Hansa Biopharma AB (publ) (STO:HNSA)

CMD 2020

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Oct 29, 2020

Good afternoon, and welcome to the Hanse Biopharma Capital Markets Day. My name is Claus Sindel, and I'm Head of Investor Relations at Hanse Biopharma. I'm very pleased that Hanse Biopharma is hosting its 3rd Capital Markets Day here in Copenhagen on the back of an eventful summer with many milestones achieved, milestones which essentially is transforming the company into a commercial state biopharmaceutical company. I'm also really excited about the program and the lineup of speakers we have this afternoon. The presentations will take us through very interesting aspects of Hansa Biopharma both in terms of our recent progress, but also highlight opportunities outside of kidney transportation in new areas such as gene therapy and autoimmunity. This also underpins that we have a very unique technology asset with very broad commercial opportunities also outside kitten transportation. I also wanted to introduce today's moderator, Rachel Curtiss Grausen. Many of you would know Rachel from her long career with Genmab, where she worked as the Senior Vice President of Investor Relations and Communications. Rachel is also a seasoned healthcare professional with more than 20 years in biotech and pharma and is now working as an independent consultant. Rachel will lead us through the program this afternoon and will moderate questions from the audience. With this, I will now leave the word to Rachel to go through the speaker lineup and the agenda. Rachel? Thank you very much, Claus. It's a pleasure to be here. As Claus said, Hanse has had a very exciting year with a lot of milestones. And the company is now transitioning into the next phase of commercialization whilst really holding on to the roots of being an R and D company. Let me just take you quickly through the agenda for today. We're going to take stock today of the achievements that Hanse Biopharma has already achieved, but also looking towards the future to discuss the vision for the company, the different areas of research, the launch plans, of course, to the recently approved drug, but also looking across at the actual vision and the financial stability of the company going forward. So over the next 4 hours, on your screen now, you'll see we're going hear from different senior leaders in the company. We're going to be talking about the corporate strategy, the commercial strategy, the launch of Imlifidasa. We're going to be talking about the R and D focus in the coming hours as well. We're also going to hear from some key opinion leaders who are going to talk about the areas that Hansa is working within. So let me just take a moment to run you through the agenda. As you'll see, we're going to do this in 3 distinct blocks. So there will be some breaks in between because I know it's a long time to sit for us looking at a stream, but this is our new reality that we do everything virtually. So what we're going to be doing is starting very much with a look with presentations from the company's CEO, the Chief Financial Officer and the Chief Scientific Officer, and they are going to be taking us through the scientific base, the corporate development and the financial foundation of the company. After a quick break in probably about 10 minutes, we're going to have 5 speakers who are going to look ahead at imlifidasa in kidney transplantation telling the story from development perspective but also, of course, the commercial launch that we all want to hear about. Another quick break, and then we're going to have some more speakers who are going to look ahead at how Hansa can really leverage the technology platform that they have in different indications. As I said, we're going to have Q and A sessions after each of the different blocks of speakers. It's very important that you use this opportunity to send in your questions. On your screen, you'll see at the bottom of your screen a little button that says or ask questions. Just press that button, type in your questions, it will come to us. My job is to try and make sure we get through as many questions as possible, and I will try my best to do that. So send them in throughout the coming hours. We will also have a sort of summary Q and A session at the end you can see on the agenda where any kind of questions can come, but do send them in throughout the day and we'll be monitoring them. Without further ado, because we have a lot of things to get through, I'd like to introduce Hanse Biopharma's CEO, Soren Tolstrop, who is going to start the meeting with the first presentation outlining the company's strategy and the vision ahead. So welcome, Sern. Thank you very much, Rachel. And also from my side, a very warm welcome to this Capital Markets Day, a broadcaster here from Copenhagen. As you've just seen, we have a very extensive program lined up. And all of the speakers, both internal, handset biopharma speakers and external partner speakers, have looked very much forward to this opportunity to review and discuss current status and outlook, go through key company assets and also discuss our value creation strategy going forward. Before we start though, just the usual warning that many of the presentations today contain forward looking statements. And as such, you should apply appropriate caution. I also want to show this slide just to make sure that we all are aligned that when we talk about IDI4X, this is the regulatory context. So with this, let's get started. The timing of this Capital Markets Day is really very appropriate. The first drug candidate from our internal pipeline, IDEFRX for enabling kidney transplants in highly sensitized patients has just received regulatory approval in the 1st key region, namely the European Union and associated markets, I. E, the European Economic Area Countries. We're very excited to soon become then a commercial stage company and launch what we think is a product that clearly has the potential to transform therapy and bring much value to patients as well as society at large. But the Hanse Biopharma story is so much broader, and our level of ambition is so much broader than just using IDIFORIX as a way to establish a leading position in the transportation field. Given the versatility and flexibility of our scientific platform, the strength of our organization and the support from shareholders, we truly believe that we have what it takes to, over the coming years, become a leading player overall in rare diseases. The source of our self confidence really is the successful journey that we've been on so far, the strength of our company assets and also the strong momentum we have as we meet here today. Looking at our technology platform, it has received validation in at least 3 different ways. First of all, the approval of IDFRICs, of course, serves as documentation that we have a platform that can be used to develop approvable drugs. 2nd, the anti GBM data that we will discuss in more detail later today during Professor Morten Siegelak's presentation served to essentially provide proof of concept that our platform has the potential to develop products in the broad range of autoimmune diseases. And 3rd, the deal we made with Sarepta just before summer serves as external validation of the potential large and promising field of gene therapy. Looking at the IDe4x launch, as I said, we're very excited to be ready to launch this product. We truly think that it has the potential to transform therapy. And obviously, it is something that is bringing hope to the thousands of highly sensitized patients across Europe that currently are waiting almost against hope for a compatible kidney. So this brings hopes to these patients, kidney. So this brings hopes to these patients, but it is also a significant commercial opportunity for us. In my more than 30 years of experience in the pharma and biotech industry, I've had the great fortune and the privilege to be involved in a number of breakthrough therapy product launches at companies such as Merck, Novartis and Shire. And I can truly and honestly say that the IDePhrix launch really comes at the very top end in terms of the degree of innovation and the potential to deliver true patient value and societal value. So we're very excited about this opportunity. Obviously, you need a strong organization to ensure successful launch and also develop a valuable pipeline. Hansel Biopharma is still a young company. It's a small team, but we've already been able to assemble what I clearly think is a very, very strong team, And we'll discuss that in a bit more detail. A highly motivated and focused team that really is able to pursue innovation in an agile manner. This team has already developed significant shareholder value over the preceding years. The current market cap of the company is around $1,000,000,000 which dwarfs what has been put into the company financially since the inception of the company. So significant shareholder value has already been created. And based on that track record as well as the strength of our assets and the momentum, we're recently able to raise significant new capital, more than SEK 1,000,000,000 And with this, we're well funded for the coming couple of years as we embark upon the exciting journey ahead of us. So as we set out on this journey, we have 3 very clear overall strategic priorities. The first is to advance our platform in new indications and therapeutic areas. And in doing so, we aim to establish 4 full fledged franchises: transplantation, autoimmune diseases, gene therapy and oncology. In the transplantation area, of course, the approval of IDAFRIGS and the coming launch is a very significant step into that universe that has great potential per se. But as we will discuss later today, we truly think that there are many other opportunities in this space. Other organs, label expansion and other geographical markets than those that will be the early launch countries. Looking at autoimmune diseases, I mentioned anti GBM, but really anti GBM is just one of more than 100 currently known autoimmune diseases, many of which are very, very serious diseases, many of which have no approved therapies for them, And many of which are driven by IgG as a key part of the disease pathology. And IgG is the target of our technology platform currently. So we think that there's great opportunity in this space. The 3rd area is gene therapy. Gene therapy is very exciting. It's a growing field with lots of promise. There are more than a couple of 100 ongoing projects and several approved products already. But a great challenge that the gene therapy companies, or at least many of them are struggling with, is the fact that neutralizing antibodies will make it very difficult for some patients to see the transduction of the healthy gene. And we think based on very promising preclinical data that were most recently published in Nature and Nonhuman Primates, that imliphidase and other enzymes has the potential to do away with these neutralizing antibodies. And we'll discuss that in further detail, as I said. The 4th area is oncology. And here, we have generated very encouraging data in a mouse model indicating that amyloidase and other enzymes potentially can potentiate the effect of immuno oncology therapies. We're currently hard at work generating additional proof of mechanism. And once we have that, we're ready to also invest further in building a franchise around that. The second key strategic priority is to use the IDeforex launch really as a first step towards realizing the blockbuster drug potential we think the amylithidase molecule has. Obviously, initially, we'll focus on the launch in Europe. But medium or even short term, we'll start to also look at markets where we can build off of the EMA approval to gain market access. There are significant opportunities in markets outside of Europe that match this description. We also have our eyes firmly set on the U. S. Opportunity, which is very, very significant in the kidney transplant space. We have already achieved overall agreement with the FDA around the regulatory pathway forward towards potential BLA submission by 2023 under the accelerated approval pathway. This agreement entails us running a limited randomized controlled trial and we're ready or getting ready to initiate that trial next year. The 3rd key strategic priority is to then build organizational capabilities and expand our platform. So first, of course, right now we have the core commercial and medical affairs infrastructure in place already that will support the early launch countries with IDAFRIX for IDAFRIX. But of course, as we roll out this product, we will further increase the footprint. And that will help the launch, but it will act as an asset per se that we can use when we are to launch other products coming out of our pipeline. We will also continue to expand our R and D capabilities and strengthen our platform by accessing complementary platform assets. And as we do this, we will fully leverage the partnership pathway to access external source of innovation. I truly believe that in this very complex and fast moving industry, companies that are able to position themselves very centrally in the innovation ecosystem and access external innovation and integrate that in their own internal efforts are much better positioned than companies that only build up internal resources. So that's something we will certainly continue to focus on, and we've already made our first important partnership in the gene therapy space with the Sarepta deal. So those were the key strategic priorities overall. Pursuing these, we're also pursuing the end vision which I talked to initially, which includes extending and improving human lives and delivering value to society. I think we can say that we're already well underway here. Looking at IDAFORIX, Ideforex has demonstrated in the Phase 2 trials an ability to enable lifesaving kidney transplants. In fact, in 100% of the highly sensitized patients treated, IDAFRIX was able to enable kidney transplants. So I think we can at least partially check the box there around extending and improving human lives for IDOFRX. Of course, we need to now generate also real life data post the launch. We have also developed already a comprehensive health economic dossier, documenting the cost effectiveness of IDHIFRX versus the alternative of remaining on dialysis. This is a cost effectiveness story that resonates very well with payers. We've already reached out to quite a number of these payers, of course, in Europe. And even though here also we, of course, need to show that in a real life setting over the coming years, I think we have lots of confidence that IDFRICs can ensure much better and much more productive use of the 100 of 1,000,000,000 of dollars that are spent annually across Europe, the U. S. And the rest of the world on dialysis. As we pursue our vision and our strategic priorities, we are putting in place and leveraging a very well