Bonesupport Holding AB (publ) (BONEX) Earnings Call Transcript & Summary

Thank you. Good afternoon, everyone. Welcome. I'm Emil Billbäck, the CEO of Bonesupport. Happy to see so many people here. We're live on broadcast, and also this Capital Markets event will be recorded and broadcasted afterwards. So we invited for this Capital Markets event because we're going to enter in the next month, the biggest commercial milestone in the company history. When we launched CERAMENT G, with gentamicin into the U.S. So the purpose of today is to establish, actually, a new platform, share that platform with you and give an outlook into 2025. I would like to give a very warm and special welcome to Professor Anand Pillai from the University Hospital of Southern Manchester, Wythenshawe. So Anand is our guest speaker today. I also would like to give a very warm welcome to Professor Mary O'Connor. She is Professor Emerita at the Mayo Clinic in the U.S. and also, one of our recently appointed board members. Let me also shortly introduce my team who is here. Håkan Johansson, our CFO. Most of you will recognize Dr. Michael Diefenbeck who is our Chief Medical Officer and responsible of clinical affairs. And we have Mike Roth here somewhere. He's in the very back. He is our Executive Vice President for the North Americas. Let me also introduce Charlotte Stjerngren, who is our partner at our Investor Relations agency. Those are all the introductions. Okay, very good. So let's get started then. Let's take a look at what we had in mind as of a program and agenda for today. Well, you know that the centerpiece of our market penetration is the evidence that we have behind the product and the indication where the product is used. So a large part of what you will see today in the agenda will actually circle around the clinical overview, which will be held by Michael Diefenbeck. And then Professor Anand Pillai will speak about how is CERAMENT and CERAMENT G in particular, used in clinical practice. What is his experiences from using this product. I'm proud to say that Professor Pillai has been using CERAMENT since the very foundation. Since Professor Pillai has to leave almost mid-session, we have 2 sessions of questions and answers. So 1 follows immediately after the clinical part, the clinical block. And then we have a Q&A also at the end that will be monitored by -- sorry, moderated, maybe also monitored, by Charlotte. And there will be a break in the middle. So if everyone could please also remember to shut off your cell phones. I'm sure there'll be plenty of time for you to use them again at the break. The presentation -- this introduction, I wanted to start also with a brief recap. What has happened since we launched our strategy in 2018 and how did it all begin. Well, as many of you know, the founder of Bonesupport, Professor Lars Lidgren is a great clinician and a great scientist. He was the Head of the Orthopedic Department for many years in Lund University Hospital. And he, together with his fellow surgeons, despite having modern equipment, sophisticated instruments, tools, an armada of antibiotics, they were struggling with bone infections, insufficient bone healing and amputations. And Professor Lars Lidgren made it his quest to find a solution to the problems that he was seeing daily in terms of insufficient patient outcome. It took more than 8 years of research and development before they had CERAMENT, and at least I can say Professor Lars Lidgren's struggles ended at that time because he discovered that he had made a breakthrough with a product that mimicked natural healing and could elute antibiotic to protect the bone healing at the most critical stage. In 2018, we launched our updated strategy. The focus of that strategy was really to go from internal to external to leave the research world behind and start promoting our product more aggressively, to not only have the best bone graft substitute in the world, but also to tell the world about it. And at that time, we significantly increased our commercial infrastructure. We almost doubled the amount of salespeople in 2019. And we also redirected a large part of our back office function, the science function, but also on the regulatory side; and on the clinical side, to pursue the vision of getting CERAMENT G approved in the U.S., a milestone that we achieved in May of this year. We also set a guidance at that time, a target to ourselves to grow with 40% per year. In 2019, the first year after setting the strategy, we grew with 55% in constant currency, Then the pandemic came. The world changed. The focus of the hospitals was instead to care for patients with breathing problems or patients infected, and the number of surgeries, the number of procedures in the orthopedic area dropped quite dramatically. First year indications that also dropped between 16% and 20%. And in a recent study from McKinsey that came out in June, the level of orthopedic surgeries procedures is still 12% below pre-pandemic levels. But during this period, CERAMENT kept growing. In 2020 and 2021, CERAMENT grew with roughly 20%. Giving us a CAGR from 2018 to '21 of 30%. So during this whole period, CERAMENT kept increasing market shares. And you've seen many times, in our quarterly presentations, how the COVID pandemic brought CERAMENT growth rates to a lower level. But as we're now starting to approach a more normalized stage, COVID is still there, but we've learned somehow to live with it and it's not as prominent anymore in restrictions on how we adopt ourselves in a general day. Our sales is again growing over proportionally. And recently, we finished a big market model. So we have made internal estimates, but we've also based it on data that we have acquired, and then we have externally validated it to figure out what is our market share in the countries where we direct, where is our market share in the U.S., what is our market share in all of Europe and all of the U.S. And as we have shared with many of you before, the total amount of procedures relevant for CERAMENT in 2022 is around 340,000. Now one of you might say, well, I've heard numbers between 360,000 and 380,000. Yes. But in the year 2022, it is about 10% to 12% less than it was prepandemic. So due to staff shortages and the previous restrictions made, the procedures are still not up at the level of 2019. And if you look then at our market share in these big European countries, the total market share is between 2% and 3%. But let's look at those markets where we are direct. Look at those markets where we have had a good representation since pre-pandemic. The market share in U.K., Germany and Nordic combined is 4% in volume or in pieces. So 4% of the total procedures is where CERAMENT is used. And if you then look at those procedures where local antibiotics is used, then the volume share of CERAMENT G and V is 8% or just above 8%. If you want to translate that into value market share, you can double the number. Why am I showing you this? Well, I'm showing you this also to give an impression of where we have been present and where we have accelerated our marketing and penetration efforts from the 2018 program. This is what we have accomplished. During the pandemic, we started a direct organization in the Netherlands. We have 3 people, they are excellent in attending [ to ] the needs of the clinicians. But starting direct in Netherlands during the pandemic has not been easy because during the pandemic, the access to hospitals was severely restricted. But now they are there, established with good relationships and network. And as the market is coming back, we'll also start to see very strong results. Also during the pandemic, we had the courage, based on the successful accomplishments in other markets to set up a hybrid structure in Spain and Italy. That will add another 100,000 procedures to the potential for CERAMENT. And going forward, of course, dependent on the outcome of the conviction study -- the data will come in 2025, with the French market, about 70,000 procedures, one of the biggest markets in Europe, but with very low prices. And a tsunami of local manufacturers of bone cement, conviction is there to show strong differentiation and potentially even give an individual reimbursement code. So in 2025, there is a phenomenal opportunity potentially for CERAMENT to add also France as a growth market. And we just recently started to prepare the regulatory work to, in the future, be able to enter the Japanese market, which holds another 120,000 procedures. So you will see later on in the slides how we're constantly adding to our total addressable market. The program today, the agenda today is very much going to follow the structure of our strategy. We have 3 pillars in our strategy: it's innovation, evidence and commercial platform. Now the meeting is focusing on the next 3 years, to give a guidance over the next 3 years, what we expect over the next 3 years. So in terms of innovation, it's really only tactical innovations that can come in play. We will, I promise you, come back at a later occasion and speak more about our pipeline also in terms of the organic and breakthrough innovation, but that's not for today's meeting. Today's meeting is going to focus more on the evidence, where I will soon hand over to Michael Diefenbeck to speak about some of the recent clinical studies that have been published on the product and why they matter for our future market penetration. Then Professor Pillai will share some of his cases and we will end the day with speaking about the marketing and sales programs in the U.S. for CERAMENT G. This is our commercial platform. It might sound strange to have that as one of the strategic pillars, but -- for us, it's really about clinician interactions. Having great evidence is not enough. To change the standard of care, we will have to break habits. We will have to provide instructions, education, training, contract management, reimbursement. And this is why in Mike's presentation today, you will also hear about a booster program for the U.S., where we're adding 7 FTEs to do exactly that, to drive these parts now that we have received a very favorable listing for CERAMENT G in the U.S., both with Premier and Health Trust. And with that, I hand over to you, Michael.

