defects. Yes. So the biggest challenge with prosthetic joint infections are recurrence of infection, bone loss and implant biofilm. 93% of surgeons expressed that PDI is a challenging condition and 84% of the surgeon express lack of available technology and techniques that would enable the transition to one stage procedure, things that CERAMENT can meet. So to leave the arthroplasty segment and go into Spine. In 2023, when we were here, we said that we were going to start looking into the spine as well. And what have happened since this? Yes, we have obtained clearance for CERAMENT BVF use in interbody fusion. We have done preclinical studies specifically looking into application methods. We have done a lot of research and talk with customers in the spine market to understand the unmet -- clinical unmet need. And we have also started a targeted CERAMENT BVF launch, which is ongoing. And we have also initiated and established a plan for how to take antibiotic CERAMENT to the U.S. market. The latest research we have done in Spine and this is also telling about how big the need is for antibiotic eluting CERAMENT. There is in spine everywhere in the body, it's a problem if you get an infection, but it's super hard if you get an infection in the spine, you can't take away the spine, you need it. And therefore, these surgeons are even more prone to use local antibiotics to prevent infection or to find a lot of different ways to not make this happen. So -- and in the research, 86% of the surgeons are already using local antibiotics for [Audio Gap] at least some patients, specifically if there are comorbidities. And 75% of surgeons use local antibiotics for surgical treatment if there is an infection. The most usual way to do this is to dumping antibiotics, although almost all of them believe that it's not an optimal way to do this. So -- even though they do it, 82% of the surgeons consider the approach suboptimal. When we talk about how CERAMENT G is working, expressed a need for that kind of a product in this area. So it's about that's the same for arthroplasty. We see really high unmet need and he really high numbers for wanting to have a product like CERAMENT. So this is my last slide, and this is telling about what we are right now doing and have initiated when it comes to spine. [Audio Gap] going over those numbers I showed you in this area really driving up those numbers. So they are even higher than the ones that I showed. And the idea is to build the foundational spine data across the full same portfolio. We are starting right now pilot studies to guide model selection and study design. And in the next phase, we'll do pivotal studies that could be used for presubmissions and then finally, also submissions to the [Audio Gap] the timing for that is around 2026 and 2027, we hope to be done with that. The clinical strategy is also [Audio Gap] has also started to take for, and we plan to do basically 2 studies initially, 1 single center case series around 20 patients around CERAMENT and then a multicenter PLF study on antibiotic eluting cement versus standard of care. And the cost -- estimated cost there is expected to be around SEK 80 million to SEK 90 million as previously said, and timing starting in 2027. Regulatory pathway strategy, we believe it will be a de novo pathway likely due to the novel spine indication and the claims. And we expect that to be done no later than 2031. Overall, what we see is a large and growing market from the market models that we saw. We have gone from 380,000 procedures to 460,000. We see that there is a need and a future where this serviceable market will continue to grow in all of the segments that we have now decided to focus on and to build upon. We believe that CERAMENT have and solves the really unmet need for both patients and surgeons. And we hope that we will help a lot of patients coming back to life, avoid amputation and stay healthy. And with that, I leave over to our Chief Medical Officer, Michael Diefenbeck.