designed and clear value creation model. And you can see it depicted on this slide here. At the core of this, we have the IgG cleaving enzymes, amylithidase and other enzymes. And as we develop drugs from these enzymes, we will seek to control the key value chain elements all the way from the laboratory to the bedside of the patients. Now such control does not precondition ownership, outright ownership. Rather, it's a question of having management's control so that we can capture the lion's share of the economic upside and also ensure optimal usage of our drug candidates. When it comes to the later stage, the commercialization phases, as you can see here, there is kind of a bifurcation later on looking at transplantation and autoimmune diseases, given the fact that the target audiences are quite concentrated and we control many of the assets needed. It is our intent to go all the way to the market ourselves. Whereas for gene therapy and oncology, given the fact that we need to access complementary assets and also the fragmented nature of the marketplace, we intend to use partners to a large extent. Now this is not black and white. There will be some overlaps between the 2. But overall, as I said, this is how we intend to move forward. And then we will monetize the resulting assets in the form of different income streams, including sales, upfront payments, milestone payments and royalties. Now, no model is better than the people inside it, the people who have to operate it. And even though Hanse Biopharma is still a young and small team, I'm very comforted by the quality of the team that we have assembled. We have put in place a very dedicated effort to access global talent wherever in the world it's based and regardless of gender or race. And for that reason, we have been able to sample a very skilled and experienced team. A full 35% of our team members have relevant PhDs. And even though, as I said, we're a young company, the average experience industry experience is 20 years. So it really is a very, very solid and an experienced team. And what is even more important, I would say, is that it's also a true team. It's not just a collection of individuals. It's a true team and it's highly motivated as evidenced by the results of a recent employee survey that we ran in collaboration with a Great Place to Work Institute and which documented that an impressive 95% of team members would recommend Hanse Biopharma as a truly great place to work, which puts us right at the top of our peer group. So this team has already accomplished a lot. They have built a scientific platform. They have taken the first products from discovery all the way to regulatory approval. And now as we discussed initially, we are on the cusp of becoming a commercial stage company. And as we move into that new space, we'll be focused on building and capturing value in new indications and markets. And this is something that we'll discuss quite extensively today. And as my team members will discuss this, they will use this navigation chart that we call the, HANSA Biopharma Growth Circle to illustrate the opportunities and the different growth trajectories. And as you can see here again, we have the platform at the core in the center of the circle, amliphidase and other IgG cleaving enzymes. And then we have the growth trajectories into the different universes, autoimmune diseases, transplantation, gene therapy and oncology. And you see then little dots here, pentagon shaped dots. They all represent either a concrete ongoing project or an opportunity. And I'm hopeful that at the end of today, you will agree with me that looking at our landscape, there is really a lot of pentagon shaped dots out there representing opportunities. So in conclusion, I think it's fair to say that we've already come a long way even though we're a young company. We have generated clinical validation, external validation, regulatory validation of the scientific platform. We have established very sound and validated manufacturing and overall supply chain. We have generated strong IP, built an exciting pipeline, which is growing as we speak, and we have a very strong team in place. As we look ahead and navigate towards our key strategic priorities and the Envision, we have, of course, also put in place some very clear and measurable milestones. Expanding IDAFRX, the label into transplantation and into other solid organs, obtaining regulatory approval in anti GBM, GBS and AMR, demonstrating proof of concepts in our next generation enzymes, the NICE program, expanding partnerships in gene therapy and oncology, advancing clinical studies with amnipidase in pretreatment in limb girdle and Duchenne with Sarepta, and showing proof of concept in new indications such as oncology. As we achieve these milestones over the coming years, I'm confident that transforming Hanse Biopharma will become reality And that when we meet 5 years from now, hopefully, at the other end of the COVID-nineteen pandemic, so we can meet face to face, Hanse Biopharma will be recognized as a global leader in rare diseases across multiple broad therapeutic areas with several market leading products and a highly valuable pipeline of late stage drug candidates. So with this, I'll hand back to you, Rachel. Thank you so much. Thank you. We will come back to questions. We have had some coming in already. And as a reminder, you just press the button at the bottom of the screen, which says ask questions and you can write them in. I am looking at them, I promise you. So, CERN outlined the building of a business. So, to follow that, I'd now like to invite the Chief Financial Officer, Donato Spotter, to come and take us through how you're going to pay for it. Thank you, Rachel. So building on what Soren outlined, I will provide you with an overview on what we see as our key priorities to focus our investments on in the next few years. But let me first start by looking back from where we stand today. The last 13 years have been actually a period where Hanse formed and developed significant shareholder value through its activities. During that 13 years, we have been validating our technology platform both internally and externally. We took a Mercedes all through development to market approval in Europe, investing about SEK 100,000,000 in research and development. Starting then from 2018, we built a commercial organization to step into the next phase of Hanse's mission and very soon launch our first product, IDFRX. And we grew the market cap of Hanse to more than US1 $1,000,000,000 which means about 10 times return on our investments in R and D. Over the past years, we also did meet a number of significant value inflection points, primarily related to the successful development of emlividase in kidney transplantation and this paved the way to successfully financing the company out of a position of strength. And most recently in July this year, we raised another US121 million dollars on the back of a positive CHMP opinion and the agreement with Sarepta in the gene therapy space. So leaving us with a significantly strengthened cash position. So by the end of September, we had about US150 $1,000,000 in cash, which is a solid position allowing us to invest in our future growth and value creation. At the same time, we've also been focusing on diversifying on our shareholder base. Today, we have a strong international base of shareholders with 70% of our capital being held by institutional investors, including some of the most renowned and leading global life science funds. And as well, we have been able to diversify also in the regions. We have more than half of our or about half of our investors coming from the U. S, from the U. K. And Continental Europe. So we believe that this shareholder base will allow us to will allow for continued support in upcoming financing rounds as we continue to exploit our highly investable platform. And on top of that, also to potentially do a U. S. IPO in the not too distant future, which remains a key strategic priority for the company. So as mentioned before, we have a highly investable platform. And with USD 150,000,000 on hand, a solid cash position, which does allow to actually broadly exploit this platform, while at the same time invest in a successful launch of AMLIVIDAYCE in kidney transplantation in major markets in Europe. So what do we see as our financial priorities for the coming years? First of all, we want to fund the commercial expansion of EMPLIVIDAYCE across Europe to make this first launch a successful launch and we are targeting reaching product profitability in Europe for INLIFO days or actually for IDO4 rigs in the midterm. 2nd, we want to continue and maintain the level of investments in developing kidney transplantation. In particular, we are looking at approaching the U. S. Market with IDOFARIGS in kidney transplantation, but also making sure to maintain the EU approval and support the EU approval. So in that area, we foresee that the level of investments will approximately meet what we've been investing in the past. 3rd priority, that is to accelerate the investments and the activities in progressing the new therapeutic areas. Soen had mentioned it, in particular including autoimmunity, gene therapy and cancer. We want to build on the promising anti GBM data and the partnership, the successful partnership with Sarepta aiming for regulatory approval in anti GBM, in GBS and in AMR while expanding our partnerships in gene therapy, but also entering into new partnerships in the space of oncology. We therefore do plan to accelerate the investments over the coming years and over current levels to force the progress in this area. And last but not least, the 4th priority is to increase the investments in the development of the next generation of enzymes to allow for repeat dosing, potentially opening up for a whole set of new indications as Bahram will be alluding to later today. So in summary, Hansa is very well positioned to continue its journey to become a global leader in the rare disease space, both financially with a solid cash position that will fund operations presumably into 2023 and even more important with a very promising and highly investable enzyme platform. So we look forward to keeping you updated on our future progress. Rachel? Thank you, Donato, and thank you for outlining the financial foundation going forward. Now I'd like to invite the company's Chief Scientific Officer to take us through the R and D priorities going forward. So, I'd like to invite Christian Schillman to come and address the audience here. Christian has been part of Hansa for a very long time and so has actually seen imlifidasa move through development and to be approved in Europe earlier this year. So as a seasoned R and D executive, Christian's role has actually just been expanded. So you're also now the Chief Operating Officer, I believe. So Christian, Yes, I will talk about the vision, the scientific vision, our potential future. But before I do that, and I would like to start talking about our greatest achievement so far, and that is to obtain a regulatory approval for iDFRICs in the European Union. This is a great achievement for Hansa because it's a validation of our technology. It's also a great achievement for the organization, for the team, for the people working at Hansa because we have shown that we can do this. We can bring a drug candidate from the lab bench to the bedside of the patient. And we can do this in within the expected time of drug development that is 10 to 12 years. And we can do it at a significantly lower cost than the expected cost. In fact, we did it for 10 times below the average cost for drug development. But this is also a breakthrough for the patients, for the patients that need a kidney transplantation but cannot access it. And then I would like to spend some time on the indication because who are these patients? It is the indication is about kidney transplantation. It's about desensitization. It's about transplanting patients against a positive cross match. But more importantly, it's about transplanting the patients who are unlikely to be transplanted given the current allocation systems and priority programs. So in fact, this is really the patients with the highest unmet medical need. And you will hear more about this this afternoon from different speakers. They will talk about these patients in different contexts. So with this, I will move back to the vision, the scientific vision. And I will use this graphics that Soren introduced before, where we have our technology in the center, Imliphidase, combinations with Imliphidase and then our next generation program. And then I will talk about how these this technology can be used in transplantation, in autoimmunity, oncology and gene therapy. So let's start at the center of this graph with the technology. This technology forms the basis of our continued evolution. It's about evolving the proteins and it's about combining the proteins with other technologies. If you look at the center of this graph, you can see pathogenic antibodies after emliphidase treatment. And in the top graph you can see a short time period, 30 days. Below you can see a longer time period, up to a year. And what you can see is the rapidness and the effectiveness of amylithidase, how it very rapidly within 2 hours lowers the IgG levels to basically 0. Then after a week, you can see that the antibodies start coming back. If you look at the graph below, you can see that this is transplanted patients. You can see that antibodies eventually the levels are reduced and they go away. So this is an opportunity for us to and a challenge for us to continue to work on this what we call the rebound of antibodies, to try to have a longer lasting effect. And how do we think around these enzymes? If we start with amlividase at the core, it's a lot about indication selection because we need to identify indications where this temporary effect of imlifidase adds a clinical benefit to the patients. We have shown that in kidney transplantation, and later today you will hear Martin, Seager and Mark talk about anti GBM. But it's also about advancing patient management because if this is kidney transplantation, maybe you shouldn't treat the highly sensitized patients with the same immuno suppression that you use for any transplanted patients. Maybe you need to further develop that and that is that is something that we at Hansa will will work together with the scientific and medical community to develop. Then if we move on to the next ring here, you will see imliphidase plus combinations. And this is really to think can we use emlividase as an induction therapy and then combine it with another maintenance technology, maintenance therapy. And there are several opportunities for this. The one that I am very interested in is a technology that also targets IgG and that is the SRM blockers. These technologies are developed by I think 3 different companies right now. It's argenx, UCB and J and J. These