Perfect. Thank you, Emil, for the kind introduction. Dear ladies and gentlemen, my name is Michael Diefenbeck. I'm Bonesupport's, Chief Medical Officer, and I'm going to present an overview of the clinical evidence of the CERAMENT portfolio. Some more details about myself. I'm an orthopedic surgeon. I've been with Bonesupport then 2017. So this was some months before we did the IPO, as a full-time employee before that, even after working for Bonesupport as a consultant. So in total, I'm know about 7 years with the company. And before that, I've been working in a different position in German hospitals as an orthopedic surgeon, mainly level 1 trauma centers. In my last position, I was working in a bone infection unit, where I was treating osteomyelitis and fracture-related infections, similar to the work Professor Pillai doing at the moment. And of course, this knowledge comes quite handy now talking about all these diseases. Clinicians want clinical evidence on the safety and efficacy of medical devices, which they use in their patients and Bonesupport always provided this clinical evidence. We have clinical evidence on different levels, starting with publications about material science, cell cultures over to animal models, up to case series, case cohorts and a randomized controlled trial. The randomized -- the green numbers show -- the green figures show the numbers of the publications on CERAMENT BONE VOID FILLER. And the most important, clinical evidence, comes, of course, from the RCT, the randomized controlled trial, CERTiFy, where CERAMENT BONE VOID FILLER was used in tibial plateau fractures. Just a short summary of this study. It was a randomized controlled trial in 135 patients, indication: tibial plateau fractures and patients were randomized to 2 groups. In 1 group, the fracture was treated with open reduction and internal fixation. Screws and plates were used to stabilize the fracture and the bone voids filled with autograft, the gold standard. In the other group, exactly the same surgical technique, but now the bone voids were filled with CERAMENT BONE VOID FILLER. And this study was done in 20 German orthopedic centers, level 1 trauma centers. The outcome parameters were, of course, preset. Primary outcome parameter of patient reported outcome measure, the SF-12, co-primary endpoint of pain level at 6 months, and then the secondary outcome parameter, the most important one, the bone healing on radiographs. And the study was always designed to show non-inferiority of CERAMENT BONE VOID FILLER versus the autograft versus the gold standard. And to make it really brief, CERAMENT BONE VOID FILLER checked all the boxes. CERAMENT BONE VOID FILLER achieved all the primary and secondary outcome parameters, basically showing that CERAMENT BONE VOID FILLER is noninferior to autograft or in other words, simpler words, as good as the gold standard. I couldn't stop myself to put in this radiograph, maybe some of -- you've seen it before, but it's so impressive that I just wanted to share it once again. The top row is the group -- are radiographs from a patient from the group where autograft was used, the gold standard. On the second image from the left, you can clearly see this tibial plateau fracture. On the next following image, it is stabilized with screws under plate, and the bone defect is filled with autograft and you see beautiful bone healing. On the bottom row, exactly the same procedure, similar fracture. Clearly, it's seen here on the CT scan, stabilization, again, with screws and the plate, but now the void filled with CERAMENT BONE VOID FILLER, which is clearly visible due to the iohexol, the radio contrast agent, so in this bright white color. And then after 6 months, completely remodeled into bone. Let's have a closer look at the clinical evidence on CERAMENT G. Here, we have 17 well planned and well conducted case series and different indications, starting with fracture-related infections, diabetic foot osteomyelitis, trauma, open fractures and some other indications I'm not going to touch today. I will present a very brief overview of each market segment or each indication than our clinical evidence. And in the next presentation, Professor Pillai will show a case to each of these indications. Let's start with the fracture-related infections. The definition is quite new in 2018 and international expert groups defined a fracture-related infection as a fracture -- as an infection related to previous internal fixation. And that is confirmed by at least 1 clinical microbiological or histopathological criteria. And the criteria, you can see here, they're, for the clinical science, quite straightforward. A fistula sinus or a wound breakdown with communication to the bone and the implant, which you can see on the image where the implant can be seen through the skin or if you find 2 -- the same bacteria in 2 independent deep samples or if histopathology shows bacterial growth. Now the key clinical evidence for CERAMENT G and fracture-related infections, there are 2 publications, both are prospective case series, one on 52 patients, the other one on 33 patients. The same treatment was used despite it was done in different hospitals, surgical debridement, application of CERAMENT G, stabilization of the bone and soft tissue coverage. One study was done at the University of Manchester. So you can be sure that Professor Pillai will present 1 of the cases from this series. And the other was done in the University of Munich, Klinikum rechts der Isar, and remarkably, 2 different hospitals, different surgeons, even different countries, coming to the same result with an infection eradication rate of 92% or 91%. Now probably you want to compare this to some benchmark. And here, I picked the PMMA beads, which is a 2-stage procedure. So in the first surgery, the PMMA beat are placed in the bone void. They elute antibiotics, but they're not resorbable, so they have to be removed again and the bone void filled with autograft. In a publication, which comes from one of our key opinion leaders, when he used PMMA beads about 30 years ago. The eradication rate of infection was 86%. And when we looked at a lot of publications in a major analysis, we came to the same result, 86% of eradication rate. So now what does this mean? It means that CERAMENT G gives better results in just 1 surgery, in 1 single surgery. And this is, of course, important to the patient just having 1 surgery with a better outcome, not having 2 admissions to hospital, not going through surgeries with a postoperative pain with the anesthesia and all of that was -- follows on. The second indication I wanted to focus a bit more on is diabetic foot osteomyelitis, a real hard-to-treat indication. Diabetic foot osteomyelitis is mostly a consequence of soft tissue infection, that spreads into the bone. And the typical sequence is -- how I see it, there is some debate on it, but an easy model is that it starts that the tendons in the diabetic patients shorten and they develop a deformity of the foot. They had this [ claw ] toes, and then the metatarsal had -- 1 and 5 become prominent. So the bone is pressing against the skin and the shoe is pressing, from the other direction, against the skin. And this is -- would be usually really painful. But since there is a lack of protective sensation, they don't feel the pain. It starts the development of superficial foot ulcers, followed by deep foot ulcers with infection. And then the infection spreads into the bone, creating this osteitis, which is a different word osteomyelitis or diabetic foot osteomyelitis. Here again, the evidence for CERAMENT G in diabetic foot osteomyelitis to retrospective case series, 1 with 70 patients, 1 with 48. Again, different hospitals, but the same surgical technique used One study comes from the University of Manchester and Professor Pillai will, again, present a case from the series. The other one from the United Lincolnshire Hospitals NHS Trust, and remarkably, same results with an eradication rate of infection of 87% and 88%. Diabetic foot osteomyelitis is more severe with a higher risk of amputation. So here, even the amputation rate is stated with 7% and 6% compared to the benchmark from the literature, which is up to 24%. And now what does this mean to the patient? I think that's not what I need to explain if you can salvage or save a life, a limb of a patient. And often, after the first amputation, several amputations follow, which then shortens the life span of the patient. The final indication or market segment I want to mention is open fractures, an open fracture is a fracture with an open wound or break in the skin on the side of the broken bone. Once the skin is broken, bacteria can enter and contaminate the bone and the wound with a high risk of infection. And the most problematics and the most common open fractures are the 3B open fractures in this classification. And here, we have 2 publications, both coming from the University of Manchester to prospective case series, 51 patients and 80 patients. Again, the same surgical technique used, a 1-stage protocol with debridement, bone stabilization, use of CERAMENT G and soft tissue closures with different methods. The infection rate for the short follow-up was 0%, so no infections were found and then with a bit longer follow up 1.3% compared to the literature standard, the standard of care of up to 15%. Well, what -- this is really important data and it means, for the patient, it's a disaster for the patient to develop an infection after an open fracture, which means prolonged hospital stay, a lot of systemic antibiotics, a couple of revision surgeries and, of course, a prolonged rehabilitation. And therefore, it's so important to reduce the risk of infection by using CERAMENT G. This slide is on the U.S. market approval. And the data, which we used here to get FDA approval, the clinical data was collected at the Bone Infection Unit at Oxford and a total of almost 17,000 data points were submitted to FDA. The treatment group and the bone infection was mainly trauma. So the injuries leading to the infection were fractures and leading to fracture-related infection in osteomyelitis. And 1 keystone of the data we submitted was the extensive morphometric measurement on the radiographs. Results for CERAMENT G, as I mentioned before, single-stage surgery, recurrence rate of infection 4.3% after 2-year follow-up; or 5.5% after a 4-year follow-up, which is indicated on this bar here, compared to the PMMA beads, which are already explained, bone cement eluting gentamicin, non-resorbable so it has to be removed again, with an infection recurrence rate published, about 13% and in our midterm analyses again, 13%. So this data led the FDA to say that CERAMENT G is safe and effective in the treatment of bone injuries, superior to PMMA beads and allowing a 1-stage procedure. And this made the clearance of the product in the U.S. possible. So to wrap up, I presented strong and convincing clinical evidence.in the key indications for the management and prophylaxis of bone infections. CERAMENT G is the only bone graft substitute with proven bone remodeling, which was shown in the CERTiFy study, is the only bone graft substitute with convincing clinical evidence for the safety and efficacy in bone infections, proven with all the evidence I just showed, and basically what convinced the FDA to clear the product for the U.S. market, leading to the first cleared gentamicin eluting bone graft substitute in the U.S. Thanks for your attention. We'll continue now with the presentation from Professor Anand Pillai from the Manchester University Hospitals.

Thank you, Michael.

Anand, the stage is yours.