Thank you, Emily, for the kind introduction. I will continue with the clinical update. The clinical update will follow the already established market segments. I'm sure that you're all really well familiar with the market segmentation. But to me, as an orthopedic surgeon, it was somehow new how easily you can apply market segmentation to medical topics and if we look at the definition, we just have to exchange users with patients, we will share similar characteristics, and this would be specific diagnosis or specific diseases. So here are our 4 market segments, as mentioned before, foot and ankle trauma, arthroplasty and spine, I will go through all 4 segments and following basically the same structure. I want to start with a patient case, then I'll follow with publications since the last Capital Markets Day. And then we look into ongoing and future clinical studies. So let's look into foot and ankle. And this is a case of a patient, male diabetic patient in the age group 51 to 60 years. He has a diabetic for [Audio Gap]. And the Charcot deformity of the midfoot. Now maybe you're not so familiar with the Charcot deformity. But basically, what you see on the top is the normal anatomy of a foot, and the bones are kept in place by ligaments, tendons, muscles and the muscles are [indiscernible] by nerves. And in the -- with the progression of the diabetic disease, all these structures are weakened [Audio Gap] ligaments are weakened the tendons. The [Audio Gap] anymore by the nerves. And then the whole architecture of the foot collapses, which you can see here on the right side, in the middle. And for example, in this case, the mid foot, the tallus, the bone in the middle points down and pushes out this part of bone. So now the arc that you usually have on your foot is reversed into a bump, which you can see on the clinical picture in the right corner. And if the patient walks on this bump, of course, the pressure increases on the sole of the foot, it creates pressure ulcer or diabetic foot ulcer, which leads to contamination, infection and the DFO. Now in this case, Charcot deformity correction was performed by doing bone osteotomy and wedge osteotomy. So basically parts of the bones are cut out. And then the architecture is restored. And internal fixation use, which you can see on the fluoroscopy, this structure here is the intermediary locked with some screws and plates and screws, and [Audio Gap] onwards a file with CERAMENT V. CERAMENT V is quite well visible in black and in the middle picture. But then we use a new software where we can mark the decrement and it's marked here in purple color. So it's easier in the follow-up to find the region of interest, which is here at 6 months. CERAMENT starts remodeling into bone. And here in the follow-up at 9 months, the architecture of the foot is well in place. The hardware is not broken, has not moved, and CERAMENT has remodeled into bone, now marked in green. So CERAMENT V has here protected bone healing and promoted on healing. This is the first publication I wanted to mention. It comes from the group of Professor Hans Gottlieb from the [Audio Gap] Hospital in Denmark, Copenhagen, it's called Closeup, a favorable protocol for limb-sparing surgery in DFO. And here are the highlights of the study. It's a 1-stage procedure with local debridement or minor amputation, settlement bone settlement and primary wound closure in 92 patients. Then for systemic antibiotic [Audio Gap] protocol was followed. So this means a short duration of intravenous antibiotics followed by a 5-week duration of oral antibiotics. And if we look at the results, failure rate, 13% with only 4 patients who had amputations. And please keep in mind, the benchmark, the amputation rate from the literature is up to 24%. So the conclusion of this study was that the defined protocol with CERAMENT leads to favorable results. The second study I want to show to you comes from an [Audio Gap] group from Manchester, the title is adjuvant local antibiotic therapy in the management of DFO. And here come the highlights of this study. It was 105 patients, all had surgical treatment. But then the group was divided into 2 groups. One group received CERAMENT V, which is called the local antibiotic group. And the other group had the conventional treatment without local antibiotics. If you look at the results, reinfection rate, almost 20% in the CERAMENT group versus almost 50% in the nonlocal antibiotic group. [Audio Gap] rate, almost 2% in settlement versus 12%. So a huge significant difference. And as I mentioned before, the benchmark, 24%. So now the conclusion is very similar to the conclusion before from the Hulu group [Audio Gap] defined protocol with CERAMENT leads to favorable results, but now in direct comparison to a group, which did not receive local antibiotics. On the next slide, I wanted to show you an overview of ongoing and future studies. I have the slide for all 4 segments. So I wanted to introduce it to you first. On the top, you can see the time line. In short term or midterm and long term, starting over 0 to 2 years, 2 to 5 years and 5 to 10 years. So starting at 2026 and then adding up to 2036 [Audio Gap] we have the studies color-coded here. So this is the normal progression of a study. You start with a planning phase, then comes after the study protocol has been finalized. The agreement signed the enrollment follow-up data analysis, then the manuscripts written submitted to a journal and published. So here, we have 4 studies in the foot and ankle segment. I have an individual slide for each of them. So I'll just give you the overview here first. preserve. That's an ongoing DFO study in forefoot in the Netherlands. CERAMENT is done at the moment in Basildon and the U.K. again, DFO of the foot. But here, with a short duration of systemic antibiotics. So they already applied the early findings from the SOLARIO study. In this study and [Audio Gap] Spain and Madrid focuses on a special surgical technique to introduce a new third technique, you could say, how to treat special anatomical locations of in the forefoot. In the planning phase, so not written in stone yet, but very far advanced in the planning is a randomized controlled trial, standard of care versus standard of care plus settlement in the U.S. So let's have a deeper dive. The first one is the Preserve study, a prospective K series, DFO on the foot on 53 patients. The technique was a debridement and onward filling with CERAMENT G, and that was done in 10 hospitals in the Netherlands. The first results were already presented at, the orthopedic bone infection Congress at Oxford this year. And from a starting point, 107 patients were treated with conservative treatment, so systemic antibiotics and wound care. For DFO, but 50% failed this initial conservative treatment. And this is really an interesting finding on its own in the beginning because it shows that the standard of care at the moment in leads to a failure rate of half of the patients, and they needed to have surgery and would have benefited if they had earlier surgery. So these 53 patients were included into the trial. And after a follow-up of 20 weeks, there were 15% revision surgeries. So if you remember from before, that's in line with the HERO data with 13% of the data with 18% from Manchester. There were no major amputations, which is really great for the patients, of course. And the wound healing was around 70%. [Audio Gap] period is that CERAMENT promote bone healing protect bone healing for the ulcer healing that's more dependent on the deformity, reconstruction and on the wound care. The second one I mentioned is the study going on in Basildon, in the U.K., London area, 25 patients enrolled. They are now in the follow-up phase. And this is the one with the short duration of systemic antibiotics. And the 6-month results are submitted for presentation at the European [indiscernible] Society Meeting this year in Portugal. Mitano, this is the surgical technique, 20 patients enrolled and they are now in the follow-up phase. It's a quite established technique. It is called resection arthroplasty, where to correct the deformity a part of this phone and the joint is resected and then CERAMENT is used to fill the bone and around the bone. And the idea of this study is to establish surgical technique, which can be used exactly in these very common cases of the diabetic foot infections on the metatarsal heads. Finally, last slide on is the planned randomized controlled trial here. The planning is quite advanced. So I can share some more details with you. It's on the DFO on the foot. Oh, why always forefoot the [Audio Gap] we find in diabetic patients is on the forefoot. So this is why our focus is on the forefoot. 100 patients, 50 versus 50 million standard of care versus. Standard of care plus CERAMENT G. And the study will be done at the University of Texas at 2 sites, UT Southwestern and UT San Antonio. Follow-up will be 12 months. I said we are quite far with the planning. So the study protocol has been finalized. We are in the phase of signing the agreement. So fingers crossed, we hope we can enroll the first patients until the end of the year. This was foot and ankle, now continuing to trauma. Food & Ankle is our largest segment. So the other segments will be a bit shorter. But in trauma, I have included some slides for Solaris maybe about the same size of foot and ankle. Starting with a patient case. So this is a patient, 30 to 40 years old, fracture-related infection of the right tibia. After a gunshot injury and [Audio Gap] to fixation with an intramedullary nail. The case was provided from a surgeon in South Africa. The nail was removed and the [Audio Gap] and filled with 10 milliliters of CERAMENT V.. And systemic antibiotic started. And you can see on the right hand in this right white column now where CERAMENT V was placed and again, color coded down here. And if we follow up the patient now at 8 months, CERAMENT remodels into bone, creates new bone, which we can see quite good here. So this is the area where CERAMENT was placed. And here see how nicely new bone is built, color coded on the lower side and then the 13 months follow-up, full weight bearing and the patient doing well, if you ask yourself maybe what these little white dots are, this is Shamil, which is left from the bullet. So that will stay with the patient. Looking at publications since the last Capital Market Day. The first 1 comes from Dr. Sands from Florida. It's intermediately nailing with CERAMENT G in fracture-related infections, and osteomyelitis. Here come the highlights of the study. It's a K-Series 7 patients with frac-related infection with the [Audio Gap] aspiration system was used. So this is a tool where you can clean the inside of the bone and at the same time, flushed or irrigated and at the same time, remove the debris so that nothing stays behind. And then CERAMENT injected via the 2 can. And when necessarily in case of instability, a new nail is introduced. Mean follow-up was 14 months, no recurrence of infection, no major complications or amputations. And here, the benchmark, the recurrence rate usually is around 13% from the literature. And the 13.3% was the same benchmark we used for the FDA approval for CERAMENT G. Now the conclusion of the study. And for the conclusion of the study, I just put it these 2 images here, this is exactly they show how the 2 is used to precisely inject settlement at the place where it's needed at the fracture site or where the infection is. And we heard that 7 patients is it is not a large number. It's a small case series but this is exactly what the surgeons in the U.S. are interested in to see how CERAMENT can use in a minimally invasive technique here. How it can be used successful coming from 1 of their colleagues to describe this technique. And of course, this is a perfect promotion material for our sales force in the U.S. to show how to use CERAMENT -- the next publication is quite similar, same author. Now it's on the intramedullary nailing but now for fracture-related infection prophylaxis. So this is now open fractures and to prevent infection after open fracture, same setup, a K-series of 9 patients with severe open fractures, using intermedial remailing with RMNG through the 2 again, mean follow-up of 9 months. All fractures were healing, achieved union in no case of fracture-related infection and no amputation. And the conclusion, again, on this slide, a practical guide how to use CERAMENT with this instrument, the 2 can, which you can see here. So the 2 can is basically a cannula inside cannula and you inject through this and place exactly the CERAMENT inside the bone where the fractures and a bit around and then a nail is introduced to stabilize the fracture. Final publication on open fractures. So this is a publication you might be more used to a bit more heavier on the science side. It comes from Professor on Pillars Group in Manchester, adjuvant local antibiotic prophylaxis in it's difficult to treat 3B open fractures with a 10-year follow-up. The highlights, it's a retrospective evaluation of 76 patients, which is [Audio Gap] 3B fractures. Infection rate, 5%, with 4 cases of osteomyelitis after a fall at 8 months. So if you do the math, that's about a bit more than 7 years. And the benchmark is here around 15%, so far beyond the benchmark of infection from the literature and the conclusion that CERAMENT G is a safe and effective option for local antibiotic delivery to prevent infection. This is the slide on the evidence pipeline. Now for trauma. You are used now to the setup -- the SOLARIO study, we talked about this before previously. It's close to publication, then there is a combined study where it's done in Gothenburg, here in Sweden, where CERAMENT GMV is applied in together in a bone void. The [Audio Gap] study in the U.K., that's a post-market surveillance study going on at Oxford and the conviction trial, randomized controlled trial in France, and they go through this in detail, starting with Solarius. I took this picture at the AGS 2024 meeting, where Professor Martin Magneli is presenting the first results on Solarius. Just to remind you, SOLARIO stands for short or long antibiotic regimes in orthopedics. The design was a multicenter randomized non-inferiority trial. Indications were a wide set of orthopedic infections with osteomyelitis, FRI, DFO, PGI and -- it was done in 500 patients randomized in 2 similar-sized groups, 249 patients standard regime, which means at least 4 weeks of systemic antibiotics and 251 in the short regime, which was a maximum of 7 days of systemic antibiotics. Now to the treatment. All patients had debridement and all patients in both groups had licensed antibiotic-eluting bone effect fillers and initially systemic antibiotic therapy after surgery. And at 7 days, the patients were randomized in half of the patients, the systemic antibiotics were stopped. And in the other half continued up to the suggestion or advice from the ID physician. And then the follow-up was a 12-month. These are the top line results. The end point was met. The short regime was equally good in infection are education as a standard of care. So if you spin it around the short duration of systemic antibiotic was noninferior to the long duration of antibiotics. And if we look at the numbers, so the shorter systemic usage was 5 days versus 37 days and -- or an average reduction of 47 antibiotic days and a total reduction of more than [Audio Gap] days just into this -- just inside this trial. And the SOLARIO team did the calculation. If you take the weight of a small antibiotic pill, how much antibiotics were safe just in this trial and it is 15 kilograms. So now time comes a huge suit case, 15-kilogram of antibiotic were safe just in this trial. And this has, of course, a huge impact for the patient because this short regime reduces the adverse events. And this is shown here on the right-hand side. So you have on the Y axis, the patient numbers. and you have the adverse events. And the blue 1 is -- the dark blue is the no adverse events. So 80% in the standard in the long group had no adverse event and up to almost 150 in the short, had no adverse events. And then if we look into the adverse event, moderate adverse event 70 in the standard group and this was reduced to 35 in the short arm and in the severe adverse events, the reduction was even more significant. Why is Solaris so important for CERAMENT and for bone support? This is explained on that slide. So as mentioned before, all patients at local antibiotics and empiric systemic antibiotics, and 19 different products were used in this study, about 80% were resorbable like settlement and CERAMENT V and 20% were nonresolvable. So that's the PMMA, the bone cement. 81% of the Resolve products were seen CERAMENT V, which means 64% of all the procedures. So CERAMENT, so this study relies heavily on the results from CERAMENT G and CERAMENT V. In summary, on Solarius, the advantages of using CERAMENT plus short antibiotic regime, it promotes patient well-being by reducing the side effects, the adverse events. It reduces the antibiotic costs. That's clear by saving the systemic antibiotics. It reduces costs associated with diverse events. And that's quite important because the adverse events are a cost driver in these studies. So this would be readmission of patients, maybe we needed to be admitted to intensive care unit. And then the costs really go up for these adverse events. It improves the patient adherence. Torbjorn already talked about that. So the surgeon or the physician does not rely on it, need to rely on the patient taking his medication. The medication implanted by the surgeon. It improves antibiotic use because it's placed at the site of infection at the right site at the right time in the right dose, and it decreases the risk of creating antimicrobial resistance. With this ex course on Solarius, I come back to the other planned and ongoing studies in the trauma segment. This is the study where CERAMENT G and V are used together in the same bone void on the right-hand side in pink, you can see the size of the bone void where the products are placed. And then in the follow-up, the bone healing. The study has been finalized and the manuscript is submitted to a journal. The conviction trial in France, which is run and organized by the Creo centers in France. It's a randomized controlled superiority trial. The indication is chronic osteomyelitis. The aim is to enroll 200 patients at the moment, 48 are enrolled. And it's the 2 groups, debridement without that space management versus debridement with seemed. 8 sites are now enrolling, but the enrollment is, as you could see, far below the forecast. So the Cryo group will probably need to come together. They are driving this study and to decide if all these 200 patients can be enrolled. The next study is Certitude. This is a post-market surveillance study with a very long follow-up of 3 years, and this was demanded bones or demand from Bonesupport from FDA in the Novo approval. It is a consecutive case series frac-related infections, patients plant, 20 enrolled. It's done at Oxford. So the Oxford protocol is followed at the invention place basically. It's a long study, but we're happy to do it for with a 3-year follow-up. So the last patient included around end of 2027, 3 years follow-up clinical study report in 2031. So for these results, we have to wait a bit. This was trauma. Now coming to the third segment, arthroplasty. So this is a 54-year-old patient, with a PGI or periprosthetic joint infection and the osteolysis of the right tip. If you have a close look at the radiographs on the right, you can see this is the prosthesis, the shaft, the head and the cup. And you can see around this translucent lines here in this whole. So this characteristics of a bone infection. And then the surgeon would do a joint aspiration. You'll see if he can or she can find bacteria. And when bacteria are found, then it is an infection like in this case and the one-stage exchange with CERAMENT G was done. So this is how the surgeon is applying the CERAMENT G. He's augmenting the cup and the stem. And so by this, the CERAMENT G is transported or delivered into the bone voids around the cup and around the stem and then by implanting the cup and the stem. And here is a follow-up radiographs of these patients with this one-stage exchange only one surgery for this infected Hep. One study I wanted to mention on arthroplasty, and this is coming from Charite, Berlin, it first author is Dr. Meller and Dr. Kakad and Dr. Meller will present after the coffee break online. So I will leave this presentation or the details of the publication to his presentation. Here are just the highlights. It's a prospective study on 20 patients with confirmed PGI, recurrence rate, 0%, no recurrence and the follow-up of 3.3 years and the benchmark here for the infections is around 15%, but all the details of the study and of the surgical technique then with Dr. Meller after the coffee break. An overview of the ongoing and planned studies, the overview seachange, a 2-stage study in Germany with used in the first stage. CeraHep-2.0 is a continuation of the SeroHePstudy at Charite. It's in the planning phase. And in the planning phase, not written in stone this settlement in arthroplasty heavier lift, a multicenter RCT. The details, this one is the SERAChange study. It's a pilot study, a small pilot to see -- to gauge the differences in the results in a treatment in a 2-stage hip exchange. So in the first stage, this hip. Here you can interest in. I would suggest, I'm not going to touch this. I just continue with my presentation. I wanted to show you because you're experts now is the radio growth. You can see here again this radiolucent lines, which shows that the hip is the prosthesis is and probably infected. So usually in the 2 stage, the prosthesis is removed and this PMMA space or bone cement space are introduced. And in this study in the CERAMENT group, no spacer is used, but CERAMENT is injected into the cup or into the acetabulum where the cup is placed in the proximal female. It's done at the University Hospital in Munich, and I have some more slides on this. So the first stage is the removal of the prestige, the placement of CERAMENT, which can be seen terming here into the proximal femur and into the acetabulum. Here is the acetabulum, the look. And then after 6 weeks, when the revision is on CERAMENT is still in place. So the one healing has already started and the huge antibiotic elution led to the eradication of the infection and then the new hip is implanted. This is the continuation of the CeraHip study, SeroHyp-2.0, the PGI of the hip, 30 patients. There are 2 new things. One is that this 1 comes with a retrospective with 2 retrospective control groups, 1 is Cerahip on its own because this new 1 has a shorter duration of systemic antibiotics. So again, following the Solarius results. And the second is a control group where no local antibiotics have been used. Final slide on arthroplasty. So this is the plan again, not written in stone, international multicenter as PGI the hip of the knee. We're probably aiming around 300 patients, but that has to be confirmed in a statistical sample size estimation. It's a single state exchange. The idea is to have 1 group with Calm and the short duration antibiotics systemically versus the standard of care, which is no local is and the long duration. This will be done at -- we think about 20 hospitals, and we are in the planning phase with our advisory board and with international experts in the field. And the costs have been estimated as Torbjorn said, with SEK 40 million. Finally, spine -- my colleague, Emily AnelibaVikne has already talked about spine and the strategy here. So I just jumped right into the planning slide. 2 studies are planned in yellow. The first 1 is a single case series on posterolateral fusion. It's for deformity corrections of this. It's not a standard approach. So usually, you have just a tiny indication this year is to correct scoliosis. So to reconstruct the shape of the spine, it's 20 patients are planned. The treatment is the combination of CERAMENT plus autograft and instrumented posterolateral fusion and it will be done in a single center in Canada. While Canada because in Canada, all 3 CERAMENT products are approved to be used in spine. And the second study, the heavier lift, the multicenter study, posterolateral fusion in high-risk patients for infection. So this is to show the prevention of infection to reduce the risk of infection, the same number of patients as an arthroplasty with antibiotic eluting CERAMENT plus autograft, multicenter and again, in Canada, estimated costs around EUR 80 million. And with that slide, I hope I gave you a good overview of the market segments and the clinical update. And I would hand over to Charlotte to moderate the Q&A session. Thanks for your attention.

Perfect. Thank you very much, Michael. So please stay on stage and a little perhaps you want to come up as well. So we have microphones in the room. And could we get a microphone immediately, please because Kristofer here has a question.

A question on the market model. So the 430,000 procedures, do you think that you could penetrate all of that eventually with CERAMENT G and V and also I'm looking at the figure, 115,000 ongoing infection and then you have 190,000 for the use of antibiotics. Is the difference there prevention, just to make sure I understand it or should we add them on top of each other?

I'll start with the first one in terms of what's reachable for us. So if we look at those numbers, you saw the penetration levels, depending by segment. It's a couple of percentages on trauma and arthroplasty and it's slightly higher on...

