Good afternoon, welcome to Gothenburg for those who braved the elements and came here inside. A big welcome to those of you who are listening in on the live broadcast. This is a very special day. It's the inaugural Capital Markets Day for XVIVO. Today, you will learn about operations, gain clinical insights, and also learn about the strategic roadmap for XVIVO during the coming years. My name is Lars Frick. I'm a journalist at Tidningen Börsveckan, and I will be moderator here today. The Capital Markets Day will be hosted by management from XVIVO as well as clinical partners who will participate. It will be broadcast live, and for those of us who join on the internet, you can ask questions too. Just use the Q&A field, which is below the screen on your browser, and then I will forward these during the Q&A sessions.
On a practical note, today is divided into three main areas. First of all, it's the economic side of operations with markets, trends, strategy, and health economics. After that, there will be a Q&A session. For those of you who are present here, just raise your hand, say your name and your organization, and then we will pick it up with a mic. After the Q&A session, there is a 15-minute break, and then we move into the middle part of the CMD, where we will hear more about heart and abdominal, the new areas here for XVIVO. There's another Q&A session, a break, and in the final part, we will focus on the current core business, the lung business, and also gain some insights into the future of transplantation. With that, I would like to introduce the CEO of XVIVO, Dag Andersson. Welcome.
Thank you very much, Lars, for an excellent introduction. Welcome all to GoCo Arena, which is a location where we are at right now. This is going to be the leading life science cluster in Sweden in the coming years. Why do we organize a Capital Markets Day? Lars touched upon it. First of all, I would like, of course, to introduce the management to you all. Secondly, I would like to tell our story and why XVIVO is a company to invest in. Thirdly, but not least, our strategic roadmap, which will be presented during the afternoon. Starting by introducing the management team. I will start with Johan Holmström, Chief Commercial Officer. He is accountable for ensuring that we sell enough products at the right price, to make it very simple. He has a background from Mölnlycke and from Permobil.
Charlotte Walldal, Global Head of R&D, accountable for our exciting R&D portfolio. Background from leading positions within R&D at Essity. Katrin Gisselfäl t, Global Head of RA QA. Has worked a couple of years at XVIVO, and previous experience from QA, RA at ABIGO Medical and R&D at Art Implant. Andreas Wallinder, Chief Medical Officer. Started in his position approximately at the same time as I joined the company in May, June last year. Previously, cardiothoracic surgeon at Sahlgrenska and Alfred Health in Melbourne. Christoffer Rosenblad, Chief Operating Officer and Head of Bus Dev. Been with the company nine years and served as a CFO until end of last year. The young person on the block, so to say, Kristoffer Nordström, CFO. Also worked a couple of years at XVIVO and CFO since end of last year.
We have Rodney Jones, General Manager, North America, who has traveled all the way to participate in today's Capital Markets Day. We also have Arjan van der Plaats, Global Head of R&D Abdominal, meaning kidney and liver, who has joined us from traveling up from Groningen, Netherlands to be here today. Welcome all, and I will start off by talking a little bit about the need for transplantation. Only 10% of the total need of organs are transplanted in a year. 160,000 versus 1.6 million needed. Why is it like this? Well, there are two reasons. Number one is that the number of organs donated is far too low. By the way, hand on heart, how many of you are registered as organ donors or live in a country where the opt-out model is applied?
I'm not going to ask you to raise the hands, but ask yourself that question. Second reason for the low unmet need, so to say, is the organ utilization. It's very low. Many organs are wasted, and we will talk about this later on and explain what we can do to solve this problem. In the U.S. alone, 150,000 people are waiting for a new organ. Even worse, 25% die while they are waiting for a new lung or heart. Every 10 minutes, a person is added to the waiting list.
Just to give you perspective of what it means to be on the waiting list, the median waiting time for an individual's first kidney transplant is 3.6 years. The good thing with kidneys is that once you reach what is referred to as the end-stage renal disease, there is the option of dialysis, but it's costly and does not make your life very easy. The average wait for lung transplant in the U.K. is 18 months. 18 months of suffering, of anxiety. Now it is time for you to meet a patient, and not just any patient, but a patient we know. Bea, this is your story.
It was 11:30 when the call came. The nurse asked me if I was ready. It was time.
Did you know that more than 150,000 organ transplants are performed every year around the world? Still, thousands of patients die while waiting for a new organ. This is due to a worldwide shortage of organs for transplantation, but also because of many organs that could save lives go unused. At XVIVO, we believe in an extended life of organs. By collaborating with the best scientists and clinicians in the world, we push boundaries to extend horizons in transplantation. XVIVO's technology for preservation, assessment, and transport of donor organs ensures safe use of more organs and gives more people the chance of a life-saving transplant. With our flexible solutions, we help transplant teams to succeed in what they do best, saving lives. Our offering covers technology for all organs and defines new standards in life-extending technologies.
With more than 20 years of experience, XVIVO are the forerunners of the transplant industry. We are research-driven. We are customer-centric. We are collaborative, and we have a strong purpose.
Our driving force is that we believe in an extended life of organs, because nobody should die waiting for a new organ.
When you felt sick for as long as I have, you don't long for big and amazing things. When you long for an everyday life. To be able to work a whole day, and then to have the strength to do something nice in the evening, right? Have a dinner with my family or just walking the dog. That's exactly what I've been longing for, and I love it.
Every time I watch this movie, I'm very touched, actually. Bea is 23 years old. She lives in Lund, south Sweden. Three years ago, she received her first pair of new lungs. Unfortunately, they are no longer working, and she's on the waiting list for a new pair of lungs. Bea, a young person who just wants to live a normal life and who deserves to be given the opportunity to do so. At XVIVO, we believe in an extended life of organs. Nobody should die waiting for a new organ. This is our purpose. This is XVIVO. XVIVO was founded 23 years ago here in Gothenburg, where the head office sits. Listed on Nasdaq Mid Cap since 2016. 6,627 shareholders, lost count, including several pension funds.
I dare to say that our large shareholders, many of them present here today, have a long-term perspective on their shareholding, which somehow shows the faith they have in the company and in our future. XVIVO is a so-called all-organ company, and we address all major organs with the exception of pancreas. We became an all-organ company October 1st last year when we acquired the Dutch company, OrganAssist, providing unique technologies for kidney and liver transplants. Addressing all organs means that we provide advanced machines and solutions for the preservation and/or evaluation of these organs. As you can see from the picture here, kidney is the most transplanted organ in the world. One reason for this is that end-stage renal disease has become an incredibly critical chronic disease as more and more patients around the world end up on dialysis if they are not successful in receiving a new kidney.
There are today more than 4 million people on dialysis. You can imagine the unmet need for a new kidney. Liver is the second most transplanted organ. Lung and heart make up together 10% of all organs transplanted. Our technology saves organs so that others can save lives. This is a strong statement. What it actually says is that it takes lives to save lives. What is it that XVIVO does to actually save lives? We increase the availability of organs with our technology. We improve the preservation of organs once they have been removed from donor body and during transplantation to the transplant hospital. Our unique technology improves organ functionality and consequently the survival of organs. The key is to ensure that new organs function for as long as possible in the recipient body.
A transplanted kidney lasts on average 10 to 12 years. You can do, of course, several kidney transplants during your life. This was the introduction. I will now talk a little bit about the market and the key trends on the market. I mentioned in my introduction that only 10% of the need of organs is transplanted, and that the reason for this is lack of enough organ donors and poor utilization of organs. Starting with lungs, how many donated lungs do you actually believe are today successfully transplanted? Not many. 20%. One in five. 80% are wasted. The utilization rate for heart is not much better. 30%, less than one in three. Kidney, better, but 1/3 of all kidneys wasted. Liver, approximately the same. A third of all liver is also wasted.
Today, most organs are donated by patients whose death has been confirmed using neurological criteria, also known as brain death or DBD. There is low or no use of organs donated by patients whose death is diagnosed and confirmed using cardiorespiratory criteria, referred to as DCD. It is, of course, more challenging to identify suitable DCD donors, hence the very low use of DCD organs, particularly in thoracic transplantations. Organs do deteriorate after retrieval for both DBD and DCD patients. For natural reasons, organs are easier to assess for DBD donors, since this is a slower death process than DCD. Sounds a little bit brutal, but that's how it is. When it comes to the world and the future, we forecast that by 2030, equal amount of organs will be donated by patients whose death has been confirmed using cardiorespiratory criteria, DCD.
This will lead to more organs available for transplantation, provided that the organs can be transplanted. This is where machine perfusion, once again, is so critical. The more DCD organs, the more need for machine perfusion to evaluate the organs. Just as a side note, I'm sure that some of you are thinking here, Why does it say 39,000 donors when there are 160,000 transplants around the world? Well, one donor can do a lot. You can actually save eight lives. You have two kidneys. A liver can be split into two. You have two lungs, you have pancreas, and you have a heart. You can save eight lives. When it comes to XVIVO and the product range and assortment, we have a unique product range to preserve and perfuse organs.
This product range will be explained and described later on when we talk about the strategic focus areas. Just to show you the full range of products that we market today. When it comes to the key takeaways from market and trends, I would just like you to remember the following. Remember the shortage. Demand is 10 times higher than supply. Remember also that utilization of organs is incredibly critical. Only one in five lungs and less than one in three hearts today can be transplanted. Machine perfusion is proven to increase utilization. We have the widest, and I must say also the best, machine perfusion offering in the world. This was market and trends. Moving into the next section, strategy.
There have been some publications today related to XVIVO in Dagens Industri, the latest one that came this morning not the latest, second latest, actually. It stated in the press release that strategy is about making choices and about deliberately daring to be different. Always for us, considering our overall vision, that nobody should die waiting for a new organ. Talk a little bit about strategy for the coming five years. I just want to give you a little bit of a feeling for how we reasoned when we had our strategy workshop here in Gothenburg in August. One of the very few management books which has really inspired me is a book called From Good to Great. It was written by Jim Collins in 2001. Fantastic reading. If you haven't read it, read it.
In this book, Collins examines the performance over 40 years of 1,435 U.S. companies. Out of these 1,435 companies, only 11 were classified as great companies based on certain criteria, hence the title of the book, "From Good to Great." These 11 companies managed to take complexities and boil them down into simple, yet profound ideas. This was done by asking three very simple questions. one, what shall and can we be best in the world at? Second question, what are we actually passionate about? Third question, what is the economic denominator that best describes our economic engine? When we as a management team and some other members of the organization met in August to set the direction of our company, we concluded the following. Number one , what we can be best in the world at is machine perfusion.
Perfusing organs enables more organs to be successfully transplanted. Number two, our passion is to extend the horizons in transplantation. Remember Bea and the short movie we showed earlier. three, economic engine. Our economic engine is revenue per installed machine. The machines are installed to ensure that they are utilized to perfuse organs as often as possible. This is how we make money and will make even more money in the future. Summarizing our strategy on one single page, which can sometimes be a little bit difficult, just to give you an overall view picture, our purpose, as earlier mentioned, is that we believe in an extended life of organs. Nobody should die waiting for a new organ. Our strategic objective is to develop our position as a global leading all-organ company.
Our economic engine, which I mentioned as a global leader in machine perfusion, is to maximize revenue per installed machine. I will now very briefly touch upon the strategic focus areas, and they will be repeated by my colleagues and people invited here later on during the afternoon. Just to give you, let's say, a first feeling for the strategic focus areas. I will start with becoming global leader abdominal with initial focus on the U.S. Today, the U.S. is the largest transplant market in the world. We are global leader in lung transplantation, meaning that we sell machines, consumables, and solutions for the preservation and valuation of lungs. Strong position in the U.S., and we will now embark on the same journey for the abdominal organs, kidney and liver.
Starting with the unique Kidney Assist Transport, which will be launched end of this year once we have received the 510(k) clearance from FDA in the coming weeks. You will hear more about this exciting product and the go-to-market plans later today by Arjan van der Plaats and Johan Holmström. We have strengthened the commercial organization to make as much impact with this product from day one as possible. Just remember what I said earlier, 4 million dialysis patients around the world. In the U.S., between 700,000-800,000. The need for kidneys is consequently very high. Our transport device is absolutely unique and provides the best outcome for transplanted kidneys. We also have a liver perfusion device which will be launched once we have achieved FDA registration. A process which has commenced. Focus is now on kidney. Second one, second strategic focus area.
We have a game-changing heart preservation technology which will be commercialized 2024 in Europe. Our technology will transform heart transplantation. Clinical trials ongoing in Europe, where close to 45 patients have been included and new sites are being added as the interest in participation in this study is very high. U.S. trials will start first half next year. One of the challenges with heart transplantation today is that ischemic time is limited to four hours or less, meaning the time a heart can be outside a body. This makes it impossible for many hearts to be transplanted. That is why only 30% of donated hearts are transplanted. This is one strategic focus area. You will hear much more about this during the afternoon. Third one, we are focusing on increasing the penetration of machine perfusion. Remember the economic engine of XVIVO, revenue per machine installed.
Clinically, nobody is arguing against the very clear benefits of machine perfusion. The challenge with machine perfusion is that it adds time to the transplantation process. Rather than simply moving an organ from donor to recipient with highly uncertain outcome, machine perfusion provides the opportunity to evaluate and also restore organs. It takes time and adds cost. Therefore, we are working with organizations such as Lung Bioengineering in the U.S., which you will hear about later. We have a person participating digitally from Lung Bioengineering talking about the hub concept for perfusion. Digitalization is another area we are working with to predict the outcome of organ transplantation better. We have a pilot ongoing in the Netherlands in the new university medical hospital in Groningen. We will also soon launch a U.S. pilot. Number four, health economics, all-inclusive reimbursement.
Health economics is incredibly important to prove cost benefit in order to secure a good reimbursement rate. We are now actually making health economics part of our research projects. More and more countries are adding and/or increasing reimbursement for transplantation, and particularly so far, machine perfusion initiatives. You will hear more about this from Johan Holmström after the short strategy introduction. For an organ such as kidney, health economics is very easy, actually. A patient on dialysis in the U.S. costs approximately $80,000 per year. $80,000. A kidney transplant in the U.S. costs approximately $140,000. Payback can be quite easily calculated. Last but not least, China. China is today the second-largest transplant market in the world after the U.S. With 1.4 billion people in the country and rapidly growing need of new organs, China will eventually overtake the U.S. How long this will take? Hard to predict.