Thank you. Good afternoon, everyone. So I think as a consultant orthopedic surgeon, I think it's a very different audience I have today, speaking to nonmedical audience. So I'll try and keep it as simple as I can, but equally, I fully appreciate that your interest in this product is very different to what mine must be. A little bit about myself. I'm an orthopedic surgeon, but I'm also the clinical director of a large hospital group, the largest one in the U.K. at the moment. And my hospital, where I work is the outskirts of Manchester, next to Manchester Airport, if you've ever been to Manchester. So in front of the hospital, we have the largest council estate in Europe. So we got a lot of interesting trauma that comes in, lots of interesting accidents as well. It's quite an interesting subset of patients. On the back of the hospital, just beyond the car park, we have probably the most expensive real estate in -- anywhere in the U.K. where all the footballers live. So there are 2 large teams, I'm sure you know about them. So what I'm going to show here is 3 stories, and I think -- bear with me on that because ultimately, at the end of each of the indications that Michael mentioned, there's a patient from my point of view -- ultimately, we are trying to treat a patient and give the best outcome possible irrespective of the cost. So there are 3 stories which I'll go through with you, and I'll try and explain to you, from a patient's viewpoint, how this product has changed our approach to it and potentially, hopefully, will change a lot of other surgeons in other parts of the world once they have access to product. We'll look at things differently, hopefully and also hopefully will lead to further innovation in other areas which we currently don't know about. So Michael initially spoke about fracture-related infections. So what are they? Simply put, I think if you have got a break in the bone and your surgeon decides to fix it with a plate or a screw or an implant of some sort, ultimately, as the body is concerned, it's a foreign body. It's not meant to be there. So always there's a potential of infection, either early on or a number of years later and perhaps you have a cough or a cold or a chest infection, then the implant can get ceded by bugs that float throughout your body. So on average, you're looking at probably about a 10% risk. If you do got a large metalwork in your body, you always carry with it a certain risk. For example, we would tell people who have got a large metalwork in the body that if you're going to a dentist for a dental filling or something, make sure you take some antibiotics. And sometimes when you do have infection -- implants in place, it's quite difficult to get it off because it's not just the bone you're trying to treat, it's also the fact that you've got a metalwork in there, which potentially is contaminated now from the infection. So this young lad, I can't say his name. He's 19. He comes from the front of the hospital. That's the rougher part of town, so to speak. He was involved in a petty theft and he was running away in his motorbike. Unfortunately, he got chased by a few policemen and ultimately, crashed his bike and he sustained this injury. So you can see from the fact, when you look at the x-rays, what you see on the top and the bottom is that -- I'm pointing to it, it's a growth plate. That means that he's quite young still. He's not skeletally mature. He is less than 17, if that makes sense. So he's got a break there, which needs to be fixed. And the surgeon who did the operation did an excellent job, put a large metal plate in there, put the bones back together nicely in line. You can see that in both views. It looks like a leg again. It has been fixed together with lots of metal work, lots of screws, lots of steel, kind of semi-bionic. At least you can't break that leg again. Okay, the positive thing. But then life takes many turns. Unfortunately, a number of years later, he's a bit older now, because the growth plate is now healed. He gets into a scuffle with some of his mates. And some of them decide to sit on him and the rest of them decide to beat him up. So unfortunately, he sustains a break to the bit which is below the metalwork the surgeon put in. I think, Sod's law. He could have broken the other leg, but unfortunately, he had to break this leg. So this presents a problem. So you have got a break in the leg already. There's already metalwork in there and just now got a break underneath. So there's some clinical pictures coming up, so if anyone of you is a bit squeamish or doesn't like to see wounds or blood, please do look away. I've been asked to warn you about that. So it's not that gross, to be honest. So unfortunately, this is what happened to the chap, okay? So he had his metal work in the leg and because of the assault, he sustained -- he broke his leg just below that. And you can see what happened. Not just a break, he also had a wound in it. So this is one of my patients. I treated him a number of years ago. It is probably about -- probably coming up 10 years ago, I think, probably. So given the gentleman's history and the fact that we know that he has had previous -- he has had prior, so to speak, we want to do the least possible to try and get things back together again. So what did I do? I put more metal work in there, okay? So I thought I need get the leg back together. It seemed the right thing to do. I'm an orthopedic surgeon, I like to fix things, so we fixed it. So you can see that in addition to the metalwork he had from when he was a teenager, I've actually put more metalwork in there. And also my friendly plastic surgeon colleagues managed to cover the wound. We thought, fantastic. We have sorted him out. At least, he can't break that leg again. We are okay, yes. But then unfortunately, a number of months later he comes back with puss coming out of the wound. So now you can understand what the problem is. He had a fracture. And now he had a wound and the wound is now infected. And the likelihood is that the metalwork underneath is also infected and the bone is infected. So this is what we call a fracture-related infection, okay? So the problem is that you have a situation where perhaps the fracture itself is not healed, number one. You have a situation where the bone is infected. On top of that, you've got metalwork to deal with, which is also infected. So traditionally, what we used to do for these would be that the metal work needs to come out. By and large, it needs to come out because the metalwork is coated in puss, so to speak, so you can't leave that in there. You can't simply wash it out, so you would take it out. But then what do you do with the wound? A lot of the time from previous experience and historically, these injuries is be treated with multiple operations. You'd go back in to wash it out. You'd go back in and take the metal work out. You may go back in to put more bone substitutes in. And lastly, you may have to go back and once everything is clear to try and fix the bone back again. Does that make sense? You can see here, we opened the wound to have a look at it, and you can see where the metalwork is, which is my metal work. The other metal is at the other side. So you can see that, that's not looking very healthy. So we took everything out. Unfortunately, it means that everything had to come out. So fortunately, this is a time that we started using CERAMENT. And you can see that we have filled the gap between the bone bits with CERAMENT. What I'm pointing to you now is the darker area in between the 2 bits of broken bone is where the CERAMENT has gone in. And you can see that quite a lot of the bone had to be taken out in that core of the bone had to be evacuated where it was not good bone. It was actually infected bone and it's been filled with antibiotic-eluting bone substitute. The good thing about something like CERAMENT is that it helps to control the infection and to fight the infection. And also, it helps to allow the bone to heal and regenerate. Because the fracture was still not healed, we put a cage on the leg to hold the leg like a leg, ideally to keep it straight and make sure that it's not bent or it's not -- there's not a kink in it, so to speak. And the wound was closed up. And you can see how the wound goes on to heal, the infection settles with time. And finally, the bone starts to heal. He had the cage on for about 6 months all together, and that's the final product. You can see how -- you can see the gap is gone. The bone is healed. And that again, if you look at the bone, the bit that's broken and didn't look good in the previous x-rays now looks like normal bone again, okay? So in this particular circumstance where -- which was one of the indications that Michael spoke about a fracture-related infection, I think that with the use of CERAMENT, we managed to avoid repeated surgery. We managed to treat his infection, has known union or the broken bone and the failure to heal in 1 go. And the best thing is that the outcome in the longer term looks pretty good because we have an infection-free, like, for sure. In addition to that, we have a leg, which looks pretty normal. If you look at those x-rays and if I didn't show you those initial pictures, you would think that, that looks pretty okay. It doesn't look that bad. There has been injury, but it doesn't look as horrifying as some of the pictures I showed you before. So that's the advantage. So that's one of the indications for this product. So moving on to diabetic foot infection. So I think Michael gave a very eloquent and simplistic view on how diabetic foot infections manifest with an ulceration and then infection happening. But one of the things that he probably forgot to mention is that, that is a single largest growing market for CERAMENT or any antibiotic product in the world. okay? About 10% of the entire NHS, that's the health service budget in the U.K. is spent on treating diabetes and diabetic complications. One in 9 people in this room will be diabetic or will suffer from diabetic in their lifetime, okay? So probably none of us know that, but that's a national statistic. If you look at this room, there are about 40, 50 of us here, 1 in 9 will be diabetic in their lifetime. So that's the stock. If you look at the world as to how many people are going to be diabetic and how many of them end up having infection and ulcerations, that's a huge number. What also is quite well known is that if you did have a diabetic foot infection, and if you had to have an amputation, you lose your leg, about 50% of them die in 5 years, okay? So the mortality of a diabetic foot infection does not come from the infection. The factors that moves, diabetics need to control their blood sugar. For that, they need to be active. They need to exercise, they need to walk, they need to get out and do stuff. The moment they have an amputation, they lose that ability. So they sit at home and they're not able to have the same cardiovascular exercise, so the regime they should have, which means that the diabetic control goes out the window, which means that the life span literally gets reduced quite significantly by -- from having had a foot infection, which is sort of treatable. Okay. We have done some work on this, and Michael showed you the outcomes of the studies, not just ours, but also from other centers regarding how CERAMENT Q help in controlling diabetic foot infection. So I've got some pictures here. So on the left side is a classic diabetic foot heel ulcer. What I'm pointing to here is -- that is somebody's heel, an MRI scan. You can see that Pablo's skin is missing there, okay, which means that the bone is exposed to the ground. So you can assume what that looks like. It's got a big hole here and the same here, which means that the bone is now exposed to surroundings. The gentleman is walking in it and ultimately, it gets infected and it becomes osteomyelitis. The problem with diabetics is that diabetes is not just a blood sugar problem. It also affects other organs of the body. It affects your blood vessels. It affects your kidneys. It affects your eyes. It affects all parts of the body. It's a systemic disease. And one of the key things with diabetes is that you get diabetic vasculitis, which means that the blood vessels are not quite what they ought to be. So you could give these people as much IV or intravenous antibiotics or oral antibiotics, but it does not quite get to where it should do because the blood supply is quite poor, okay? So the role of local antibiotic therapy in high doses, which you possibly could not give them intravenously or orally has been very fairly well established. What we didn't have so far is a way to deliver that locally in a fairly consistent and predictable manner so that it works and also stays where you apply it for a number of weeks or months till it actually gets rid of the infection. So that's what CERAMENT probably gives that little added edge in being able to deliver antibiotic locally to the bone at the area that is infected, rather than -- for example, if you got a leak in your house, you go and patch the leak. You don't put an umbrella over your house, do you? So the difference is that when you give somebody IV antibiotics, it goes everywhere. Only a proportion of it goes to where it needs to. And a lot of the time, those antibiotics can have also side effects elsewhere where they're not meant to act. Okay. Moving on, it just shows you how this chap's heel ulcer is. It's just an MRI scan. It's just a cross-section of it, but you can see that all across his heel, there is no skin, okay? So the heel is exposed. So the treatment for this is that -- what we do is that we would get rid of the infected bone and try and treat what is salvageable. So what is dead needs to come out, because that obviously needs to go. But some of the infected bone is treatable. So we are hoping that by having local antibiotics applied, they can conserve some bone and not have to take too much bone off, so that we can conserve or keep a foot and some function because I want my patient to walk. I wanted to keep his leg. I equally want the infection to be cleared, and I want him to be around for a lot longer. So this is the treatment modality. We would take out some of the heel. Some of the infected bone gets actually removed and then we'd apply local antibiotic locally. So if you look away if you are a bit squeamish. I've got a clinical picture again. I do apologize for this, but it is pertinent, that's why I'm showing this to you. So that is part of the heel taken out, okay? And once we've taken out is got, it's got CERAMENT which is a white powder, which you can see on the heel applied quite liberally into the bones. So you can apply it directly into bone, into the infected bone, so it will work locally and control the infection locally, okay? So you can see the outcome of that. So you can see as time passes, the first x-ray I showed you. I've been showing a picture where the heel is actually exposed. You could look at the leg and see the bone through the hole. As time passes, you can see how the wound heals. Okay? It doesn't look pretty, but he still has his leg, and the infection is gone compared to the previous scans. You can see how he's healed over, and the bone is no longer exposed. You can see, there's a cover across the heel. And that's what he's working on, okay? He has got some of his heel left, but he's infection free. The wound has healed up, and he is able to ambulate and walk. That means that he managed to salvage the leg. So that's another clear indication for something like CERAMENT. Because it's not just -- it elutes antibiotic. It's [ ready ] to apply to certain areas, which otherwise, we probably did not have an opportunity to treat directly by accessing the wound and also to apply the product very locally, so it can work in really high concentrations and try and help control the infection. So lastly, I'm going to talk about open fractures. This is just probably one of the other indications that Michael spoke about. The open fractures are very common. Probably it's probably less common than, let's say, a turn of the century ago, where there was a lot more building work and a lot more industrialization going on. Historically, until the turn of the century up to about 100 years ago, if you had an open fracture, i.e., you fell down and you broke your bone and the bone came out of the skin, the routine standard treatment for that was an amputation. You take your leg off because it was felt that's not salvageable. That's pretty much the case till about the Vietnam war. That's the '50s and early '60s, because the infection rate is very high and there's a new way of salvaging that leg. And that was thought to be -- that was considered as the -- pretty -- the normal way you would manage those. We have come a long way since then, because we have realized by the work of people like us deal with that. We need to wash the wound out, which you think would be second nature to most people, but it took a while before we accepted that we had to wash it out quite soon. Secondly, the fact that antibiotics are helpful. That is -- again, there was a work by [ Patakis ] that came through the 70s that suggests that early antibiotics and 3 doses of IV antibiotics was what is necessary. And later on, Marko Godina from Milan, came with a concept of covering these wounds quite early on. So we have come a long way in the management of injuries over the last 30, 40 years, but still, in some parts of the world and a lot of centers, the infection rate was anywhere between about 25% to 30%, which is considered fairly norm. So this pleasant gentleman here was -- with his permission, he was working in one of the stadiums in the Middle East. He's going to host a very important football match later this year. He's a lighting engineer. And unfortunately, one of the scaffoldings fell down and it went through his leg, unfortunately. So you can see what has happened to this leg it's -- what you see here at the left hand of the screen is the knee and ankle will be somewhere here. So that's his proximal leg. You can see that it's been literally blown to bits, because it's just been shattered. I can't use a better word. So that's what it looked like. Again, I do apologize for the picture. So we had a steel girder which went right through and through and shattered his leg. So these are very complex injuries. And I think it's important to mention that. Because these happen to young people who are sometimes are the only breadwinners of their family. These are young, fit people who, for 1 instance, they are working, riding a bike, doing sky diving or bungee jumping or something really high octane, high energy. On the next movement, life changes, okay? Life changes, not just for them. Sorry, but also for their families. So you can see here that his proximal tibia is literally in smithereens. So does anyone want to count the pieces? So I think I gave up when I got to 17. So you can count if you want but I counted to 17 and as I told, there are more pieces there. So what happened was that, again, some clinical pictures. So he had this frame put on, and it was transported back to the U.K. after a number of weeks after he was stabilized. So we were faced with a dilemma because he had a big wound and have his leg looking at you. And it doesn't look very good. It kind of looks not very happy. So what happens that -- then, the bone gets exposed to that extent and when there's such a sufficiently severe injury, the bone dies because the covering of the bone is peeled away. So suddenly, it becomes dead bone in situ. So suddenly, this becomes not that different to the diabetic foot I showed you, which is infected and some of the bone had to be taken away. So this is a situation where a young guy -- it's an injury, but it's a situation where the bone has died because of the velocity of the injury and the stripping of the periosteum or the covering of the bone, where the bone gets blood supply from, which meant that we had to take that bone out. You can understand that in someone who's in the late '20s, if you have to take out a large segment of bone, you'll end up in a situation where -- how do you make this heal? So you got a wound, you got an open wound who's been open for a number of weeks, infection, bone loss, fairly shattered proximal tibia, so a number of problems. And the difference is that unlike we showed you -- my first patient who has broken a couple of bones before. He's a bit of a -- he'll probably break something else again. And the second chap, sure he's had a diabetic foot. There's a young guy. He's a young guy whose expectations of the outcome of this is very different. He wants to be back working next month. He's got a contract to finish. He's got a baby on the way. So we took the bone out, and we managed to put the bones back together, and you can see the interface in between the bones was full of CERAMENT and a little bit of collagen mesh to keep the CERAMENT there from leaking out, because the defect and the void was so large. Then we proceeded to hold the leg together with a cage just to get the alignment back and to compress the bone fragments together. So you can see what it looks like now. So that bit is where the CERAMENT went in to try and fill the void, which is left behind by the wound being lost. We managed to line the leg up to dock the bits together and put a cage on to get compression as well as some stability and also alignment, which is really important because you want the leg to heal and you want the leg to be walkable, if that makes sense. He had the cage on for almost, I think, 18 months. That's how long it took to heal. And he also had the wound closed and a small flap put in, skin brought over to cover the bone. So you can see how it looked like initially, not very pretty. I told you there was 17 or 18 pieces. You can still see some of the pieces here with the cage on and some of them still here. So ultimately, we managed to make it look like a leg, line it up like a leg and to stabilize it. So that's what it looked like when we finished, okay, from what we started. You can see it looks a bit better. You can't see bone anymore. The wound has been closed and the leg has been stabilized. And he's kind of walking within limits. And with time, a bit of luck and the infection being controlled, the key thing is that you don't want infection, okay? The wound heels. And you can see what the long-term outcome looks like. So the bone is healed up. The leg is still aligned and lastly, final picture. And that's his leg. So I'm pleased to say that he's actually -- he will be in the big football event in November, although he didn't expect to be there, so he's very fortunate. Thank you.