Could I just interrupt because that was my second. When you talk about penetration, is that out of 430,000...

Yes. Okay. Yes, yes. So when we talk about penetration, I prefer to use penetration, but you can argue market share but penetration is that we define the number of procedures where we really we can be in as a bone graft and/or with antibiotics. So that's 1 piece. And then we always count procedures. We don't count value. We always count procedures. And then, of course, in some procedures, more CERAMENT is used in some procedures, less seen use. But we start with that procedure count because that's important for us. So what's reachable? I think in the U.S. And the reason why we say that we're still on the growth journey early on the growth journey is simply because if we look at the U.S. where we are now, number one, it's only a few years since we actually launched CERAMENT G. Just a couple of years. It takes time in Orthopedics. That's number one. Number 2 is that if we would achieve, let's say, the same level of penetration in the U.S. that we have achieved in certain regions and countries where we've been much longer. Then we will get not 100% of that potential in the short term, but a long runway. We know that we have data points where we reach 60%, 70% of the penetration. And in some countries where we haven't been as successful, we've only reached to 30%, 40%. So we definitely think that, that range is definitely doable in the foreseeable future. Longer term, we expect this total addressable market to expand -- we talked about the cascades of patients. So we're not overly concerned that there is room for us to grow. We just focus on making sure that we get that penetration day by day, quarter by quarter. And then, let's say, in 2 or 3 years, do I think that the market size will expand even more? Yes. But this is the data that we have today. And also, that is what we see today, everything else equal, but Emily showed also the so-called the preceding segments. I think that is a very interesting dynamic for us to follow in the medium to long term. But exactly how that will play out, we don't really know. But it's, of course, a very strong tailwind for us, if that answers your question.

The difference between 19, 115. Is that prevention?

Well, the way that you -- I would think about it is that, first of all, you have the total number of procedures where bone graft is used and some of these bone grafts are used with antibiotics and some of them without, whether prevention or not, yes, you could draw that conclusion, but there are also other nuances that we should take into account. But I don't know, Emily, if you have more I think in principle, you're right, there -- but there could be ongoing infections where you're not using local antibiotics today.

Absolutely. Yes, absolutely.

Great. Sten, did you want...

It's on the same topic. I'm just trying to understand the model. Previously, you talked about impacted patients also may like this around 50,000 and some 90,000 in prevention. So how do we go from those numbers to this 115,000 and 190,000?

So from my perspective, I prefer to talk about the segments as they are, meaning foot and ankle trauma, arthroplasty and stick to the definitions of in foot and ankle, you have the diabetic foot osteomyelitis. In fractures, you have fracture-related infections, and in arthroplasty periprosthetic joint infections. That using the term osteomyelitis is a bit confusing and different data points interpret the term ostomy lights differently. That's why we try to stick to that. That would be my starting point. And then, Michael, I don't know if you can share why is that sort of use of these different terms, different in the different categories around osteomyelitis, fractionated infections and paraprotein joint infections?

Well, I think we -- over the last probably 10 years in orthopedics, we got more focused and we have now all these definitions on these specific infections, which we didn't have before. So before everything was thrown into 1 bucket, which is ostomy -- sometimes it was even called surgical site infections. And the numbers were a bit all over the place. And now it gets much more specific publications coming up with definitions of these infections and treatment regimes. And this is another way, which we follow with this market segmentation as well.

So I can answer directly on your number, maybe Emily will give a little bit more flavor.

Also because what we say is that this proceeding segments are now coming in with more patients that we were not counting on being able to provide treatment before. So we see more and more in the diabetic foot. You can preserve more and more of the foot. And we believe that, that is numbers that has come in and grow our the impacted size number, also in the revision arthroplasty or the prosthetic joint infection, we very much underestimated the use of local antibiotics together with a bone graph there. So that has also increased this number.

Okay. But the 190,000, is that the preventive use?

That is total. So that is both infection and prevention and also based very much on these market research that we have done that shows that there is a much higher use of local antibiotics already bone graft there preventatively.

So Torbjorn, you started your presentation today also mentioning the costs of these studies, and Michael reiterated them. Can you talk a bit about you put so much more money in 1 of these segments and how you distribute it over the years?

Yes. So I'll talk more strategically how we allocate the capital, and then Michael can provide sort of the assumptions behind why is 1 costing more of them. So on spine, we want to achieve 2 things we're doing the study, regulatory approval, surgeon buy-in or being able to use it. That's number two. In arthroplasty, we have all the regulatory approvals. We're not doing it for regulatory approvals. It's all about creating more science, more evidence to convert more surgeons and increase the penetration. That's really important. When we look at the total potential of these 2 segments, Arthroplasty much more here and now closer to us less risk. It's just to go out and get it, so to say. Spine, we're not there yet. So new indication, new regulatory approvals, but both of the segments to us look very attractive and dependent on how we see them. So that's why it's almost a no-brainer to do the investments at this stage. Now the 2 studies that we, at this point, preliminary look at they are designed slightly differently, and that's also the cost. So Michael, feel free to share what are the thinking around the studies.

Yes. And thank you, Torbjorn. And you mentioned some of the parts, so the spine study, as you mentioned, comes or should -- will be used for regulatory approval. So this needs a higher scrutiny. This has to be perfect to be used with the regulatory authorities in the U.S. In spine, we are not so far in the process compared to arthroplasty. In arthroplasty, we have an advisory board. We have a lot of surgeons which are interested in doing the study and which want to contribute to the study. In spine, it's a starting point, we have to go out and find the interested surgeons. And concerning the cost, the calculation is that in spine, we need a CRO, or clinical research organization, which we have to rely on heavily to get the study done to all the standards for regulatory approval. With arthroplasty with the key opinion leaders. It's not written in stone, but it could be driven by one of the key opinion leaders, meaning that we don't need the cost for a CRO and the cost for clinical research atfor these studies are significant. So these are the 2 differences.

You're saying significant, but not as much as has been speculated in the market.

I mean what's being speculated in the market is up to market to sort of answer to -- we're -- I mean, on spine, let's be honest. The number that we communicate today here on spine is exactly the same number that we've communicated all the time. There is no -- nothing new on that. For those of you who have been in meetings and been in presentations when we get these questions, what we say now is exactly how we have answered that question. So around 80 million to 90 million. Now if other people have better or other estimates on how much studies cost for bone support and CERAMENT, it's up to them to answer that.

So I have 3 questions. The first 1 is, yes, you implicitly share the volume split between the 3 focus segments in the U.S. So it implies a quite clear major representation in diabetic foot, of course. So 2 questions there. So in your opinion, is any factor we should account for that suggests a lower market share in trauma and revisions long term, which you consider? And also, I think what would be helpful is if you could share the sort of volume split in Europe between these 3 segments where we've been before in certain markets?

Okay. Good First question. No. So I don't see that there is a different sort of threshold that we can reach in foot and ankle versus what we can reach in trauma versus arthroplasty. All of them look very attractive. At this point, we don't see a ceiling that 1 is going to be drastically different than the other. They will be different, but we don't really know yet. Foot and ankle has been a fantastic segment for us. [Audio Gap] fantastic for us. But it's early days. It takes time. Arthroplasty, again, we're just scratching the surface. So all 3 of them are very important for us in absolute terms. It's easier for us to provide this level of granularity for the U.S. simply because we have much more granular data. And that comes from the go-to-market model that we have in the U.S., which I said earlier, it is nonexclusive call point based independent sales rep model. And that call point based, what that means is that we get data for 80% of all the procedures done in the U.S., we know what is the individual surgeon who is he or she, what is he or she using it for. So we have that level of granularity in the U.S. In Europe, we don't have the granularity. It's more anecdotal and we can make estimates. So it wouldn't be fair to give an exact number for OUS because we simply don't have it. But do I think it will look completely different OUS than the U.S.? No. That would be my estimate. Good. Those were 2 questions. What was the third one?

No, I think maybe it's 4 questions here. The next 1 is how big a factor is the ability to plan the procedure when it comes to the decision of the surgeon to use CERAMENT G or not? I think maybe some words on the diabetic foot versus trauma, for example, would be helpful.

I think it's a great question that we can ask Dr. Matuszewski, when he presents. So part of that question then you hear it right from the surgeon. I think from our perspective the principles are the same. You have to -- number one, you have to have an innovative product, we do that. Number two, you have to have the evidence. That depends a bit in which procedure you're going after. Third, you have to do it surgeon by sign. So I have to convince certain -- you could argue, well, are the trauma docs easier or harder to get in front of versus the foot and ankle docs? Some say yes, some say no difference. For us, we don't draw any sort of major conclusions on that. The principles are the same. You have to convert surgeon by surgeon with a normative product and with the evidence. And so far, I think it's still too early to tell, and we don't have enough data to say that, yes, 1 is absolutely more difficult than the other. We have enough demand on all 3 segments as it is today.

Good. And then in years here post 2026, let's say, 10 years out in time, how much faster do you think the local antibiotics patient cohort will grow compared to the total procedures? And a question to that is also, do you think SOLARIO is yet to help to hedge these patients higher? And also do you think SOLARIO, could have an impact on the U.S. behavior? What do you think of [Audio Gap]?

It's a very good question, and it's it is basically the orthopedic community has been waiting for this study. It has been waiting for these results. and has been waiting to reduce this long duration of the antibiotics. So I think if you can avoid these problems for the surgeons, for the patients by reducing the duration by local antibiotics. This is a driver towards the local antibiotics and to settlement GMV. So I think it has a high impact. The question in Europe, it's a European study. In the U.S., it is -- will probably take some more time to make it public and to get the adoption because the MES is quite known for the long duration of antibiotics. They kind of will stick to their rules first. But on the other hand, if you compare it to the AVEVA trial, the OVEVA trial is where it was shown that oral antibiotics pills are as good as intravenous antibiotics. This was adopted quite fast in the U.S. because they immediately saw the benefit and the , then we don't need this 6 weeks of intravenous antibiotics, the special application, cannulas and so on and so on. So could go both ways, but I think it would be more conservative in the U.S. for the adoption of the Solarius. But what we see starting now, and I mentioned this a bit in the clinical studies that there is a huge interest now to prove the SOLARIO concept in the segments. So we have -- we hear a lot about old diabetic foot, can we do a study on a shorter duration like it's done in Baseline now. So this topic is coming more and more and will help to get even more evidence behind the large SOLARIO trial.

And I think the key point, which I'm not really sure I cannot really quantify, but I think it will have a significant impact, and this is actually something that is over the last, I would say, year has been referenced in relation to the SOLARIO study. Because 1 of the key things that Professor McNally says when he presents this is that this study gives more decision power on the orthopedic surgeons. They don't have to rely as much on the infectious disease stocks and the systemic antibiotic receives. So it gives them more evidence, more decision power. And I think it's not only good for society and the patients as such. I think it's also going to benefit with us. But exactly when, how we don't really know.

How important is the full publication do you expect to get an extra boost from that? Or is this -- I mean, it's already published the top line?

Yes. So top line results published in every conference that I go to or that we go to, salary has mentioned. It's been talked to -- it's been referenced. They talk about the results. And every time McNally and his team are out presenting they're presenting the data. So from an orthopedic surgeon perspective, it's already getting traction is already talked about. So that's 1 thing. However, in many hospitals and hospital systems Well, actually, the topic that we're in, it's not only a decision for the orthopedic surgeon. It is a multidisciplinary decision involving the infectious to see stocks. And -- what that means is that they -- in several areas, in many cases, they say, well, a great study, love it. We're definitely going to go with this. But where is the publication -- last time when I was at was it Novus in -- on the West Coast of Sweden. This was exactly this. This is great. I will use it. But I cannot start using it because I need the publication, where is the publication. So yes, it will have an impact, but exactly how and we don't really know. And we have really good reasons to believe that it will come soon. but it's out of our control.