In China today, there is no reimbursement for transplantation at all. A kidney transplant at Jiahui International Hospital in Shanghai costs $62,000. A liver, $98,000, a lung, $170,000, and a new heart, $160,000. Not too many patients can afford this. Reimbursement will come. Our focus today is on securing regulatory approval for the key products we want to launch in China. We have a sales manager recruited, and we continue to reinforce the organization in China. This is the only strategic focus area which will not be further explored today, but this is a strategic focus area for us, and China will grow in importance. I would now like to hand over to Kristoffer. Are you ready to talk about financial targets and commit ourselves in front of this audience?
I am more than ready, Dag.
Great.
Thank you. Hi, everyone. As Dag mentioned in his introduction, I have been with the company for a couple of years now, four years. For me, and I think I speak for all of my colleagues as well, becoming an all-organ company in 2020 was a true paradigm shift. It was the beginning of a journey. I think that is a mindset that we should continue to have during this presentation and also during the day, that we are now taking steps on a very interesting journey. For the last 20 years, we have developed an expertise within lung transplantation, and we have actually created the market of lung preservation and lung evaluation. What we will do now is that we will take the experiences and the knowledge that we have from lung and transfer that into other organs as well.
For example, it's about delivering a profitable business model to other organs. It's about establishing a global market presence for other organs. Also very important, it's also to navigate in a strictly and a pretty complex regulatory environment that we have experience in. What is our business model, then? As Dag has mentioned earlier, we have an economic engine, very strong. Strong focus on machine perfusion. The leading KPI for us will be revenue per machine, because that is what it all boils down to for us. It's about to drive volumes of solutions, volumes of disposables. We have this so-called razor blade revenue model, meaning that we don't necessarily need to make money on our machines, but we need to get the machines out there and build a solid install base. We should offer flexible financing solutions for our customers.
If we take a little look at the historics of XVIVO in terms of sales growth, we have had a 21% sales growth up until 2029. That only includes lung sales, as you all know. That is driven by machine perfusion. 42% annual growth rate of machine perfusion, which is very strong coming from us introducing a new product to the market. Static preservation, meaning Perfadex, has more or less grown with the market, 6%-7% per year. Steady growth. How big is the transplant market? Well, that depends on how you define transplant market. Is it pre-care, aftercare? Is it xenotransplantation, et cetera? That's not really easy.
What we focus on here today is the potential market value of machine perfusion. By that we mean if all transplants today came from machine perfusion, if that was used on deceased donors, it would have been approximately $1.3 billion. That does not include machine sales, it's only sales per procedure. The potential is huge because today only 15% of that total potential market value is realized. We all know that the total market will grow with the number of transplants and machine perfusion will grow as the technique is adopted, more usage of DCD, et cetera. It's also interesting to look at the value split per organ of the market potential. Liver and heart, around 30% each. Lung and kidney, around 20% each.
If we look forward a bit in terms of ex vivo sales, our ambition and our strong belief is that our abdominal sales will equal the size of our thoracic sales in the end of the strategy period. That will be driven by our introductions of our new techniques on new markets. Sales by region will not differ that much compared to what we see today, but in monetary terms, we believe, as we have said, that Asia and China in specific will come. My final slide on financials today, profitability. We think it's important to send a message that we will have focusing very much on top line, of course, of sales, but we will do it in a conscious way, also focusing about our profitability. EBIT, 20% end of the strategy period, EBITDA, 30% at the end of the strategy period.
We will achieve that by delivering on our five strategic focus areas, and also keep a very high focus on pricing and our work with our gross margins. That will be very important. All this while we will continue to reinvest strongly in our R&D portfolio because that is what really will bring us to a very bright future. It's time to wrap up the strategy session and the financial ambitions, and I would like to invite Dag Andersson once again to do this. Here you go, Dag.
Thank you, Kristoffer. We have truly committed ourselves to deliver. Just to conclude, key takeaways. You have seen the five strategic focus areas, which will make us the leading all-organ company. We talked about machine perfusion. We'll talk more about that this afternoon. The revenue model for lungs will be applied to kidney, liver, and heart as well. Revenue per installed machine, and we have our profitability targets. This was the end of the strategy session.
Thank you very much, Dag, and thank you, Kristoffer, for your excellent presentation on markets and strategy. Now it's time to move into health economics and questions of reimbursement, where Johan Holmström, Chief Commercial Officer, will guide you. Welcome, Johan.
Thank you. Thank you, Dag. Dear audience, in this section, I will give you an overview of the activities which XVIVO is involved with when it comes to reimbursement and health economics. As you heard during Dag's introduction, the global organ shortage is a major challenge for healthcare today. Only 10% of the need for transplants are met today. Obviously, the health benefit from solving this is obviously very large. The waiting list situation is one indicator that we often talk about, and that is visible, but it actually fails to capture the true magnitude of organ shortage.
There was a study a couple of years ago that was published showing this. If you look on the graph to the right, you can see that there are more than 14 times people dying from end-stage organ disease than who are assigned to the waiting list every year, and this is U.S. only. When you translate this, it was the same conclusion from this study, the possibility to replace organs and tissues on demand, meeting supply with demand, will leave a health benefit on par with curing cancer. Quite fantastic, says something about the magnitude of the market that we are operating within. Obviously, health benefits is the driver to reimbursement. New technologies, products, et cetera. When you can show the health benefit versus the cost are the same, it's the driver to secure reimbursement. Clinical evidence is the foundation for this.
Something that XVIVO obviously have in our background for our products. What is also interesting is that all reimbursement today is on a national level. Very often, individual countries, particularly in Europe, want to do their own clinical investigations to make sure that they get the right clinical guidance for clinical practice, and in the next turn, being able to give the financial guidance that can conclude what kind of reimbursement level there is. This is, of course, extremely important for us as a company. XVIVO is directly or indirectly involved in a number of initiatives that will open up reimbursement in Europe for machine perfusion in particular. We will talk more about Europe, but just a few comments about the U.S., which you will hear more about later today, is that it is basically covered through what is called CMS, the Centers for Medicare & Medicaid Services, in combination with private insurance.
These also follow each other. The metrics which private insurance are setting are defined or very similar to the metrics which are defined by Medicare and Medicaid. In Asia and China, there is hardly any reimbursement today. It's out of pocket, most of it. In Europe, which is obviously a well-reimbursed market in general when it comes to healthcare, the intervention of transplantation as such is reimbursed. When it comes to utilizing new technologies like machine perfusion, it's only reimbursed in very few countries today. The market is about to open up against this. We see a very positive development today through the different initiatives which are ongoing today. France is one. You will hear more about that. Belgium, Netherlands, Germany, and the U.K.
Even more so, we had the opportunity to participate in end of August in Milan in a congress for the European Society for Organ Transplantation. What was very clear takeaway from that meeting is that the debate is not so much about the clinical value and the health benefit from using machine perfusion, which it probably was a few years ago. Today, the debate is about how do we secure funding for this? How do we make sure that money is fueled into this in Europe? In the U.K., a very positive announcement was made in May, where NICE, and NICE is the National Institute for Health and Care Excellence, they issued their recommendation when it comes to using ex vivo lung perfusion, EVLP, for preservation of lungs. You heard from Dag, waiting list up to 18 months in the U.K.
This was the kickstart for initiating the reimbursement process for EVLP in the U.K., where now in September, October, there will be a start of a national EVLP program in the U.K., which will be driven in a hub model. XVIVO is very much involved in this, and it will be our machine, XPS, and products that will be used for this. This will commence over a 12-month period, from which then the financial guidance will be met and the expected reimbursement to be defined in early 2023 latest. Most likely it will happen earlier than that. France is a very progressive case. It is one of the countries in Europe that has come the longest when it comes to machine perfusion. Both EVLP and machine perfusion for kidney is granted reimbursement already in France. When it comes to lungs, it was granted in 2019, and kidney a little bit earlier.
What's interesting here as well is that this was also demonstrated at the European Society for Organ Transplantation in Milan earlier this year, was that they have shown significant increase in available organs and improved transplant outcomes from this. Very, very positive. They were also showing very clearly how these have made savings to healthcare, particularly for kidney, and where post-transplant dialysis costs have gone down, and overall cost for renal services has gone down, whilst increasing number of transplants. It's a very good case for how reimbursement can be made in the area of machine perfusion. When it comes to liver in France, it is also, they say, on its way. XVIVO is well involved in this, in close collaboration, where Liver Assist, our machine perfusion machine for liver is used in what's called a HopeX trial. It's a multi-center with eight different centers today running this.
Timeline for when is not known yet, but it will come. Netherlands, we have some very positive news, the latest. Kidney machine perfusion was reimbursed successfully a couple of years ago. What we have learned also from our meeting in ESOT is that EVLP will now be granted full reimbursement from January 2022. Secondly, also liver machine perfusion will be granted full reimbursement from January 2022. France, the Netherlands are probably the most leading countries today in Europe when it comes to developing reimbursements. To wrap up and leave you with some takeaways from this session, I think the health economic benefit from increasing number of transplantations is very clear today, and it's something that will continue to increase. XVIVO as a company, we are supporting and are participating in a number of initiatives to drive reimbursement and funding to this field.
Clinical evidence, which is one of our strong points, is a key driver. Last but not least, which is something we think is very interesting, is that the clinical acceptance of machine perfusion is there. The debate is rather how do we secure more funding in Europe and European countries against this technology. Thank you.
Thank you very much, Johan. With this presentation on health economics, the first segment of the Capital Markets Day has been concluded. Now there is time for questions and answers. For those of you live, I remind you, just fill in the Q&A field below your screen in the browser. I will forward those questions. For those of you present here today, just raise your hand. You will get a mic. State your name, organization. We will take your question, too. Dag, at the core of the financial side in XVIVO, you mentioned revenue per machine as a key metric. Could you say something about what characterizes a good question or a good customer or a profitable customer? Is it mature centers with high volume, or maybe there's a regional difference?
No, there are certain centers, taking U.S. as an example, where hospitals such as Cleveland, for example, is using our XVIVO Lung Perfusion technology on a very frequent basis. That is, of course, an ideal customer. We want customers to use our products as much as possible. If we take the case of Cleveland, they actually have a success rate using our technology of 70% of the lungs actually transplanted, comparing with the 20%.
Right
If you don't use the technology. It's a very proven technology, and they love it, so they use it a lot. Sometimes you have an organ or a lung, which you can see from the beginning that we don't need to perfuse it's perfect condition. You don't have to apply the technology. Ideally, whenever there is some kind of uncertainty, you should use our technology. The answer is quite simple, Lars. We want our customers to use our machine perfusion technology as much as possible.
Yeah. Can you see a maturity thing there, that perhaps customers who get the first systems installed and that there is a learning curve, they learn to use it and appreciate it, and maybe that will, over time, extend into more cases per machine?
Absolutely. I think it has also to do with, at the end of the day, leadership and how hospitals are organized. If taking Cleveland as an example again, they have a specialized recovery team who flies out to collect the organs. They have a special perfusion team who uses our XVIVO Lung Perfusion technology, and they have the transplantation team. If you're well-organized, you know how to do things, you will of course do it also really well. Not all customers are like that, unfortunately. There are many hospitals in the world, which we all know that don't function that way. You need to have a certain organization and structure in place to reap the full benefit of machine perfusion technology.
Right. you need the infrastructure.
Absolutely
around it.
It helps.
It's a system.
It helps.
Kristoffer, we have a question from our online audience, which I think will be perfect for you. Peter Östling at Pareto Securities wants to know why you don't have a goal for sales, and perhaps you could expand a bit on your view on top-line growth during the strategy period 2022, 2026.
Thank you. Yeah, I know Peter, and he always has good questions. My first answer is that this is the first time we provide some guidance on our financial ambitions, and the strategy period is not over yet, so that might come. We are at the stage in the company now, as I said, Bill, on a journey where there are some very important milestones ahead of us as well that we're not fully in control of. We are in a very regulated environment, and for those reasons, we do not give any forecasts on sales at this moment, but it might come.
Right. Peter Östling has a follow-up question as well regarding the revenue per machine KPI. He wonders, is this something that you will share with the market in forthcoming quarterly reports?
Yeah. Initially, that is an internal KPI for us that we need to work and will focus very hard on internally. We will of course discuss that when we get answers, but to have that externally in our reporting, we're not there yet.
Right.
We're very clear that that is a key metrics for us.
We have a question from the audience. Please, name and organization.
Great. Thank you very much. Ulrik John at Carnegie. Just going back to the fundamentals, looking at the U.S. market, obviously the most established ones in terms of number of transplants and reimbursements, just give us your highlights on what's holding back the adoption and utilization. Looking at what you have done so far, obviously a good relationship with Cleveland Clinic, United Therapeutics, with Lung Bioengineering, do you believe that everything is in place right now to increase utilization, and we're now approaching a sort of tipping point, or what's holding back the adoption?
Right. I'll just repeat the question so it's clear for the live show as well. The question is, what's holding you back in the U.S.? Are there any factors that are limiting penetration, or do you see us coming closer to a tipping point where efforts such as in Cleveland could perhaps be an inflection point and a boost for sales and revenues there going forward?
It's a very good question, actually, Ulrik. If you look at ex vivo lung perfusion penetration globally, it is in the U.S. that we have the highest penetration of lung perfusion, whereas Europe is still far behind U.S. In the U.S., we have some very large customers, that's correct. We have Cleveland, we have Lung Bioengineering, which we'll listen to later on. We have a number of machines installed in the U.S., and we are talking about, I think, around 30 machines, around that. The potential is there to do much more than we do today. I think somehow we just have to work closer with the hospitals. Every hospital knows the benefits of this technology. That's not an issue, trying to explain that. We don't need to.
Financial reimbursement is there, and in the U.S., you get more money if you are successful with transplantation than if you fail with transplantation. Everything is there to make it work, Ulrik, and we are increasing penetration. If you look at historically, the way we have grown, Kristoffer, with ex vivo lung perfusion in the U.S., we are talking about very high growth rates.
Sure. Yeah.
Penetration is increasing, and we will just continue to do more work with all hospitals where we have machines installed today. Yes.
I think there's a follow-up question from Ulrik.
Yes, please. Thank you very much. Two questions, actually. One to Kristoffer and one to Johan. Perhaps start off, do you believe that your pricing model for the XPS system is sufficient or sort of cheap enough to penetrate the small markets or the small transplantation center markets, or is there a way around this to simplify these procedures or to sort of look at the leasing segment of this business? To Kristoffer, as you're not guiding on top line, but you're guiding on your margin profile, give us some clarification on what type of products are included and what type of research products that should be then concluded by 2026. Is this to be assumed a pure transplantation, i.e., as you might realize that I'm alluding to the PrimECC research program. Is that to have been concluded in 2026 in order to realize your margin targets?