technologies, they don't have the pronounced effect and the rapidness of emliphidase, but they can be used for long term management. So I think a combination of those 2 therapies could potentially be very interesting. And then there are other technologies that you can combine. It's complement inhibitors and it's new technologies that are targeting the cells producing IgG. And then at the outer ring, we have the NICE technology. That's the next generation enzymes. That is where we in house are genetically modifying the enzymes to improve them, to get to reduce that immunogenicity and reduce the immune response against the enzymes to allow repeated dosing. So now I will continue in the graph and talk about transplantation. And now for the first time, patients can access iL4x to enable a life changing kidney transplantation. So what we're doing today is to launch the product in Europe. We're launching patient by patient, centre by centre, country by country. But then we're going to use the current phase 2 data and the authorization acknowledgement that we got from the European Union, our regulatory approval to enter new markets. And then of course we continue to develop to also be able to enter the future markets such as the U. S. But maybe even more importantly, it is about generating evidence to generate experience, to generate data and trust for IDOFRICs. And this is something that we will continue to do because we have our commitments from the regulatory approval in the Europe. We are going to do a post approval efficacy study to further study the molecule. We are going to do pediatric studies. We are going to do IIT to collect more evidence. We of course on the market going to collect real world evidence, And we will continue to work with the transplant community to shape this new standard for desensitization. And then it would be even more future looking, there are more opportunities for us because our label states deceased donor transplantations. But it's really, really the highly sensitized patients, they are listed for deceased donor transplantations, but many of them might have a living donor that is incompatible. So so it's a it's a reasonable assumption that label expansion into living donor transplantation is possible. And then there is the solid organ transplantations, like lung transplantations and heart transplantations. The medical need is as high or maybe even higher than in kidney transplantation. But so are the risks. Because in kidney transplantation, you have the fallback position of dialysis. If something goes wrong, you can go back on dialysis. You cannot do that after heart and lung transplantation. So this is something that we need to develop once we get a better understanding of the desensitization standard. Then I would like to move on to autoimmunity. And Morten Segelmark will today present data from the anti GBM study. It's an IST study that Morten has sponsored. The data that he will present I think is the first indication of proof that imlifidase can have a clinical benefit in autoimmune diseases. And this really means that we can take anti GBM further in development. We can move the molecule and development towards a regulatory approval for Antigua in Europe and in U. S. And we will do that. But it also conceptually shows that the emliphidase can work in autoimmune diseases. And we have ongoing studies in Guillain Barre syndrome. It's a European proof of concept study. And we have an ongoing study in AMR, which is a randomized international study. And you will hear more about these studies later today. And then if we think even further beyond that, there are several opportunities in IDG driven or IDG associated autoimmune indications where our technology in lithidase or the next generation molecules or the combination opportunities can be developed. And that also opens up partnering opportunities for Hanse in the future. Then oncology. Oncology is also about enabling and potentiating cancer therapy. And perhaps the most easily accessible opportunity for us is within bone marrow transplantation. Bone marrow transplantation is used to treat several different cancers. It's usually like lymphomas, leukemias or myelomas. But this usually you use the patient's own bone marrow cells in the transplantations, but a better source and a more accessible source is to use allogeneic bone marrow cells. And what you experience when you do that is a situation that is very similar to the kidney transplantation situation where the patients may have and in fact more than 30% of the patients have preformed antibodies to the bone marrow cells. And we think that the emliphidase can play an important role there to enable these bone marrow transplantations And we are right now looking into how would the development program and the regulatory path forward look like in bone marrow transplantation. If you take that concept even further, then how about CAR T cells? Again, autologous CAR T cells is the standard today, but to be able to use allogeneic CAR T cells from not from the patient, but from another donor would open up that therapy. But then if you want to do that and you want to use the therapy repeatedly, I think that you will experience a situation with donor specific antibodies. This is something that we are pre clinically looking at right now, but it could be a future opportunity for us. And then we have the ENSA concept. That is where we have shown in animal models that if you pretreat the animals with IDOFRICs, you cleave all the IgG and you release the full potential of the effector cells in immune oncology, in antibody mediated cancer therapy. And this is something that we are we are continuing to look at and it's a future partnering opportunity for us. Gene therapy. This is where the vision is being realized right now. In gene therapy it's about neutralizing antibodies. As many as 60% of the normal human population have antibodies to the gene therapy vectors, to the AAV vectors. And these antibodies, they prevent the patients from receiving gene therapy treatment. But even more complicating is that once you have received a gene therapy treatment, these these viral vectors are very immunogenic. So the patients develop high titers of antibodies against the gene therapy vector. So it's very difficult to treat the patients again. And then the question is can emliphidase help in this situation? Can emliphidase enable gene therapy in patients with preformed antibodies to the vectors? And can imliphidase even enable repeated treatment with gene therapy. So this there was a publication in this summer in Nature Medicine that quite elegantly illustrated this. They could show that yes, emliphidase or IDES can enable gene therapy in animals with preformed antibodies. And the data actually also indicates that imliphidase could enable repeated treatments with gene therapy. This is very encouraging. So what we have done quite recently, as you know, we have entered a collaboration with Sarepta. And this this partnership is really about exploring this opportunity, developing emliphidase as a pre treatment in muscular dystrophies, primarily Duchenne's and limb girdle. But beyond that opportunity there are more partnership partnerships opportunities for Hansa within a range of different indication all the way from neuromuscular diseases, bleeding diseases, inflammatory diseases. And then being a little bit more visionary, how about if Hansa should develop one of the next generation enzymes specifically for gene therapy? I think we can do that and I think we should do that. And what about the new technologies that is coming up, like the gene editing technologies where you actually repair the damaged genes in the patients, like the CRISPR cause. I think there is there I think there is an opportunity for our technology also in that context. Finally, I would like to talk about the most important element for continued growth and success at Hanse and that is the people. Because it is people that are doing this, the people at Hansa. And to keep and maintain the agile and entrepreneurial mindset at Hansa, to allow the smart, brilliant, hardworking people at Hansa to thrive, to build our organization and develop our ways of working. That is our it's my most important mission for the future to ensure that Hansa continue to grow and to be successful. And I would like to take this opportunity because I know that many of you are actually looking at this. I would like to take the opportunity to thank the people at Hansa. I would like to thank you for your engagement and your commitment and your hard work. Thank you very much. Thank you, Christian. That was very good. I believe you're going to stay to do some questions and answers with us now, and I'm going to invite Soren to join us as well so that we can run through some of the questions that are coming in. We won't get through all of the ones that you've sent in so far now, but we're going to have a stab at getting through some of them before we're going to go to a break. So actually, I wanted to start, we've had a question. I think actually it might have been Donato, but I'm sure, Soren, you can take it. Mentioning access external sources of innovation, does that mean acquisitions? Potentially, yes. I mean, right now, certainly, we have enough on our hands, right? So we don't need that. But clearly, at some point in time, there may be complementary assets that might be a good fit for us. And if it's doable, we'll certainly also look at that. But right now, I mean, we're fully focused on really leveraging our own platform and also partnering. So it's not a short term priority. And maybe this is a follow on question because we had a question coming in asking about fact that Spark have published some preclinical data. Do we have a deal with them? We don't have a deal with Spark at this point in time. So the data set that was generated there was generated by some scientists at Spark, but also at Genethan and other places, right? So that's made with the amlividase. But at this point in time, we don't have a deal with Spark, no. So maybe moving on, Christian, this is probably a question for you, but let me just check with Sande first. In terms of the EU approval, conditional. What do we need to do to actually get the full approval? What are the steps, data, timelines, those kind of things? Sure. I'll hand over to Christian, Terrain. Yes. We have a commitment and that is to run an additional clinical study. It's a single arm study. It is to generate more data from more patients. And it's a reasonable scope of the study. And we also have a pediatric commitment that we need to fulfill. So in terms of the EU approval, is there any way that, that can lead to accelerated development in other indications? Is there any way that other studies can become pivotal regulatory approval type studies because of the EU approval in kidney? Not because of the approval per se, right? I mean, obviously, once you're approved, there is the ability to expand your label in various ways, right? But the approval per se does not give that expansion, right? So you need to still generate additional data. So the development will stay as it is. We won't be changing some of those development studies. I think that's what the question is asking. Are any of the current studies going to change status by adding patients? No, no. You can label EXPON within transplantation by doing and collecting additional data. But if it's different indication the regulators will view it as that and you will need to do. We also had a question asking about the impact potentially on the FDA of the EU approval. If the FDA look at what's happening in Europe when the drug is actually launched? Obviously, I mean, clearly, you're generating real life experience in Europe, right? And we're doing that also through the post approval commitment that we've signed up to here with the trial. But really the situation in the U. S. Is unique in that the reason why the FDA has requested us to run now a trial before submitting a BLA, which marketing authorization application is called in the U. S. Is the fact that they have a kidney allocation system that they want us to generate data versus. And you can argue about that position, but it is what it is. And as I said, we have an overall agreement with them around the path forward. So that really is a separate situation. And we think we can run this trial in a time compressed manner. It's limited in scope. And we're quite certain that we'll be able to generate very good data based on what we know so far. I think we have time for at least one more, maybe 2 if we're quick. And I think this is a question that came in following your presentation, Christian, about can we expect larger pooled allogeneic stem cell treatments to be developed now? Larger pooled allogeneic stem cell transplantations. I think that that is always an issue in stem cell transplantation to identify the donors. And you are restricted to matching in HLA. So you're restricted to either the patient's own donors or the or a bone marrow register for instance. But to have that opportunity to access a donor, it could be a parent or a sibling that has a half matched phenotype, that could be a really good source of bone marrow and it is being developed, it grows. But then you have this issue with sensitization that we might be able to address. I've got time for, I think, one more really quick one, which is definitely one that I think, Zerna, you're going to want to answer. Donato talked about a priority of Can you explain more about the sort of plans for that? Or is there any time lines? Or maybe you can just expand a bit on what he said? There are no specific time lines. But clearly, as Donato indicated, it is a strategic priority for us to make sure that we can access all of the resources that are in the U. S, not lease capital. We've been able to do that quite effectively and efficiently so far through our listing in Stockholm. We've brought on board some really top notch leading life science investors based in the U. S. But clearly over time we want to be able to have a more efficient approach there. And so so as and when we become ready for that, we certainly want to be able to execute on that, yes. Very good. I think we're going to take a quick break now. It's going to be 10 minutes. We're all in different time zones from so 10 minutes from now, which is about 22 whichever hour you are. So join us again in 10 minutes. Thank you. Welcome back to Hansa Biopharm's Virtual Capital Markets Day today. Before the break, we had presentations covering the corporate, financial and scientific ambitions of the company. Now we're going to turn our attention to the clinical evidence and the commercial planning for immunofidasa in kidney transplantation. Now, the next three presentations are actually not from people that are here with me in the room. They are remote in different geographical locations, but I will introduce each of them. Also, we will take a Q and A sort of halfway through