So after following you for many, many years, a couple of years ago, you did this Booster program to get sales up. Now it seems you're today talking a lot about the clinical side. But isn't there a potential still to do some type of booster programs. So what is hampering would be the wrong word, but what is holding your growth back? Is it the clinical side? Or could you -- you have the money to do booster programs as well?

You know what you on tells me all the time. We're doing all of this booster. We need to reduce the amount that we're boosting the -- we're doing a lot of booster recently. I mean, what has been announced has been announced. But if you look at '24 and '25, we've invested a lot in the hybrid markets OUS. We've invested heavily in the U.S. in '25 and also since I joined, we invested a lot in the back office functions to support the organization to drive more sales. The good thing, as we grow, we build a stronger base, larger base. We're not shying away from investments and commercially in the U.S. as well as OUS. And actually, the good thing is that they pay off. If you look at the H kan will talk about the investments in the hybrid markets after the break. It looks really good. We continue to invest in the U.S. In the last 2 years, we have invested to boost production. We have doubled the capacity of the business. That's something that we've done over the last 2 years. I cannot really see it on the balance sheet, cannot really see it on the P&L. So we continue to do that. But the reason why we put so much emphasis on this is a lot of exciting stuff on evidence around CERAMENT. And this is part of the strategy. We have an innovative product. But in order to get it into the hands of surgeons in a segment-specific way, we will continue to invest in evidence. So we don't really change the strategy. We just continue to what we've done historically, and it's more of the same really.

So we have a question on the web from the web on CERAMENT covers gram-negative organisms and CERAMENT gram positive. So how is the termination between when to use GMV made? Are there an increasing amount of procedures where GMV together would be appropriate?

These are very good questions. So CERAMENT G with gentamycin is the broad spectrum covers gram-positive and gram-negative. So this is basically the go-to product. because even if -- so this is especially for the one-stage procedure where you're not 100% sure which bacteria you're facing, you could use M&G Settlement is more focused on the grand positives, not for the grand negatives. And this is a good choice. If a patient, for example, is fewer already a surgery has been done somewhere else, and they found gram-positive bacteria, maybe even resistant to gentamycin. And then this is a really good case to use CERAMENT V. So when you know that the bacteria there and that they would react really good to vancomycin. But they go to is CERAMENT V. for the [Audio Gap], the grand positive. And there is 1 part which is interesting for the PGI, the periprosthetic joint infections Here, the surgeons are doing this joint aspiration. So they find the bacteria even before they do surgery. And there are a lot of grand positives, bacteria and vancomycin works really well against. So I think there's a really good space for CERAMENT in PGI. I hope they are happy with that answer.

So there's 1 thing that you have announced lately that we haven't covered it all, and it's the buybacks. And there has also been some questions from the web, why aren't you addressing this at all today. Perhaps H kan will, but now we have you stay.

Yes. I mean, Hakan, for sure, we'll address it when he shows his favorite slides relating to cash flow. I mean we're in a fortunate position. We're generating more cash than we actually need to do this. So we have plenty of cash. And also, please bear in mind that the Board proposed to the AGM to give approval for a buyback program, the AGM gave that. Now we didn't only do that for fun because we did it because we think it's adequate and relevant to do exactly when and how we will announce that in the correct way. But now the focus for us is to continue to operate the business the way that we want to invest in the business that we have done and that we show now that we want to continue to do -- and I'm sure what comes soon will give more information about how we start executing on the approvals that we have received now from the.

So in a while, before that, we're going to have some coffee. And just please -- remember the A, B or C that you got when you entered the room. So now there is coffee, but please, as soon as possible, go to your A, B or C, and then we're going to rotate. So you get to see to of the product demonstrations before we are back here at 3:30. And we have the eminent and great support of Karen, who's the Director of Medical Education in Euro. She is responsible for the foot and ankle demo. And for trauma, we have flown in Candis Maxwell, who runs medical education in the U.S. And for orthoplasty we have the eminent Paolo, the Director of Product Management. So take the opportunity, you get to feel the stuff. It's really fun. You get to feel the product and ask a lot of questions. Thank you. [Break]

Welcome back from the coffee break. I hope you had some time for good conversations and some time to experience the product. We continue now with the clinical experience session. And it's an honor for me to introduce 2 surgeons who will present now. We have first, Dr. Sebastian Meller, is a consultant for Orthopedic Surgery. He is the Head of the Department of Hip Arthroplasty and Infection Surgery at the Charité – Universitätsmedizin Berlin from Germany. And of course, he will present on the arthroplasty market segment. He will have the first presentation now online. And then after that, Dr. Paul Matuszewski will present. We brought him over from the U.S. for this presentation in person. He's Associate Professor of Orthopedic Surgery, Chief of the Trauma Service and Chief of the Trauma Research at the Department of Orthopedic Surgery and Sports Medicine College of Medicine in Kentucky, University of Kentucky. With that -- and of course, he is presenting on trauma at the expert for Trauma. With that, let's continue and see if Dr. Sebastian Meller is online. Sebastian, can you hear us?

Yes, I can hear you, Michael. Hello. Can you hear me as well?

Yes, we can hear you here in the room. Now we can see you and we can see your presentation. Wonderful. So thank you for spending the time with us. And we are now looking forward to your presentation on arthroplasty. The floor is yours.

Yes. Thank you. So once again, Michael, thanks again. Hello, everybody. I'm Sebastian here from Berlin. It's an honor for me to talk here for the investor meeting, and I'm presenting our experience with CERAMENT in our PGI cases. So let's start. PGI. So [indiscernible] joint infections means challenging diagnosis. We have big problems. We have time-consuming surgeries. We have high cost, worse function, worse outcome, and we have a high morbidity and mortality on the side of our patients. In some cases, we have higher mortality rates than in some cancer cases. So it's really a big problem. What means PGI? PGI, it's an infection of a joint replacement and the surrounding soft tissue and bone tissue. It's biofilm driven, and it's mostly caused by bacterial pathogens. The diagnosis could be difficult. So this is why we need clear classification systems like the [indiscernible] or the Charité definition. The PGIs often requires revision surgery, implant exchange, prolonged antibiotical treatment. This is why we have to talk about the treatment in future. Why we're doing hip revisions? These are the data from the German arthroplasty register. And you can see that almost 30% of all hip revisions are being caused by infections. So we are talking about a high number of patients, a high number of cases, which we are dealing with in hip and also knee revision. If we look at the re-revision rate, so these are patients which are revised and again revised after a hip revision, we see that in septic cases, and these are the -- is the blue line. In septic cases, you have 30% of knee revision rates after 1 year and higher in 2 or 3 years. Even in aseptic cases, this is the red line, and you see 10% up to 20% in 5 or 6 years. So we're talking about not as good results in the real world. So this is why we have to improve our results, and we have to talk about strategies to improve these results. And this is why I would like to present our surgical treatment strategy for these patients. The goal is to take the less invasive approach with the best results. And you can see here, this is the treatment algorithm for chronic PGI treatment. In a chronic PGI, you have to remove the prosthesis. You can do it in a 1-stage, in a 2-stage or in a 3-stage exchange. Let's talk about the single stage, so-called 1-stage exchange. For that, you need good patients. You need good soft tissue, good bone and no systemic infections. These are the indications for a single-stage PGI treatment from our point of view. The current gold standard worldwide and most -- the most frequently used technique is the 2-stage. The 2-stage means in 2 surgeries in the first one, you explant the prosthesis and in the second surgery, mostly after 6 to 8 weeks, you go for reimplantation and reimplant the new prosthesis. So this is called a 2-stage surgery, and this is the most frequently used technique in the meantime until now. The single stage is an option, a reliable option, which is getting more and more popular, increasing application, mostly in centers. And the success is comparable between the single stage and [indiscernible] in PGI of the hip in selected patients. So in good host, in sensitive pathogens, this is a point which we have to go if we talk about the single-stage exchange. However, the treatment failure rate in PGI, in single stage and 2-stage remains high. We have reinfection rates with strict criteria with more than 20%. So it's really, really important to identify and modify risk factors which can be involved for better outcomes. That means host factors, local antibiotics, defect and dead space management. These are the 3 key points from our point of view to modify and to improve results in PGI treatment. So let's talk about our surgical approach for a single stage exchange in these patients. And to illustrate our procedure, I want to present you a case. This is a typical case, 59 years old lady, PGI of the right hip, hip arthroplasty a few years ago. You see also on the right side, a CT scan with some holes around the cup with some defects. So from our point of view, a good patient for a single-stage exchange. So what we did, we did a function, an aspiration before the procedure. We found a pathogen, Staphylococcus capitis in this case. So we decided to go for a single-stage PGI treatment in this lady. We used CERAMENT G with some allograft in the bone defects in the acetabulum. You see it here on the video in the middle, we fill the defects with CERAMENT and allografts, and then we go and implant the new prothesis in this new filled -- point in this new filled acetabulum, and then we are happy because we have local antibiotics, we have defect management for the new implant. So let's talk about on detail about our augmentation technique using CERAMENT in these cases. So what we do usually, in the first step after removing the prothesis, we absorb blood and fluid and then we go deeply in the femur and fill the whole channel retrogradely without pressure deep into the femur under the stem with CERAMENT G. You see it here. It's quite deep after removing the compress, filled retrogradely. This is step 1 and step 2. The next step is an augmentation of the implant. You see it here. Every implant surface has some glue, some notches, some holes, and you can augment these implants with CERAMENT like we did it in this case. And then you go straightforward according to your standard protocol and implant the prosthesis to this position like it's planned. You see here again the augmentation of the surface of the implant 360 degrees on the implant surface and then you go on with the implantation of the prosthesis. In the next step, it's step #5, we fill and augment the dead space. You see it here in between the prosthesis and the bone, there's always some dead space. There's always some defect. So we go and fill it up with CERAMENT to avoid dead space, to avoid hematoma because this could be the next position and the next space for bacterial infection. This is why we fill it up with CERAMENT. And in the next step, step #6, we dry the CERAMENT. You see it here. Usually, I say a compress and push, compress the CERAMENT 8 to 10 minutes, wait until it's fully set and hardened. And then you can see it's very nice, hardened, fully set and then we are happy and can go on with the surgery after the CERAMENT is dried. And in the last step, according to your protocol, make an X-ray, check the position of your implant and you can also check the position of the CERAMENT. You can see it here in the [ red marked ] areas, the CERAMENT in the approximate also in the distal part of the prosthesis. This is our augmentation technique for the femur side. And sure, we also have acetabulum. And this is what I have here, the CERAMENT and the cup revision. And this is the same principle. We dry the bone, we absorb blood, use some compressors, use the suction device because you need a good dry area for a good visibility and application of the CERAMENT. In the second step, you go on with the application of the CERAMENT. It's applied into bony defects. You see it here, these osteolytic areas, the holes in the acetabulum are filled up with the CERAMENT like it's here shown. You can do it without or with allografts. If the defect is a little bit bigger, you can also take some allografts like I will present it in the next second, again, some CERAMENT. You see it here layer for layer. And then after the CERAMENT, you take some allografts. You see it here some chips and then you can put it on the CERAMENT, make some compression, go on with a reverse reamer or with a pusher, you can compress it and fill up the holes and the defects very nicely, and you will get a nice osseointegration in this case. In the next step, it's step #3. It's again the augmentation on the implant. You see it here also here on the surface of the implant. Also here, the same like in the female revision, you have in the acetabulum also implants with notches, with grooves, with holes, and you can fill them with CERAMENT. And then according to your standard protocol, you go on with the implantation of the prosthesis in the prepared acetabulum like you do it routinely. You can complete it as per standard protocol. So you put the cup inside and then, yes, now it's in, take the right position and then fix it with the hammer. Step #5 , also here, filling and augmenting of dead space and defects. You see it here in between the cup and the bone, there's also remaining dead space, some cavities, you can fill it up and you can fill it up and close these defects with CERAMENT. And also in the last step, step #6, you can compress and dry the CERAMENT 8 to 10 minutes until it's really fully set and hardened. And in step #6, you do the X-ray. And also in the X-ray, you can see the CERAMENT around the cup in the holes, in the cysts. And then this is also ready and the patient has a new hip after one stage PGI treatment. So what are pitfalls in using CERAMENT? From my point of view, first of all, the incorrect patient selection. So you need a good strict selection criteria for a single stage. This is necessary. And the further pitfalls from my point of view, are insufficient drying of the bone. It will bring a poor adhesion. So dry the bone. The next point is high pressure application. Don't use high pressure, make it slowly, take your time. Otherwise, you will get a misdistribution in the system. Number four, the incomplete filling of the defects of dead space. So residual spaces between implant and bone remained. So again, take your time, fill up the holes, fill up the dead space with a CERAMENT, make an X-ray, check if there are some holes and you can fill it up with CERAMENT. And number five, don't close the wound too early, wait until the product is hardened up to 10 minutes. And if it's hardened, you can go on with a good soft tissue closure and then you are happy and also the patients will be happy. So to verify now the things I told you and to verify our protocol, we performed a prospective study, which was published a few months ago, the cementless once-stay hip revision arthroplasty with CERAMENT in infected hips. So we called it [indiscernible] study. It was a pilot study. and I want to present you the design and the results of the study. So it was the first prospective study using CERAMENT in PGI cases. And we included confirmed PGIs according to the [indiscernible] criteria, and we involved 20 study patients in this prospective study with a follow-up of at least 2 years. And we used CERAMENT with gentamycin in defect in dead space around the STEM and also around the cup, like I showed you before. So then we follow up the patients with a standardized protocol like it's typical in our unit. So the patient characteristics, we included 20 patients, 10 men, 10 female with PGI of the hip, the mean age, 66 years. 16 patients were cementless in the previous surgery. 4 patients had a cemented total hip arthroplasty. The stem was cemented in the cases. 6 patients one had previous revision, but it was aseptic. So it was no PGI case before. So the intraoperative characteristics, we confirmed PGI in all patients intra-operatively. We had positive microbiological or histopathological results. And in mean, we used 13.2 meter CERAMENT G per patient. Postoperatively, 19 patients reached a follow-up. One patient had a lymphoma, was not able to follow up. We had one aseptic dislocation of the cup. We had no wound complication, and we had no drainage after the discharge of the patients. We found 60% of coagulase negative Staphylococci, so a typical cohort. staphylococcus epidermidis was the main pathogen, polymicrobial infections, 20%, culture negative 20%. So a typical microbiological finding in the PGI cohort. The results -- the postoperative results for the [indiscernible] score, they improved significantly. Also, the EQ-5D-5L improved, that's a life quality score. So the patients felt better after the surgery, were happier. And also the pain evaluation improved in the hip cohort in the hip study also significantly. So very good results in this cohort. And we can say after now 3.5, more or less 4 years follow-up, we had no reinfection. We had very good excellent functional results, good radiographic results and the limitation, longer follow-up and more patients are necessary for future investigations. But you can see it works and our study could prove that it works in our hand. So let me mention that we're also using CERAMENT in 2-stage exchange procedures. So I brought you also to one case for a 2-stage exchange. That means this is a typical case for a 2-stage. You can see it here on the left side, a lot of surgeries in before hip replacement of the left hip, explantation, reimplantation, fracture, also some different pathogens. So the patient was referred to our unit. We did an explantation and [indiscernible] procedure, like you can see here on the right X-ray, you see no implant inside. So after 6 weeks, we go and made a reimplantation in our unit, and we decided to use CERAMENT mixed with some allografts for the defects. There were some defects in the bone around the acetabulum, also around the femur. So this is why we use CERAMENT also in the 2 stage in the reimplantation procedure in this case. Until so far, the patient is good. And I wanted to mention that we also use CERAMENT for prophylactic use. That means we have patients which are like at high risk, patients after rerevision, patients with some comorbidities. And this was also the case in this lady. You see it here, she got a nail after a fracture on the left hip. And after a few years, she developed an osteoarthritis. You see it on the left side, she suffered from pain and was not able to walk probably. So what we did, we removed the implant. And in the same session, we cut the neck. We removed the head, we cleaned the acetabulum and we implanted a primary hip arthroplasty like it's shown here on the right side. And because she was very old, she had a surgery before, she had some comorbidities, we decided to protect the implant with local antibiotics to do it like in a prophylactic way to save and to hope that the implant will be safe for the future. So we used it in single stage, 2 stage and also here in prophylactic patients. So let's go to my take-home message. I would like to say that the 2-stage is currently the gold standard. The 2-stage is the gold standard, but the single stage is getting more popular. We're getting more brave worldwide, and so more and more surgeons doing single-stage in PGI cases. For the single-stage revision procedure, we need a critical patient election. This is mandatory. I showed you our algorithm for these patients. CERAMENT G is in our department, firmly established in the treatment protocol as a local antibiotic eluting bone graft substitute for defect augmentation in the PGI treatment. The CERAMENT G is utilized according to a standard protocol. So we do a debridement, bone preparation and then we applicate in defects and around the hardware in the acetabulum in the femur and also around the knee. The CeraHip study showed good functional and radiographic results. And we also could use it prophylactically in high-risk revision cases like I showed you before. So this is my team. I always say thanks to my team, and thanks you for the attention.