Right. Two questions here, pricing in the U.S., and then a little bit of flavor on your targets here. Perhaps, Kristoffer, if you'd like to start.
I think I can start answering Ulrik. I start from the back.
Yeah
PrimECC, we definitely believe that there will be a launch within the strategy period. That is our ambition. To say, it's not taken in consideration, though, in the guidance on the profitability that we have guided on. Because we haven't really decided upon the price point, et cetera. That is beyond that. What was the last question? I don't remember.
Yeah, the pricing question.
Pricing was also on XPS.
Yeah, XPS.
XPS system.
Too expensive.
alternative.
Yeah. I think that is a question that Johan might-
Sure
answer.
Yeah. For the U.S. specifically and in general, I would say we are working with not just direct purchase of machines to the customers. Alternative models, like you mentioned, leasing options, price per intervention, et cetera, is something we have full flexibility for. When it comes to pricing, where there is no reimbursement, of course, the investment of a machine becomes a big investment, particularly in Europe. In the U.S., I think the game is completely different, or we know and we see something very different, where a lung transplant on its own is the most profitable intervention that a hospital can do in terms of reimbursement for it. In light of that and the investment of buying the machine and buying the consumables is not really the biggest hurdle that we see today.
As Dag also said, we are increasing our prices again now from first quarter four in the U.S. The buy-in to the concept when it's there, the cost hurdle is not the issue necessarily. There is a balance to that, of course.
Right. Were there any more questions from the audience? Yes. We have one on the right side. Mic is on the way.
Thank you so much. Mattias Häggblom, Handelsbanken. Two questions, please. DCD donors is expected to accelerate to 12% per year going forward from today's very low level or no use at all. It wasn't clear to me what's driving that and to what extent that's even more beneficial for you as a company. Secondly, on the five strategic pillars, which one of the five do you feel most comfortable in reaching, and which one is most out of your control, so to say?
Right. With regards to the five pillars, which one do you feel most comfortable with and which is perhaps the most stretched target?
It's also a very good question. I would say all strategic focus areas have to be ambitious. That's why you make a strategy. We believe that we can manage all of them. Some we are already doing a lot with today. For example, machine perfusion. We are in machine perfusion. It's about developing that further. We are working with health economics, but we will also do that in a different way. I would say the one which is probably the most challenging short term is China, because China doesn't have reimbursement today for organ transplants. That, of course, makes it challenging to sell in China. We are selling, and we have employed our first person. We have an office in China. I'm pretty certain that reimbursement will come in China.
As an example, reimbursement for dialysis was gained not long ago, and now they are sort of paying quite well for dialysis, and that's why suddenly there is 1 million dialysis patients in China. It will come. I would say that out of these five, it's probably China where we have to work with new models, which we haven't done too much in the past. That's my question or my answer back to you. Machine perfusion, we are doing it now, so it's evolution. China is new, even if we have taken a few initial steps.
Right. There was the question from Mattias Häggblom, regarding DCD.
Yes
It's going from virtually zero to also high.
It is also a very good question because if you take a DBD patient, when you die from brain death, it is a controlled process. You are in the hospital for quite a long time, typically. You slowly disappear. During that time, your organs can be monitored. That is why it has traditionally been so much easier to use organs coming from patients dying brain death. Some countries in Europe, strangely enough, Finland, our neighbor, and Germany, they are still forbidding DCD organs, which I find absolutely ridiculous. Sorry to say that, but that makes it hard to achieve your transplant targets. In the future, there will be more organs coming from patients dying circulatory death because there are more of those patients dying circulatory death. With our technology evaluating the organs, you can assess them, you can evaluate, and you can use them.
With traditional technology, it has been very difficult, and that is why it has been forbidden in a number of countries. It's opening up. Many countries have opened up to DCD organs.
Yeah.
Did that answer your question? Good.
I think Johan has a comment here as well.
Yeah, just to build on that, this is also what we see in France. We see that in Netherlands, and we see it in the U.S. Just the recent numbers we had on kidney, for example, where the growth of the transplant from DCD organs was up 15% year to date in August, in the U.S.
Following up a bit on that, Johan, looking at the European reimbursement landscape, it's very heterogeneous, with some countries obviously in the lead, like Netherlands and France, where some are lagging. Do you think that when one country in the EU moves towards reimbursements, that it puts pressure or at least gives some incentive for other nations to follow the lead? Or is it completely independent variables?
European countries, they look at each other. What's going on? If you take the issue of NICE guidelines in the U.K., for example, all countries are looking at NICE recommendations.
in the end, as one example. Of course there is a positive contamination
Yeah
cross border when it comes to reimbursement trends in this area. They learn from each other, and you see that also in congresses like ESOT, where we are participating.
Right.
There's a lot of cross-border exchange. Decision on reimbursement is national.
Yeah. Peter Östling from Pareto Securities would like to know more about the reimbursement situation in Germany. Can you comment on that, Johan?
I can comment. Germany is a little bit more behind many European countries. I actually was in Germany last week and met with one of the bigger hospitals in there. The quote, Of course, it will come. It will take some time. That's what they say. But it will come. We have to because we can't manage our situation without it. We also need to manage DCD organs over time. It will take some time. It's a different political situation in Germany as well in this area. Yeah, the hospital we were talking to, a very prominent, say, This will happen. It will take a little bit longer time.
Right. Kristoffer, even though you don't have a stated or formal revenue target, but could you say something about the revenue split during the coming strategic five-year plan, in terms of organic sales versus inorganic? Do you foresee any acquisitions? Is that part of the plan?
This strategy we have presented now does only contain our organic growth ambitions. I think it's a very short answer to that.
Right. Yeah, we have more questions from the audience. Please.
Yes. Thank you. Caroline Banér, Danske Bank. I was just wondering if you could share some color on the hub setup you're looking to launch in the U.K. Is this an opportunistic approach, or is it also something that you would have liked to seen regardless?
Could you please tell us some more about the hub?
Absolutely. It's something we definitely want to see. It's something, actually, it's part of our strategy to encourage as well. You will hear more from Lung Bioengineering later on. That you can say it's a hub model, where they are perfusing lungs for other hospitals. In the case of the U.K., it was actually on the initiative in that, I believe it's Harefield who will be the lead and where they will become the hub for perfusing lungs for a set of different hospital. I will not go into each of them, but it's a group of three or four hospitals during this first 12 months period, where they will do their clinical evaluation of it.
In the end, when you look at EVLP and lung perfusion, it's something we believe is a very good setup to go for, because you also get the critical volumes of lungs into it and that learning curve that needs to be from both our side as a company, as well as the clinical side of it. U.S., it's been proven very successful. Yeah. Hope that answers. We see it very positively.
Another question that I'm interested in. In the presentation, you talk about forward integration as part of the plan within machine perfusion. Could you say some more about what that entails? Is it sort of moving into services related to the machines, or?
There are many aspects of that. We believe that we need to make life easier for our customers in many cases. As I said during the presentation, it adds extra work for hospitals to perfuse organs compared with the traditional old, call it ice box technology. If there are ways that we can cooperate with companies, logistic companies, service providers, team up with them to maybe in the future then create an offering which will make it easier for our customers to perfuse more organs. Forward integration in terms of cooperation with other entities, definitely. We are looking at that all the time to see what are these opportunities, especially on the U.S. market right now. It will, of course, even also impact other countries around the globe.
Right. Thank you very much, Dag. Thank you, Kristoffer, and thank you, Johan. Unfortunately, that's all the time we have for this Q&A session. Now there is a short break. Please join us again in 15 minutes. Thank you.
[Break]
Back to XVIVO Capital Markets Day 2021. It's time for the second segment of today's presentations, where the heart and abdominal therapeutic areas will be presented. Starting off with heart, Chief Medical Officer Andreas Wallinder will guide you now. Welcome, Andreas.
Thank you. Dear audience, dear listeners, the next 30 minutes we're going to spend talking about heart transplantation, XVIVO's heart preservation technology, and the early experiences from users of this technology. First, some key facts. The annual global number of heart transplantations being performed is around 8,600, and we have about 350 centers globally performing heart transplantation. The organ utilization rate, as been mentioned now a couple of times, is low. Three out of 10 donor hearts are eventually being used for transplantation. The main market challenges are a growing need for heart transplantation, and that will require use of DCD hearts, and also that the transport time, meaning the time that a donor heart can be without circulation, is limited today, and that puts restrictions on how many and how far you can go with a donor heart.
Before we get into the heart transplantations as such, I want to spend a slide talking about the underlying disease of heart failure. Heart failure is describing the condition when the heart is not doing its job properly, meaning not pumping enough blood to supply the organs with oxygen and nutrients. Heart failure is a chronic illness, and once diagnosed, the medium survival expected is often around two years. Once heart failure progresses into the final stages, the patients, they have an extremely poor quality of life, and actually the medium survival at that stage is comparable to many of the most aggressive cancers, between six and 12 months. Heart disease is a leading cause of death globally. Around 25% of deaths are attributed to heart disease.
As an example, me, a white male in the mid-40s, my life risk of being diagnosed with heart failure is around 30%. At the final stages of heart failure, transplantation is a life-saving and prolonging treatment, but it's just available for a very small minority of all people or patients that have developed heart failure. Looking at heart transplantation today, this is data presented by the ISHLT, the International Society of Heart and Lung Transplantation. As you can see, the number here is different from the 8,600 that I just mentioned. This is the largest organization that collects and reports data from heart transplantation. This and the following slides will be based on data from this organization.
The last couple of years, an increase in the number of heart transplantations performed, and as you can see, that increase mainly consists of increased activity in the U.S. Heart transplantation relies on the altruistic gift of someone, the gift of an organ, in this case, a heart. The heart donor and the heart recipient, they are located most often in different hospitals, in different cities, in different regions, or even in different countries. The transport of the donor heart between the donor and the recipient site is critical. The time is critical for the result or the outcome after heart transplantation. Today, before explanted, the donor heart needs to be flushed with a cold solution that arrests the activity of the heart, cools it down, and allow for low metabolic activity during transport.
Today, as during the last 50 years, which is actually the full history of heart transplantation, hearts have been transported in cold solution in plastic bags on ice. Once the heart is arrested, and the absence of circulation, nutritions, and oxygen, that induces a progressive degradation of the tissue of the heart, and we call this ischemic injury. When the heart is restarted in the recipient, the extent of that ischemic injury will be reflected in the performance of the heart and eventually the outcome for the recipient. The impact of this ischemic time. On the x-axis here, we have the ischemic time in hours, and on the y-axis, the risk or hazard ratio of mortality at one year. What you can see here, when we move from three hours to five hours, we actually increase the risk of death at one year with almost 50%.
This graph looks very similar to the first one. Here, instead of ischemic time, we have age on the x-axis. This corresponding risk increase, about 50%, you achieve by moving from a donor age of 35 to about 50. Taken together, each hour of ischemic time we add to the donor heart adds 10 years of age to the donor heart. This is a critical thing. This also restricts how far you can travel to collect a donor heart. Here, displayed as Sweden or Gothenburg being the center of the picture. For a transplant center in Gothenburg, the area of uptake or the potential travel time restricts us to use donors from Northern Europe or Middle Europe. Just an extension, a safe extension of to 6 hour, would allow us to go much further for collecting donor hearts.
This will allow for optimal allocation and matching between donors and recipients, but also extend the number of available donor hearts for people on the waiting list. Already short ischemic times have impact on outcome. Failure of the transplanted heart is actually the leading cause of death during the first 30 days after transplant. This injury is caused, again, by the time the heart has been preserved on ice during transport. To summarize, the challenges in donor heart preservation is the ischemic injury to the donor heart during transport on ice is causing, and that translates into poor function after transplantation, it is the limited ischemic time allowed, ideally below four hours. This is one of the reasons why surgical teams still turn down about 70% of available donor hearts.
A better preservation technology could improve post-transplant outcome, but also increase use of donor hearts from on further distances. Professor Stig Steen in Lund, he recognized this problem almost 30 years ago. He started to develop something else. He wanted to move away from the ice box or even the ice age into something new. Piece by piece, he developed a new technology that eventually became a continuous perfusion of the donor heart during transport, with a tailored or special solution for this purpose and the continuous supply of oxygen. This is what we now call a non-ischemic heart preservation. A large number of preclinical publications have proven the benefit of this technology. It's demonstrated that the reduced ischemic injury during transport translates into better organ quality after transplant.
In a very extreme experiment a couple of years ago, this technology provided evidence that hearts can be preserved up to 24 hours outside of the body and then successfully transplanted. This technology also, for the first time, allowed successful transplantation and long-term survival in xenotransplantation, meaning transplantation between species, and we will hear more about this later during this afternoon. This is the sort of prototype that came out of the research at Igelösa on the left-hand side, needless to say. This is on the right-hand side what the product looks like today. The technology, again, creates an optimal environment by continuously providing critical substances and oxygen to the heart during the transport. It's got three components, a device or the machine, a portable device that is used for the preservation.
It's got the solution, a specially tailored solution for this purpose that is then again oxygenated, and then it's disposable. A single-use set is installed and connected to the heart machine. After a long preclinical phase exploring and refining this technology, the first-in-human experience was published in 2020. This came from Skåne University Hospital in Lund and described the first nine patients that were transplanted with hearts using this technology. A control group from the same center and the same time period was used. What we can see here is during the first six months of observation, that we had a full 100% survival in the group transplanted with hearts from this technology, and then no major outcome related to graft failure. The recruitment is still ongoing for this study. In parallel, a group in Melbourne in Australia have started to look into the extended ischemic times.
Remember the graph I showed you a couple of slides ago, the risk increasing when you move above three hours. This group already now have started to explore the effect of using hearts preserved with this technology for between six and eight hours. The first hearts with extended time have been transplanted successfully in this trial, and we will definitely hear more about that. Over to the ex vivo sponsored studies. The 2 previously mentioned studies from Lund and from Australia, they use the ex vivo technology, although they are run by investigators. XVIVO sponsored studies. Currently, we have a multi-center trial in the EU ongoing. We will hear more about that. We are currently recruiting at six sites, and we are investigating hearts within the normal transport span up to six hours.
In the U.S., we are in ongoing discussions with the FDA and in preparations for an IDE submission later this year. We do additional pre-clinical testing, actually today we perform transplant studies at Igelösa in the south of Sweden. We aim to have this submission to the FDA end of this year to start the study during the next year. To sum up, the key takeaways from heart is that XVIVO's technology have absolute potential to change how we see heart preservation today. We think we can improve the outcome of the heart transplantation by replacing what we have today, heart in an ice box, with a technical solution, giving perfusion to the heart during transport with an oxygenated solution.