Anand, please stay. Thank you.

I hope those pages won't be tough on you, but this is the reality, Professor Pillai.

I'm moved and also touched by your -- when you talk about the patients. We often forget that when we talk about the product. This is fantastic to hear how much you care for them. So -- some questions. Please, if you have any questions, just raise your hand. I think you'll get a microphone. And also, you can ask your questions on the web by writing. I'll start off with -- we can see great use here for CERAMENT in all these 3 indications. Is there any favorite you have of these where you use it the most? And also you talked about seeing other indications outside of this.

I can't say favorites, but I think one of the indications there, really, it has probably revolutionized and possibly changed our practice, not just ours, but probably across the U.K. and now increasingly across the world is in diabetic foot infections, because it's always been a bogeyman for -- not just for orthopedic surgeons, but also for some surgical podiatrists. It's an area that people try not to venture into or they're not interested to be involved in [ because ] outcomes were so appallingly poor. And eventually, when I used to -- when I was a trainee a number of years ago, if you were operating or treating a diabetic foot, my colleagues used to make fun, oh, that's a spaced amputation. He'll be -- you'll be taking -- tearing a couple of times. Ultimately, the leg is going to come off anyways. Why don't we just do that from the outset? They don't laugh at me anymore. I'll put it that way.

So that being the most important. And any other indications that you could see?

Yes, I think we have also dealt with a large bone voids in trauma patients. We have had experience with combining CERAMENT with autograft, that's bone, taken [ largely ] across for large voids. It's been both in fracture situations and also in situations where you had the excise large volumes of bone. One particular example would be that we had a series of high energy ballistic injuries not so long ago when we had the Manchester bomb attacks. So we learned a lot from that in a sense, CERAMENT, along with your own bone, it tends to help to control larger voids, which potentially, you would not be able to manage with either 1 on its own. And increasingly, we find that the use of CERAMENT with open fractures is expanding. And some of the pictures I showed you, we use the cage to hold the bone together. That's partly because we were afraid to put more metal work in there in the presence of infection. But I think we've moved on from that. We've got the confidence to fix these more robustly on occasions and put more metal work in there, if necessary, because we're fairly confident that the CERAMENT and the antibiotic will prevent further infection.

I understand. Is it so that you use CERAMENT G for indications where you actually didn't need, but just as an extra precaution, you use the antibiotic in the [ wound ]?

I think it's -- orthopedic surgery is very different to any other surgery. Anecdotally, I can say that when I was a trainee, my -- one of my trainers who used to say that you can -- when you're doing somebody's abdomen, we are opening somebody's belly, you could spit in an abdomen, nothing would happen, but you can't breathe into a joint. It'll get infection. You might have seen pictures where people operating on joints have this full body exhaust systems and they look like spacemen. So orthopedic surgery, by definition, is done in ultra clean air theaters. We've got filtration systems, air changes, people, like, increase or double-glove. We wear body exhaust suits. So in those circumstances, you're dealing with metalwork being implanted, either small or large, I think any little help to prevent infection would be welcome.

We have a question from the audience.

I mean, I'm sure you have come across some other synthetic bone grafts across the years. Based on what you've experienced, what are the key sort of attributes to Bonesupport's bone graft? And what's the most important differences for you.

I think the most important thing from CERAMENT G's point of view is the fact that it's probably the license or CE marked antibiotic carrier that we have compared to those of other off-license products. Before we had access to CERAMENT G or V, we used to mix in our own antibiotics to some of the other off-the-shelf products. The problem there is that the elution has not really been studied yet. So when you're mixing something together, how do you mix it? Do you mix it in a bowl? Do you mix it in a tray? How many times do you stir it? And we don't know whether the antibiotic is in clumps. It's like baking at home, isn't it? I'm a very bad baker. Some days, my cake turns out amazing, other days it turns out to be, like, not very good. And I'm blamed, saying that I didn't prove the dough or I didn't mix it enough. So it's very similar. What you want is that you're dealing with somebody else's leg, life, career and outcomes. You want consistency every single time that you do it. And it has to be predictable. That's what CERAMENT gives me. I think it's the predictability, the consistency and the fact that it's not just me telling you this, a lot of what I'm telling you is evidence based, which is what Michael's slides very clearly show. It's not a one-off thing. I think I would be wrong if I stood here and said that, I got these results because I'm a great surgeon. It's not just me. I think across the spectrum of users, we are finding that it has been beneficial to patients.

We have another question, yes.

How would you describe the awareness about the products among orthopedic surgeons in general in Europe, maybe other parts of the world?

I think it's still -- I think there is awareness but it could be better. It could be better. I think what you probably don't realize that a lot of us are creatures of habit. A lot of what we do is muscle memory, okay? Because when I operate, it's sometimes like driving in the sense you do go through the motions of doing something because you ran it so many times. And surgery is like music and it's by -- it's deliberate practice. So whenever you have a new product or a new intervention or a new way of thinking, it's not always easy to buy into that or probably to listen to it. And I think -- and also, there are people who are more happy with change. Some people are not that happy with change. But the awareness is there, but awareness could be better. But the main thing is that as much as awareness about a product, it also is awareness about the different way of managing some of these indications and the usefulness and the importance of local antibiotic therapy. Because of 2 reasons. One is antibiotic resistance is a big problem, because -- that's because when you give people antibiotics, it doesn't get to where it needs to. And if it does so, it's in kind of subtherapeutic volumes or concentrations. You get resistance. And secondly, if you look around, there are large companies that haven't made new antibiotics in the last, I don't know, probably a decade or so. So you're running out of antibiotics. You've got a problem.

Magnus, please.

I was wondering, for how long time you have been working with CERAMENT G, and also the easiness or hardness to convince others in the field to start using this?

Personally, I have been exposed to the product since, I think, 2014. So probably 2014, '15, that's when we started using it. And I would agree to your second point, because the representative for Bonesupport, who used to -- she's not with the company anymore, but who introduced me to CERAMENT first. She said that she waited for a year to see me. Apparently, she did see my secretary for about nearly 14 months, asking for appointments to come and show us the product, which I thought really? It forms bone? And per regulation, I've never heard of this before. And Bonesupport from Sweden, Lund? Come on. I mean most big companies are American, come on. So it took -- the problem is twofold. One is that it's a new entrant. Secondly, it's a new concept. But then compared to 2014, we are now a number of years down the line. There are definitely people and key people who believe in it and possibly had some experience with it. And then the evidence is building. So I think probably somebody now was trying to tell me what Bonesupport or CERAMENT, I would probably not make them wait for 12 months.

That's good. We have a question in the back.

So on the topic of sort of driving awareness and sort of getting the word out there, what type of clinical data do you think is missing to really promote uptake? The -- there's an ongoing study called SOLARIO for example, looking at systemic antibiotics, et cetera. Could you comment a little bit on the sort of clinical evidence out there and what you believe could be sort of the -- sort of a game changer really drive that uptake?

I think when you talk about uptake and the game changers, I would say there are 3 things. The first thing is the clinical evidence. Because as a surgeon, I need to be convinced that I'm doing the right thing or I'm doing the right-ish thing, if not anything else. So for that, you need to have a lot of clinical studies, either case supports or case series, and the best evidence will be RCT. You randomize people into 1 arm or the other, and you show that 1 arm is superior or it's not inferior. The SOLARIO trial is an excellent study because it compares all antibiotics to local antibiotics in osteomyelitis. And I'm proud to say we are part of that study and hopefully, you should have some evidence next year, and I think it'll be promising evidence so far, promising results so far. I think once you have an evidence base as a buildup, the next step would be to convince people to follow the evidence. And I think talking to surgeons like me is possibly the wrong thing to do. I think I probably got 5, 10 years to go before I'm out the door. There's another generation of surgeons coming up. They're fellows, they're trainees, they're residents who are the generation Z or they are far more tuned to the Internet, Instagram, Facebook, Twitter. So that is your target market. If you really want to penetrate, that's your target market. So they are more aware of what's happening. They are more attuned to change. They know that set in their ways, and they are the surgeons of tomorrow. If any one of you here has a problem in a number of years, they are the ones who might be treating you. So I think they are your target market and that's where the focus should be. For example, I'm not sure. Do you have a CERAMENT users group in Instagram? Well, you should, because I've got a lot of implants I use that are -- there are patients who come and see me, take a picture of the foot and the next thing I know, it's on Instagram. So it's moving on. I think you have to be -- people are aware of things. And the social media drives a lot of things, because I get patients who come and say, I saw it on Instagram or Pinterest, can you do that for me? I sometimes go to the next room, Google it myself, so that I don't look like an idiot, go back and say, yes, sure, I've looked at it. I'm aware of it. I know what it is. Otherwise, you think -- they'll probably think I'm a dinosaur, so. And the last thing is the financial aspect of it, because most of what we do, we work with a large hospital groups or large practices. So the finances need to match up. One, the use of the product needs to be for the likes of Håkan and Co., from a financial point of view, it has to be reimbursable. The tariffs need to match up. And lastly, it has to be in a way that the hospital surgeons get reimbursed for doing something. If I go and tell my manager that, listen, if I use this very expensive product, the patient won't come back for another operation, that doesn't really cut any ice with the manager because they want the patient to come back for another operation, technically. Did you understand what I mean? So that's the -- so there are different -- I wouldn't say competing interest, but there are different viewpoints to it. So I would say these are 3 things that you probably, to CERAMENT, to take things to the next level with any medical product for that matter.