Fantastic. Thank you. Thank you, Sebastian, for this great presentation. And I think I'm not sure if you could see the audience, but what was really appreciated with the videos, I think. And I saw some smiles when we were hammering in the prosthesis. I think this is one of the highlights of each implantation procedure.

So all of you are invited to come to my surgery room if you want to see it live. No problem.

Sebastian, we have some time for questions. You just can hear my voice, so I would repeat the questions. And I would ask the audience for questions, but please formulate them short so that I'm able to repeat the questions. So no numbered questions like 1, 2, 3, 4. Okay. Let's start with Christopher.

Would you say that CERAMENT is as beneficial in the 2-stage procedure as the single-stage procedure? Or is it mainly in single stage that this is useful...

Thank you. So no, from my point of view, if the indication, if you need local bone graft substitutes, if you need local antibiotics with a high concentration, if you need a substitute for defect management, for death space management, it's also a good idea to use it in a 2 stage. The CeraHip study was about single stage, but we also do it now in some cases, if the indication is right in 2-stage cases as well, yes.

Great. Great answer. And it's fantastic, of course, when you use the microphone, then I don't have to repeat the question, though that was a mistake on my side. So Stan, the next question?

Yes. So Dr. Meller, approximately how many sort of wise or percent of your overall procedures, do you use CERAMENT G today? And where do you think that, that number should be 5 years from now or...

So in the moment, we use CERAMENT G in all our single-stage hip procedures. Why? Because we had these good results like I showed you in the CeraHip study. So we have a good working system, so never change a winning team. So this is why we use CERAMENT G in these single-stage exchanges. We will look up how our results will be in 2-stage and also in prophylactic patients. But I can imagine that if it works and if the results getting also good, we can go and use it also there as a maybe standard product if you have defects, if you need a high concentration of local antibiotics.

My second question would be, would it make sense to use it prophylactically in primary hip procedures?

So the question is, if there is some space for the CERAMENT. Normally, you have -- there are no bone defects. There is not much dead space, so you don't use it. But some primary cases are difficult. In some primary cases, you have osteolysis, you have defects. And there, it could make absolutely sense, makes sense to use it in these cases, yes.

Yes, that's a great answer, and it really depends on the -- if there are bone void, CERAMENT is, as you, of course, know, bone void filler. So if there are bone defects to fill, then it makes sense. But sometimes there are no bone void, so then the application is tricky. Great answers. I think we have time for one more question, if there is interest. No further questions. So Sebastian, once again, thank you so much for presenting from Berlin, all your experience from the Charité.

Thank you. Have a nice day. Bye. Good luck.

Thank you. And now it's an honor for me to introduce Paul Matuszewski, Dr. Paul Matuszewski, Associate Professor at the University of Kentucky, presenting on trauma. I come down. And next place for you.