We can safely extend the time a donor heart can be outside of the body and with that allow for long distance transport, for better allocation of donor hearts, and very importantly for surgeons, remove some of the pressure that is always there with the time limitation that they work against. Also increase the utilization of donor hearts by moving into extended criteria hearts and also with longer distances. With this slide, I'll introduce the next speaker, and that is Professor Filip Rega from the University Hospitals Leuven. Filip is a cardiac surgeon and also the principal investigator of XVIVO's EU trial. Over to you, Filip.
Thank you, Andreas. Welcome everyone. My relation with Stig Steen goes back 20 years ago. I was a research fellow in Leuven in the laboratory, working on how to extend the preservation interval during lung transplantation. I had to fly to Lund in order to find out what Stig was doing and to bring it back and made research on it. It ended in my PhD presentation in 2003. You see here on your right-hand side the acknowledgements. I owe a lot of credit to the knowledge that I learned from Stig Steen. Leuven is a small medieval town, quite close to Brussels, 20 minute drive, only 100,000 inhabitants, but a 2,200-bed hospital. We do about 30 heart transplants a year. On your left-hand side, you see a diagram of the International Society for Heart and Lung Transplantation depicting the number of transplants performed per center.
Then you see that actually most centers only perform between 10 and 19 transplants per year. Once you go above 20, you reach a lower number of transplants. We reconnected with Stig Steen's research group in 2018. Also in Belgium, we have this problem of an important donor organ shortage, and we wanted to extend to the so-called donors after circulatory death, DCD donors. Here you see two of our research fellows, Vincent Vanzoele and Katrien Vandendriessche. The main reason to go in communication with Steen was how to evaluate heart function in these new type of donors. It resulted in the onset of the initiation of a successful clinical program, and earlier this year, we were able to publish our first few cases.
Going back to non-ischemic heart preservation, of course, when we arrived in 2018 in Sweden, we learned about how far they were with machine perfusion and heart preservation. Standard cold storage was the standard method, as Andreas alluded to, for more than 50 years. We flushed a heart and stored it on ice and never thought about it, whether it was a good way or a bad way. There are important limitations to this preservation. This, again, is a slide from the International Society for Heart and Lung Transplantation depicting the outcome survival at one year in relation to ischemic time. You see it starts to inch up somewhere between 180-210 minutes. These are data from 2007. Did we change something over the past decade? On your right lower hand side, the data from 2018.
Also here, survival comes down or the risk to die increases once you arrive at three and a half hours. We didn't change anything. By storing a heart on ice, there's absolutely no possibility to assess the heart function. Of course, since it's a static procedure, there is no opportunity for organ repair. We were in need in the clinical field to extend the possibilities of our preservation protocol. Over the past 20 years, Professor Stig Steen came out with always small pieces of the puzzle on how to preserve the heart in the ideal way. There was the reasoning behind the temperature. There's an optimal low temperature to preserve the heart, which is probably somewhere between eight and 10 degrees.
Secondly, there is the reperfusion solution, which is basically an extracellular type of solution with a high oncotic pressure based upon albumin and a low hematocrit. As Andreas alluded to, it eventually led to a publication where Steen was able, in animals, to preserve hearts and successfully transplant them afterwards with a preservation interval of 24 hours. This led to the onset of the first-in-human trial by the Lund people, and now initiated in the end of 2020, the EU-CE Mark trial. This is an open-label trial, randomized, and we plan to include 202 patients, 101 standard cold storage preservations, and 101 machine perfused hearts. The primary endpoint is outcome at 30 days. It is a composite endpoint consisting of death, the use of ECMO, primary graft dysfunction, and acute rejection. The secondary endpoint is more or less a similar composite endpoint, but then looking at one year.
If you look to the milestones of our own center, we submitted the research file, the clinical trial file in June 2019, and we finished all of our administration by June 2020. June 20, the first patient signed the first informed consent document. Also in Belgium, our clinical activity was importantly impacted by COVID-19, so our transplant activity only restarted in September 2020, being able to include our first patient on November 25. These are some pictures reflecting the emotions in the night of the 25th. You recognize on the left-hand side how we mounted the heart on the cannula and on the machine. On the pictures with the persons, you might recognize me. In the middle is Karlien Degezelle, the chief of our perfusion, and Michiel Marijnissen, our Senior Resident.
On the picture, probably a bit too small for you, but you can recognize Katrien Vandendriessche, our research fellow, assisting Stig Steen in Igelösa, Lund, Sweden. You can start video number one. This is what happens when you come off bypass, cardiopulmonary bypass. Normally, if the video starts, video number one, then you see a very enthusiastic heart. On your right-hand side, this is the echo, and I can assure you both ventricles did perfectly fine. If you're able to start video number three now, then you see the heart function. This is the left-hand picture of the heart at 1 month. Perhaps a bit of pericardial fluid. Patient, by the way, being at home. Then the right-hand side is an echo with myocardial function, video number four, at three months, and you cannot recognize the difference between this heart and a normal heart.
Where are we now? Well, we included 14 patients. Six of them were randomized in the machine perfusion group. Seven are randomized to control. In one patient, we only found out during the preservation with the people being on site that the donor was operated in the chest as a child, and this is an exclusion criteria to be included in the trial. I mention here, actually, we only have one refusal of a patient, and actually we were still in communication. They didn't sign the informed consent. That means that all of the patients on the waiting list eligible for a heart transplant did sign their informed consent. In Europe now, six centers are actively including patients. The three first were Leuven, Gothenburg, and Paris. Later on, Munich, Madrid, and Berlin followed. Actually, if I'm informed well, Bad Oeynhausen has actually finished all of the administration.
Heidelberg, almost the same. Newcastle, Birmingham, Bordeaux, and Padova will follow soon. By now, we have close to a bit more than 40 patients included. That means that in September, we reached officially our 20% milestone, and we plan to conclude the trial. The last inclusion is expected to be in December 2022. What are the potential benefits? Of course, we have no access to the trial data. This is simply an emotional expression of what we observe. What you see here is a text, a WhatsApp, written by Steffen Rex, which is one of our most senior cardiac anesthetists who was on call last Friday to Saturday. I received it, as you can see, 9:00 A.M. You probably do not all understand Dutch, but this is a translation. XVIVO heart was again terrific.
Even with severe pulmonary hypertension in recipient, no real problems." I leave open between brackets, but this is what he said, Also thanks to top anesthesia, of course. What are other long-term benefits? Well, you see them summarized over here, going from graft outcome to expanding the type of donors we use. Looking at graft outcome, and this is on your right upper hand slide, you see one of the molecular or biochemical data from the first in-man trial, looking at enzymes that are released when myocardial cells die. They were much lower in the machine perfusion group versus the standard cold storage, and this with only a low number of included patients. It's probably not really on its place here, but sometimes patients with end-stage heart disease are helped out with a mechanical support device. Now we're almost at re-implanting so-called third generation devices.
Result of research going on for more than 30 years. I can assure you that neither the life quality or the life expectancy comes close to the quality of life and the survival after transplantation. What about logistics? Imagine that we can preserve a heart for 24 hours. Imagine we can even do it longer. It means a lot of opportunities to optimally match the donor versus the recipient. It means that the atmosphere in our OR and with our transplant coordinators will really slow down to a much nicer and workable pace. Also much more difficult patients can be enlisted for heart transplantation, patients that are on a mechanical support device.
We expect that the number of patients with congenital heart disease that have been operated two, three, four, even five to six times, where you expect a very long explantation time, well, with machine perfusion, we think we have an option for them, too. What about other types of donors? Well, this opens the door to use donors from so-called marginal donors, marginal quality, but also, and it has been mentioned previously, so-called donors after circulatory death, where you take out the heart and you can place it on the machine. With this, I hope I can conclude my slide and I conclude my presentation. Thank you for your attention.
Thank you very much for an enlightening section here on heart, where Professor Filip Rega gave us some real insights and some films as well. It's time to move on in the schedule and in the body. We're happy to welcome Arjan van der Plaats, who is Region R&D Director, who will talk about the abdominal product line and the U.S. go-to-market. Welcome, Arjan.
Thank you, Lars Frick. Dear audience, now I think it's time that indeed we continue with our journey and we leave the thorax for what it is right now, and we move our focus towards the abdominal area, where we can find our liver and our two kidneys. In contrast, basically to the heart, we have a fairly high amount of transplantations in the abdominal area. With 62,000 kidneys and 28,000 livers transplanted worldwide each year. Even though, as Dag Andersson mentioned before, the utilization rate is quite high. It's more than 60%. Still, we have the challenge that there's a big gap between the demand and supply of donor organs. That forces basically the surgeons to use more and more the lower quality DCD organs.
To support that, XVIVO, especially since the acquisition of Organ Assist last year, we have now placed in the market devices for liver and for kidney transplantation, and even second-generation devices already underway. Focusing on that abdominal product line, what we then have is for kidney, we have the Kidney Assist Transport to optimally preserve the kidney during transport. We do that by cold oxygenated perfusion. Basically, as I said, the entire period between taking the organ out of the donor during transport, all the way towards the recipient. On the other side, for liver, we have the Liver Assist, which is a platform that can also provide cold oxygenated perfusion, but on the other hand, also can do warm perfusion for evaluation of the liver. In contrast to the Kidney Assist, the Liver Assist is basically a stationary device that is used in the recipient hospital and not during transport.
Zooming in then further into the Kidney Assist Transport, what we then basically see is that the concept is not that different than the concept of the heart system, as was just now presented by Andreas. We also have a device with a single-use perfusion set, and with that, we pump solution through the organ, in this case, a kidney. We cool the machine by ice, and by that way, we have cold perfusion. Additional benefit of our systems is the oxygenation. Same as in the heart, we really believe that it is beneficial also in the cold to have full and active oxygenation of the solution. By that, we have made now a machine that can preserve kidneys better during the transportation phase. Literature tells us that cold perfusion, even without oxygen, is already beneficial compared to cold storage for all donor types.
We see that in a less injury of the kidney, but also an improved graft survival. If we then add the oxygen, what is our specific feature, we see that these results are even better than without oxygen. We have a better function, we have a higher survival rate, and we have less complications. These conclusions we can take from a very nice multinational clinical trial that was led by Professor Ploeg from Oxford, and that was published in the prestigious Lancet at the end of last year. What we did in that study is we compared standard machine perfusion, so cold machine perfusion without oxygen, with cold machine perfusion with oxygen. We could really study the effect of the oxygen. Both groups were perfused in the Kidney Assist Transport first generation. A nice feature of this study is that it was completely blinded.
For the perfusionist, the person operating the device, but also the surgeon, the donor surgeon, but also the recipient surgeon, were completely unaware if the oxygen tank was filled or not. It was completely blinded for the whole team involved. We included for that 106 kidney pairs originating from donation after circulatory death donors with age 50 or higher, which basically is about 80% of the DCD population. That gives us another nice element of the study. As you see, we have a paired design, meaning that since we have the two kidneys in one donor, we could have one kidney randomized to non-oxygenated perfusion and the other kidney to oxygenated perfusion. That paired design was all the way through the analysis. That gave us a very nice insight in the effect of oxygen.
What we saw is that we improved kidney function, but more importantly, we drastically reduced the graft failure by more than 70%, and that's an enormous result. That was mainly due, we think, by the fact that we have a major reduction in rejection of the kidney. That's rejection of the kidney after transplantation purely by the oxygen. In conclusion, we can say there that our Kidney Assist Transport machine providing cold oxygenated perfusion is really beneficial for the kidney during transport, and it brings us more towards our mission to have an extended life of kidneys, and in this case, DCD kidneys. Same concept we have developed for liver, where we have the Liver Assist in cold oxygenated perfusion, but only, as I said, in the recipient hospital itself.
What we see here from literature is that indeed this process gives us a lower injury of the liver, and that leads again to patient benefits like a reduced length of stay in hospital after transplantation, but also an increased graft survival and even an increased patient survival. Very nice clinical data there gathered by the team of Professor Robert Porte in Groningen in a multinational study, again, comparing static cold storage. That's the standard of care in liver preservation. We compare that to static cold storage, but then followed by a short period of only two hours of cold oxygenated machine perfusion prior to transplantation. For that, we included 156 livers also originating from the DCD donor.
What we then saw is that we not only indeed prevented injury of the liver, but we had a tremendous decrease in biliary strictures, and that is exactly the Achilles heel in DCD liver transplantation. That gives a lot of biliary injury, and that leads to large interventions, therapy, and even retransplantation. Also here, what we see is that a short period, only two hours of cold oxygenated machine perfusion already gives us a better preservation, and we need that indeed to lead towards an extended life of organs. We can do more. As I told you, the Liver Assist is a platform that can also do warm perfusion. We do that with blood or a blood-like solution, and that allows us to evaluate the function of the liver because it is fully functioning, hopefully.
This is a protocol that is implemented in the university hospital in Groningen, again, Robert Porte's group. What they have seen, if they evaluate livers that were declined by all the three liver transplant centers in the Netherlands. They evaluate it and they comply to their viability criteria that those livers are perfectly well to transplant, and it's safe to transplant, and they function pretty good. By implementing this protocol, they have now seen that in their program, they have increased their liver transplantation by 20% already. As of today, that number is growing every week as they are using it more and more. What we see here is that the warm perfusion increases the utilization of livers already in the donor pool. That brings us closer to our second mission. Nobody has to die waiting for a new organ.
Zooming out a little bit again, we can ask ourselves the questions, do we really need to pump all livers? Probably not. If you can imagine a healthy DBD donor, a sportive guy, well, maybe Andreas. No smoking, no drinking, probably that liver will not benefit from machine perfusion. We also saw that if we have the lesser quality DCD livers, that those really benefit from cold oxygenated perfusion, even though it's a short period after cold storage. Our true potential lies in the high-risk donors. The donors of which the quality of the donor livers of which the quality is now unknown.
There we see that if you apply the cold oxygenated perfusion to improve the quality of that organ, and then evaluate it with the warm evaluation machine, then you can still decide based on the viability criteria to transplant the liver or discard it after all. At least it is an informed decision to discard the liver. In summary, what I have shown, hopefully, is that cold oxygenated machine perfusion is a better preservation method than cold storage for both DCD kidneys and livers, and that the underlying clinical data is very solid and even published in the two top-ranked journals in our field. Last but not least, what we also saw is that warm perfusion allows us to evaluate the liver, and by that, we can increase the utilization rate.