Yes, we have a question here.

Yes. So I want to touch a bit more on habits. And I don't know if you've been a user of PMMA beads, but the problem, as Michael touched upon, was the operation and the 2-state procedure it. But I've heard the potential of re-absorb-able PMMA beads and that may be in the pipeline in the coming years. I mean how much would that change the clinical relevance of CERAMENT if that comes?

So as things stand, we don't have any resorbable polymethyl methacrylate that's bone cement. The 2 aspects of barriers to PMMA. Number 1 is that it generates heat as it sets. So it doesn't really lend itself to be pushing into areas that you possibly don't want to kill off bone because it generates a lot of heat. You can set it with beads and then put them in, but you can't really press them in the cavity, so you can't mold them into bone. You can't inject it directly into a void without having some destruction around it, which would be counterproductive, you get heat necrosis. Secondly, the antibiotic elution from PMMA is excellent for the first couple of days up to a week or so, then it kind of drops off like a cliff edge. It's not sustained for the 28 days that you have. Thirdly, the elution itself is a little bit iffy. You get -- for about -- the first 24 to 48 hours, you get a lot, then it starts dropping off quite rapidly. The good thing about the elution studies that we have from CERAMENT is that it does 2 things. One is up for the 28 days, you got above MIC, which is your minimum inhibitor concentration. It kills the bugs. In addition to that, for the first 14 days, it's about the bio-film concentration. So bio-film means that is a slime that bacteria produce and coats implants. So for the first 14 days, it protects implants, which is actually an added advantage, which PMMA won't let you do. And the last thing is that all the x-rays I showed you, I intentionally picked the x-rays where things have gone on to heal. When you look at the last x-rays, it still looks reasonably like bone. So the fact that it's not just calcium sulfate, which elutes antibiotic and dissolves, it also has got hydroxyapatite which forms a scaffold to form new bone. I think that would be where PMMA, even if it became resorbable, may not be able to achieve. What you don't want is that the chap I showed you -- I showed you the last guy with the scaffolding, yes, I put something in there, filled all the holes. In 6 weeks' time or 3 months' time, the hole just magically reappears, because things are just absorbed away and nothing has healed. That would put me in a bit of a difficult situation.

And then I also have a question on -- I guess you're at conventions. You talk to other orthopedic surgeons who may be using PMMA beads or something else. I don't know if it's a common discussion to have what sort of products you're using. But if CERAMENT comes up in discussions with others, what's the usual pushback to why they may not be using that product?

Price point.

Price point?

Yes.

Do you -- have you heard anything on what it would need to come down to for them to use that instead?

I think we have been very fortunate because we were an early adopter, and we have a certain volume of work going through, so the company has been very supportive to us from that point of view. But if you are somebody who is starting out or you're trying to convince my finance director to open his purses or purse strings to start using the product or put on the shelf, it's a very difficult conversation when you have price in the thousands. And on the other hand, you've got Michael from company x saying that, I've got to me-too product that's GBP 10. It does everything that other guy says. But the problem is a lot of the things that you have, your competitors may not be as evidence backed. But then having said that, Håkan, who's a finance man, he's not bothered about the evidence. All the RCTs, all the residents, he's bothered about his end of March, April, U.K. financial year, he needs to be in the black. He doesn't want to been the red. So the focus is very different when you talk about [ Jeremy ]. And as an orthopedic surgeon, I'm not the best person to argue with the finance guy. I will lose out every single time.

We have a question behind you.

You mentioned diabetic foot ulcer as a key indication. I wonder if the use of CERAMENT G is, I mean I'm presuming there's been a skin graft to this patient that you showed as well and whether the use of CERAMENT G is impacting skin grafts and...

No, we don't use skin grafts because in the heel, any weight-bearing aid, if you skin graft, it dies very quickly. So you need to allow it to granulate and heal very slowly. For that matter, you won't have a sustained ability to provide that antibiotic cover, so it doesn't get reinfected. We use lots of bagged dressings, the bagged dressing is where you put a dressing over the sponge and the tube connect to machine, which sucks away all the blood, so it doesn't congeal and coagulate, but is going to heal with time. Honestly, it's interesting because these are diabetic patients, but it doesn't mean their ability to heal is any more hampered than anybody else. Once you clear the infection, it heals.

Any further questions? So would you give some advice on the way to Bonesupport before we end off?

I think I'm not the right person to do that, but I think it's a very unique product. And I think it's got certain advantages that other products cannot offer. And we have used CERAMENT for a number of cases, I think, probably in the hundreds and we haven't had any adverse events, which is really important. We haven't had any antibiotic toxicity. We haven't had any wound breakdowns. We haven't had any fractures. And we have had good success. And I think the right hands, like everything else in life, the right hands for right indication, it can actually be a game changer for the right patient. I think that's what I would say.

Thank you very much for being here, professor.

Thank you.

So we're going to have a short break and at 3:30, please be back. [Break]

Welcome back, everyone. I'm delighted to present to you Mike Roth, who is our Executive Vice President in the U.S. and our General Manager. And for the next 30 minutes, he's going to share with you how we intend to launch CERAMENT G in the U.S. After this, we'll have a short session where Håkan and I will speak about the updated guidance that we gave this morning. And then followed by a question-and-answer session. The stage is yours Mike.