the session once we've heard from 1 of the KOLs who's going to speak today. But before we continue with the presentations, let's just take a moment to be reminded of why HANCER is actually doing what it's doing. And we're going to hear from a patient who's on dialysis. I'm not a typical transplant case. With having antibodies at a 100%, I'm a difficult match. People think that I'm the superwoman. They look at me and they said, I would never think that you had kidney disease. I would never imagine that you're on dialysis. And I say, yes, I am. And while it's good to convey that and look strong and look healthy, my body very much is tired and and not very strong. I still think about every day, am I going how much longer can I go on dialysis? You know, you you think about that in the back of your mind. So I still have the same emotional challenges. So even though I choose to keep fighting behind closed doors, I am still very much a vulnerable person that still wants to live. A surface level what I go through. There's 37,000,000 Americans with chronic kidney disease in the US. That number is scary on its own. But if you think about the fact that 96% of people with early kidney disease have no idea that they have it, that 37,000,000 is a really scary number. Each person is literally going through a battle each treatment or each day. But we are essentially tricking ourselves each day to keep hope alive, if you will. I think the ultimate goal that all of us have is a future where, a, either no one's getting kidney disease in the 1st place, or b, having some kind of a new treatment where someone is either getting a kidney very quickly or getting some kind of an implantable kidney that eliminates the need for dialysis. And for me, that's one of my biggest fears. And it's just, you know, your body can only go through so much. It doesn't matter how strong you are. So I wonder what that day is for me. Products for orphan indications that answer unmet medical needs. Educating medical professionals on what IMLIFIDASA can actually offer is important. And medical affairs is one of the departments that cancer is now building up. The Vice President Global Medical Affairs, Vincenzo Nigro, is responsible for building that organization. Vincenzo has 3 decades of international experience in the field of medical affairs, in the life science industry. She's currently based in the US, so she is sitting remotely a long way from us in Europe today, but she's an important part of Hansa's expansion plan. So, Vincenzo, I'd like to hand over to you now to take the next presentation. I wish I could be there with all of you. But it is with great excitement that I share with you the medical affairs journey as we launch this new transformative therapy. Next slide, please. Medical Affairs is a fully integrated partner in the Honza team and the launch team. This is so important because as a company, we can help patients like Melissa access a promising treatment like IdiFERIX and a potentially lifesaving kidney transplant. Next slide. With Idapherix, as Soren presented, we are paving a new path, a new way to transplanting these patients and a new journey. We will do this in a very focused way, clinic by clinic, one patient at a time. Our objectives are to have a positive impact on patients and physicians as we shape the area of desensitization and integrate IdaFERIX into the transplant community as a new standard of care. This is a major strategic approach for us since Idoferix is the first and only approved drug in desensitization in the EU. Next slide. Next slide. We are creating value across the kidney transplant ecosystem. And as medical affairs, we're dedicated to the transplant teams at the clinics to educate them on Idoferix and prepare them to smoothly integrate IdaFERIX into their transplant programs. We work together with multidisciplinary teams to ensure appropriate use and approach to enabling kidney transplants with Idaherics. Next slide. The opportunity lies in identifying the right patient that would benefit from rapid and effective desensitization and that is in need of a deceased donor organ offer like Melissa. Our indication, as Christian highlighted, allows for transplantation of the very targeted population of highly sensitized patients with a positive cross match against an available donor and who is unlikely to be transplanted within the current kidney allocation system or prioritization programs and unlikely to be transplanted with a compatible organ. Our target population is definitely the higher immunologically complex patient. Next slide. As we shape desensitization within the EU, we're very engaged with the transplant community within the key centers. We are creating awareness around the unmet need and publishing on our 46 patient cohort of data with 10 abstracts, publications and presentations in the past year. We've sponsored 5 Hansa sponsored symposia at major congresses, and we just recently published our pivotal international trial from the U. S, France and Sweden recently in the journal Transplantation. In addition, we have established a unique collaboration with the European Society of Transplantation with their transplant learning journey 2.0, where they have dedicated a work stream to desensitization to bring European consensus. Next slide. As you can see from this slide, in the European Union, there is not a single allocation system. The systems are comprised of regional systems, national systems and international systems, such as uro transplant and scandia transplant. While the allocation systems have improved access to transplantation for these highly sensitized patients and have prioritized them, there's still a population of patients who remain disadvantaged because they are immunologically complex. Having spent most of my career in transplantation and since launching the transplant franchise at Roche, Idafirix is certainly the most groundbreaking, exciting new therapy to come along in the past 20 years. And Idoferix will have a big impact for patients and transplant community. With us to talk more about this unmet need and how ideoeferix can help some of these patients is Professor Ramud, who leads the U. K. Largest antibody incompatible transplant program. Thank you. In the field of transplantation, Professor Nizam Mahmood, who is joining us from London, again remotely. He's professor of transplant surgery at Guy's Hospital in London. I will just want to remind you that we will be taking questions after this presentation. So the things that Vincenzo has talked about and what Professor Mahmoud is going to say, we'll be able to take questions on that. Professor Mahmoud, he's also the author of almost a 100 scientific articles in prestigious journals such as The Lancet. And, as if that wasn't enough, he's actually also had a little film career. He was part of, The Crown very briefly, but he was there, playing a surgeon to the king. But, anyway, I'd like to turn it over to you now, Professor Mahmoud. And thank you very much for joining us today. Thank you very much. And thanks for the invitation. Next slide, please. So these are my disclosures. Next slide, please. So the key messages I want you to take away from this talk are that kidney failure is a major global health problem and it's rising. There are an increasing proportion of patients with antibodies who we can't transplant and existing methods of treating these patients up to now have been inadequate. Next slide, please. So according to the WHO, there are well over 100,000 solid organ transplants done every year across the world. And we can transplant all sorts of things from hearts and lungs to hands, face, even uterus. But you can see from this data that by far the largest group are kidney transplants with over 69,000 kidney transplants done across the world every year. And many of you may think that kidney diseases is not a particularly common problem, but a paper published in The Lancet earlier this year suggests that in 2017, nearly 10% of the world's population had chronic kidney disease. That's nearly 700,000,000 people and that resulted in 1,200,000 deaths. And that is predicted to almost double by 2,040. So it is a major problem and it's one that's rising. And I've shown you in these diagrams and the gory picture on the right, I thought you might be interested in how we actually do the transplants. So we tend to put the kidneys in to the lower part of the abdomen onto the vessels which go down to the leg. If we're putting in an adult kidney into a small child, then the kidney goes onto the main blood vessels, the aorta and the IVC, which you can see to the right. Next slide, please. Now if you look at the graph in the bottom left, what you can see if you look at the green line is that if you're 65 and you have kidney failure, your 5 year survival is about 30% and that is worse than most major cancers. So you've heard Melissa's story, you've heard the quality of life is very poor on dialysis, survival is very poor, and your experience of complications generally speaking is very high. In addition to that, there's a very significant cost in the UK about £40,000, £45,000 per year to keep somebody on dialysis. If you look at the graph above it, these are the results from all U. K. Centers, 5 year survival rates after a living donor kidney transplant. And the survival rate for the patient is 90 4% and for the transplant is 93%. So really excellent survival rates after transplantation. If you look at the graph on the right, you can see that we've actually been very successful in recent years in reducing the waiting list for transplants. We've increased the number of transplants and our waiting list has fallen from over 7,000 to under 5,000. But you can perhaps see that that fall is leveling off. And part of the reason for that is that we have effectively transplanted the patients who are easy to transplant. And we have an increasing proportion of people who are difficult to transplant often due to HLA antibodies. Next slide, please. So what are HLA antibodies? Well, HLA antigens are proteins that appear on the cell surface and they differ between different people. And you've often heard in films, TV programs, when people talk about being a good match for a transplant. And what they often mean here is whether the HLA proteins from the donor match to the recipient. And we term a good match a 0 match and a poor match a 222. Now we can still do a transplant if it's a poor match. It's just that the kidney won't last quite as long. And this is different from the cross match and this is has a different implication than a positive cross match, which I'll come on to later. So we have these antigens, these proteins on the cell surface of the organ transplant. And if we have HLA antibodies in the blood of the recipient, These will bind to these proteins and initiate a process through a variety of means process of rejection, which effectively causes the cell to explode and loss of the transplant due to severe rejection. So why might you have HLA antibody? There are 3 key reasons and they all relate to being exposed to foreign human proteins to non self. So that's previous transplant, blood transfusion and pregnancy. And because we're very successful in transplanting young people in particular, all transplants will not last for your whole life, they'll last for 20, 25 years. So, if you have a transplant as a child, you're likely to need a second or even a third one and you're likely to be sensitized and have HLA antibody which will make that second transplant more difficult. Next slide, please. So why is HLA antibody so important? Well, if you have HLA antibody, you will not be offered a kidney from the deceased donor waiting list if you've got antibody to that particular organ. If you've got a living donor, then and you've got HLA antibody to that living donor, then we carry out the cross match, which I referred to earlier. And if that antibody is strong enough to cause a reaction, so that's when we take cells from the donor, serum from the from the recipient, mix them together. If there's a reaction that's a positive cross match and we can't go ahead unless we institute some treatment to either get rid of the antibody or suppress it. In the U. K, we have something called the CRF to measure the degree of sensitization. CRF is the calculated reaction frequency and that's the percentage of the last 10,000 deceased donors in the U. K. To whom you have HLA antibody. And that represents about 7 years worth of donors. So if your CRF is 100%, what that means is you wouldn't have been offered any of the organs that became available over the last 7 years. Next slide, please. And this data shows the frequency of sensitization across Europe and the United States. There are slightly different methods of measuring the same thing. So we use CRF. In the U. S, they tend to use CPRA, but essentially it's all pretty much the same thing. And if you look at the proportion of those who are very highly sensitized, so for us that CRF over 85% is between 20% 30% of the transplant population And that's rising, as I said earlier. So it's a really very significant problem for the patients on the waiting list as well as those who have a living donor. Next slide, please. So if you are sensitized, what does that mean for you as a patient? Well, as I said, 1st of all, you don't get an offer of a deceased donor kidney. Secondly, if you have antibody and we manage to do a transplant, you're at risk of antibody mediated rejection. And in particular, you may be at risk of early aggressive antibody mediated rejection. And if you look at the graphs on the right, look at the turquoise line in the graph at the top, that is the total donor specific antibody in this patient. So all of the HLA antibody to the donor of that organ. And you can see it starts around 30,000. We remove some antibody, we get it down, we do the transplant and then a week later the antibody goes up to extremely high levels 80,000, so well above baseline. And we think this is a memory response. And once you've got antibody up to that level, it's very, very difficult to do anything about it. The graph below shows the patient's creatinine rising so the kidney is shutting down. And in many cases we will lose the kidney in that situation or sometimes we'll actually lose the patient because we hit them hard with very powerful drugs in an attempt to control this response. So high rates of acute rejection and worst long term graft survival. So if you look at the graph in the middle with the yellow line, that shows the graft survival over 5 years in patients with HLA antibodies compared with compatible transplants. And you can see that the HLA incompatible group tend to lose their grafts at a faster rate over the years and that we think is due to chronic antibody mediated rejection. Next slide, please. So what do we have up our sleeve at the moment? Well, the mainstay for removing antibody is plasmapheresis or double filtration plasmapheresis. And the diagram on the right