All right. Well, it's a privilege to be here to talk to you guys today and all the way coming from the United States and certainly, good to share our perspective. My job that I wanted to impart to you all today was essentially to get a little insight into how we use it and how it's been helpful for us, but also understand really what the burden is. I think that you can talk about market share and things like that, but I think it's really important to understand from a patient's perspective and a worldwide perspective, how big of a problem infection is for us. So the socioeconomic effect in the treatment of fracture-related infection is quite high. And some of the prior speakers talked about this, the rate of infection has largely been unchanged. It's anywhere between 1% to 30% in patients. And why is that? Well, it turns out that we're getting better at taking care of patients. So it used to be that patients would have traumas and they would die. But with advances in automobile safety and also some of our trauma care, we're able to keep these patients alive. So when these patients survive their injury, then they become the broken man, so to speak. And that's where I come into play. And so as these patients survive more, we have a higher rate of complex injuries. When you have complex injuries, you have a higher rate of infection. So when you look at it from a worldwide perspective, the burden is huge. So each year, there's about 178 million new fractures. And that corresponds to about 1.8 million fracture-related infections, which is quite a bit of infections every year. So treatment for infection is expensive, right? So it could be anywhere from up to 6.5x more expensive than it would be for the original cost of fracture care. And an older study published, it said about $108,000 per case, but it's likely more. And a lot of that cost comes from staying in the hospital. These patients get admitted with their problem and they stay in the hospital and they there for several days and often multiple times. And that's followed by the cost of the implants and the pharmaceuticals. And as these patients become more sick, older, so on and so forth, that expense increases. So when you think about that worldwide, extrapolating those numbers, if you're spending about USD 100,000 per infection and you have $1.8 million, you're talking about upwards of $200 billion a year spent on taking care of infection. And then when you look at it as a society, that number is probably a little bit lower than what we really expect because the cost is tremendous. In the United States, you have about a 45% increased odds of requiring some type of governmental supplemental financial support, meaning patients are in the disability and receiving benefits from the government. So -- but what about the actual individual? I just talked about the numbers to society. Well, the cost is tremendous. And you have to think about it and look at it from the perspective of how good we are at taking care of infection. Well, it turns out that for infections, we're about 60% to 70% successful for the early infections. And when someone has a fracture, they get the surgery, they wind up with an infection, we can treat them with a debridement, washing things out, retaining what they have and they get antibiotics. And that's about a 6-week time line, give or take. But if you have a later infection where the infection is set more into bone, that's when we talk about removing implants and debridement, cleaning things up, giving antibiotics and returning to the operating room potentially for another stage, not dissimilar to the PGI literature. Similar success rate, but now the time line has increased. So now we're talking about 3 months. So these time lines are really only if it's successful on the first try. So that's historical data. So we've looked at this at my institution, and I have to say as an egotistical surgeon, this is prior to my tenure. So I don't know how much better it is now, but only 43% of patients were successfully treated with 2 stages. 29%, 3 stages, 27%, 4 more stages. And that's with an overall success rate, including those stages of about 60% and with 32% of having recurrent infections. And with those recurrences happening between 8 and 9 months. with multiple complications, patients receiving amputations and complications associated with the IV antibiotics, delayed wound healing and things like that. So getting back to the patient, I love this picture. This is a perioperative care pathway from our preoperative unit at my hospital. It shows how straight line everything is in a hospital. But we talk about primarily the diagnosis, and we talk about eradication. But there's a lot going on during that time. I just told you that some of those time lines are 6 weeks 3 months, 6 months, 9 months, a long time goes by. Think about yourself, you were out of work for that amount of time, what would have happened? So upon first diagnosis, patients are frustrated. It's like having they've heard cancer. We heard that earlier, but then they're out of work. They can't go to work. Maybe they have some benefits from the government, maybe they do, maybe they don't. They have pain. They have divorce happens during that time. They have problems in their family. They lose their job, and they develop chronic pain and all sorts of things happen before the eradication. So the effect is tremendous on these patients. And they can be devastating. Patients have problems with the mobility, they get amputations. They have complications from antibiotics like we talked about. They lose function. They don't get back to where they were. And some of them go down the path of substance abuse disorder where they're addicted to certain substances. And the emotional and mental impact is tremendous, anxiety, sleep disturbance, pain, concentration problems, depression, even suicide is associated with this. So the long-term impact, though, is even worse. So once that eradication occurs, it's still -- those problems still exist. They get past the infection, they move on. They're not in the hospital anymore, but they have decreased quality of life and the psychological burden persists even beyond 4 years. And as that time increases, those themes they worsen. The more time for longer treatment, the more complications, the more problems, the higher psychological burden and so on and so forth. So where does that leave us? Well, the fractures are increasing and patients are becoming more complex and these complications and infections are increasing in prevalence, but not necessarily incidents. So more and more patients, even though we're getting better at taking care of these patients. So how do we do better? And what have we learned, at least in the trauma space? Well, we can actually take some of the data from the joint literature folks because they've shown in revisions that there are certain things that we can do. In the joint arthroplasty space, they have moved, at least in the United States, more towards outpatient procedures. So patients are no longer staying in the hospital for 3 or 4 days. They're staying maybe 1 day or even less than a day, and they're going home. And guess what, patients do better. They have less complications, and they just overall mentally feel better. And then when we look at infection revisions, my colleague talked about this a little bit. But when you take a single versus a dual-stage procedure, it's a big difference for a patient. I just told you about all that time, right? So you have -- you go to the office and you get diagnosed and they said, okay, we're going to take out all of your implants and then we're going to come back 6 weeks later, 3 months later. Think about how you feel while you're sitting there waiting to find out to get your next surgery. There's a lot of anxiety associated with that, a lot of problems. So when you change that to a single stage, the mental impact is tremendous and patients feel so much better. So if we take that to the FRI, the fracture-related infection side of things, we can easily -- if we decrease the number of procedures, decrease hospitalization and stay and also the length of stay, logically, we think that we have the same effect. So can we do it? Well, I think we're working our way towards it. And I think that some of the evidence that was presented earlier helps sort of frame this and give this context for us. It all has to do with recent improvements that we're taking advantage of and combining those techniques. So number one, local antibiotics. Local antibiotics are a huge thing in the treatment of infections, right? So historically, IV antibiotics, we give them to patients. They get it via an IV, they go home with this. Every day, someone delivers a bag of antibiotics to their house, and they have to administer and sit there for 30 minutes. Well, the problem with IV antibiotics is you can only have a small dose that's in your system because if you get a higher dose, it will kill you or you have severe complications. So we can only give so many antibiotics, whereas if you flip the script and you give it locally, you can give orders of magnitude increased concentration. So instead of 10 units, you can give 10,000 units, so to speak, which is sort of like a battlefield approach to things if you think of an overwhelming force in the war, if you hit everyone with everything that you've got as opposed to a little bit of a time, you tend to be more successful, right? We look at some of the gorilla warfare and strategies that have been used in the past and how it just takes a long time for these conflicts to go on and on. If you have an overwhelming force, things tend to deescalate pretty quickly. So what is the clinical evidence? So there's actually a lot of evidence that's available, right? So you can use it in both prevention and treatment. We talked -- some of the prior speakers have talked about that. So in the prevention space, there's been a couple of trials in this looking at vancomycin and tobramycin, which is another aminoglycoside not dissimilar to gentamicin and showed decreased infection rates when we use this in the initial treatment. So for treatment, and we've talked about this before, there's multiple studies also that have shown that if you use local antibiotics, it benefits the patient, okay? What about the decreased reliance on IV antibiotics? I talked about this a little bit. Well, IV antibiotics are problematic because there's a high cost of delivery, it's inconvenient, and there's lots of complications. And one of the prior speakers talked about some of the findings of the SOLARIO trial, which I'll touch on. But if you have an indwelling PICC line or an IV line in your arm for 3 months or 6 weeks, there's a high probability you wind up with an infection that usually is a bloodstream infection, which is a big problem for patients. And that can create all sorts of systemic issues and can even cause sepsis and death. So it's a really serious thing. And when you treat patients with IV antibiotics because of that, the guidelines aren't clear. There's a lot of disagreement. Should it be for 6 weeks? Should it be for 12 weeks. So there's confusion surrounding that. So oral antibiotics are very attractive alternative, right, because it's easy to give. It's a pill. It's lower cost. You don't have the complications. And actually, there's plenty of evidence now. So in the U.S., there was the POvIV trial, which demonstrated that oral antibiotics are noninferior to IV antibiotics in the treatment of fracture-related infection. And the AVeVA trial, which was mentioned earlier, shows a non-inferior result, meaning it's as good -- what about single-stage treatment? Well, historically, I talked about the dual -- the single or the multistage treatment, but a more modern version of this capitalizes on this, right? So if you use local antibiotics at the site of infection, you can actually be better than if you don't use it. So now when we use those local antibiotics, we can take advantage of that in a single-stage scenario because we don't have to rely on those systemic antibiotics much. So the biggest thing is really a combination of all 3. And with sort of our powers combined. I chose this graphic here because this was popular when I was a child, and I read it was popular in Europe, too. But I don't know if you guys recognize the cartoon Captain planet, but it's all about combining the forces together to create this guy captain planet. And so the SOLARIO trial is a lot like that. So you combine the local antibiotic therapy plus the short course of antibiotics, and we showed that -- they showed that it was noninferior to a longer course, which you heard about that with a decreased rate of adverse events. So if we combine these improvements, it changes the landscape dramatically, right? Local antibiotics, oral antibiotics, single-stage therapy treatments. changes that paradigm completely. And CERAMENT G plays a tremendous role in this because in the United States, that's the only thing that's available and approved to be a bone void filler that's combined with antibiotics. So that means that you get the local antibiotic delivery to help improve the eradication of infection. And then you get the bone graft substitute to fill the hole, right? So that's the single-stage part. So before we'd have to go in, take everything out and there's a big hole, we put something temporary in and then we come back later once the infection is eradicated and we put something back in. So CERAMENT G allows us to do both at the same time. So here's a clinical example for you that I think can be illustrative to kind of make these points. So this is a 41-year-old lady who came to my clinic, very active lady. She had a prior trauma. She was treated by another surgeon for ankle fracture. And she was a long ways out actually, and she started to develop infection in her way. And this is what our x-rays look like. And if you look at our X-rays, you can see screws at the bottom of our ankle. And if you look really [indiscernible] there, there's something that's in there. That's actually a drill bit from the surgery, which happens. It does happen. And to get that drill bit out in the middle of a surgery is kind of tough. There's a significant morbidity associated with that. So a lot of times, we leave that in there. And so if you look really closely, you can see at the tip of that drill bit, there's a little bit of fuzzy stuff there. And what that fuzzy stuff represents is some type of reaction to something. most likely infection. So with this patient, I've got 2 choices, right? So the traditional treatment is I can bring the patient into the operating room, admit them to the hospital, do my surgery, take everything out, give the antibiotics, send them home and then bring them back after we've confirmed that the infection is gone for a potential second procedure where we might bone graft because I just told you that in order to get that drill bit out, I have to make a hole in the bone. So I have to create a hole. So how do I fill that? We'll have to go back and bone graft that or hope that it's small enough that it doesn't matter or maybe take advantage of some of these techniques and use more of a modern strategy where I can do everything in one shot. So bring the patient to the operating room, take it out and go ahead and put the local antibiotics with the CERAMENT G in it to fill the bone at the same time, discharge them with oral antibiotics, maybe IV antibiotics and then follow them as an outpatient and let's see what happens. So I chose #2 because that was going to be better for this patient. This patient is a mother of 3. She's got to go home. She's got to take care of her children. She can't be in the hospital. There's no one else there to take care of her kids. So we did her outpatient surgery day 1. We did what we said we were going to do. We removed the foreign body. We put our biphasic calcium sulfate/hydroxyapatite, CERAMENT G. And then we took cultures, and we discharged them home on the same day. We gave them 2 weeks -- we gave her 2 weeks of oral antibiotics. It turned out she did have infection or cultures were positive, and we referred her to ID for a referral. Now mind you, if this was the traditional way, those positive cultures that I just talked about on post-op day 3, patients still would have been in the hospital waiting for those things to percolate and then they would get their IV line, which would take another day and then they could be discharged home and then all of the stuff that's associated with that. So she actually wound up not getting any systemic antibiotics because she had complete resolution. So she didn't need any further treatment. So this is definitely a success, minimal disruption to the patient's life. She's back to work quickly, no additional visits or procedures. And how does the hospital look at this? And is there any evidence for improvement? Well, we actually did look at this a while ago where we looked at the health care economics of this, and it all has to do with time. So the more time you spent away from work and the more time that you have to spend on procedures, the worse it gets. So when you change to a single-stage procedure, you have a tremendous savings. This is probably a lower estimate of about 30,000 or so with a large part of that being the surgery. And there's also an improvement in life years and quality adjusted life years as well. So the bottom line, it's good for the patients, and it's good for the payer, the health care system. We talked about that. But what about the hospital? Well, actually, the hospital is a little bit more complicated. In the U.S., if you have a complication, the hospital still gets paid for it. So more procedures, more complications, more revenue, right? Because things aren't really tied to performance. Now that might be evolving over time, but currently, that's how it is, at least in the infection management space. So the hospitals look at these things more on a per case by basis, at least they did in my hospital. And what we found is that when you look at the cost of care associated with infections, it's usually a loss for hospitals. They don't want to treat infections. That's why a lot of the centers in the United States that are the academic centers that take care of these complicated patients, they're referred from other outside hospitals to take care of them. Why? Because the government supplements their overall revenue cycle to keep them alive. So that's how it function in the United States. So when we looked at our cases, specifically CERAMENT G, shortly after bringing it -- it was brought on to the market and I got approval in my hospital, they said, you're losing money. It losing about $4,000 a case from these patients. And I said, "Well, wait a second, what if we flip this on the side?" And so when we flipped it on the side and we took this from an outpatient perspective, all those things I talked about, it turns out that we actually were making a profit. Well, the health care administrators love that. So my health care administrators are split. We have some doctors and then we have some folks which are more into the finance. And the doctors say, this is good for patients, so you should be doing it. But then the administrators on the other side and say, we like that. But if you could do it as an outpatient, that would be better, which it turns out it's better for patients anyway. So it's not just the money, though. It's about our ability to take care of these patients a little bit more creatively than we were able to before because not every patient is the same. Not every patient can be outside of work. And every patient is a little bit different. I talked about that mother and how she was a little bit challenging to treat because she couldn't get away from home. But there's other things that are involved with this and patients tend to avoid traditional care. They are afraid to go to the doctor because they don't want to have to deal with what's going on, which leads to even more problems before. So consider this case. So I had a 48-year-old female. She had a bicondylar tibial plateau fracture. That's a very traumatic injury to the knee, and she had an implant infection. She had treatment of the infection. She had removal of the implants. Guess what, it wasn't successful. She came back and she -- after about 6 months after the antibiotics was stopped and she had a recurrence of her infection. And she had drainage. So she had a hole in her leg and she's draining here. And this is a picture of her X-rays on the right, where you can see there's a hole. It's pretty obvious that that's there. And then on the left, that's an MRI sample, which shows a white spot. The white spot represents fluid, in this case, that represents infection. She had an infection in the middle of the bone. But this patient is a sick patient. She's not healthy. She's someone who has multiple medical comorbidities. And the last time that she had IV antibiotics as an outpatient, it was poorly tolerated. She had severe nausea, she had diarrhea, she had kidney damage. So the IV antibiotics caused damage to her kidneys. She had a really rough growth. So she said, I'm not doing that again. I don't want to be stuck in the hospital for 3 months or 6 weeks because she went up being stuck in the hospital for a while for that. And she wasn't interested in following up with our infectious disease colleagues. She didn't like them, but she likes me. So what do I do? Do I refuse her the surgery and say, if you don't do it my way, it's a highway. Or do we take more of an authoritarian strategy and say, no, you have to have this, but will that patient comply? Or will there be an issue? So with these new techniques and these ideas and concepts and things that are evolving, we could take advantage of these findings. And I can offer her outpatient surgery with local antibiotics and debridement and oral antibiotics. She was okay with that. So this is her post -- this is her intraoperative photo, which shows the CERAMENT G that's been placed in the area of that hole that I showed earlier. And she had complete resolution of her symptoms. She did great. This is 2 months postop, and you can see that the hole is getting smaller and smaller by 5 months. So this was a success story. She was very happy and able to get around with her life. With this nice lady, 49-year-old female, psychiatric, schizophrenic, okay? This is someone who's in and out of the hospital, disappears, doesn't come back. You see them 1 year and they might disappear for 2 or they might have all sorts of issues and just compliance is an issue. They cannot go to the hospital. They cannot make their appointments. This is a standard problem that I see almost every single day, okay? She had a prior trauma. She had external pinsites on her arm from an external fixer and she had a draining wound. She's had this draining wound for years. And if you look on the x-rays and the MRIs, you can see in the red circles, you can see where it almost looks like something has exploded out of the bone. And what that represents is the infection, and you can see it confirmed on MRI. There's that white spot that I was talking about before. So a chronic, localized infection, difficult social situation. So what do we do? We do exactly what I talked about, local treatment, minimally invasive, oral antibiotics and referral for outpatient antibiotics. So that's what we did. So here we are, this is a good example. I'm very proud of this picture. Someone took this with the phone and it looks like it was part of a CERAMENT G brochure. So this is a small incision right here, and there's a cannula, which you might have seen in the presentations in the hallway there with me injecting the local antibiotics. So decision right here. And what that looks like on an X-ray is just that. So that's the humorous, that's the top part of the bone and her infection is on the low part of the bone. So that wire is introduced, and we use that wire to guide to put a hole in the bone to sort of enter the middle of the bone. And then we use cannulas to get all the way down to the side of the problem. So that's a chisel that's used to get down to the side of the problem. And then once we clean that out and wash it out and core it out, that's the [indiscernible] on X-ray. And you can see there's a wire over here, which has directed me where to go, and I slide that down into the bone. And then at this point, this is where I am with it. And then we put the antibiotics in its path. So this area here, where you can see it's hard to see actually on the projection here. But if you look pretty closely, there's a shadow. And that shadow represents the CERAMENT G. So I'm able to do that from all the way up here for something that's all the way down here to avoid flaying the arm open. So historically, what we would do is we would open this whole arm open, huge surgical approach, and I can do that through a pretty limited incision. So that's a big benefit for patients. So patient grew out MRSA, which is a tough bacteria. They were discharged on the same day, and they followed up 1 to 2 weeks later. Infectious disease prescribed an antibiotic. It happens to be a pretty expensive antibiotic. And guess what? She never got it. So that's not ideal, but pretty common, especially for me. But the local antibiotics, I can take a deep breath because the patient is still getting treatment and they're still being compliant, 100%. I don't have to worry about it. She disappears, that's okay. She's taking care of. So here she is at 6 months. Mind you, I don't have any x-rays before that because that's when she came back 6 months later. We only see patients at 2 weeks, 6 weeks, 3 months, 6 months. She came back at 6 months. Her [indiscernible] removed somewhere else, someone else took them out. I don't know who, but she did great. So conclusion, the number of infections, they're increasing. And the complications in these scenarios and the complications of the patients continue to rise. And the patients deserve better. We're not that good. I just told you that when it works, it works 60% of the time. But guess what, it doesn't always work on the first try. So outpatient pathways can help us do that and single-stage procedures really improve the quality of care and the cost of care. Thank you.