Thank you, Emil. And again, my name is Mike Roth, the General Manager and Executive Vice President for Bonesupport in North America. And just in terms of my background, I'm 30-plus years into the orthopedics industry, started off early on in the sales capacity with Howmedica which is now a part of Stryker. And then segued into a company called Wright Medical, which is also a part of Stryker. But I bring up that background to that sales representation in the '90s, segue into management and the 2000s to my current phase now. Because at Wright Medical, so I spent years selling the full bag as they say, in orthopedics, from hips and knees and trauma devices all the way through orthobiologics. Orthobiologics really came into being in the end of the '90s, Wright Medical was on the forefront of that. And I was involved early on from a sales representative standpoint in the Boston area all through the early phase of management and launching products from Osteoset to Ignite to PRO-DENSE and others within that product line. And I bring that up because during that time period, 1 of the main goals of Wright Medical at the time, and this is around 2003 to 2007 was to get FDA approval for a product that some of you may be familiar with is called Osteoset-T. That never occurred. And after my years with Wright Medical, I still keep up with a lot of the guys that I worked with over that time period. And we never let go of the fact that it was a major disappointment. It was a major source of frustration not to get that. So I always -- we always said, if the opportunity ever came up where we could be associated with a breakthrough product like a bone graft substitute that elutes antibiotics. That's the product to get involved with. So when Emil, I first met Emil and we talked about the opportunity to -- where they were in the FDA process and my knowledge of orthobiologics and how it applies from the trauma standpoint, et cetera, I became very enamored with this opportunity and pursued it. And I have to say I'm extremely happy that I was given the position and got to be part of the process for me, which is a lot of closure to actually see this product get FDA approval and now be at the point where we're actually launching. And it's great, and I appreciate just this opportunity. So I want to say that. Make sure I have this correct as far as moving forward, I do. So with that, we're on the cusp of our launch. And -- but really to give you a little bit of background here. We've set a tremendous foundation in North America for success, and it's already proven out because we're already very successful in selling CERAMENT, CERAMENT without an antibiotic. And that in and of itself, as Dr. Pillai had alluded to, it's a busy space. There's a lot of different products out there. It's hard for the surgeons to differentiate from one product to the next. But we've been very successful over the last 2 years to grow that business in an otherwise very difficult setting. And we've done so because we have a really strong organization that's in place. And I'm very proud of this group of individuals and just give you a basic overview. We have a structure -- Aaron Lepper is our Vice President of Sales; Doreen Smillie is our VP of Marketing, finance, operations, clinical, we've established a very good team to support all the sales efforts that are going on. But as far as our sales structure goes, we have -- it is an independent sales structure. We work with distributors across the country. These are all distributors that are focused on orthopedics. So they're in the major market segments of foot and ankle, trauma, recon reconstruction, primarily hip and knee reconstruction as well as ortho-oncology. And -- so we're dealing with distributors in these -- all these market segments, and part of our goal is to make sure we've identified strong distributors in each market segment in each region. And this has been an ongoing process that we're putting in place, and it's working for us. So just working for us to sell CERAMENT G, but it's -- excuse me, CERAMENT, but it's setting the stage for success with CERAMENT G. And with that, these individuals right here, my 12 direct region managers. So we've broken up the United States in 12 regions. This has been kind of a process over the last 2 years that we've got to this -- arrived at this number. And we have very good coverage, excellent professionals in each of these positions. They all have orthopedic sales backgrounds into management, very dedicated, very excited about this opportunity with CERAMENT G and have been following a process that I think is key to our success. It's that we continually update our plans, our annual business plans on a quarterly basis to focus in on growing the existing business now and developing relationship in key accounts so that we have a base of business in our bone graft substitute that can lead us to entree or opportunities for CERAMENT G. So that is our organization. So we're -- as far as just speaking to that in terms of our growth from establishing that strong network of individuals, the growth of CERAMENT in the United States despite the pandemic and being 1 headwind, but we're not alone in that, obviously. We had moved away from an exclusive distribution agreement with Zimmer Biomet back in 2018. And that's our yardstick. Every -- how have we done since that change, which was a very big move to make. So the belief was that we could handle this independently because they were really penetrating only certain parts of their distribution system. So some of those distributors within the Zimmer Biomet distribution channel were successful with CERAMENT, others just kind of put it aside because they had other products to sell or they focused on different areas. So that's the reason the company made the move. And so a bold change like that, I'm happy to say that we've had tremendous growth. If you look back at 2019, that -- from that period, we had 216% growth onto 2021. It was 40% growth on top of that. And then currently, at this point this year we were SEK 87.2 million. So continued growth there. And if you saw that trajectory on a graph, which Emil actually showed earlier on in the day, we're quite proud of it, but also we get a lot of strength from that because we know we are moving in a very good direction here with our base business. So -- what that basically shows us is that we have very strong sales momentum. Håkan and I have spoken about this, that we have a very high gross margin at 93.5%. And we have a scalable platform. Whatever we feel like we layer on to this, we're going to be successful with. So I've kind of already touched upon this that we went from 8 all the way up to 12 regional managers. And in and of that, we were able to really expand our distribution network, and we did so by bringing on additional distributors, but really targeted in certain market segments where we knew we would see success. Primarily foot and ankle and trauma are 2 areas where we're seeing a lot of growth, and we expect to see quite a bit more kind of in conjunction or I guess just following up on some of the cases that Dr. Pillai had presented. And the way this has also played out as we've been focusing on particular accounts where we either have access or wanted to gain access to and just in particular, the Mayo Clinic, Cleveland Clinic, Hospital for Special Surgery, Mount Sinai, in Baltimore, Mass General and the list goes on. We've been very successful in gaining access of existing attending surgeons who are influential and are training the surgeons of tomorrow. Another aspect of our success is this national contracts side of the equation. In the U.S., there were these GPOs and IDNs. These are the buying groups that really do dictate how a lot of the product is approved within the whole hospital system. We've been very successful. I'll delve into this in coming slides. CERAMENT G also recently, along with getting the FDA approval opened us up to the opportunity of getting a new technology add-on payment from CMS and that is known as NTAP. We'll talk about that a little bit more as the talk goes on, but it's significant. The amount is $4,920. It goes into effect October 1. And what you'll see that, that actually really will have impact for us in terms of the decision process that the hospitals have relative to the cost of the product overall. So this supports the premium pricing that we have, and we're still being very judicious with our discounting, and we're going to go step-by-step with that as we move further. So ultimately, though, CERAMENT G really -- it's a strong unmet need and there's a lot of pent-up demand for CERAMENT G. So Dr. Pillai was talking about this in general and that you have a product that is engineered for this application as opposed to mixing a bone graft substitute with antibiotic off-label. You just never know exactly how that's going to turn out. We see it within surgeons that are using CERAMENT at times. We know it from the competitive situation. So there is definitely a strong demand for a product that you know that is reproducible, consistent, easy to train your OR staff and orthopedic team on. So that you can use this product just pulling it right off the shelf as time goes on. So what is the U.S. bone graft market? What is it composed of? So there are 360,000 surgical procedures per year in the U.S. in which bone graft substitutes are used. This right here breaks that down for you in this pie chart, but we'll focus on the 50,000. So you've got -- the purple is infected cases. The 90 refers to the noninfected cases where surgeons may consider using an antibiotic prophylactically for prevention. And then the 220, the blue, that's non-infected cases that would also involve systemic antibiotics. Our approval is for this 50,000 cases. So those cases that can be treated with local antibiotics. And that's significant. It's a huge market in and of itself. By having an FDA-approved product, we have really a license to go after that business. And it -- as we dig into just that number alone, although we've experienced tremendous growth over the last 2 years, and we're on a great trajectory, it opens us up to a lot more opportunity there. So looking at the -- so all current use of bone grafts and local antibiotics in the U.S. are off-label currently. So that gets back to we're the first and only product, which is extremely exciting and currently right now, I have to say that because of this situation, we're probably one of the hottest companies that's being talked about in the U.S. right now. So rather we go to the foot and ankle MD meetings or podiatry meetings, there's a few companies, the trauma meetings as well, the few companies that they're focusing on in each market segment, Bonesupport, CERAMENT comes up, and we're kind of the [indiscernible] company right now. It's great to be associated with that. CERAMENT G feels an obvious unmet market need. And sort of breaking it down when you look at it from 3 different aspects, the problem, what is the problem? It's bone infection. Bone infections are difficult to treat. The patients are complex or the cases themselves are complex. You saw that earlier in presentations. There's a lack of innovative treatment options available, sort of just have been using the same PMMA beads for years to treat these surgeons. And now they've looked at different off-label options because there hasn't been anything that's been available on the market approved by the FDA. And there's very high infection rate with these patients. So we -- this information right here on the reinfection rate at 24% of -- on an average 24% of U.S. bone infection cases result in reinfection that came from an independent study. And it was -- Dr. Pillai actually brought that up towards the end of his talk, not knowing that we have this number that we're sharing here, but it's the same kind of -- it keeps coming up in that range, right around 25% or so. As far as the need goes, the need is for a better dead space management. Multi-stage procedures are the norm in the United States. They're very -- I mean, we didn't really get into this earlier today, but from a health economic standpoint, yes, we have a more expensive product on a case-by-case basis, but the fact that we're able to provide the option of a single stage that whole dynamic, the whole patient journey and that dynamic within a hospital is huge. So if we can go from multistage procedures and the treatment of these patients to 1 single treatment it's going to have impact on a national basis. And these GPOs and IDNs that we referenced earlier are going to see that and feel that. So this is a message that we're continuing to work through and work on and drive with. And there's also a lack of safety and efficacy surrounding the evidence relative to off-label mixing, there's liability associated with that. So those are all 3 major concerns, and we have a solution for all 3. We're able to grow bone and treat infection in these cases. So also from this independent research that was performed relative to the treatment preference, 92% would prefer a single stage procedure. So just kind of building on what I had said that's the reaction that the surgeons have relative to treating these patients. And also the hospital administrators. They don't want these patients to come back in. They want to treat this infection. They're looking for a solution. And this is why I think they've been standing right with us in terms of the frustration with the FDA -- why is this taking so long for a product like this that seems like that there's such a big need for, why are we waiting for this for so long. So we're finally here, we have still tremendous support from the surgeons that use CERAMENT and say they can't wait to use CERAMENT G and others that are talking to us about just this innovative technology. Then the solution, solution CERAMENT G from our perspective, it's a dual mode of action in that you can treat infection and grow bone. It enables a single-stage approach, and it's clinically supported. We have -- as Michael had mentioned earlier, tremendous body of evidence to support our efficacy. So with that, this -- the outcomes that we've posted here -- these are from published Level 1 studies out of Oxford, 96% success rate in eradication of infection, 58% reduction in readmissions, 39% reduction in length of stay. So this data really references the fact that not only is it good for the patient, it's good for the system -- the health care system in general. So as far as our sales strategy, and a lot of these points have been brought up before, but I'll just really essentially reiterate. So we know that it's really all about quality, not quantity, especially out of the gate here. We want to be successful. We want to put it in hands of surgeons who are going to be successful with it. So we're not taking this random approach of saying, hey, everybody, we have CERAMENT G now just start calling us for orders. We really want to work with those, we've done our research, so we know we are the high-volume hospitals and surgeons are who are treating osteomyelitis and fracture-related infection. So we have the data -- we can then hone in on those institutions that need this product first and foremost. And with that can also teach their associated surgeons, their colleagues and also the young up and coming surgeons, the benefits of the product. So secure early adopters and success with CERAMENT, these are the points that we're following through on, identifying qualified surgeon champions of which we have a lot. We have a very large body of key opinion leaders who have been working with us throughout the last few years and continue to do so and are very happy that we're finally at the point where we're launching, drive local hospital approvals. So this is a key factor in that we're focusing on getting the approvals from the GPOs and the IDNs. However, it still is -- the decisions are still at the low local level with the hospitals. So having that in place, the approvals at the network level helps us with the decision process at the local hospital level. Focusing on customer care during the onboarding. This gets down to really training. We need to make sure that the surgeons are extremely comfortable with the mix, we need to know that the nurses and the orthopedic team that is involved in the surgery, are well trained and everything goes smoothly. So we're going to be very hands on as we have been with CERAMENT. We're just taking that same mindset and applying it here with CERAMENT G. And then gathering products and clinical feedback. This is another thing of working with particular -- our KOLs and certain champions who are interested in gathering data. We have systems in place, registry, et cetera, where we are going to be gathering this data to support our evidence as we move forward. And then targeting high-volume bone infection sites. So in particular, once we've made our -- we've done this analysis, as I've said, and low and behold, a lot of these sites are the academic teaching institutions around the country. So we have these relationships. We have a base of business there. In fact, in all of our regional managers' business plans, we've required that they utilize the data that we've gathered and target the institutions within their regions and start working to sell CERAMENT there. This has been in place for about a year, 1.5 years, so that we have a base of business and we have relationships that we can tap into for CERAMENT G. And now we're poised for this launch because we have that access. And we have the interest of these attending surgeons to train their residents and fellows on this next generation. So in terms of changing the standard of care, it's a difficult process, but this is integral to the start of the change. Active CERAMENT bone void filler users, that speaks to what I just mentioned. We have a very strong customer base that is growing in all different market segments currently. And then leveraging strong distributor network and purchasing and administration relationships, this speaks to this distribution network, a lot of these distributors around the country, they know orthopedics. And they've seen other bone graft substitutes used. They know what works in certain applications, and they know it doesn't work. So CERAMENT has been a product that a lot of guys call us up for and say, listen, if you don't have representation in this hospital or this region, I want it. And it's a great sign. We have some really good partners out there, 40 plus currently with a growing network that's really, really essentially a great partnership that we've developed from the success of CERAMENT to this point. And then we'll be utilizing our KOLs, our advisory board and all the strong surge in relationships to continue with our whole Med Ed medical education push. We've got to get the word out there about CERAMENT G, and why it's a difference maker, why using an engineered product that has already proven more success in Europe is more advantageous than mixing off label and not being able to control that whole process. And these surgeons are on board with us to do that and whether it's the foot and ankle societies, the trauma societies, or the large joint recon environments. So this moving back to the national account scenario. So this is a little bit of a deeper dive here. But -- so we -- we know that at a high price point, CERAMENT is -- it's going to take a lot of effort for us to have approvals at accounts. So at least we assume that going in. But -- given what we've done with this product, we really analyze what the pricing should be. And we looked at it from a 1-year standpoint on out to 3 to 5 years down the road to see how things would play out. So we've put a lot of research into our pricing. And what's interesting to say is out of the gate here, we already have approval. We're on contract at Premier and HealthTrust. So these are these 5 buckets here. Four of them are the 4 GPOs that really dictate a lot of the business in the United States. We've also included the government on here, too. But Premier HealthTrust and the government market, that's the Veterans Administration hospitals and the Department of Defense facilities. We have access. We are approved vendors on contract at all of those facilities. And there's other things that we're pursuing within there to see if there's any more strategic advantage that we can leverage from those approvals. As far as Vizient and the resource group, we are still in the process of going through submission. They're looking at us now -- at first, they looked at us to see if they could put us in one particular bucket, but it didn't necessarily make sense. So there may actually be creating a new bucket for us because, again, we're the first and only in this category, there's no category on the bids. So this is an ongoing discussion. I think it puts us in a tremendous position of strength. One other point on this slide here is that relative to Premier and HealthTrust and Vizient and the resource group. Of those 4 GPOs, Premier and HealthTrust are the more compliant of all of those 4, HealthTrust being the most. And by compliant, I mean, they do require that their hospitals follow their approval process. And what that means to us is the -- with HealthTrust, we really wouldn't have any access to those hospitals if we didn't have this approval. But now we can walk into a HealthTrust hospital. And if we have surgeons that have said, look, we want to use CERAMENT G. We have a really good conversation then with those hospital administrators. They will immediately check to see where we stand from an approval standpoint, we're on contract. Okay, now we can sit down and negotiate and talk. Otherwise, we wouldn't have that access. Premier isn't as compliant as HealthTrust, but that is a card that a lot of the hospitals will play. They'll let you know, they'll tell you that they're premier and we'll ask you where do you stand from that standpoint? Because they can push back. They can say, no, we're just not going to bring anything new into the hospital. But since we have the approval, we're in the game. And then as far as reimbursement goes in terms of overall national status, this was brought up a little bit by Dr. Pillai, but currently, bone grafts fall under a DRG bundle in the United States. And CERAMENT G has been awarded a unique ICD-10 code, which is relative to the hospitals and NTAP, which I referenced earlier, the new technology applied approval. That all came as a result of -- well, first and foremost, the FDA approval, but also the breakthrough, the fact that we actually broke through and then we're able to work towards that. But the great news is that we were awarded the NTAP and it goes into effect on October 1, which falls really good -- in line with where we stand from our actual product launch this fall, having product available. NTAP, just quick summary here. It provides $4,920 for CERAMENT G to patients in these procedures. So if they exceed the DRG for the procedure, that for this particular case, this is additional money that goes into that bucket. So essentially, it really could offset the cost to a tremendous degree depending on how much their spend is per case. Emil alluded to this earlier on in the day. This is our Booster program. We call it that, but essentially, it's a human resource program, because we know with -- we see what's coming. We're going to be growing this business. There's a lot more that's going to be happening over the next year. So we've kind of phased this where we looked at year 1, and we're already discussing year 2, 3 and beyond. But our goal here is to push to invest in resources that help generate U.S. sales growth to 50% or more. We see the opportunity. We're already digging in to go after it, and that's what we're focused on, getting to a 50% growth status in the U.S. And in and of that, we also need to develop the resources to support the increase in anticipated sales. So driving aggressive growth market penetration with the NTAP and GPO, as mentioned, and this overall push, this is really looking at the year -- the coming year 2023. The overall cost is approximately about SEK 8.5 million is what we see. But -- this is, again, we'll invest more on this if need be, based on our projections as this launch progresses. The key hirings relative to this. So on the push side of the equation, we see the need for working closer with orthopedic surgeons that are using the product. When we initially started talking about this, we want -- we initially thought we would hire an orthopedic surgeon directly. But in kind of looking at things a little further, we have come to the conclusion that having surgeons who we work closely with currently in each market segment, particularly foot and ankle and trauma, are going to really serve us quite well because they have the interest in the product. They have the experience in using the product. And they also have a network of surgeons that they know who to talk to. And those surgeons are open to talking to them. So this symbiotic relationship is something we're going to be taking advantage of as we move forward. And then as far as reimbursement goes and billing, -- you -- I know I spent a fair amount of time talking about NTAP reimbursement. This is going to grow as time goes on because here we are at the beginning of this with NTAP, we may end up hiring somebody directly here, but out of the gate, given the relationship that we have as a consulting firm that has a program that can put right in place for us. So we're going to adopt that program and really plug and play, so that we know we have the resources to talk -- so that our hospital customers, surgeons can also talk to our coding specialists to discuss things and outs of reimbursement. That also give us more insight into some of the moves that we might have to make and pursue down the road. And all along, this is all about driving market access. And then the last leg of the push is on the medical education side, Med-Ed is extremely important to our success currently. We are good at what we do with this, but we know that we're going to have to drive further. So we're going to be expanding the team. A lot of this is run currently out of our marketing department, but we're going to be looking -- we're already in the process of bringing on -- we've started the interview process for bringing on a lead person for running medical education and then a support person along with that. And as far as the development side, helping support the business, those check boxes are -- those checks are in place because we've made these hires already. We've added a customer service representative. We have added a financial controller to help with more data analysis to give us more insight on what's going on, and also a marketing associate to assist in all of the industry relations that we have. So all told, there's about 7 either direct or close consulting relationships that we're going to be establishing just in the first year alone of the launch. So just to review, we're really poised to expand. We're a well-oiled organization that's -- we're battle tested. We know what to do. We all believe in the whole mission and I've got a great team. Strong and growing customer base. I alluded to that. I can just say that even this past month, we've seen sales increase to a level that's pretty exciting, just with CERAMENT alone, I think the reason behind that is that we're out talking about CERAMENT G already. So more surgeons are starting to find cases in which they can start to work with us. And all those surgeons that are using us currently now are booking cases because just the interaction picks up and the energy and excitement is there. So it's great to see. The approvals that have been granted and are in motion are extremely key to our success going forward, and we can already feel that because of just the interaction we're having at the hospital level. One thing over and above just the approvals I mentioned at the GPO level, we are already having hospital, the IDN networks and particular hospitals give us approval, which is an early sign that our pricing is in line. We're in a good place. And then the reimbursement, we spoke to that and the Booster program itself. It ties everything together. Thank you.