We, as XVIVO, we are very proud that these technologies are now more and more introduced in clinical practice in Europe. Of course, we want more. We want to expand that. One of the expansions is going to the U.S. For that, I would like to welcome Johan Nordström again, Holmström, we have a lot of to tell us all about that. Johan.
Thank you, Arjan. Thanks for having me up here again. I'm not sure I will tell everything about our go-to-market plan for U.S., but the purpose is to give an overview of what our plan is about. U.S. market is obviously the single largest uniform market today when it comes to kidney and liver transplant. You heard from Kristoffer and Dag about one of our strategic imperatives to become a leading position for abdominal in the U.S. Clearly, that's a priority that we are now planning towards and investing towards as well. U.S. market is not just the single largest market in absolute terms, it also the fastest growing market today when it comes to kidney and liver. There is a perfect, as we see it, market opportunity for our technology to meet this development. U.S. transplants are expected to reach 50,000 by 2026.
A big part of that obviously will come from a disproportionate growth of utilization of DCD organs. This is where our technology fits well into this. Our estimate is that we can address at least 75% of that market with our technology that this will be needed for. What's interesting, I think I said that in one of the questions earlier, when it comes to the development of transplants in the U.S. for kidney and liver, we have seen this year in 2021 and where that growth is coming from DCD, that kidney is increased 15% already and 8% for liver. This should be compared to only using DBD organs, which is at the relatively flat level of 2%-3%.
The initiative to increase number of transplants to 50,000 by 2026 is a commitment and endorsement by AOPO, which is the Association of Organ Procurement Organizations in the U.S. What we think is really interesting here is when you look at some of the initiatives that they talk about to make this real, particularly number three and number four here, maximize organ utilization. That means that they will start to utilize much more of DCD organs than ever before, and perhaps that's where we also come into the picture, the use of innovation, so new technologies like machine perfusions, for example, is going to be very important to realize this objective. While this is true for kidney and liver, it's also relevant for EVLP and our lung perfusion business in the U.S. A very positive development.
When it comes to launch, the first product we will launch in the U.S. will be Kidney Assist Transport. You heard Arjan van der Plaats talk about this product. We announced in May when we did our filing for 510k for this product in the U.S., but we now are waiting for the final FDA approval. Since then, we've been in a launch planning phase, really starting to plan our commercial activities for the market release and starting to build the right capabilities behind the launch. Our objective is to get the market clearance during quarter four this year. Go-to-market model and value proposition. Kidney Assist will be positioned as a premium product with a value proposition that improves both the clinical outcomes that you have heard from Arjan.
Also, we want to make sure that we also can support the performance metrics that the surgical centers and the OPOs are set against when it comes to reimbursement and the levels they need to stay at to keep their license. In the U.S., the Centers for Medicare and Medicaid Services, CMS, is, as I think we said earlier, is the single largest payer for healthcare in general and for transplantation in particular. Most commercial payers, also those insurance, et cetera, they follow the same sort of lead metrics that CMS is placing on OPOs and surgical centers. That's important for us because with our products, we know then that we can help OPOs and surgical centers to both improve and stay within those defined metrics, securing reimbursement, securing the right quality, whilst at the same time, increasing the availability of transplantable organs.
It's a very strong story with very strong clinical evidence behind it. When it comes to the go-to-market model as such, it's something we will have a variable model for. We realized that one of the things that is very important is to build an installed base as quickly as possible. In some cases, different customers are in different cycles when it comes to how they make their investments. We will have a blend of placing machines as well as direct sales of machines, of course. Back to our economic engine, revenue per machine is what we will drive. Building an installed base, taking market share in that way is going to be one of the methods we will do, of course. There will be a dedicated commercial team for abdominal.
We have a team for the thoracic area today. We have now started to invest also into Abdominal, both when it comes to marketing capabilities as well as sales capabilities. This will continue slightly ahead of the curve, but also in pace with our development, of course. In the end, making sure that this will enable that we have a strong pull and push strategy to create demand from transplant centers, but also to make sure that the OPOs can keep on that level where they need to be. Target launch dates for Kidney Assist Transport. As said, we expect market clearance during quarter four, which will enable us to start doing pre-launch activities. To have more of a, let's call it, full force launch in January 2022.
When it comes to liver and Liver Assist, which will be our second product, we're right now in a process for FDA application and the definite timeline for when we will actually enter the market, that is too early to say today. Kidney Assist Transport is number one. Before I close, some of the key takeaways that I want to leave you with is that, first of all, there is a very clear ambition within the U.S. to increase number of transplants. DCD organs will be one of the key drivers behind that, the utilization of DCD organs. With our technology of machine perfusion, it fits extremely well to that ambition. 2022 will be our focus for kidney, and liver will follow after that. Thank you.
Thank you very much, Johan. That concludes our second segment of the Capital Markets Day here, we're moving into the Q&A session. For you who are viewing us online, remember, post your question in the Q&A field below the screen. For those of you who have joined us here inside, please raise your hand. I see we have a question already from the audience, let's start there.
Great. Thank you very much. Ulrik John from Carnegie. I'll just start off with a question for Professor Rega, in terms of you mentioning the utilization of marginal organs. Just your perception among you and your colleagues, how big of a difference does XVIVO's heart machine do in terms of increasing the utilization? Where do you see this progressing over the next few years?
Thank you for your question. It is pretty interesting. I think the answer consists of two elements. First of all, what you see on the waiting list, the number of patients, does not reflect the real need because we know we do not have enough hearts to transplant. One of the reasons is because we are much too strict when it comes to accepting an organ. Very often in a small donor hospital, you do not have all capabilities, like to make an angiography of the coronary arteries or a reliable echocardiography. Once you start to doubt, you reject the heart, in fact. Yes, imagine that you can use the non-ischemic heart preservation machine and assess in a way, biochemically or in another way, the heart function, then that will open an enormous amount of opportunities to assess those hearts and eventually accept those hearts.
To give you a number on how much that will in reality give us. We are doing 30 transplants a year. This is half of our annual Belgian transplant activity. Imagine that you add 5 to 10 hearts per year for an 11 million population, we jump that year with 10%. You make for these 10 patients the life completely different. We still have to prove that scientifically, but at least now we have a tool to do that. We look forward to the future on that.
Right. I would like to continue to expand in this direction because it seems like two opposing forces. On the one hand, you have this great unmet need, which sort of forces you to explore perhaps less ideal donors, like circulatory death, obviously. I guess in the specific situation, when you are a surgeon and you are in the decision process, should I go forward or not? I guess I would be a bit afraid as a clinician to go into this DCD and organs that were previously rejected. Do you think this fear could mean that it will be sort of a slow adoption among clinicians or perhaps concentrated to a few centers where they have the abilities you discussed before?
Mm-hmm. Yes, I think you need to concentrate that activity definitely in the early phase of the introduction. I think in Belgium we are doing this. We only have seven transplant centers, which is actually already perhaps even a bit too much for an 11 million population. I must contradict you on the DCD heart-
Right
because in DCD, you can do it both ways. Either you take out the heart and preserve it on the machine, or either you go through this new process of normothermic regional perfusion, where you assess the organ function in the donor. There are two ways to deal with DCDs. In the second phase, you truly have a very good idea on the organ function.
Right.
What we observed is that DCD donors over the past three years really did increase the amount of donors. It did work.
I stand corrected. Thank you, Filip.
Yeah.
Do we have any further questions from the audience? We have a couple here. Let's start perhaps with Mattias, and then move forward to you, sir, with the red tie.
Thank you so much. Mattias Häggblom, Handelsbanken. Two questions, please. Dr. Rega, you showed data that most clinics does 10-19 heart transplants per year while your site did 30. What's the correlation between long-term outcome for the transplanted heart and number of transplants per year a hospital do? Maybe for you, how many of the transplant clinics do lung, heart, kidney, and liver transplants, or to what extent are they focused on one of each? I'm trying to understand cross-selling synergies here between the different organs.
I'll repeat the question. The first is about the correlation between the number of transplants and outcome, if I get it, and then overlap between different transplant areas.
That's a dangerous question to answer. We're not allowed to answer that in Belgium because centers are afraid that if we look to their outcome and really compare them, you might find a correlation. Intuitively, you're right, and there is a correlation between activity and outcome. The more you do it, the better your outcome is. I cannot give you numbers on that.
Right. We had one more question, please. Step forward for Mattias.
Yeah. Just two questions, Professor Rega. First on maybe your perspective on the TransMedics OCS device and maybe some of the reservations that have emerged from the ATC. Your perspective would be very much valued. The second question would be on maybe how the pathophysiology of patients changing with cardiovascular disease, hypertension, these kinds of things interplay with warm and cold perfusion and oxygenation, that being important with these patients being unhealthier going forward. Thank you.
Right. Two sections. A comment on TransMedics. Second, the demographic change with sort of decreasing physical status among the population affects perhaps the supply of possible donor organs.
In our center, we never implemented the OCS technology. If you read carefully the editorial on the famous Lancet paper, one of the observations we made was that they described that five patients were not taken into account into the final analysis because something, I'm not going to say went wrong, but did happen in the process of putting the heart on the OCS device. If you take them into account, then actually I'm not sure that in their trial non-inferiority was proven. That made us a bit skeptic. Actually for heart, I think conditioned cold perfusion is for us the way to go. The second question was?
Demographics among donors.
Yep. Demographics. They are changing, these demographics. Patients indeed become older, become more diabetic. Medication improves. Yes, we see the number of patients in end-stage heart failure increasing. Probably also there, this will extend the limits we implement now. For example, age. Up to now, there is an age limit that comes close to 70 years to be listed on the heart transplant list. Sometimes there is this 72-year-old person that four weeks ago did climb the Mont Ventoux in the south of France. Yeah. A very healthy person. Do you not put such a person on the waiting list? These questions become reality. We will push the limits in the future.
Great. I like that you wove in some cycling references here in the Q&A as well. There are several questions from the online audience regarding TransMedics. Perhaps some other from the panel could add a little bit of flavor on the competitive landscape. Do you see them as a direct competitor, or is it more like a difference in procedure and efficiency? I don't know if anyone else could pick up on the TransMedics issue.
Well, maybe I can give it a try. I think it's, for many reasons, two different technologies. It's one technology relying on a warm and beating heart during transport, and the other one is with a cold heart, but being perfused with oxygen during the transport. Yes, the evaluation and possibilities with a resting heart might be smaller, but it's also another layer of safety. Imagine that you have something happening during the transport with a beating heart. You have ischemia and its injury to the heart from the first second. With a cold heart, you have a layer of safety. In the worst case scenario, perfusion stops, for example. You just revert to what we have today, cold static storage on ice. That, I think, it's a big difference between the two technologies.
That sounds like a very significant aspect of it, because obviously risk minimization must be top of mind in this area. Johan Unnérus from Redeye has a question as well, and it regards the time horizon for liver and FDA submission, and he wonders what's holding you back from setting this now. Perhaps, Johan, would you care to pick up on that?
The only thing I can give a very brief answer is that we are in the preparation phase for submission.
Until then-
Right
It's difficult to give an exact answer.
A projection.
We are not being held up ourselves. We are working on this.
We have another question from the online audience, which is interesting for me as a layman. Given the very nice clinical results you've shown with, for instance, the graft rejection was almost halved in the liver right study. Joe Wang from Viewforth Investment Partners would like to know if you could elaborate on the potential use of warm perfusion and cold oxygenated perfusion in terms of treatment and repair of organs as opposed only to storage and evaluation. Is that sort of a possible application that you could treat an organ before transplant?
Yeah. Of course. What the situation now is that we come from 50, 60 years of static cold storage, and we are now changing that into an improved preservation with our cold oxygenated machine perfusions. Now that we have proven that we can do that.
The next step was the evaluation. We increase the temperature. By that, we could evaluate the organ to see if it's suitable or not suitable to be transplanted. Indeed, the next step is, of course, if we then say that it's not suitable for transplantation, can we do something about it?
Then you come in the area of treatment, and that's not yet clinically applicable.
Right
I can tell you. That is, of course, a very interesting research topic for the future.
Yeah.
Yeah.
Maybe a future development. Please raise your hand if you have any questions, and we will take them. We have two minutes more. Filip Rega, sorry. You sounded quite optimistic in terms of the possibility to prolong the viability of an organ to the 24-hour range or perhaps even beyond. Is there a cutoff point when you do this evaluation? We saw the ischemic curves with a hazard ratio, how it changes, or also with regards to the donor qualities. What's an acceptable range? Is seven, eight hours, for instance, would that fall within the tolerances, do you think? Still awaiting clinical data, of course, but your feeling for this.
To be honest, at this point, we cannot give you that number because within the CEU trial, actually, we will be dealing with standard preservation intervals. We know those data from experimental data, but also from what the Australian centers are doing with these long-term preservations up to seven hours. What I recall mentioning these colleagues is that, Look, these hearts come off cardiopulmonary bypass without important inotropic heart-stimulating medication. That, to me, is extremely promising when it comes to long-term preservation and the outcome. I cannot give you a number.
Yeah
at this point.
No number. I understand.
Yeah.
I suppose there is a cutoff, because we saw the regional map. Four hours, you cover a certain region. If you go bump it up to six hours, it's a considerably larger area. I suppose you don't need perhaps to go to 24 hours to capture a very large portion of the benefits, because if you go to 6, 8 hours, maybe the coverage is so big that you have a very efficient matching of donor and recipient, even at that number.
I can only answer in a sort of emotional way. What happens now is that you cannot imagine how much phone calls there are between the transplant coordinator in the donor center and the recipient team to optimally match the timing and to keep the preservation interval as short as possible.
Yeah.
By simply doubling the current preservation intervals, you relax that whole process, and then probably will allow the heart to perform better after transplantation.
Right.
Thank you very much, Filip. Unfortunately, that's all the time we have for this Q&A section, so it's time for a short break. Please join us again in 15 minutes. Thank you.
[Break]
Welcome back to Gothenburg and the final section of XVIVO's Capital Markets Day 2021. In this section, we will look a little bit in depth at the current core business, which is lungs, then we will have a glimpse into the future of transplantations. To make it even more exciting, we will have two presenters with us on link. First off is sales director for North America, Rodney Jones. Welcome.
Thank you, Lars. Thank you for this opportunity to present here today. I want to apologize in advance. All the eloquent speakers have already given you their stories, and now at the end of the day, you're forced to listen to me. Nonetheless, I'll do my best. Some of the key highlights that I want to make sure that we cover, and when I say we, it'll be myself and my colleague in the U.S., Brandi Zofkie, to talk about trends and innovation in lung transplant and where we're going for that. Just some highlights to start to frame this picture. Globally, there's about 6,700 lung transplants, and you've already heard multiple times today that's only 20% utilization rate.