Wonderful. It's really impressive to see these tough cases and all the complications we may be sometimes to think about or how difficult it is sometimes to treat -- to deal with the patients, not just to treat them.

Are there questions from the audience. Yes. Microphone is coming.

Thank you for that. Very good presentation. I have a question if you could talk a little bit about the process of deciding the risk of a patient potentially developing an infection. How clear is this typically to you after this assessment?

So what's the question being that what -- how do I decide that someone is high risk? Well, part of that is already set in stone for the patient. So some of these injuries have a pretty high risk of infection. So when you look at open fractures, for instance, the infection risk is quite high. If you look at the risk of what we call periarticular injuries, meaning injuries around the joints, the knee joint and the ankle joints and the foot joints, the risk is anywhere between 12% and 25%. So these patients are very high risk, and they -- those were the targets of some of those trials that I spoke about earlier to try and help prevent. So we try to identify these patients. But what's interesting about that is that when you look at that risk, we look at the high-risk injuries, but the question becomes is really who's to gain? Is it the high-risk patients or the low-risk patients? Because the patients that are high risk, they might actually wind up getting infections anyway from other reasons, whereas sort of even the patients that are low risk, if you have a 1% infection risk and you can take that to 0.5%, that's actually a tremendous amount because the number of those patients is much greater than the higher-risk patients. So I guess to reframe that, I think it doesn't matter really because both groups of patients benefit from some type of preventative treatment.

Good. And then I had a question before, which I will try again now with you here. So I imagine you're in a very stressful environment at work. So when it comes to the factor -- so the ability for you to plan procedures is not typically there, I guess, when it's acute procedures. So do you -- I typically get the question, so if that's a decisive -- or if that's a factor for the uptake of CERAMENT G use compared to procedures that are easily planned and you can plan for, for weeks ahead?

Well, we see both versions of that in the acute setting and then also in the reconstructive setting. So my practice is taking care of acute trauma, but also I have a little bit of a niche where I take care of some of these patients that have had surgeries and infections treated many times over. So to your point, does it help having the time to plan? Absolutely. But I think that this is something that's on the shelf for us that we can grab whenever we need it. And sometimes these patients come in right in the morning, and then we have to make a decision minutes later. In my institution, every -- we each have a day that we're responsible for. So whatever comes in the night before, we don't know what it is. It's going to be a surprise, and that's what we have to take care of. So we don't have a lot of time to think about that. But certainly, this is a great tool to use, and we do use it on the fly. We don't get approval and then wait. We have to treat them right away. And it's perfectly it's -- it's just the same.

And then if a patient treated with CERAMENT G returns with an infection, what would you believe had gone wrong?

Well, nothing is perfect. And these patients are complicated, and it depends on the clinical scenario. And sometimes that can happen. Sometimes it could be as a result of an error on the surgeon's behalf or an inadequate debridement. We try to put it on ourselves. But sometimes these things are more complicated. I had a patient that we had treated for infection and had used CERAMENT G and it failed. But they were better off this time around than the last time. So the first time I used CERAMENT G as part of a larger, much bigger procedure where they had extraction of implants and all sorts of things done and then an antibiotic-coated implant and the CERAMENT G was used to augment things. The patient came back with a small area of concern of infection. Now the big infection had been taken care of. So I just took care of this patient right before I came here, actually. And so we're able to go in and target it. That's one of the nice things about is you can take a bigger problem, make it less complex and then make -- turn into a small problem. We can address that and still use it again.

Thank you. Great questions. Here's a question from Christopher. We just need the microphone. But yes, pass it on. That's great. It saves time.

Considering your discussion here about the cost benefit with the product, I don't know if you were here earlier when there were a discussion about the new reimbursement proposal from CMS and that CERAMENT G use would automatically maybe trigger a higher reimbursement. Is that something you see would drive the use of CERAMENT G or in any way?

Absolutely. I think that one of the barriers, and I think the others touched on this to CERAMENT G as it entered the United States is the cost. So any time that we add something that's new, there's a significant cost associated with it, and it's not cheap. So when -- I just told you that on that [indiscernible] and when we looked at our value that we had a small negative margin when you talk about the fracture periods -- infection period is $50,000, $100,000. So we lost $4,000, Well, those are the kind of margins that we're dealing with. And these conversations do occur. So the bottom line is that it's a huge burden because the hospitals are looking at it and they say, well, does it work. And they say because we're not going to spend the extra money to get it in. So when you add something like that for the DRG and supporting that, it's a big benefit because now in those cases, even in the inpatient cases, where you see reimbursement goes up just a little bit, that's enough actually to turn that margin positive for the hospital. So when the hospital looks at it, they say, okay, I know it's better for the patients, and it's actually allowing us to make money. So it's a big thing for hospitals. And that was a big burden for me. That slide that I shared with you was an analysis after we got the CERAMENT G approved. And when I went to my Board to talk to get approval, we -- I said, okay, they said, how many times are you going to use this? And I said, "Oh, 6 or 10." I don't know. And about 6 months later, they said, okay, well, you used it like 40 times. That's a lot different than what you expected to use it. Well, there are other people using it, too. And I said, well, that just happens to be the way it is. And so they looked at the cost. And they said, "Wow, this is costing a lot." And so that board consists of administrators and doctors. And the doctors say, "Hey, this still works and this works well." So we're going to give you approval, but you need to be judicious about using it. Well, the administrators say, yes, but why don't you use it as an outpatient preferably to try and make that work for you. And that was a big thing. And this only adds to it. And at the time, when I first started doing it, there was a -- and you have to correct me on the terminology, there was a new technology code where the hospitals got extra reimbursement for the first 18 months or 12 months.

NTAP, it was called...

And when they said, "Oh, wait, that's something that exists." And I said, yes. And they look back and they said, "Oh, yes, we actually did get that. And then those numbers were even more positive. So these things are huge because hospitals are going to be very resistant to approving something like CERAMENT G without that. And now they have that, that's a big deal. It's wonderful. It opens up the door because surgeons are waiting for it, and that's a common conversation that we have. When I teach other people how to use this at all these conferences and they say, well, I got to get approval. This is how you get it. And then it just opens up the usage.

That was a great answer and great to hear the feedback from the administrators. And you already mentioned a bit the feedback from colleagues and surgeons, ID physicians. Do you hear any reactions there on your single-stage approach with CERAMENT G? What are they saying?

Well, I think that one of the things in the conversations and the questions were coming up that I think that everybody is forgetting to talk about is that physicians are very stubborn, especially surgeons. So getting change is tough. The things that I'm talking about, my colleagues, some of the elders that have more gray hair than me, they're very resistant to change. And it takes a long time. It's like trying to move an aircraft carrier. It doesn't move very quickly. So -- and the same thing goes for the infectious disease collegues. They'll see one study, and they'll say, "Oh, I saw that, but I don't believe it." Or they go, "Oh, well, maybe, but it's hard to go against dogma that's been around for decades." When you look at the standard of treatment was 6 weeks of IV antibiotics followed by a consolidation phase of oral antibiotics. That's something that's sort of been beaten down over the course of many years. And to go beyond that takes a little bit of sort of really [ wealth ] of confidence to do that. And I think that some of those slides that I shared about those studies, that's what that gives me that, to do it responsibly. And when I first started doing this in my practice, I used this in conjunction with the most difficult patients because they had no other choice. So I said, we've got to take advantage of what we know and how can we do this. So I'm going to use it for the difficult patients. Otherwise, they're not going to get anything. And when you look at that, then the infectious disease colleagues say, okay, and I force their hand. So I don't even tell them about the patient now. I take care of them in the operating room and then they follow up with them a couple of weeks later as opposed to before, they'd be admitted to the hospital and now they have complete control over what happens in terms of getting antibiotics and staging it. So I set the stage now for these patients.

Great answer. Thank you so much for answering the questions. Thank you for your great presentation. And I ask now Håkan Johansson, Bonesupport's CFO to the stage for his presentation. And I think it's the -- it contains the final conclusions, right?

Well, that I will do also together with Torbjorn later on.

Exactly.