All right. So we're coming to the last session. Håkan and I will speak a little bit about the updated guidance that we gave this morning. But 1 clarification also. Thank you, Mike, for your presentation. The sales number you showed is year-to-date, it is not LTM. If you want LTM, you can raise it significantly. So it was year-to-date and the growth rate was correct, though. So the guidance that we released this morning is 40% sales growth on average normalized for currency over the next 3 years. And in arriving at that objective and that guidance, we did our market model. We looked at the market conditions. We looked at the current penetration rate. And then we looked also at a couple of growth vectors. That will have impact on our top line over the next 3 years. Let me just quickly run through some of those. You know about the new distribution platform. Mike shared a little bit more details. You've seen the growth rate and the penetration that we have already with the BVF in the U.S. In 2019, we increased salespeople all over Europe. And the salespeople in Europe are yet to be able to double sales before they reach the peak in productivity. So there's a lot of penetration activities still going on. The COVID headwind that we've experienced for the last 2 years is turning to a tailwind. There will be more procedures taking place over many years to go to deal with that big backlog. I only yesterday listening to the radio, the Swedish news for complementing on -- commenting on that the depth, the mountain surges that have to take place has never been greater. Hybrid market. We have spoken about that. In terms of the Booster program now Professor Pillai has left. And I think there's still a bit before we'll start some Instagram group with surgical pictures. But what we can say is that part of the Booster program, when Mike said Med Ed, that's medical education, 2 people in medical education and 1 medical liaison. These 3 people will work with residencies, they will work with surgeons that are about to become orthopedic surgeon, that are about to go out and start having surgery. So we're starting earlier. He spoke about Generation Z. That's what we're targeting with our medical education. So we know that there are professors in Germany, in the U.K. that have written books about autograft. They're sometimes reluctant to change to this new product, but the younger surgeons and actually count on to one of them are very much progressive in looking for these new ways. Mid-next year, this, I think we spoke in plenty of. Mid-next year, between either before summer after summer, we're working hard on this already to make sure that we can submit to FDA an extension of the label that we have, and it's going to be in the direction of prevention, and with a focus to go after trauma, but more details to follow on this. This is our ambition, and I will keep you posted on how this work is progressing. In the future, we can also expect further geographic expansion. Now I want to make it clear that 40% of top line growth over the next 3 years does not account for any outcome of conviction study. It doesn't account for adding the part. So those are future potential opportunities that will come. Now, many times today, it's been mentioned that orthopedic surgeons are a bit slow in adopting new practices. This is true. Whatever there is a new product, it takes time. We have to go from clinician to clinician. Sometimes we have ambassadors who haven't used the product for a long time, like Professor Pillai that speaks to his or her peers and say, this is a great product, I would like you to use it. But sales only take place when the product is actually used on the patient. Now on this page, I listed a few factors where we think these will contribute to a very strong and fast market penetration for CERAMENT G. In general, the orthopedic industry is a slow mover. But here are a few factors that actually separate CERAMENT G from the crowd. Michael showed the clinical studies, and I think you heard it also very clearly from Professor Pillai, there is a difference in result. There's a superiority proven in all these clinical studies versus standard of care, that increases the pace of the penetration. What has been done already with CERAMENT BVF since 2018 has created a big foundation of surgeons that are used to use CERAMENT, and now comes CERAMENT G with the addition of gentamicin. It's the only product on the market. We spoke about the NTAP. And in the market insight, we have done an extensive market research with U.S. orthopedic surgeons where they stated that 92% would like to go to a one-stage procedure. So we have market insight that have prepared us also for how to position the product on the market. And the great news from this morning, of course, is that we are both on Premier and health costs. And this makes us conclude that CERAMENT G will be part of a great opportunity for the U.S. market. So we will listen to some sound and then go to the final slide of this presentation, which Håkan, if you support me on this, I think the key message here is, as we progress over these 3 years that we've depicted and outlined today, you can expect that the gross margin of the product is going to continue to increase. It will do so from mix, and it will do so from scale. It's also very fair to assume that once we come into profitability, there will be a very high cash conversion. We're not a capital-intensive company. And as for 1 thing, we have about SEK 1 billion in tax losses aggregated that will need to be depleted before we start paying taxes. So again, another factor that drives a very high cash conversion. And finally, Håkan, if you would like to comment on the share swap, which I know has been a little bit difficult maybe to interpret, but how has this influenced our cash position?

Well, thank you, Emil. So following the AGM this spring, we had the ability to settle the share swap that we entered into previous year. And we did that during the summer -- and that resulted that we could return and add SEK 50 million to already available cash that gives us substantial headroom and stability to execute everything that you've heard today. So we are in a very solid position. And in the next month, we're going to enter the most important commercial milestone in the company's history. And that's how we end the presentation today and would like to open up a Q&A session.

Fantastic. Håkan, you look so happy talking about all the cash?

I do.

Yes, we have a question here.

Almost to the day a year ago, many of us were severely hit by the FORTIFY study and what I saw as lumpiness, not realizing that the patients did not come back to follow-up in the study, what are you doing to avoid such things in the ongoing studies?

Yes, there was a very tough moment. Trust me. I did not sleep well. I think there are several measures that if you look at the biggest study like SOLARIO, for example, if you look at the conviction studies, it's run with very tight centers that have a strong relationship and contact with their patients. These are patients with an existing bone infection. The FORTIFY was prevention. Of course, if you have a bad condition, your greatest wish is to have it cured, right? We also know from tradition that in our European centers, we have a significantly higher compliance following up patients than we have in the U.S. I'll let Michael comment on this -- but on top, the FORTIFY study had young males. I'm no longer part of those -- that target group. But they don't take these things seriously enough possibly. In the U.S., construction workers that move from one place to another. So when there was time for the follow-up of the study, they were somewhere else. In the SOLARIO study, the age group is higher, hopefully, also more disciplined people to fully participate to such a study. Would you like to mention anything about this, Michael, as well? Is there something we should add?

Now it's on. Now, it's on. I think if we get to close, then that's the problem here. I think you summarized it very well. For the FORTIFY trial, it was a very tough patient population. It is exactly what you said is it's young patients with a trauma, with a fracture which don't come back to the follow-up. And we know that in this population, the follow-up is lower than the pandemic hit. And they didn't show up. And I think there are -- this is different in Europe in the patient population you mentioned. There is a closer relationship between the surgeons and the patients, which make them to come back and it's kind of more the standard of care in Europe for the follow-up. And what we could see for the FORTIFY data that the compliance and the follow-up was better in Europe than in the U.S. And this will play a role for the studies we are now mainly conducting in Europe, which is -- and the U.K., which is SOLARIO and conviction in France.