Globally, again, there is about 250 lung transplant centers, and those challenges are how do they grow their programs, how to eliminate deaths on the waiting list, and how to optimize the use of suboptimal organs. Through that, we will talk a little bit about our products, what we are using, or what the industry is using Perfadex and specifically for cold static storage and then for EVLP, of course, is the XPS platform with STEEN Solution. Again, when there were some really good questions about the use of DCD donors and brain-dead donors and how that happens and why we see growth in one particular area versus another area.
Right now the standard of care has been since 1969, when the Harvard brain death criteria came out and organ donation moved from, it's actually we're going back to the future, moved from donation after circulatory death to brain death. That's been the standard. Through that, all of the injuries that happened to the thoracic organs, especially during brain death and herniation, have led to this 20% utilization rate. When we go back and look now at donation after cardiac death or circulatory death, we believe that by taking advantage of this with our technology, that we can move up to 40% for the number of lungs transplanted.
When you think about that, especially for me when I think about it in the U.S. where I'm from, going from 2,700 lung transplants to almost 5,000, a little over five or close to 6,000 transplants, that's pretty significant. When you think about our purpose at XVIVO that nobody should die waiting for a new organ, I think we have a good chance of achieving that, being able to bump that up. That's fantastic for me that we would have that opportunity to eliminate deaths on the waiting list. XPS, the XVIVO Perfusion System for warm machine perfusion with lungs and Steen. That was started in a clinical trial in the United States in 2014, and April of 2019, we received our FDA approval for that. We were the first company to receive FDA approval for warm machine perfusion for marginal criteria lungs.
That's how we're expanding the donor pool now. One of the earlier questions, it was behind me, I didn't see who asked it, was about the EVLP penetration, the questionnaire used a term that I had been using that are we close to the tipping point, and what would that tipping point look like? I do think we're close to that. I think COVID pushed us back a little bit, now we're getting closer to that as we move forward. I'm going to give you some examples of how that penetration is growing and how I believe that we are getting closer to that tipping point as I go through the next just a few slides here. This is information you've seen several times today. We're talking about steady but predictable growth of lungs transplanted.
If we look at the opportunity within the DCD community, what does that really look like? The potential of expanding the donor pool through that. I just have a couple of slides that I want to share some really novel examples of how that's happening. This first slide, this is one of our key partners. This is from Toronto. They're a key partner for us in North America. Professor Shaf Keshavjee that runs the Toronto group is really, along with Professor Steen, another pioneer in EVLP. They took a look at a population of donors called controlled donation after cardiac deaths, and these are donors that have a terminal illness.
That donor, along with their family and their caregivers, have elected to move toward end-of-life care. They evaluated those patients to see if they would be potential lung donors with consent of the donor and/or the family. At the time of death, when these patients died, 14 of those candidates were put on EVLP, so 14 sets of lungs. You can see from this paper that five of those 14 ended up going to transplant. It is worth noting, when this paper was published, we were talking about prolonged ischemic times, that one of these patients was up to 13 hours, ischemic time. We are talking about a completely different population of patients, adding those to the donor pools, thereby also increasing the number of transplants that can happen. You can see these were marginal lungs. These have never been pursued before.
Now, with these five transplants in this small feasibility study, there was zero PGD at 72 hours, there was no 30-day mortality, and there was an 80% survival rate at one year. This is just fantastic. Another indication that we're getting close to the tipping point is the number of articles that have been published over the recent years. Specifically in 2019, there were two really key articles, one out of Toronto, but another one out of Japan. That article out of Japan was a metadata analysis that looked at EVLPs around the world, I think close to 800 cases. Those, it was found that this is 10 years out now, that these patients who have received transplants from marginal criteria lungs that otherwise would not have been transplanted, underwent EVLP, had outcomes that were not statistically different than a standard criteria lung transplant.
This is really great data. These papers that keep coming out this way are really good indications that we're getting very close to this becoming a standard of care. Something more recently that's taking place right now, something we're all familiar with, that we've been living through for the past 18 months is COVID. You heard a little bit earlier, Dag talked about one of our partner sites, the Cleveland Clinic. When they started using our technology in 2016, 1% of their transplants came through EVLP. During COVID, they were actually able to use our technology to increase their numbers. This is only one of four centers that does over 100 transplants a year, so they're a high-performing center, and 25% of their transplants now are coming through EVLP.
One point of this conclusion in this article that I just want to draw your attention to was the last sentence in here, where they conclude, In the future, these newer EVLP indications may be applicable beyond COVID-19. This is great. These are forward-looking thinkers, high utilization, high impact centers that are going to help drive EVLP forward. When we talk about innovation, this absolutely has nothing directly to do with transplant. In these two examples, I'm talking about our lung platform. Actually, preclinical drug discovery is a fantastic opportunity for all of our platforms, for our kidney platform and our liver platform as well. When we look at the preclinical drug discovery market, the CRO market, it's projected to have a growth rate of anywhere between SEK 6 billion and SEK 8 billion.
If you can think about this, taking a new compound and testing it on an organ to determine its safety and efficacy before giving it to a patient and actually potentially harming them in a phase I clinical trial, that is a big deal. That's just another opportunity for us to look at as we go forward. It's not our key area. Obviously, transplantation is what we're all about, but this is just another opportunity to leverage our platform for the good of humanity. My last takeaways, before I introduce Brandi, are the following three points. EVLP is safe and efficacious way to increase the number of life-saving transplants. The pandemic has demonstrated that there are potential new indications for EVLP. EVLP growth is trending upward and is a standard of practice in high-performing transplant centers.
As we talk about high-performing centers, it's a perfect segue into our next speaker, Brandi Zofkie. It's my pleasure to introduce Brandi. She's the Director of Lung Bioengineering. Brandi and her team are truly transforming the way traditional EVLP has been practiced, so I'm excited to hear Brandi's story.
Brandi, morning.
Good morning.
Great. Yep, go ahead, Brandi.
Excellent. Well, thank you for the very kind introduction, Rodney. It's good to be here. As Rodney mentioned, I'm the Director of Lung Bioengineering here in the United States, and will be talking to you today about our model in which we utilize ex vivo lung perfusion. A little bit about Lung Bioengineering and how we came to be. United Therapeutics is actually the parent company, and it was founded by our President, Martine Rothblatt. At the time, Martine was actually the founder of what is now Sirius XM Radio. You may be wondering how someone from the satellite community ended up in biotech. Well, unfortunately, at a very young age, her daughter was diagnosed with pulmonary arterial hypertension.
After creating a foundation to try to find a cure, the researchers came back and said, Listen, there's a drug sitting on a shelf that no one wants to develop because the cost is too high and the patient population is too small. Being a woman with resources, not taking no for an answer, she basically went back, got her PhD, and started United Therapeutics. She didn't really stop there. Now we have four FDA-approved drugs on the market specific to pulmonary arterial hypertension. That still wasn't a cure for these patients. That's when Martine created Lung Biotechnology, which is the U.S.'s first public benefit corporation of a biotech company. Something we're really proud of. Their mission is to create an endless supply of organs, one way or another.
We have multiple different modalities in which we're exploring being able to bring an endless supply of organs to patients. After a conversation about ex vivo lung perfusion, Martine partnered together to bring ex vivo lung perfusion to American transplant centers in a different way than it was being done before. One of the frustrations that was being relayed to Martine at the time was the resources that it took to do this within your own program and the expertise of evaluating a lung outside of the body. That's when she actually built our first facility in Silver Spring, Maryland, at our headquarters, and we launched Lung Bioengineering to be able to provide an ex vivo lung perfusion service to multiple transplant centers. Everything that I'll be describing today is only available in the United States.
Just want to make sure everyone is aware of that. Oops, looks like my slide didn't progress. Sorry about that. Lung Bioengineering was founded as a way to be a service provider. We actually have the devices in our facilities. We provide all of the staff and the resources to be able to bring that to the transplant center, knowing that it continued to be a challenge with the organ shortage, as Rodney was describing to you. Lung Bioengineering is using the ex vivo perfusion system to fill the void between the number of organs available and being able to provide data and information back to the transplant team in order to make good decisions for their recipients. The way that we do that is through our centralized service model. There we go.
That consists really of four main pillars, our facilities, our team of excellence, our FDA-approved device through the ex vivo platform, and the case management exchange that we use for data sharing and repository. Unlike most EVLP modalities, typically you see these devices in a transplant center. Our process is a little bit different, where the organ is actually recovered at the donor hospital, cooled down, put on ice, flown to one of our Lung Bioengineering facilities, where it is put on EVLP, and then after the organ is accepted for transplant, is cooled back down, put back on ice, back on a plane to go back to the recipient hospital. Really there are seven benefits that we want to highlight in terms of what the centralized EVLP service looks like.
Our robust experience, our flexibility that we can provide to our transplant center partners, the trustworthy data that we are able to obtain and share, the expansion of the donor pool, overall resource savings and risk management, and our continuous logistical assistance. In terms of our experience, we do have a lot of experience compared to some of the centers that are doing these smaller quantities per year because we are serving multiple transplant center partners. As of this month, and actually this number has already changed because we just did another one this morning in our Maryland facility, but we had 291 donor lungs coming into one of our two facilities, with 188 of those being accepted to transplant and transplanted into 191 patients. The discrepancy there is that some of those doubles were split and went into two single recipients.
Our experience of our team is really unmatched. We come with a lot of backgrounds in donation and transplantation and EVLP, and we do collaborate. Rodney was mentioning the team in Toronto, and our training program is in collaboration with our Toronto fellows, and we utilize their expertise in being able to train our team. Another unique thing about us is, besides just our experience, is that we're a 24/7 operation. Any day of the week, any holiday, middle of the night, we're available to our transplant center partners. On top of that, we have a different level of quality assurance that comes with having standard procedures and oversight from a regulatory perspective. Our service allows for optimized decision-making as well for our transplant center partners. One of my colleagues actually coined the phrase of turning a no into a maybe.
Now transplant surgeons, when they're assessing these organs, now have a way to be able to get more information and make better decision for their recipients. The XPS platform allows for single or double lung EVLP, which is unique compared to some of the other devices on the market. EVLP allows for essentially scheduling of some of these transplant-type procedures that are normally being done in the middle of the night. Because of the time, the extended preservation that comes with it, physicians are finding that they're able to plan appropriately and not have to do some of their procedures in the middle of the night.
Even better, it results in some reduced travel because, typically, thoracic teams would never have allowed another team to procure organs for them, because if there was a mistake and they're not able to use it, that would be significantly impactful for their recipient. Now, because of the EVLP technology, if they're allowing other teams to do the organ recovery, the lung is sent to one of our facilities. They can be reassured by the data that we provide them and by our assessment that the lung is suitable to go into a patient. My slides got messed up there. In terms of the data that we provide, not only are we providing the data, but we also have everything integrated to be able to view all of the data from their mobile device.
They could be at dinner with their families or lying in bed at night in preparation for a transplant and be able to see everything, including being able to remote into the actual procedure and discuss live in real time with our clinical team. On top of that, all of our facilities are outfitted with really amazing AV capabilities, and we also have medical consultants available that have expertise using STEEN Solution-based EVLP technologies to be able to allow for peer-to-peer discussions that transplant centers new to the technology have definitely valued in their onboarding with our program. This is a little example of what our charting system looks like. We collect a ton of data. On top of that, we're also collecting video feeds of bronchoscopies and overhead video, and we're collecting X-ray images, et cetera.
Like I said, all of that is available to our customer at their fingertips. We also believe that working with Lung Bioengineering in a centralized model helps expand the donor pool. Lungs that may not have been used before are able to be reassessed, gather data, and consider organs from distant hospitals that may not have been considered before. Even better than that is that because our facilities have multiple EVLP procedure rooms, so we now have two centers with four XPS devices, it really ensures that business continuity, that we will always be able to say yes when a customer calls needing ex vivo lung perfusion services. One of the things that I feel Lung Bioengineering is really tasked with is to change the culture of transplant programs.
Before, an intraoperative decline would not have been used, and with EVLP and with Lung Bioengineering being able to help facilitate additional time for data, these lungs can now be considered. DCDs, as you've heard already multiple times today, very high potential to be able to use those organs. A double lung perfusion where you're intending to perfuse the lungs for one patient and then find out that there's an issue with one and only one can be transplanted and having to switch recipients. Then, as I mentioned previously, utilizing other procurement teams for the recovery of that organ. As I mentioned, we have two facilities. Our flagship facility has six operating rooms and is located in Silver Spring, Maryland. Our second facility is where I'm calling you from today, down in Jacksonville, Florida, where we have three operating rooms.
Our centralized model also results in reduced resource burden. Onboarding a device isn't just buying a device and using it. There's the cost of the personnel to run the device, all of the training and capital investment, the technical issues, and the learning curve that comes with evaluating a lung outside of the body, the OR time, the consumables, et cetera. We feel that being able to provide all of this allows for the customers to not have to manage all of that themselves. In addition, we also feel that the increase that may result in the lungs reduces the overall burden to the transplant center by getting patients transplanted sooner.
Just overall in risk management, allowing physicians to have information that they didn't have before, especially when it comes to DCDs, especially when it comes to those organs being procured by another team when they actually don't have their hands on it, especially those organs where they're given very little notice, especially in the time of COVID. The American donor hospitals, some of them are really, really stressed, and they need to get the organs out so the ICU bed can be used again, unfortunately. Being able to facilitate the recovery of those organs and evaluate after they're outside of the donor. Even more importantly, and something I haven't touched on yet, is the ability to reallocate organs.
A lot of times, if these lungs go to a single transplant center, and for some reason, something would change with the recipient, so maybe the double-lung recipient isn't available or can't be transplanted today. Typically, the way that works in the United States is just identifying another recipient within that transplant program. With our services, we are able to help the organ procurement organization identify a transplant recipient that's next on the list that may actually be at another transplant program. Then continuous logistical assistance. I touched on the fact that we have additional flights to get the organ from the donor hospital to Lung Bioengineering and from Lung Bioengineering back to the transplant center. Lung Bioengineering can actually assist the programs in facilitating all of those activities.
If somebody's not able to get a plane or ground transportation, Lung Bioengineering actually facilitates that as well. More importantly is what we're doing, we consider to be really just a platform for what the future looks like. Lung Bioengineering's goal is to fill the void and to provide a 360-degree service to transplant center partners, and whether that means an expansion of organ perfusion services, increasing the number of our facilities to be able to provide these services to transplant centers all across the United States, transport innovation, and streamlining procurement services. We do feel that Lung Bioengineering is going to be the answer for all of the in-between of getting the organ from the donor and into recipients. With that, thank you so much for having me today. Looking forward to the questions.