shows how we do this. So we take blood out of the patient, we pump it through a circuit, it goes through 2 filters. And effectively what that does is remove antibody. We put the blood back into the patient. And the problem is that it doesn't just remove antibody, it removes a number of other proteins including clotting factors and the patient therefore tends not to clot. And as you can imagine, that's the last thing we want immediately prior to or just after major surgery. Other options that we've got are immuno absorption where we try and absorb the antibody out and that can be effective, but is expensive. IVIG, which is a cocktail of antibodies which we use to try and suppress the antibody, Sometimes that has some effect. It's difficult to obtain and increasingly expensive. And then a variety of drugs, most of which have no evidence of efficacy, complement inhibitors have been useful, but we have seen a significant morbidity and mortality related to infections when we use these. Next slide. So as well as removing antibody prior to transplant, we might want to try and remove antibody when we get rejection after the transplant, which can occur in 40% to 50% of these patients. And problems, bleeding and infection. And again, plasmapheresis and again, powerful drugs like ATG and complement inhibitors leading to the same two problems, bleeding and infection. Next slide, please. So as Vincenzo mentioned, Hansa is very kindly supporting an initiative through European Society of Transplantation, where we're trying to produce a guideline across Europe to answer these three questions. How do we define sensitization because different places use different methods to define it. So we should all be talking about the same thing. How can we remove or inactivate antibody And how can we treat antibody mediated rejection if it occurs after transplantation? Next slide, please. One other technique that we have up our sleeve is something called delisting. And the diagram on the right shows some results from our center, which we presented at the European Society last year. And effectively, what we're doing here is either trying to ignore low level antibody or just do a little bit of antibody removal prior to transplantation in the hope that we can get organs into patients despite them having a little bit of antibody. And the results are not bad, but you can still see a significant amount of graft loss and indeed patient mortality. Next slide, please. So when this paper came out in 2017 in the New England Journal, those of us working in this field were extremely excited. And this describes the effect of amylithidase. If you look at the graph at the top right, what you're seeing with the red lines are individual levels of HLA antibodies. And you can see there are a variety of antibodies at quite high levels. And the blue graph at the bottom, the blue lines at the bottom of that graph show those antibody levels 6 hours after treatment with emliphidase and really quite a profound fall very quickly. So this really excited us. Next slide, please. As I'm sure most of you know, the drug cleaves IgG and therefore neutralizes it. And those effects when it binds with HLA antigen in the organ are therefore inhibited. Next slide, please. So this study, which Vincenzo also mentioned is just coming out now in transplantation, was very interesting. So this is where they took patients with a positive cross match. So these are patients who have sufficient HLA antibody to react with the cells from the donor and therefore normally we would not go ahead with this transplant without some attempt to remove antibody. And these patients were given emliphidase and then the cross match was repeated at intervals and when it was negative they proceeded to transplantation and followed the patients up for 6 months. Next slide please. Oh, I think we've jumped on. Yes. So you can see that these patients were very highly ties. So their CPRA was nearly 100%. And you can see the number with high levels of antibodies. And they were very successful in this study. Within a very short time, they were able to convert these positive cross matches to negative and to go ahead with the transplant. Next slide, please. And you can see here what happened to the antibody levels. So they fell very quickly. And by 2 weeks post transplant, the antibodies came back, but not to the same level as pre transplant and then persisted at a fairly low level. And the graft survival was almost 90%, which is really very good for this group of patients where we would expect reduced graft survival compared with compatible transplants. Next slide, please. And this slide shows something called the EGFR, so the estimated chlamarel infiltration rate. And this is essentially a marker of kidney function. So for most of us, we would have a GFR of around 100. Obviously, that's with 2 kidneys. These patients had one working kidney. And you can see that again after about 2 weeks, they've achieved a GFR of around 50 and that's maintained through the 6 month follow-up. So good results in terms of kidney function and graft survival. Next slide, please. So in conclusion, what we're finding is that highly sensitized patients with significant amounts of HLA antibody are an increasing problem, particularly on the deceased donor waiting list. And they are faced with a long wait, perhaps an indefinite wait, where they will suffer a poor quality of life, a high number of complications and a significant mortality rate as well as expense for the healthcare system. And edefarix, we think is a promising desensitization treatment for patients who otherwise will have very few options. Thank you. Thank you very much, Professor Mahmoud. We really appreciate that. I just had a there's a question that's come in that I think you're in a very good position to answer. Traditionally, highly sensitized patients have been seen as being a bit too difficult to treat by the medical community. How is this going to play out now? How can the medical community really sort of look at changing perspectives? Yes. So I think what's tended to happen over the last decade or so is that treatment of highly sensitized patients has tend to be increasingly concentrated in specialist centers because of the difficulties with desensitization. I think if we have a drug which allows us to remove antibody with minimal side effects and early results from Deferix seem to suggest that, then that would spread out more widely across the transplant community. Because I think if people were able to either remove antibody pre transplant or to treat antibody mediated rejection after transplant in a simple and effective way they would do that. I think it's also worth emphasizing that although we've talked about antibody mediated rejection occurring at a high level in highly sensitized patients, We shouldn't forget that antibody mediated rejection occurs in all of our transplant patients, albeit at a lower level in patients who didn't have baseline antibody. So there's a need throughout the transplant community for a good treatment, which deal with those antibodies. And again, the standard treatments really are not adequate at the moment. Thank you very much. And I think that actually brings us nicely on to the next phase because, of course, the important thing is actually being able to get people to have transplants that perhaps weren't able to have them before. So, let's turn now to the commercial plans for the launch. And I want to introduce Hansa's Chief Commercial Officer. Just change the slide and make sure that you can all see who because he's also remote. Joining us from the Netherlands, Henk Dowd, van Truesvik. I hope I pronounced that correctly. Henk, I'd like to turn the presentation over to you now. Yes. Thank you very much. And it was pronounced in a very nice way. So the coming 20 minutes, I want to take you through the launch activities and our launch readiness. And I would like to have the first slide, please. So the 2 territories we're focusing on at the moment are Europe, obviously, and the U. S. And the reason to go for Europe and the U. S. In the first place is that these are large markets, but also they have a well established transportation structure in place. And also in those countries, there's a lot of support functions and protocols in place to support the transportation. But also from our perspective, from the Hansa perspective, these territories are important because we have been there before. We have worked on pre marketing activities. We have had interactions with the key opinion leaders, and we also had some clinical sites there. And it's important to know that for both territories, we have a strategy and we have a plan. Then focusing on Europe, as one of the previous speaker already alluded to, we have a label so we can move to the commercial setting right now, and that's really important. We also have established a very strong and integrated commercial and medical team to be very close to the physicians and the hospitals to move, idoferix further in its development. The strategy, so we have a launch strategy, We have launch tactics. We have a launch team. We are launch ready. And then building awareness among key opinion leaders through our MSLs and later also commercial field based persons is important because at the end of the day, Ideophirix will be launched hospital by hospital, patient by patient, and that is driven by the physicians themselves. Then of course, building the infrastructure, we have already a great infrastructure in place. We have the best people. We have a good structure. We have processes in place, and we have a very robust supply chain. Then to focus on the U. S, as was highlighted before, the U. S, we are engaging with FDA at the moment. We are working on a study design in the U. S. So in a commercial setting for the common period, we will remain more in a pre marketing setting, so to say. So we will continue with payer strategies, entertaining relationships with the large patient foundations and obviously support our medical and regulatory colleagues in their way forward. Next slide, please. Then to talk about the launch strategy. So the launch strategy has an external part and an internal part. The 1 patient part is clearly external and the 1 handset part is the internal one. And it is important that there is a leverage that's a synergy between those pillars, those two strategies. One of the I mean, if you look to the most important thing is that we actually identify we have identified our patients. Every country, every system will have their own definition of a highly unlikely to be transit patient. So that means that all the countries have different algorithms in place. And for us as a company, it is important that we have a tailor made approach if we enter those territories and hospitals. Then also we complement the allocation systems and programs. Allocation systems are there to create access and equality to patients, and we are there to enhance those systems and equality for patients as well. And then we have a lot of medical support in place. We have an initiation package. We have medical information and pharmacovigilance established. Then to move to the Wave 1 centers, I will explain later exactly what the Wave 1 center is and what the definitions are. This is more important to understand that we have some positions and some activities in a central way. So strategy and marketing are conducted in a central way within Hansa. The reason is that we want to avoid duplication in efforts. It is important to know that although we have a central strategy, the rollout of the territory will be done with local adaptations, for example, language adaptations and compliance adaptations, but it will be secured in a central way. And marketing in a central way is very important because you want to create consistency in the messaging that all our MSLs, that our territory managers, that everybody working in this company speaks the same language because the key opinion leaders we work with are tightly knit not community. And then of course, central functions also speed up implementation and save money in the end of the day. And then talk about patients and hospitals, then the introduction in those hospital, it's all about development and learning. Transplantation itself is a very complex process, and we have a huge data. We have very compelling data. We have to combine that. And now after the clinical setting, idiopherics will be introduced in hospitals, and we will get more hands on experience. But by definition, that means either ferics will be used in larger groups, less controlled groups. And in those groups, there probably is a little bit less experience. So it is important that we safeguard a continuous learning circle between Hamza and also the health care professionals themselves. For example, ISTs and registries are supportive of that. Then to move to the other strategy, that's more like the internal strategy. It's important that we leverage the strength between medical and commercial teams. MSLs and territory managers and field based, the account managers later on will work together because in the end of the day, they focus on the same position, but they have clearly different roles. In that medical need, it was already highlighted by the previous speakers. It is important that we have defined the medical need because that's the starting point of every medical activity, but also for every commercial activity. So it is important that we have addressed that and defined that. Then we work with clusters. So that means that we don't have defined country in the place, but we have territory managers overseeing territories. And our territory managers are very strong professionals. They have all been general managers before with biotech companies. They built country organizations. They have they had to have P and L responsibility before, and they also participated in the European leadership teams. Clusters also will provide flexibility. So we can reallocate people and resources if needed, and it will avoid that we do have an overlap between countries and that we are going to re event the wheel, so to say. And of course, Clusters is a financially good strategy because we make the investments where the opportunity is. And then the last thing I want to say is the pivotal functions which are in place. I talked about the territory managers about MSLs. We have market access in place, global market access, European market access capable of working on the strategy, but also capable of doing the tactical implementation. And this team has already worked on HTA submissions. We submitted a very robust dossier with NICE in the U. K. We have submitted with the Swedish authorities. Further in the beginning of next year, there will be a German submission. So a lot of things are happening in that respect. And then of course, the supply chain, I told you before, in the space, we're going to have strong partnerships. Next slide, please. Then in the next slide, I want to