Side question, Mike, do you remember the dropout rate in unutilized study on the bone -- prevention of bone infection?

As far as I know, 2 or 3 patients did not come back for follow-up, but the follow-up is very high. It's a different situation.

Are you doing clinical trial monitoring or is it the surgeons themselves doing it. Because with clinical trial monitoring, your monitors should be able to see this and send early warning signals.

This is correct. What we are talking at the moment about is investor initiative studies. So it's with the sites. And within FORTIFY, we were not able to directly contact the patients, but we always contacted the sites mentioning that a follow-up visit comes up that they need to contact the patient to come back to the follow-up. So these patients in FORTIFY they were monitored, the sites were monitored and a patient was called last to follow-up, just if he was not -- the site was not able to contact him and documented this for 3 times. So they were trying to chase change the patients. But it's a tough patient population in general.

I think we can probably also say, Michael, that with the rules and regulations, now in the studies that have started since Michael and I came on board, we're doing absolutely everything we can to never see something like what happened with FORTIFY ever again. And then there are no guarantees, of course, but that's how we do it.

So those 50,000 procedures that Mike chose, they are on label. As I said, those are synthetic, but if we include autos and allos to those, how much do that figure grow to? And why are you not showing those as addressable?

So the -- you're talking about the U.S. market. And the 50,000 cases that are done when there is a current infection and the 50,000 includes all bone grafts regardless of its organic or inorganic. So it's autograft, allograft, it's bone cement. The 50,000 are all together when local antibiotics is used. All of those procedures historically are off-label, but now there's a product very soon that will be on label. But it does include autograft and allograft?

Okay. Good. And then also on the pricing aspect of all. I mean you said 15 -- 5% to 15% discount was the range. I mean, is that volume dependent so that the sort of larger GPOs are getting the larger discounts?

Mike, would you like to answer that?

So it will be volume dependent, but it depends on each GPO or IDN because they have different price, they have different structures in place for discounting. So we'll go through that process with each of them. But all the while, we're going to try to be as consistent as possible with each of the buying groups.

Okay. And then on the guidance, I mean, you showed that trauma extension was a part of that guidance. But have you in that 40% growth fully expected an extension into trauma to reach above 40%?

Yes. The guidance has the extension of the label and the focus is trauma, but there are also other indications in the prevention we will have to determine exactly how that's done. But the 40% is connected to getting some kind of extension of the label with a submission mid-next year and then execution, somewhere between 180 and 360 days after.

So should we interpret that if you don't get the extension, you're not going to reach 40% in 2024. Is that how you model it?

We cannot separate the different vectors and say, well, what about if the Booster program doesn't come out? Or what if the Booster program is super successful when we raise the guidance? No, it's a package of different variables. Some of them are more likely to happen, some less. You saw also that there's some upside, let's say, that we have not accounted for. So our guidance is 40% and then normal probabilities apply.

Okay. Have you also modeled in some off-label use into that figure? Or is that unaccounted for?

I think it's fair to say that there will be off-label use. We know that almost all the orthopedic surgeons we work with in the U.S. sometimes at occasions use it. We are also -- Anand Pillai use it. But it's not a major part of our calculation. No.

Okay. And then why did you choose not to set a margin target or at least a year for profitability?

We were contemplating this. We decided that we're still so early in our journey, and there are so many opportunities and we didn't want to set a target that we then would have to maybe modify. We could have said, of course, at a steady state, the EBIT margin would be this. The next question that you would ask is, well, when is steady state? And I would say that depends. So -- and then the that goes a little bit. I think it's clear to look at the cost structure we have, you can all make the line and see how that develops. You can see that the top line is significantly steeper than that with a gross margin, which is increasing. And then I think you can use different models to stipulate what it will be steady state. But we have decided at this stage not to guide on that. We're still in an early phase. Once we are maybe 1, 2 years into CERAMENT G, we have other things we might be closer to providing that data.

So Emil, one of the only negative things I heard Professor Pillai talk about was the high price. So we've heard that Mike thinks you're at a good price point, but could you comment on that, your price point?

Yes. I think everyone knows that our price in the U.S. is significantly higher than in Europe. In -- there are certain countries in Europe where we encounter the price conversation more. Sweden is one. U.K. is one. we are working on providing the evidence on the health economic benefits. So that surgeons like Anand can be strong also in their augmentation against a procurement manager or a purchasing manager when we are not there. We -- I would like to raise the conversation what is the cost of an amputation. And don't take it from me, take it from Professor Pillai or other surgeons with the same experience. He basically -- I couldn't have done this without this product. And what is then the cost of society or what is the cost to a patient. And that's what we're working to show that indeed, CERAMENT might have a high price, but it has a very low cost.

And another, you've talked about today that your FDA clearance, it's -- you're now alone, you're the first and your alone. Can you elaborate on the alone? How long do you think you will be? Or how does that look?

Well that's difficult to say, of course. But given the kind of -- given the extensive documentation that we have submitted, and given that we don't know any other treatment modality out there that even have that kind of documentation, which is required for an approval. If there would be a product similar to CERAMENT, it would have to go through clinical studies similar to what we have done. Then it becomes in public domain. So we should know it at least 3 to 4 years in advance. And then there is submission times 2 or 3 years. So, yes, I think we will be alone. This is our domain.

At least for a couple of years. We have another question, please.

2 questions. Starting off on the early signs that hospital VACs and IDNs are sort of giving early approvals. Can you comment on how many or sort of quantify that in terms of the addressable opportunity you have right now? And secondly, perhaps if you could comment on cannibalization, if you will, of existing BVF sales, we should expect that sort of trajectory. Can you give any more guidance or how we should think about that with the existing BVF product?

Yes. Thank you. So today, we released information that the 2 biggest and most compliant GPOs have listed CERAMENT G. Once we get further approvals on GPOs, we might either communicate it with a release or we might just inform about it in a quarterly report. But at this stage, I think it's a little bit too early because it will also set the precedence where we constantly have to update everyone where do we stand? This is a high priority for the team, of course, to get access. But great news that already Premier and HealthTrust, we are there. Sorry, the second question was?

Cannibalization.

Cannibalization. Yes, probably I pretended not to hear that because I don't answer it. It's -- we can't. I cannot answer it. It's impossible. We even -- we try internally, but we cannot. We see in Europe that once we introduced the antibiotic eluting product, it became immediately the first choice therapy for the surgeons. What it will be in the U.S., I don't want to speculate in.

A follow-up on that. Is there anything in the U.S. market that would tell you that it wouldn't look like it does in Europe where 85% of sales is CERAMENT G.? What -- maybe it's for Mike to, I don't know, to answer.

Mike, would you like to answer it?

If you will see that it's going to be 85% of sales in the U.S.? Or is this something in the U.S. that is different?

I think our experience is going to follow the European experience. It's just that the European experience started with CERAMENT G, and we had to -- we didn't have that product so we had to sell CERAMENT. Now you're going to see somewhat of a reversal, I think, over time in that we'll be selling a lot more CERAMENT G, than CERAMENT. But if I could just address cannibalization just for a second, we're going to experience some cannibalization, but in and up that, it will be at a higher price point. So it's an interesting dynamic, and we're just going to have to see how that plays out. But I think we're in a position of strength regardless.

I can look at it from -- if you try to use Europe as a proxy, we have reached 8% market share in about 8 years. But we didn't have any NTAP, we didn't have the penetration. We don't have the same kind of sales and marketing infrastructure that we do now that we have built, meticulously since 2018 in the U.S. So I think there are a lot of factors you have to weigh in.

Follow up on the previous question about GPOs, and what you have access to. Now is supposed to say if you look at the current BVF sales, how much of that comes from hospitals under the GPO contracts that you have now been able to confirm?

The only data that we have released in that based on our assumption is that about 70% to 75% of the orthopedic industry is controlled by the orthopedic product used is controlled by GPOs. And there's no reason to believe it's different for us.

Talking about the European versus the U.S. experience of launching CERAMENT G. What are your key arguments why the uptake would be considerably greater in the U.S. versus Europe versus BVF?

Versus BVF you mean?

Well, versus the nondrug non-antibiotic.

So first of all, I mean, you have to tell me if I'm answering your question correctly, now, but in the U.S. I think what you've seen since we went independent is a formidable growth in the U.S. despite COVID and how we have increased the presence of BVF. And I would say the biggest contributing factor is the NTAP in the U.S., which doesn't exist. There's a financial incentive actually to go to a more progressive product. The other is there's only one. CERAMENT G is the only product available. There are options in Europe, PMMA beads, even though we saw that they are somewhat inferior in therapy. But in the U.S., there are no other products on label, but everything is off-label mixing, which has a different dimension in terms of liabilities.

I just had a question regarding cost inflation, if you could say something more about that. You mentioned this U.S. booster program, and that was like 8 million, and I think it's 3% of your cost base. So that doesn't sound much compared to the growth you're targeting, but I mean other inflation and planned investments in the organization.

Håkan?

Well, again, a, I think that, as also mentioned in previous meetings and presentations, we expect a relatively firm and stable cost base going forward. Saying that like with the user U.S. Booster program, if we see that we can accelerate and we see chances to accelerate sales, we will take that chance. And that's also one of the reasons why we're not expressing somehow a firm date on when we'll be profitable because we don't want us to miss out of those chances. And we have, as you've seen, the financial platform to do that. So -- but in general, we don't expect any large investments. It will be like a U.S. Booster program.

But I actually think that is quite strange. You have this fantastic product. Why not just go out and sell it and employ 50 people. Why did you end up with 7 full-time employees?

No, you shouldn't look at it like that. The equation -- the right way to look at it is our expenses are over 100% of sales. The 3% is a booster on already boosting, boosting, boosting. We are already there with a massive force. We're paying also 30% commission, which is a very nice incentive. That's why we have such a strong sales team. So it's on top. It's a cream of the cream. That's how to view it.

Okay. One last question, please.

I have a follow-up on the NTAP. I mean, that's obviously going to be important for the next 2 and hopefully, 3 years, but then see if you get a label extension into trauma, does that allow you to extend that NTAP or sort of renew it in some sense?

Yes. That's correct. The NTAP is indication specific.

Okay, good. But then now obviously allows you to -- you don't have to give much rebates considering the NTAP now, that's such a big part of your reimbursement. But do you expect to give any significantly higher rebates once the NTAP expires?

Actually, no. Because we believe that the strength of the product will more than justify that price even without the NTAP. And they end up, we see it is just a way for us to have 2 years to show that, to show also the health economic benefits. We have several of those running in the U.S. to be ready well in advance before the NTAP tap expires.

So thank you very much. We're a bit behind schedule, but Emil and Håkan will be around afterwards. But thank you for today.

Thanks, everyone, for coming.

Thank you.