Thank you for an informative and interesting presentation, and we look forward to hearing more from you during the Q&A session later on. However, now we move on to the future of transplantation, where the Chief Operating Officer, Christoffer Rosenblad, will present more about this. Welcome.
Thank you, Lars. I wish you all welcome to the last, but certainly not the least, session of the day. Now it's time to take a sneak preview into what's around the corner, and together we will explore new horizons in transplantation. Today, we will present four trends in transplantation going forward. The two first ones will simplify the process for the transplant team, and you heard one of them from Brandi Zofkie. The two, second or three and four, will change how we look at transplantation and will increase the number of organs. If we start with number one, which is digitalization, it's a trend that affects not only our industry, but it will affect our industry a lot more in the next couple of years.
We can see that more information sharing, taking data-based decision making, and support the clinicians with data-based decision making will continue to increase. We have press released a pilot in Groningen. As Dag mentioned, there will be more pilots within this field in the next couple of months and years coming up. The second part, new business models. There will be coming into the market more business models such as, for example, LB, where you help the transplant team to actually focus on what they're best at, which is the transplant procedure. That's their core business. It could be third-party services, et cetera. We probably will see this development start in the U.S. and then go to the rest of the world. It will be definitely fueled by the AOPO 50,000 transplants in 2026. That will demand more services to support the transplant team.
If we look into the third trend we will discuss today, xenotransplantation. I won't go into that today because you will hear more about that very soon. Xenotransplantation is transplantation between animal species. The end goal of this is to use, in this model, pig lungs on humans. After that, we see a trend of bioprinting. It is today certainly science fiction, but if successful, it could eliminate the need for both immunosuppressants and eliminate shortage of organs. If come true, it would be fantastic. During bioprinting, there will be a step of cellularization where you would need machine perfusion. On that note, on the field of xenotransplantation, even though it feels like science fiction today, certainly that's what I feel, it could be just around the corner.
Our next guest speaker, calling in from the U.S., has been involved in the field of xeno since 1992. He has made several contributions to the field of transplantation and xenotransplantation, with over 120 publications and over 100 abstracts, as well as numerous presentations. His group holds the record of longest surviving xenograft in a large animal model. I'm both excited and humble, I must say, to introduce Professor Muhammad M. Mohiuddin from University of Maryland. The stage is yours.
Thank you very much for this introduction. Thank you for inviting me here. I am very honored to be part of this meeting. I would like to first give you an idea that what xenotransplantation is. Why do we need it. As of now, there are about 150,000 people waiting for an organ transplantation of various organs. Unfortunately, most of them will die waiting. There are other solutions like artificial heart or the left ventricular or right ventricular assist devices, which provide some relief. Still they are not the cure. My goal will be today to let you know how the ex vivo has helped us in progressing this field, which we think is very close to clinical translation.
Which it appears like that it is science fiction for now and for many years, but I certainly believe, and my group certainly believe, that we are right at the corner, and we are embarking on some studies that will lead us to clinical translation. What is xenotransplantation? Xenotransplantation is transplanting a heart. I will just talk about the heart. Transplanting a heart from one species of animal to either another species, or in our future directions, transplanting that heart from an animal into a human. It seems easy that you take a heart out from an animal, and in our case, the pig. We have chosen pig because we can easily change their genetic makeup because we know their entire genome. We can breed them in captivity.
They grow in size very quickly, so within months, their heart size is the same as that of a human. We don't have to wait for a long time to get it. We know about, or at least are trying to know about all the diseases that can be transmitted from an animal to human. For now, we know of only one virus that can be transmitted to the living cells. So far, it has not shown to cause any disease. With genetic engineering, there's a possibility of completely knocking out that genome of that virus. In other words, this process will be very safe. It seems simple that you take out the heart from one animal and put it in another, and it will function.
What we encounter in our earlier days is that this is a heart that we transplanted from a pig into a baboon. In the abdomen, his original heart was intact. When this heart rejects, the baboon doesn't die, only the heart rejects. What happens is that within minutes, this heart turns into this. This is called hyperacute rejection. This is a phenomenon you will not see in the allograft, means from human to human, or from the same species, heart transfer from one baboon to baboon or pig to pig. This is only seen in xenotransplant. It is because all humans and all baboons, which are old world primates, they have certain antibodies that recognize the carbohydrate antigen on the surface endothelium of the heart, and then attack it and immediately cause the heart vessels to clot like this.
This is the histology from the same heart. As you can see, the major vessels are completely clogged. This is why this heart rejects. This phenomenon is very different from the allograft rejection, which is mostly cell-mediated. It progresses over a period of time, and you get rejection after a few days, or months, or years. In this case, if you put an unmanipulated heart in a baboon or a human, it rejects immediately. The other characteristic features are the loss of myocytes, intravascular hemorrhage, and all that. We have shown that in the abdominal model that I have just shown to you, we were able to prolong the graft for almost three years by acting on two fronts. First, we genetically modified the pig and took out all the antigens that were immunogenic to humans or the baboon.
On the other end, we used some target-specific immunosuppression, which is sparing the generalized immunosuppression and helping the recipient combat other infections also. When we had this kind of survival for almost three years, there was a proof of concept that we can avoid xenograft rejection from minutes, now to over three years. I should mention that the grafts there after three years only rejected when we withdrew the immunosuppression, thinking that we have induced tolerance in these animals, which we found out that we cannot do. That therapy is based mostly on the use of co-stimulation blockade, which helps suppressing the B-cell response and also the T-cell response. When we had this success, the natural transition was to do the heart transplantation in its original place, which is in the chest.
This is what we are doing for the last four or five years, before I was at the NIH and now at University of Maryland. In this experiment, we are using these genetically engineered pigs, and we are taking the heart out and we are transplanting it into the baboon, which is being treated with the same immunosuppression that we use in the other model. Can I have the first video, please? Here you see that a freshly transplanted heart that is being transplanted and it is beating very well. All the technical issues and everything, we have not faced. We were able to transplant it just like we do in humans. Next video, please. In this slide, this is an echocardiogram, the transesophageal echo, that shows that the heart when we transplanted and it came off the bypass, it was functioning very well.
Next video, please. Within 5 hours to 48 hours, this heart kind of give up and it dies on us. When we looked at the histology of this graft, we saw that this heart did not undergo rejection, but it simply failed somehow. We were very confused at what's going on. There comes the role of ex vivo and the STEEN Solution. One of our collaborators from Germany, Dr. Bruno Reichart, and his group demonstrated that when they use the old STEEN box and the STEEN Solution, they can overcome this rejection, the failure of heart within 48 hours. We have termed that phase as PCXD, that means perioperative cardiac transplant dysfunction. That for our initial period, we lost several animals just because of that.
We transitioned to this procedure where we take the heart out, we perfuse it with the XVIVO Heart Solution, and put it in the Heart Box from one to two hours. We do the transplant, and then we monitor. What we did was we compared three different methods of cardioplegia, that is stopping the heart, and also preservation. In the first method, it was traditional cardioplegia that was used in allotransplantation, and the same cardioplegia solutions were used. In the second method, we used the same cardioplegia, but added blood to that cardioplegia solution. In the third group, we used the ex vivo cardiac perfusion and using the XVIVO Heart Solution as a cardioplegic solution and with the addition of blood. Here are some of the agents that we had to use when we were struggling.
We had to use inotropic support to support the heart, and also we had to use different vasopressors to help the heart get enough blood to pump out. We graded them based on their use into the five different groups. Here you see that though there were multiple genetic modifications done to the animal, I don't want to go into the details, which will take over one hour to explain what all these genetics are. Basically, the genetics are to knock out all the immune targets that are immunogenic to humans, and also to express some human molecules that will facilitate keeping the blood flowing in the vessels. There were three groups. In the first group, as I explained, was crystalloid cardioplegia with preservation. The second one, we used added blood, and the third one was with the STEEN Solution, with the XVIVO Heart Solution.
Here's the difference. If you see that in the traditional one, we were not able to extubate any of these hearts. We lost them within 48 hours. We had to give a lot of help, and their lactate increased immediately. Their base deficit was abnormal. We spent nights and days just trying to correct it, but ultimately, there was failure. With blood cardioplegia, we were able to survive them a little better. Again, not all of them survived. Finally, when we start using the non-ischemic cardiac perfusion through ex vivo STEEN, ex vivo box, and XVIVO Heart Solution, we were able to survive all these hearts. Now, since we have started using this box, we have not lost any animal to the PCXD within 48 hours. Here are some more results. There are three groups, the same groups that I've described.
As you can see that in the group where we used the Heart Box and the XVIVO Heart Solution, these are the animals that required minimal support. There was very little inotropic support required and very small amount of vasopressors that were required. I'm happy to report in the recent transplants, we are not giving any of this. These are hearts we are explanting, and they are not requiring any of this support. That, I'll credit to the XVIVO Heart Solution. Here also, as I mentioned, there were some acid-base derangements. We used to see, and we spent a long time fighting it. As you see in the green ones, that the lactate was very minimal. The base deficit also was very low, and the pH that was more physiological, in that case, with the XVIVO Heart Solution.
Here's the difference. The right line shows that when we were struggling and we were not using the XVIVO Heart Solution and the Heart Box, we were having such a great difficulty. Since we have started using, we have been able to survive the graft on a consistent basis. These animals are lost. These are animals, we have to manage them blindly because they cannot tell you if they are feeling pain, if they are having infection. We have learned how to manage them, and we hope that when we transition to human, we won't have these problems because our human patient will tell us what she's going through. This is, again, some of our graphs. Until this presentation, the longest surviving graft was six months using the old STEEN Box from Professor Bruno's group from Germany.
They taught us how to overcome this PCXD, and now we are getting consistent survival over 6 months, as you can see here. This animal died just because there were some infectious complications in our facility, not related to the heart transplantation. This animal is still going on for a long period of time, and it's gone beyond six months. We are very confident that we can keep these hearts alive for a significant period of time, thanks to the ex vivo system. Just to conclude, the graft survival was minimal with the conventional methods of cardioplegia and preservation. The PCXD, the failure within 48 hours, was the main culprit. All the transplants performed with the XVIVO Heart Solution, and Heart Box overcame PCXD, almost 100%.
Hearts, you know, and allograft after non-ischemic cardiac perfusion did not require any inotropic support and had almost no complication after extubation. In fact, we used to wait for a long time for extubating. Now we are extubating almost immediately, and these animals are doing fine. Now all our long-term graft survival utilize XVIVO Heart Box, and we are looking forward to use this in our human transplants that we intended to do. I would also mention to you that in our plans, when the xenotransplantation goes to clinic, the hearts will be procured at one center, which will be a GLP facility, and the hearts will be transported to the centers throughout the U.S. In that case, the XVIVO Heart Box will play a very crucial role in transporting these hearts.
We are about to do some pilot studies by harvesting hearts at our Blacksburg facility, which is a six-hour drive from us, and then putting the heart in and bringing it in and showing that the function is preserved. With that, I would like to thank the team that we have built, which is a village, basically. All this work requires a support from a lot of people and a huge amount of investment for which I'm thankful to United Therapeutics and Lung Biotechnology, and also National Institutes of Health who have provided us with the funding to do this experiment. With that, I would like to thank the audience for listening, and I'd be happy to answer any questions you have. Thank you very much. You can take over, please.
Thank you so much, Professor Mohiuddin. It's always a pleasure to listen to you, and it was really impressive results you showed there. I will short summarize this session in about a minute, then please stay for Q&A session. I'm pretty sure there are questions for you from the audience here. To summarize the future of transplantation and key takeaways, as we heard many times, there is a shortage of organs for transplantation, which is a factor of one to 10. The need is 10 times higher than the supply today. Machine perfusion is proven to increase the number of transplantable organs. That is in clinical use today. Kidney and liver are soon awaiting regulatory approval in the U.S., but most of our machines are used today, so it works.
We at XVIVO believe a new business model and innovation, for example, xenotransplantation as we've seen here from Professor Mohiuddin will play a vital role to one day accomplish our vision, and that is that nobody should die waiting for a new organ. With that, thank you so very much for listening.
Thank you very much, Kristoffer and Professor Mohiuddin, for excellent presentations. It's time for the Q&A session. We have a general question from our online audience, which perhaps Dag could answer. It's from Johan Unnérus in Redeye, he wonders, Can we expect XVIVO to engage in additional support networks like LBE? Do you see more of that type of partnership?
You mean with the Maryland.
I think it's Lung Bioengineering.
Sorry, Lung Bioengineering.
Yes.
Absolutely. This is definitely one way of making life easier for customers. Working with perfusion hubs is of course very attractive, and Brandi Zofkie gave a lot of examples of why.
Yeah
There is a strong benefit for doing so. As Johan mentioned earlier, we are doing the same thing in the U.K. with Harefield, which will also be like a mini hub for a number of other transplant centers. I think this is definitely one way forward to work and promote the hub concept when it comes to perfusion. Yes.
Right. Thank you, Dag. We have more questions about Lung Bioengineering. Brandi, obviously you made a strong impact here. Peter Östling, analyst at Pareto Securities, have a question for you. He would like to talk a bit about the study that you're conducting, how it proceeds as it is an open label study. The main goal of the study and the main endpoint is what? Secondly, are you planning to open additional evaluation centers in the U.S.? Did you get that, Brandi?
Yes, I did. Thank you all for the question. Yes, we do actually have two different ways of doing ex vivo lung perfusion. At Lung Bioengineering, we are conducting a clinical trial, but for the sake of today's conversation, we're going to stick with the topic of our XPS services, which are FDA approved in the U.S. In terms of your question about our expansion, we definitely will be expanding West at some point. Right now we're able to serve transplant center partners, primarily East of the Mississippi in the U.S., but want to be able to provide access for patients all over the U.S. Definitely see at least another facility or two to be able to meet needs of patients across the U.S.
Right. You have another question, Brandi. It comes from Jie Wang from Viewforth Investment Partners. She wonders if you could talk a bit about the barriers to scale. What's the main hurdle for you? Is it the CapEx perhaps, or something like that? There is another TransMedics question here as well. They're building their national service program. Have you seen them making any progress?
Yeah. The first question was, for scaling, for being able to provide this service across the U.S., is that correct?
Yes.