give you some flavor about the transplantations themselves. If you look to the European big five countries, they have about 15,000 transplantations, kidney transplantations per year. And if you add the smaller countries like the Netherlands, Sweden, Norway, Denmark, Austria and Switzerland, on average, we have about 17,000 transplantations in kidney. So if you look at this overview, it's quite clear that the traditional European Big 5 countries are important. It's also important to know that our wave strategy, the way we're going to implement hydrophobix is not only linked to the number of patients and transplantations. There are more things in the basket to make the decision. You can also see that there are some country specific differences. For example, Spain has very high incidence. And then of course, every country has their own system. Some countries have an opt in system. Some countries have an opt out system for transplantation. And then, of course, to transfer patients from a waiting list to into the transplantation, all the countries and territories have their own dynamics as well. The last thing I want to mention is that you can also see that the majority of all the countries still do a lot of disease donor transplantations compared to the living donor transplantations and remind you that our label at the moment is with disease donors. And I would like to move to the next slide, please. Yes, I already talked about wave 1 and what actually does that mean. So we are not going to launch traditionally country by country. We are going to launch idoferics hospital by hospital. And the reason is that at the moment, there's a limited experience. The reason is also that this is an ultra orphan drug introduction. And the reason is also that we want to pursue a focused strategy. So the Wave 1 Hospitals, these are the hospitals we're working on, on a daily basis. These hospitals, we know they have an infrastructure in place, and they have experience in desensitization. We also know that those hospitals are able, in a decentral way or a national way to get advanced stage funding in order to provide for, to provide for, idiopherics. And then the national systems also make it possible that we enter those hospitals, so there are no legal hurdles. There are no allocation hurdles. So that's the definition of wave 1. And the wave 2, these are those hospitals where they have probably a lot of knowledge about desensitization, but there are a little bit more hurdles in place. For example, national hurdles like legal hurdles or allocation hurdles. And I'll give you one example. Germany traditionally is a very important market for us, and it's a starting market. But in this case, in Germany, there's a very strong policy or guideline applied, which actually towards the fact that we are treating patients with Idoferix. And that means that we have to work through those systems. And we will get there, for sure, but it will take more time because we have to work through the systems. We need more policies in place to make it happen. In Wave 2, we're also going to work with potentially more partners in those countries, for example. And that takes more like a vetting process and also a contract process to be in place as well. And then Wave 3 countries. These are the countries outside of Europe and also outside of the U. S. We have a dedicated vice president at the moment who is overseeing those territories. We work on the strategy at the moment. So that means we are getting market and patient understanding. We are defining the regulatory pathway for those countries. We are working on those criteria to go to market to define the go to market strategy. We are working on partner selection and also on clinical development. So that is also unfolding as we speak. And the way 4 countries, for example, at the moment is the U. S, where again, we have to conduct a study and do and have an interaction with the FDA. Important to know is that those waves are not in a sequence way. So that's not that we work on wave 1 and then we start wave 2 and wave 3. These things are concurrent events. So those waves are concurrent and they all get energy, and they get all kinds of attention from the company and from external stakeholders to start this process going forward. Yes. And now I will talk a little bit about market access. So market access is not only about setting up price. Market access is about securing reimbursements and value creation. And Soren already told you in his opening statement that we have a global value dossier in place, and that's actually the blueprint for in country submissions because we do I mean, in the end of the day, we have one label, we have one orphan drugs label in the end of the day, but reimbursement in Europe is done in all those different countries with different systems. And the global value dossier is a blueprint to make that happen. And market access is also about data collection. This slide is actually to show you that there's you can see the potency of countries. If you look to the potential number of patients, it's important. But also the complexity in reimbursement is a very important criteria to define important countries. For example, in Austria and Denmark and Finland and the Netherlands, it's a clear way we can move forward. And then in all the territories, it might be more I won't say difficult, but it will take more time and energy to get there. And again, our team has been able to do the submissions, HCA submissions. So there's a 2 way you can look at those things. Sometimes you can have a hospital budget securing reimbursements. And in a lot of countries, you have to go through a national system to make it happen. And that's what you call an HDA submission. We have submitted in NICE. We have submitted in Sweden. We have our models in place. So we have a cost effectiveness model. We have a budget impact model in which we can convince payers about the tremendous value we're going to create for patients' families, but also to the society and the payers in the end of the day. And we have also the tools in place. So we have specific market access messaging, value messaging to go to payers. And our internal organization has also been trained by market access that is the same language if you talk about the value of Imlividase. Next slide, please. Then I will dive a little bit more into the operational setting, the hospitals. And bear in mind, if I talk about the launch, it's not only commercial launch. We also have the post approval efficacy study, which might actually also support a launch. A launch can also be that a hospital starts, for example, with an IST and then later, which to the commercial setting. And in some countries, we're probably going to launch with a named patient program, with a foreign importation program, for example, in Spain, to bridge the periods between the launch we are in right now and the official reimbursement. So there are different kind of ways of defining that introduction in those hospitals. But what we will do is to have a bespoke model in place to make it happen in those hospitals and, of course, a strong relationship with those key opinion leaders because the key opinion leaders in their hospitals have to be true ambassadors to help their own management and their pharmacy in order to understand that they have to prescribe that they need idiferics, and then we need funding for this to go forward. You can see in this overview of Europe the major centers we have depicted right now, so 1 in Norway, 1 in Finland, a few in Sweden, 3 in Denmark, 2 in the Netherlands, and then the U. K. And France and Germany. You can see it's a highly concentrated market that a lot of activities in the leading centers. And it's important to know we are very close to those leading centers. We know the key opinion leaders. We know the systems. So that is important. That's important to know, but it's a highly concentrated market. That means for the organization, we need seasoned professionals, and we have seasoned professionals. We don't need a very large organization, but we need a very flexible and we need a very nimble organization as well. Next slide. Now we move to awareness. Awareness is important around IDPherics. And awareness is not about large marketing campaigns. It's about doing things in a smart way because this is an ultra orphan setting. So we use our own internal colleagues. We have market access. We have MSLs. We have our patient advocacy person on board to make that happen. And patient advocacy, by the way, is a very important function because the voice of the patient is getting more and more important in a PR way, but also in a lot of submissions and reimbursement discussions, the voice of the patient is getting more and more prominent. Then creation of awareness is also having advisory boards. Our medical colleagues have organized several advisory boards where you bring key opinion leaders together to discuss several topics, create awareness and also bonding with the company. And then being present at the large conventions, as Vicenza also already told us, U. S. Conventions, European conventions, but also national conventions and sometimes local conventions as well. We are there with symposia, having orals and also posters in place in order to create awareness around idiferics and of course, Hansa as a company. And then of course, we have the supply chain in place, very robust supply chain. We have very professional organization around that. And they are ready for this launch to guarantee that Ideophirix is in the right hospital at the right time at the right quality. And then I want to move to the last no, not the last time, but the next slide. So I talked about the waves, but now I wanted to look at what we do internally in those hospitals to develop them further. So the starting point in a hospital at the moment is that they have to understand the unmet medical needs. They have to understand that they have to act that there are patients out there like we saw before who have really a problem and they need treatment where there's unmet medical needs. We enter in that hospital, and then we start working with those physicians and nurses, and we start education. We have an initiation package in place to guarantee that those hospitals are up to speed and have a high level of knowledge and training that they can treat those first patients with a success factor for themselves, but in the first place for the patients. And as soon as that hospital has that level of expertise and the level of confidence, they will become ambassadors. For example, if the hospital of Vienna has a great experience, then the hospital in Innsbruck or in Graz, Orleans will hear that story. And they will say, okay, but Vienna is successful. What about us? So then the good news will spread in that country. It might also spread even from country to country. At the end of the day, what we want to achieve is that those hospitals are becoming real ambassadors, are really aligned with us. They are part of our publication. They promote us, and they are bringing the whole idlerphyrics franchise forward from their hospital with their expertise. But this is about center education, and this is also about adaptation as we speak. And then the last slide, please. I want to show you our new vision, our brand vision. It's really nice. It's really nice colors. It's about idiopherics and it's about yesterday, it's about today and it's about tomorrow. And that means about giving hope. And we have to realize that a lot of us are remote. So in the end of the day, we close our computers or we leave the meeting room and we go back to our families and we have a normal life. Those patients, those highly sensitized patients have no future at the moment. They have a limited social life. They are dependent on systems, on machines. They have a low productivity, and they actually suffer day from day. Yesterday, today, tomorrow means that we, with Ideferix, are confident that we will restore hope for those patients with huge medical needs. Thank you. Thank you very much, Henk. And unsurprisingly, we have a lot of questions coming in about commercialization. So I'm going to invite Soren to also come up to be part of the Q and A session. And Henk, it may be that we also call on you, but we'll start by talking with CERN. So perhaps to pick up on what Henk just said about our new reality of COVID, how is COVID-nineteen going to affect the launch in your view? So obviously, COVID-nineteen affects the way companies operate. Does it work? Okay, like this. So obviously, COVID-nineteen affects the way that companies communicate with their audiences and their stakeholders overall. So far, we have been able to have a very effective and efficient way of communicating with all of the different stakeholders, including our target audiences on the commercial end of things, right? We've been able to conduct a lot of pre marketing activities, and I'm sure that we will continue to do so as we move forward. We've also been asked to give a bit more meat on the bone of the patient evaluation tool that's going to be used. So if we could talk a bit about the details, the differences country by country, if you can do that or if you think maybe Henk should do that? Yes, sure. I think I'll pass this one over to you, Henk, if you want to talk a little bit about the patient ID programs and how we go about that. Yes, absolutely. No, again, it's important that to know that we have a lot of clinical experience, and now we will bridge IDHFERIX for the first time out of the clinical setting in a real world life setting. And it's important that those hospitals have the right level and right knowledge to treat those patients because we are introducing innovation and a new class. So everything is basically new. And there has been a so the medical team, together with commercial team, have created a package. We call it a nation package, which actually consists out of a lot of modules in which we go into the hospital and talk with those physicians and bring them to those modules to get them on speed so they have the right education and the right setting in order to secure a safe transplantation of that patient. That package, that initiation package is a huge comprehensive package and has been validated. So the colleagues have been reaching out to several teaching hospitals in Europe, spoke with key opinion leaders about this program to really validate this program as well. This program also has got internal approval by our own processes in order to get legal and compliance approval as well, and the program is ready to fly. It's also important to know that we will know if hospitals start treating idiopherics. It's a limited number of hospitals, so our MSLs will most likely know that something will happen in that hospital. And also, Ideherics will be sent consignment stock to a lot of pharmacists. So it will be on consignment stock, so we will do a bonafide check. So we know something will happen in that hospital pretty