So thank you. And it feels like a bit of a challenge after 2 such exciting presentations, and we're starting to be quite late in the afternoon, but bear with me. I've been engaged with Bonesupport for more than 7 years, and I promise [indiscernible] new slides today. And my ambition is really to use history, use the last few years to hopefully be able to explore more clearly the underlying trend. So we have had quite volatile periods in terms of currency, for instance, et cetera. So all the numbers I will be sharing today is based on constant exchange rates, whether it's on sales or whether we talk EBIT margins, et cetera, to give a better view of the underlying performance. And again, we've been talking a lot about sales and sales and revenue growth remains a high priority on my side. When I joined back in late 2018, we were really in the starting point of changing some of the focus of the business. We made big changes in the commercial platform in the U.S. We made big investments in our European sales organization. And that was really the starting block of this journey. We have, since 2020 to 2025, delivered a 44% CAGR. So with the FDA authorization of CERAMENT G in the U.S. back in 2022, launched in October '22, sales also accelerated. And this, as you've seen earlier today with a lot of market potential remaining. Well, that's looking at the total perspective. If we look at U.S. specifically, because again, U.S. remains a very high priority for us. It's a huge market opportunity. Well, in the U.S., we had a CAGR of 55% during the same period. So now with the commercial strategy and the platform that we created in 2018, already from the start, establishing a good growth momentum and that only preparing for the launch of CERAMENT G later on and help accelerate that market pickup with CERAMENT G as we launched. And as you can see somehow, the incremental growth is increasing every single year. But in terms of the relative growth in percentage, it's coming down. But again, incremental growth increasing year-by-year. If we continue to focus the numbers because again, in all means, some of the sales of CERAMENT G is really the focus point currently in the U.S. Well, how does that market penetration go? Well, this is a slide. There's a lot of information on this slide, but this is a slide to show for every single year in the U.S., what are we gaining in terms of new access. And this is based on surgeons' first-time use. How much do we gain by adoption? So the surgeons that were recruited the year before, how much are they extending its usage? And the world is never perfect. You also lose some business, and that is also disclosed on this slide. And what is really positive, I believe, in this slide is when you look at how access is growing year-by-year as well as adoption, adoption increasing from 6 million to 11 million to 18 million. And as we have been communicated when releasing Q4 last year, Q1 this year, et cetera, we're in a stage where new access and adoption are equally important. And that's why, again, we have been talking so much about the segment-based approach, et cetera, because that's really also a good way to not only drive adoption, but it really helps, but also extend market new access. So that's really U.S. But also when we talk Europe, Europe is coming shy when compared to U.S. for 2 reasons. While it's a smaller part of sales and growth in percentage is so much smaller than in the U.S. But part of the reason for that is also that we have been doing investments lately in our so-called hybrid markets. We hybrid markets are distributor markets as a revenue model, which means that it's half the price. So how to present that to some, in a way, come beyond that and make numbers comparable. Well, I decided to look at euro sales in units because that changed the perspective somewhat. Euro in total for this period, despite quite a lot of headwinds in '25, shows a CAGR of 17% in total, increased its sales with 2.2x since 2020. Direct markets, which is a handful, which consists of U.K., Germany, Sweden, Denmark and the Netherlands had a lot of headwinds in U.K., Germany during '25, showed a 13% CAGR. But also very important, if we look at the hybrid markets where we have done a lot of investments during the last few years, starting with Italy and Spain, extending during last year in countries and markets such as Australia, South Africa, Canada, Norway, Austria, et cetera, we see sales accelerating and showing a CAGR of 38%. Turning to some of the OpEx side of things. Well, as has been said, we are constantly doing commercial investments. This is a slide showing selling expenses, not including commission and fees because they are so directly related to the revenue. This is all the rest, meaning this is people, this is marketing spend, et cetera. And we can see that we continue to invest commercially because we believe that's the right way also to support continued growth. We have been adding substantial heads, especially in the last few years. So just from '24 to '25, we extended somehow with sales and marketing functions of close to 20 people, both in the U.S., but here also in the -- what we call the [ Eurobooster ], where we extended ambitions in our hybrid markets. And what to keep in mind is that if we just take the 10 additional heads in Europe, we communicated when doing that investment that it takes 18 months until these people are returning their cost in revenue, and it takes at least 5 years until they reach their peak sales. So these are investments ahead of some of the revenue impact that is coming. So again, what else? Well, we're not only investing commercially. We are investing our R&D expenses have been accelerating during the last 2 years. And the main reason for that is that we are investing for the future. So if you look at this slide, you see in '24 and '25 colored with the dotted line, the amount that we have spent that is much more forward-looking. This is the investment we have made in terms of our CERAMENT G submission to the FDA in the U.S. This is our investments entering into spine, new market entries, clinical studies to get into new applications and product development. And we will continue to invest in that pipeline because we also believe that this is contribution to -- good contribution to our future sales growth. And we've been hearing a lot today about all the initiatives we do in terms of our segment-driven strategies and our ambition in spine and revision arthroplasty. And despite all of those investments, with the strong sales growth that we're reporting, these costs are down to somewhere around 7% and 8% of revenue. So all in all, we see when we step out of all the impact of currency and currency volatility, et cetera, a very solid trajectory when we talk operating results, in this case, looking at operating results, excluding the impact from long-term incentive programs and the operating leverage, which is marked as the gray boxes on this slide, we can see that the operating leverage remains extremely solid and stable, and we see a clear trajectory in terms of yearly improved operating result and operating margins. And as mentioned a few times, we not only sit on a very scalable business model. We extended production without impacting the P&L. And we can see that the strong operating leverage from the sales growth, we delivered a lot of profit improvements. Investments level low. All R&D expenses are costed and so on and with efficient treatment of working capital despite the fact that we hold extensive safety inventories to ensure flexibility to the market. So we have a very solid cash conversion. So the cash conversion is part steadily over time, around 70% to that adjusted operating profit. And this gives us headroom. This gives us flexibility, whether it's investing in those clinical studies, investing in the full R&D pipeline, investing commercially or somehow using part of that cash in terms of share buybacks as an optional way to create shareholder value. So if I sum that up, I believe that just by those limited numbers of shares, we can show that we have a lot of operational performance delivered during the last few years, still with a material untapped market potential being out there. So we've seen in our presentations about the low market share in all of our main segments and the market potential that remains in those segments. I think that we have proven over the last few years that we have a very scalable business model, not only in terms of operating leverage, but also in terms of the lean balance sheet that we are operating with. And again, not to forget that we have a queue of interesting triggers short to midterm. The SOLARIO study that we've been waiting for since fall 2024, and we have heard from several speakers that we believe that this is for the longer term, something that will bring value to our contacts with some surgeons, hospitals and the market. Our CERAMENT G submission. So as always with FDA, it's hard to say when, but we have a strong belief that with the experience we have in Europe of using CERAMENT G, we will get there, and we will be able to launch CERAMENT G in the U.S. Geographic expansion. So we invested in hybrid markets in the last few years. We made inroads in India early this year. We are working with the authorities in Japan to open up that market. And we will continue to open up new markets outside the U.S. And again, also, as we've shared today, our plans to get CERAMENT G or V the [ antibiotic-eluting ] properties as into spine in mid- to long term. So with that, Torbjorn, I'll leave it to you to round off the meeting.

Thank you, Håkan. You can actually feel free to stay on the stage. We're going to do Q&A later. I promise, last slide for the day. Concluding remarks. I said earlier what I thought you should bring home as take-home message. The way that I would summarize the day is our strategy is proven. We're moving into the next evolution that relates to becoming more segment-specific because customers in the different segments are different, different needs. We have to cater to that. We have upward adjusted our U.S. market opportunity. again, underlining the growth potential that we see with CERAMENT in the U.S. We continue to invest in evidence. That's one of the core pillars of our strategy with special emphasis on arthroplasty. That study is estimated to cost around SEK 40 million. We believe that we have a role to play in spine with an antibiotic-eluting product for the long term. We're not on label there yet, but we're investing in that space. That study is estimated to cost around SEK 80 million. And we hope to or aim and have an ambition to have a regulatory approval or regulatory submission no later than 2031. And most important thing, however we run the numbers, you looked at the upgraded numbers, you looked at the market potential. You looked at the pools of conditions that is an inevitability of patients in this space. And you looked at the unmet need. We're very, very early on our growth journey. We're just getting started. So even though it's fantastic numbers that you guys have delivered, I'm absolutely convinced that the best days of Bonesupport are ahead of us and not behind us. So with that, I thank you all for taking the time to be here and happy to take any final questions.

Thank you very much. So do we have any final questions to wrap this up? Yes, in front here.

It was on the adoption versus new access [indiscernible], that was really helpful. I wanted to see your thoughts of how that would look like in the future. Could you see maybe adoption sort of start to scale ahead? And then maybe to follow up on that, if you could focus on maybe sort of the ASC channel dynamics, sort of how are you growing there versus maybe other settings, that would be really helpful.

Okay. So the way that we split these questions is that I take the easy ones and Håkan takes the difficult ones. So Håkan, you take the first one, and I'll talk about ASCs.

Again, I think that's what we believe when we look forward is that new access and adoption will continue to be somewhat equally important. I think that it's also important to say somehow what we stated here is lost sales. Well, in that number, you find surgeons retiring from that certain practice. You find surgeons that is moving from a hospital where we had listings to hospitals where we don't have listing, which is in the longer term, it is not necessarily negative. So I think that when looking at that slide, it's somehow a first indication of how this looks. I think that's now being still so early on that commercial journey with CERAMENT G, we need more time until we can see some of the firm underlying trend. But I think that now keeping 85% of the business that we had with us into the new year is a good level also if we look at comparables in the U.S.

Good. And on ASC, I think it's a very relevant question, especially if you look at it medium to long term. We are a very, very small player in orthopedics. Honestly, we're like nothing compared to the big guys. The big guys invest a lot in ASCs for the right reasons. There's a lot of patient volume moving in that direction. That's not going to go away. We see that. But where we are in our journey, now our focus is on inpatient, but Dr. Matuszewski has had a really good point on that. It's going to move, and we will, of course, be part of that move. But now we like to keep things simple, straightforward. Inpatient is more than we can handle at this point, but we stay very close to the trends because in a couple of years, it's highly likely that it will look slightly different.

Perfect. And then just a clarification on the sales force. So the ROI that you projected, is that based on historical data you've got? Or is that based on what you expect in the future?

I would say both. So that's the learning we've done with the investments they've done over the years. It's -- and it's quite steadily around that. It takes 18 months to somewhat recover the cost in terms of revenue. And I think that what we saw in hybrid markets somehow very much corresponds to that.

That's U.S. and...

That's Europe because that's really where we have a direct sales force. So in the U.S., we don't have the same front-end costs.

I don't know if this is a good or bad last question, probably not. But I want to back things up a bit to just now you've showed us your plan, how hard was it to prioritize this? I mean you've had areas that you could go into where you could put money into -- you have gone into Japan. Why this? And how hard was it?

I would say saying no to things is the most important task of the CEO and the CFO. We have to do it all the time. So prioritization is always very hard, especially when it comes to CERAMENT as a technology because it's so versatile. There are hundreds and hundreds of things that we could do with CERAMENT, combine it with different things. There are a lot of ideas. Some of them really good, quite a few pretty bad when it comes to inorganic activities. So there's a lot of things that pull our attention all the time. But at the same time, when we compare all of those alternatives compared with foot and ankle trauma arthroplasty, which is here and now. It's so, I call it, easy. It always comes back to when we look at it rationally, we look at the numbers, we have to continue to focus here until we start seeing other data points that indicate that we need to look outside. Spine is actually an area where we think -- we don't know for a fact, but we think that there's a lot of data points indicating that this could be another important leg for Bonesupport in the future. That is why we're trying to get into that segment. So yes, it's hard, but it's part of the job that we do. And especially with the P&L that we have, with the asset-light model, with the balance sheet, it takes a lot to improve on what we already do today. So that's why we're pretty disciplined when it comes to inorganic activities and also moving into other segments. I think this is a very solid and logical and rational plan that we have.

Great. Thank you for a good day.

Thank you very much. Thank you, guys.

We're here for another 45 minutes.

45 minutes. Happy to take any questions either here or outside. If you want to have a couple of more demonstrations, happy to do that.