Okay. Thank you for clarifying. We do have some challenges ahead of us, and I think one of the biggest challenges is convincing and trying to change transplant center culture. For the last 20 years, organs and lungs especially, have been assessed in one way, and that is from a piece of paper, basically getting some data from the donor in the ICU on a ventilator with a closed chest, with all other organ systems basically having to be monitored at the same time. For those of you that may not be aware, one of the biggest battles in organ donation when you're managing a donor patient is trying to find a balance to protecting the lungs, which want to be a drier organ, and also hydrating the abdominal organs, with the kidneys needing a lot of fluid.
A lot of these patients end up fluid overloaded. Traditionally, when a patient has that fluid overload, or if there's any question whatsoever about the quality of the lungs, the transplant team historically would decline. I think one of our biggest barriers as we scale up is really making sure that transplant surgeons, transplant pulmonologists understand what opportunities they have to now change their program's mindset. To look at an organ and not make a decision about that organ, not decline that organ until you see it on the EVLP circuit. Get the information you need to confirm that organ maybe is bad. We would much rather see an organ fail on EVLP than not have any chance at being transplanted. I think that is definitely one of our biggest barriers.
Thank you, Brandi.
I'm sorry, the second question was TransMedics?
Yes. Now let's see.
Their service model.
Yeah. It is about the service model. Actually it was about TransMedics' competitor here in some way. Joe Wang wonders, they are expanding their service program. Have you seen them making any progress? I do not know if that is a relevant question for you to answer. You decide, Brandi.
Yeah, we are aware of that, but we feel that there's a different need for our services versus what they're trying to do.
Thank you. Obviously, you are very successful, Brandi Zofkie. Peter Östling at Pareto Securities has a question to XVIVO. Lung Bioengineering managed to use 188 of 291 lungs, which is a 65% utilization rate. XVIVO is aiming for 20%-40%, so why not aim higher? If Lung Bioengineering can do it, can you?
That's actually Oh, sorry, Dag, did you want that?
No, I think it's an excellent performance Lung Bioengineering has. As I mentioned earlier, Brandi as well, in the case of Cleveland Clinic as a hospital.
They have more or less a 70% success rate when utilizing EVLP technology. The question is why are we not promoting a higher percentage than.
let's say the 40%, maybe to 50% that we are promoting. We are a little bit modest. We know that proof lies in the pudding many times, and people who use our technology, like Brandi and Cleveland, they see the benefit of EVLP technology. To make statistical claims on exact percentages is, of course, not easy.
Yeah.
Not easy. I don't know, Doug.
I just want to make sure that the questioner understands that 40% isn't the conversion rate from lungs on EVLP going to transplant. That 40% is from the donor pool.
Right.
Yeah.
That's a different statistic.
Yes.
Yes.
Actually, to add to that, I actually feel that our conversion rate is too good, because that means transplant centers aren't taking enough risk.
Exactly
to evaluate organs.
Yeah.
They should be pushing organs in that aren't going on to be transplanted, because there's still that large pool.
Yeah.
Thank you, Brandi. Are there any questions from the audience? Yes, please. Wait for the microphone.
Hello, my name is Stephanie Tigerschiöld. I'm a private investor. I wonder when you evaluate lungs, for example, in bioengineering, how many of the evaluation aspects that you're looking on are objective, and how many are subjective? That's a really important question, whether the teams on the spot in the hospital are using mostly subjective analysis.
Right. Any one of you in the panel who feels an urge to answer this question?
If we look at all the objective criteria for the XPS machine, for example, I think it's close to 22 data points, and then the subjective would be a drop test where you disconnect the ventilator, and you watch physically the symmetry of the lung as they collapse. Outside of that and how the lungs feel, what we've done to mitigate some of that, especially how the lungs feel, is with the addition of the weight scale. Right. We are working hard to make some changes to make it more objective. I would say, and Brandi, correct me if I'm wrong, the drop test and the way the lungs feel are pretty much the subjective parts now. Everything else is fairly objective.
Yes.
Any further questions from the audience? Yes, we have one here.
Thank you. Ulrik at Carnegie. First one addressing you again, Brandi, just by curiosity, how many transplantations does your partnering clinics or centers do per annum? As well, do you have any data in terms of success rates on graft survival in comparison to sort of the general transplantation centers out there?
We actually have a wide variety of transplant center customers, some that are doing in the 20 numbers of transplants a year versus our big partners that are doing over 100. We do have a lot of variability. Interestingly, the smaller customers have actually been the ones that have really owned the technology, surprisingly to us, because of the advantages that it provides their program. The second part of your question was about data and survival. Because we just launched our XPS program, it's still too early to say. We are definitely working with XVIVO to keep track of that, about what our experience looks like in using the XPS device.
Thank you. We have a question for Professor Mohiuddin from our online viewers. Neal Beswick from Transplant Genomics has a question, and he would like to know what would be a major trigger to enable human clinical studies using a xeno organ, and how far out is this?
Thank you for your question. This is a valid question. Avoiding xenograft rejection was the main thing that we have achieved, and we have survival up to six months. Our next goal is to have survival enough to provide this technology as a bridge to transplantation. For people who are waiting for a human organ, they have to wait maybe two to three months before an organ is available. The first step into clinic will be providing this technology as a bridge. They get this organ, which will not reject within three months for sure. Once the human organ is available, then we will do it. In future, we want to extend it and make it as a destination therapy, which means that using it as an organ forever. The advantages are with the genetic modifications, which you can customize this organ.
At this time, we are sticking to about 10 genes that we have modified, and we think that this is enough to use in the human for the bridge transplantations.
Right. A clarification, of course, human studies is the first step. It would be quite a long path, I assume, moving into a stage where it can be used on a sort of wider scale as part of the transplant healthcare services provided. It's a tough question, do you have any idea how long that sort of regulatory journey would take?
We are in a process of conversation with FDA. The first step is for them to allow us to enter the human field, right? The results that we have may not be enough or they may require a certain more pieces of information. Of course, the biggest concern our regulatory agencies have is the transmission of porcine diseases to human, even the one that are dormant in the pigs, but may infect humans. So far, there is no such study that demonstrate that. Still, once we do the transplants, we'll have to monitor these patients for a long period of time and the tissue that's preserved for over a period of time. That's why the concern, until we alleviate this concern, the human studies will be a little difficult to do.
I think that we have enough answers for the FDA for to allow us to go forward.
Thank you. Professor Mohiuddin, out of curiosity, we've seen impressive data on sort of graft survival and so forth. Have you measured performance as well? I mean, compared to the baboon's original heart, is it able to perform as a normal ape, or is the pig heart in some way inferior or limiting to its way of life?
I mean, for six months to nine months that our baboons are living so far, they are doing very well. I mean, I don't know how they feel because their heart is different, but otherwise, they are still behaving like baboons. I mean, they are not doing oink because of the pig heart. Their function? Yes, the pig blood pressure and heart rate is a little bit higher than the original baboon heart. Over a period of time, we have seen that is not a factor in the survival of the heart, and it doesn't affect the animal that much. We believe that difference will not be there when we do the pig to human transplant.
Right. Perhaps it's not too far-fetched to assume that quality of life for a human recipient would be pretty good.
Pretty.
Of course. Yeah.
Also, I would like to add that in xenotransplantation, you'll be transplanting a very healthy heart compared to the hearts that we get in allotransplantation, which are from deceased donors. Right? They have their diseases to come with it. These are bred pigs in a controlled environment with a very healthy heart. This will provide an additive advantage to them.
Right. It's very interesting. Another question to you, Professor, from Jie Wang from Viewforth. How do you determine the most appropriate recipient group to receive xeno versus a traditional transplant?
Yeah, there are several groups that we are targeting. There are some diseases where the heart contractility is limited, and even if you put a left ventricular assist device, it's not able to contract that heart. These will be our first candidates who don't have an alternative like a LVAD or any other assist device. Also kids. As you know, in kids, there is a great need of heart transplantation. We think that when we transplant in kids, the immunity is still developing, and their immune system is still developing, and they can overcome the other barriers that we have left in transplant rejection. We may be able to induce even longer-term survival in the kids.
Thank you very much, Professor. Brandi, we have a question to you from our online audience, Johan Unnérus at Redeye wonders. Is it your experience that smaller centers are more ready to review their traditional attitudes and procedures, or is it more evenly spread among clinics you work with?
There's definitely variability. It's really what the program wants. Does the program want to grow? Does the program want to change, or are they looking to maintain their status quo? When you've seen one transplant center in the U.S., you've seen one transplant center. As Rodney said, we do have places like Cleveland Clinic that are a partner that they do a huge amount, and we have seen them change even their practices. We definitely know that with struggling resources, that the transplant centers that are smaller definitely do have an advantage to utilize the technology to leverage utilizing someone else to procure the organ for them. To take these organs that they may not have been able to go after themselves because of having to send someone to do that procurement and being able to leverage the technology.
There's definitely both ends of the spectrum when it comes to who is using it the most.
Thank you very much.
Rodney, I believe in one of your slides, you showed that utilization rate of one of your centers for EVLP had risen from 1% to 25%?
2016 to 2020. Is there an upper limit, like 30%, 40%?
Yeah, the answer is there's not an upper limit. As an example, Toronto, the largest transplant center in the world, 200 lung transplants in 2019, 50% of their lung transplants were from EVLP.
Right.
I don't think there's an upper limit.
Yeah. I guess it shows the potential, I suppose.
Overall market utilization rate is considerably lower, right?
Correct
than this. Maybe this isn't a question. Maybe Dag, earlier we ran out of time. I was just wondering, considering the COVID pandemic, has that in any way impacted patient recruitment? The clinical studies are very important now. Do you think you can stay on your timeline even though we have these current problems?
There have been problems related to COVID and intensive care unit capacity. Typically, what we have seen is that it doesn't happen at the same time in all countries. For example, in 2020, it was the U.S. that sort of ended in the pandemic a little bit before most of the European countries. Sales sort of slowed down last year, and then they picked up again, and we had a very strong first half in the U.S. this year. Of course, when you get variants, you get weeks of issues in certain hospitals, in certain countries. The need for transplants, you have seen it, and we've heard of it, we've talked about it all day. Over time, the number of transplants has to go up. We have to also accept and realize that. Not all countries will develop in the same strong way, in parallel at all times.
That's a fact.
It was inspiring to see Brandi's presentation on how Lung Bioengineering could expand into new service layers continuously. Christoffer, you talked about new business models earlier when you talked about the future. Can you see XVIVO doing the same journey or a similar one as to, let's say, Lung Bioengineering, following that example, adding service layers to your current machine and consumable sales?
We're looking to adding service layers. Lung Bioengineering is a partner. We want to partner up with the best companies in the world, because we share the same vision as Lung Bioengineering. We can together accomplish-
Right
great things.
This is about evaluation of lungs. Looking at, for instance, the abdominal area, it's a little bit more of a logistics solution. Can you see a similar opportunity there to provide services as well, in addition to the machines? Perhaps that should be an external partner?
Yeah, there are opportunities already now in certain European countries. For example, in Italy, just to give an example, we cooperate with a company called Avionord, who provides centralized perfusion services for certain organs there.
Yeah.
I'm sure that model will be developed, and I think it's a very good model, because not all hospitals, not all centers are equipped and resourced. There is also a shortage of perfusionists in many countries around the world. I think centralized services, when there is a center of excellence, I think that concept will grow and develop, definitely. I think what Lung Bioengineering has accomplished in the U.S., which is a fantastic journey they have had, there will be similar initiatives, I guess, also in Europe and other parts of the world. Yes.
Right. Then I suppose XVIVO will be part of that journey as-
Absolutely. I can promise you that, Lars.
Do we have a final question from the audience? If not, we're out of time. I would like to say a big thank you to all the presenters, and also thank you to all of you who have been with us today online, and of course, those of you who are here. We've learned a lot. There are lots of market opportunities. Pigs have strong hearts. I hope you can digest all of this information. If there's anything you would like to know or delve into, remember that you can always look at the presentations later on as well. Having said that, thank you very much from me. Now, Dag will wrap up today's lessons and summarize. Welcome, Dag.
Time to wrap up. Time flies when you are having fun. I hope you've all enjoyed this quite lengthy session. Since it is our first Capital Markets Day, we wanted to give you a lot of insight into the company. Before summarizing, I just wanted to conclude a little bit on what Christoffer Rosenblad just presented together with Dr. Mohiuddin on xeno. There is a race between two sites in the world right now when it comes to xenotransplantation. I don't think he's listening right now. Anyway. There is one in Maryland and there is one in Munich. The one in Munich is headed by Professor Reichart, who actually succeeded Dr. Christiaan Barnard in Cape Town, who was the first person to perform a heart transplant. Professor Reichart, Bruno Reichart, is doing the same thing as you saw from Maryland.
The question is, who is going to win? Professor Reichart believes that next year, there will be a first transplant from pig to human being. Let's see if that is right. They are both using our technology, and they can't do the work without our technology. This is fantastic. We are probably going to be part of something which is totally game-changing for the world. Just to summarize today's presentation, we live in a world with an extreme shortage of organs. I hope you're all signing up as donors after this Capital Markets Day. Demographics, chronic diseases, lifestyle, all of this leads to an increasing need of organs. The focus must be on increasing the number of organs available. In England, organ donation law has changed quite recently.
Since 2020, all adults in England are now considered to have agreed to be a donor when they die, unless they have recorded a decision not to donate or are in one of the excluded groups. Other countries with opt-out programs include Argentina, Chile, Colombia, Spain, Austria, and Belgium. Looking to the example of Spain, which is actually the most successful transplant country in the world. More organs are donated and transplanted in Spain in relative terms than in any other country in the world. They have adopted the presumed consent donation system. Intensive care units in Spain must be equipped with enough doctors to maximize the recognition of potential donors and maintain organs while families are consulted for donation. Things are happening around the world, and this will lead to more organs available.
On the supply side, the focus has to be on the utilization of organs. I think you've listened today and understood why there is an issue when it comes to utilization of organs. We all know that machine perfusion is a great enabler to drive utilization. We have a unique product range, we will be relentless in executing our strategic focus areas, I will consistently chase my team members and organization to execute and deliver. That is something I have promised them. At the end of the day, all of us go to work at XVIVO because of people like Bea. Nobody should die waiting for a new organ. With these last words, I would also like to say thank you to Lars Frick for being an excellent moderator.
Now I'm going to test you, Lars, and you can give me the answer later on tonight. Once upon a time, you said something which I found truly great. Maybe you remember when and in what context. [Non-English content] promise around and keep thin. This is something that we as a company will never do. What we focus on will be delivered, will be executed. You can all count on that. Thank you for participating in today's Capital Markets Day. Thank you all.