soon. And then of course, we will also so we will know exactly which hospitals are potentially going to move in the use of hydrophirics. And again, we have a great program in place to make this fantastic story for the treating physician and the patients because I think that if you bring innovation, it also means that you take a lot of responsibility in order to bridge this to the patient in a very safe and secure way. Thanks very much, Henk, for that very detailed answer. Let's just turn back to you, Soren, because we've got a number of questions. I'm going to try and consolidate them a little bit about the costs and in relation to the launch. Looking beyond 2021, I think is really the focus. So perhaps you could talk a little bit about how we should think about the cost of the launch? Sure. Absolutely. So we're launching a very highly specialized product really that has orphan drug status. And as we've discussed, the target audience is highly concentrated. We're talking about a double digit number of clinics, and it will not be clinics that will approach all at the same time. It will be sequenced. So clearly, what we expect is to establish a front end field force and MSLs of around double digit number of people. And so people who are calling in today can make assumptions around what it costs to employ 1 headcount here. And that really is the majority of the cost. Of course, there will also be some projects costs, right? But this is not a GP product type launch at all. We're not going to do huge country launch symposia and so on. This is highly targeted towards specialized key opinion leaders and heads of clinics and so on. So it's certainly a very manageable project from a cost perspective. And you mentioned the different countries. You've had a couple of questions in about the situation, which really relates to Brexit and the U. K. Are you planning to launch in the U. K? What's the time line for that? Can you perhaps talk a little bit about that? Sure. Thanks for bringing up Brexit. I wish I had it, but there you go. No, so clearly, I mean, the approval also is for the U. K. And so we will launch in the U. K. As well, right? As Henk talked to, we have submitted a health care dossier, value dossier to NICE, and we are making preparations to launch in the U. K. It is a very important market for us. So clearly, yes, it is among the target countries. And perhaps moving to the price because the Danish price was actually published quite recently. What can you say generally about the pricing in Europe of the drug? Well, what I can say is that the pricing really is based on comparing the cost of therapy here to the cost of dialysis, right? And the cost of dialysis is very, very significant and is well known and well established. And so this is what we've used in our health economic dossier. And as I said initially, it is resonating very well, the payers. And this is what has been driving the setting of the price. And as you said, there is a price available now in Denmark. And as we roll out, you will have different level of prices, but of course, within a certain range in Europe. So we talked a bit about the cost of the launch. There's a couple of questions about the sales force that have come in as well. How would you put this sort of average cost per salesperson and how many people do you think you're going to have at peak in that sales force? Can you talk a little bit about the makeup of the sales force? Well, as I said, the sales force in itself plus the MSLs, that will be a double digit number. And it's not going to be a high end double digit number. It's going to a lower level double digit number. And then the cost of each headcount, obviously, that varies from country to country, so I'm not going to give any specific guidance. I'm sure that the analysts and others who are making their models have clear assumptions here. And I'm not going to hand over to Donato to spend 10 minutes on this. So I think that's what I can say. And when is the peak roughly? Are we talking 5 years out or 3 years out or? The peak, well, it's going to be a gradual buildup, right? Already, we have a core infrastructure in place. We have less than 10 MSLs, but close to that. And we're building up the commercial team. We have territory managers in place and so on. So the peak, I think, is going to come in not a couple of years, but maybe 3, 4 years out from here. Thank you. I think we're going to have to go for a break now, but thanks very much, Henk, and also San for that Q and A. We're going to break now because of the whole time difference issue. Let's be back here at 11 am if you're in the eastern part of the US. There's only 5 hours difference. I've been trying to work it out in my head. So 4 CET, we'll start again, or 11 am if you're in the Eastern seaboard in the U. S. Welcome back to Hansa's Capital Markets Day. Thank you for joining us again. Let's pick it up from where we left off. We're going to turn our attention now to looking ahead at how the company can build on the technology platform in other indications. So I'd like to take the opportunity to introduce again a remote speaker, but today we're going to hear from the Chief Medical Officer, Professor Achim Kaufhold, who is, as I say, again, remote. He'll give the next presentation. So please, Professor Kaufgaard, you can take the floor now. Yes. Good morning or good afternoon, everybody. I'm excited to have recently joined Chanza Biopharma as Chief Medical Officer. And I would like to touch within the next 15 minutes or so on a few opportunities beyond kidney transplantation. May I have the next slide, please? Here you see the potential indication universe. First is the transplantation area where we are going to enter the 1st market with the first indication for IDIFERIX by our own supported by our own commercial and medical affairs infrastructure. There are, however, additional indications in transplantation and post transplantation where emlify days can potentially be used. Then there is the rapidly emerging field of gene therapy where we recently closed the agreement with Sarepta. And with the and then there is the field of acute autoimmune diseases in which we have made the first steps. And finally, there is the NISO program that was earlier mentioned by Christian and we envisage to broaden our reach also to other areas where repeat dosing would be desirable such as relapsing IgG mediated diseases and I will touch on a few of them. The next slide. Thus, our proprietary antibody cleaving enzyme technology platform holds significant potential in several therapeutic areas and we have a clear strategy. In the field of transplantation of solid organs, I want to talk about antibody mediated rejection. Then I want to touch on bone marrow transportation and specifically about the potential use of emlifidase in haploidentical donor transplantation. And I will talk about IgG mediated autoimmune diseases and specifically about GM Behre Syndrome where we are currently investigating the use of emliphidase in a clinical trial. And later, Professor Segelman and Elisabeth will cover anti GBM disease and thereafter Emmanuel and Lena will talk about the use of imlifidase in gene therapy. The next slide please. Graft survival in kidney transportation recipients but also in other organ AMR can happen in up to 50% of highly sensitized patients after HLA in compatible kidney transplantation. And active chronic antibody mediated rejection in kidney transplantation is the most frequent cause of late allograft loss. The frequency of AMR is likely to be even higher in heart and lung transplantation, but due to diagnostic challenges, the true incidence is currently uncertain. AMR episodes are driven by donor specific antibodies and are usually treated by several sessions of plasma exchanges intravenous immunoglobulin steroids and rituximab or a combination of those. Importantly, there is currently no approved therapy and all treatment recommendations are not based on well controlled clinical trials, but rather based on expert opinion. The next slide. We have initiated in a clinical trial in patients with AMR to test the ability of emliphidase compared to plasma exchange to reduce donor specific antibodies. 20 patients with a proven episode of acute or active chronic AMR will be randomized to receive emlify days and 10 patients will receive 5 to 10 sessions of plasma exchange. Thereafter, all patients receive steroids, high dose IVIG and a single dose of rituximab. Patients will then be followed up and biopsies will be performed at baseline at 1 month and at 6 months. 4 out of 30 patients have been enrolled thus far. Data readout is expected to happen in the second half of 2022. The next slide, please. Let's move to bone marrow transplantation, which is a curative treatment of several malignant and non malignant diseases such as sickle cell anemia or aplastic anemia. And it is now recognized that the presence of donor specific antibodies has become an increasingly prominent barrier to successful allogeneic bone marrow engraftment. If you look at bone marrow transplantation or hematopoietic cell transplantation or stem cell transplantation as they are often called today, we can distinguish between autologous and allogeneic transplantation. An autologous transplant uses bone marrow cells from your own body to replace your diseased bone marrow. So donor specific antibodies are obviously no issue. In allogeneic bone marrow transplantation, the situation can be different. DSAs are again no issue in twins or in haploidentical siblings. With respect to haploidentical donors, all parents and children and about half of the siblings of a patient are so called half matches. Half match transplants greatly expand the potential donor pool, making more patients eligible for the transplant. And today, their overall outcome, for example, successful engraftment, graft survival, overall survival and also other outcome measures such as the incidence of graft versus host disease is not worse than with other transplant sources. However, allogeneic stem cell transplantation often leads to poor graft function in sensitized patients, and it's clear that the current esensitization methods are inadequate in many patients. The next slide. There is a potential role for imliphidase. As said, haploidentical donors are increasingly considered, and they are considered because haploidentical donors are readily available and highly motivated for the vast majority of patients. The prevalence of DSA in haploidentical transplantation is between 10% to 21% and higher in patients with a history of multiple pregnancies. And there is a clear association between the presence of DSA and primary graft failure, delayed engraftment and poor survival. Various desensitization regimens are currently employed, but they are inadequate in many patients. And recently, consensus recommendations have been published from the EBM team. The next slide, please. Let's move on to autoimmune diseases in which the body's immune system damages its own tissue by mistake. Thus, these diseases are associated with humoral or cell mediated immune reaction against self antigens. The failure to distinguish self from non self is often termed a breach of tolerance. An autoimmune disease generally requires genetic predisposition and the onset is often triggered by viral, bacterial and or other environmental factors. The diseases are frequent, occurring around 3% to 5% of the population. They are very diverse and can affect many organ systems such as the nervous system causing, for example, Guillain Barre syndrome or Myasthenia gravis. Next slide, please. This slide shows a summary of only those groups of autoimmune diseases where IgG autoantibodies are known to play an important, a predominant role in the pathogenesis of the disease and where the application of our antibody cleaving platform may be of particular relevance. Among other diseases which can lead to rapidly progressive glomerulonephritis, there's lupus nephritis, ankle associated vasculitis and anti GBM disease. And then there are neurological diseases, and I will briefly touch on the Guillain Barre syndrome. And finally, there are skin disorders, for example, pemphigus vulgaris and blood disorders such as immune thrombocytopenia and autoimmune hemolytic anemia. The next slide. Guillain Barre syndrome is an acute autoimmune attack on the peripheral nervous system, potentially affecting anyone at any age. The disease is a monophasic disease which rapidly and progressively and bilaterally paralyzes extremities often associated with distal paresthesias and pain. It is often triggered by a variety of infectious diseases such as viral infections, influenza, Zika virus, Epstein Barr virus, cytomegalovirus, just to name a few, and also triggered frequently by bacterial infections such as Campylobacter yiuli and Mycoplasma plummonia, and rarely also by vaccinations. Most patients reach their maximum disability within 2 weeks, but progression can last up to 6 weeks after onset. During the progressive phase, 20% to 30% of patients develop respiratory failure and need mechanical ventilation in an intensive care unit. Although 60% to 80% of patients with GBS are able to walk independently 6 months after the disease onset, a protected cause over months years can result in severe permanent disability. The annual incidence is 1:2 per 100,000 and highest among the elderly. Treatment of choice is administration of IVIG or plasma exchange, which are equally effective, and supportive care is obviously important as well. Therapy should be started as early as possible. It should be noted that 40% of patients treated with a standard course of plasma exchange, or IVIG, do not improve in the 1st weeks following treatment. The next slide, please. Guillain Barre syndrome is an IgG autoimmune disease with antibodies directed against gangliosides in the neuron exons of peripheral nerves. Treatment with imlifidase showed encouraging animal data in Guillain Barre syndrome. Compared to saline, rabbits showed reduced anti GM1 IgG antibodies, a lower frequency of C3 deposition in spinal roots and approved clinical signs and survival rates. The next slide. These data encourage us to initiate a clinical trial in patients with Guillain Barre syndrome in which we evaluate the safety, tolerability and efficacy of emliphidase. So this is an open label, single arm trial in combination with standard of care treatment. Even within 10 days of the disease onset, patients are infused with imlifidase followed by IVIg. And then there is a follow-up of the patients. And 30 patients are targeted, matched to controls based on geographical region, age, presence of diarrhea and severity of the condition. And then the outcome will be compared to match controls from the IGOS database. IGOS is the international GBS outcome study. The status is that currently 4 patients have been enrolled, and it's again expected that the data readout will happen in the second half of twenty twenty two. The next slide. Let me summarize. Hanse's proprietary IgG cleaving technology is a platform technology with several potential applications. I have shown you that there is a broad potential as desensitization regimen in transplantation, not only in kidney transplantation, but in other solid organ transplantations and bone marrow transplantation. There's a potential to provide incremental efficacy in several autoimmune diseases. And the current lead indications under investigation in the autoimmune disease space are anti GBM disease and GBS Guillain Barre syndrome and the first candidate of 2nd generation IgG cleaving enzymes, the NISAP from the NISAP program for treating relapsing diseases has been identified and the first steps as you will hear later into gene therapy are underway. Thanks a lot. Thank you very much, Hakim. We really appreciate that. We're going to take questions at the end of this session. So I will pass over to some more presenters now, but I just want to remind everyone, we've got one more section where we can have Q and A, so please send in your questions. We've got quite a lot. We'll try and get through as many as we can. And the ones we don't get to, I'm sure, Klaus Sindel, the Head of IR, will, in the coming days, manage to to get some responses to you. So do send in those questions though and we'll try and take as many as we can at the end of this session. Now I'd like to turn the attention to Professor Morten Sigelmark from Lunds and Lunds Schuppings University. He's with me here in the room and also he's a very esteemed key opinion leader in the field of diseases that affect the kidneys And you've actually been involved with imlifidacy since the beginning of the first trials in kidney. And obviously, you're still working with Hansa now for the anti GBM disease. And joining him today is Hansa's Head of Clinical Operations, Elizabeth Sonnison, who is also here with me in the auditorium. So I hand the floor over to you both. Thank you. Thank you, Rachel. So as you know, this next session will be all about anti GBM or a good pastry disease. And it will be presented by Professor Morten Surgelmark, as Rachel presented. And Morten has been the sponsor and the coordinating principal investigator for the clinical trial that will be presented. And actually the collaboration with Hansa goes back several years before the clinical trial was initiated. And during the clinical trial, we had a lot of ongoing collaborations between the company and Professor Seugomart and his team. Now, so today, we're extremely happy to be able to share this very important data. And we believe that although anti GBM is an ultra rare disease, this data, this promising data shows that emilyphodase has the potential to provide clinical benefit also in other autoimmune diseases. So with that, I hand over to you, Martin. Thank you very much, Elizabeth. First, I would like to say that I'm very glad that I can be here today and present the data from our study, the Good ID study. It's an investigator initiated study and the official sponsor is Linkoping University. That was my main employer when we launched the study. And it has been conducted in collaboration with 17 major hospitals in 5 European countries, including big hospitals in cities like Prague, Vienna, Paris, Copenhagen and Stockholm. But first, before I present the data from the study, I will say a few words about anti GBM disease. Anti GBM stands for antiglomerular basement membrane disease. And as Elizabeth said, it's also have the eponym, Goodpaster's disease. It is a very severe acute onset inflammatory disease of the kidneys. A perfect functioning normal kidney can be completely destroyed within a few weeks after onset of this disease. It can also attack the lungs, leading to pulmonary hemorrhage, which can become fatal. Actually, about 1 in 6 patients die during the acute phase of the disease. It is fortunately, it is a rare disease. It's effect less than 2 per 1000000 inhabitants, which means like in a country like the U. S. There are about 500 cases per year of this disease. Most patients that get this disease will end up in dialysis. Well, anti GBM disease is just one form of glomerulonephritis. Glomerulonephritis is a term for many types of inflammatory diseases in the kidney. The word glomerulonephritis consists of nephritis, which just means kidney inflammation. And the word glomerulus that stands for the little ball of capillaries that is the first part of the functional unit of the kidney, the nephron, where the blood is filtered into urine. These functional units, we have about SEK 1,000,000 in each kidney, is whether it produced this large ultra field crate from blood to urine each day. And when inflammation starts here, it can spread through the kidney and destroy the kidney. This can take sometimes years in some diseases, months in others and weeks as in good Paget disease. These different types of glomerulonephritis have different mechanisms, but a common theme in them is that it's very common with autoantibodies. And more and more autoantibodies in glomer nephritis are detected for each year. The role of these antibodies are well less or more well known. And anti GBM disease was chosen because in this disease we believe that the IgG antibodies are the main culprit for the inflammation. Well, as a group, glomerulonephritis is not uncommon. According to data from the Swedish Renal Registry, of all patients in dialysis and transplantation, 25% have glomerulonephritis. That is more than those that have diabetic nephropathy and it's more than those that have hypertension as a cause of the renal disease. Glomerulonephritis, just like anti GBM disease, have very few symptoms to begin with. And that is why many patients are detected late. We want to target the antibodies and get rid of the antibodies and that we can do with medications such as cytotoxic drugs. The problem is that it takes a long time. It takes several months for the autoantibody production to halt. If we are in a hurry, we can try to wash the blood with different types of techniques such as plasma exchange, but that is not efficient enough, especially not in a disease like anti GBM disease. That's why we have the hope that emliphidase could make a difference for these patients. So now I'm going to not talk about glomerulonephritis in general, but I will talk now only about anti GBM disease. There are very few studies, clinical studies in anti GBM disease. There has actually not been a single clinical trial published in this millennium. So what we have is a retrospective case series from different hospitals. And here I compiled data from 13 of such studies that are published in the last 15 years or so, a total of 6 61 patients. And as you can see, as I said before, 17% of the patients were dead during the acute phase of the disease. Most patients end up in dialysis and only about 1 third have a preserved renal function after 6 months. However, this is highly dependent on when the disease is detected. If the disease is detected early, there is a fairly good chance that the standard therapy that we use with plasma exchange and cytotoxic drugs is efficient. Actually, as you see from the far right here, that 73% of such patients actually have a functioning kidney after 6 months. The problem is that most patients are detected late. And in those patients, the prognosis is really bad. And as you see, only 9% in these studies had a functioning renal functioning kidney at 6 months. So with this in mind, we designed the good ideas trial. And here we hoped that in lyfidase treatment would reduce antibodies quickly. We think if you follow the gray line that antibody production when it starts first nothing happen, but then a threshold is passed here indicated by red line and then a damage to the kidney starts. And then when we start therapy with plasm exchange, seen here as a blow line, it takes a while before we get rid of the antibodies. And during this time, the destruction of the kidneys continues. But if we give in the lifidase, we hope that we can get an immediate stop to the disease process and then healing can ensue. But that is not the only rationale for using in lymphodase in anti GBM disease. Getting rid of circulating antibodies is probably very important, but emliphidase can also attack antibodies that have already bound to the kidneys in the capillaries of the kidneys. We first showed this more than 10 years ago in mice in an experimental model of anti GBM disease that placebo treated mice, there were a lot of antibodies that could be seen as is indicated in green. But after EMLEF days, we could not detect the antibodies anymore. Similarly, when we treated some patient on a compassionate basis before the clinical study, we could see a similar thing that looking for the Fc fragment, which is the tail of the IDG molecule, we could not hardly see anything after IDES treatment, but we could see the head of the molecule still in the glomeruli. So the good ideas trial, which I said, was conducted in 17 major hospitals. It's open label single arm multi center study. We give one single dose of emliphidase at the start as quick as possible to the patient and then they also receive standard therapy, which is corticosteroids and cyclophosphamide. And then if there is a rebound of antibodies, we try to curb that with plasmic change later on. The main objective of the study was of course to see if we can save kidneys that we normally would not be able to save And of course also to evaluate the safety and tolerability under these circumstances. Inclusion criteria were that patients had to have circulating anti GBM antibodies and they should have severely reduced renal function, less than 15% of what is normally seen in a patient with healthy kidneys. We had also inclusion exclusion criteria that we didn't think that we could save kidneys that have already died. We could not really resurrect them from nothing. So patients that had not been producing any urine for 48 hours or those that have been through dialysis up to almost a week were excluded from the trial. We aimed at 15 patients for this trial and we were able to recruit the last patient just in January this year, a few months before the pandemic. We're very glad for that and we were able to get all major data from the patients even during the pandemic. And when we look at the results of the study, we can first show that anti GBM levels went down very, very quickly, already after 2 hours it was almost nothing and after 6 hours all patients had antibodies below the reference range with this assay here. There were relapses or rebounds of antibodies in about half of the patients, but in most of them they were easily handled with plasmic changes. And as you see at all the time points here, there are very few patients who are above the red dotted line. When it comes to renal function, there were 5 patients that produced less than 200 milliliters of urine when they were treated. 3 of them actually increased the urinary production quite substantially. 2 of them could stop dialysis and but only one of them was still out of dialysis after 6 months. One patient, the oldest one in the study, died in the middle of the study due to pneumonia not related to the treatment. There were 5 patients that were still producing urine, but were dialysis dependent for their survival at the start of the trial. 4 of those had independent renal function after 6 months and only one of them ended up in dialysis. And all five patients who have had very severe renal failure but not yet needing dialysis had their renal function saved at the end of the study. So this is very encouraging in anti GBM disease. And of course, it's also encouraging for all other renal diseases where IgG antibodies are important and of course in other diseases in other organs as well. So with this, I will hand the word back to Elisabeth Sonesson, who will say a few words about the future of anti GBM disease at Hansa. Thank you, Morten. And as Professor Sjergalmark alluded to, this is really encouraging data, not only for the continued development within anti GBM, but also for supporting the idea that the ameliferase will actually make a difference in other autoimmune indications. So given that, the next steps moving forward will be to engage with regulatory authorities, both in EU and in U. S. And possibly other territories to seek advice for a clinical study design that will enable market approval in those territories. Thank you. Thank you, both. Before you leave the stage, we've actually got Maybe Elizabeth can answer that. Yes, I can try. As there is a standard of care, we would probably need to compare a benefit in the arm where we add Imliferase on top of standard of care. And any ideas of sort of patient numbers or? No, that has to be when we decide on the final endpoint and the follow-up time, we can decide also on the sample size. Great. Thank you. Thank you. Thank you both. So we're going to move on now. As a reminder, this is the last chance, the next 20 minutes or so where you can send in your questions because we're going to have a longer Q and A session at the end of the next presentations. But now we're going to turn our attention to gene therapy. As most of you will remember, Hansa signed a very landmark deal a few months ago in gene therapy with the U. S. Company Sarepta. But to hear more about the future in general with gene therapy, I'd like to invite Hansa's Vice President, Business Development, Emmanuel Bierna and also Hansa's Head of Science, Lina Winstelz, if you would like to come up and take the floor here. Thank you. Thank you very much, Rachel. I'm here with Elena Winstedt, our Head of Science, who leads up our internal efforts in gene therapy on the research side. We're very excited to talk about this opportunity for Hansa both medically and business wise when it comes to partnering opportunities in gene therapy. So in the last 20 minutes of today, we're going to to describe the basic technology around gene therapy. We're going to describe a bit more about the significant unmet medical need that this technology can potentially help mitigate and solve. We're going to talk about how immuniferase might play a significant role in within gene therapy. We're also going to describe our partnership strategy in within gene therapy. So starting out with the basic technology gene therapy. Thank you. As you know, genetic disorders are caused by a defect gene failing to produce desired functioning protein. So the concept for gene therapy is to introduce a functioning gene into a virus capsid and then let the virus infect the target cell. There are different types of vectors. Most commonly used are the ones that are derived from adenoviruses, the so called adenoviruses associated vectors. And we have, for example, vectors that can infect eye or brain, local targets. We also have vectors that infect liver or muscle, and those will be distributed systemically. Since most people have been exposed to adenoviruses before, there is prevalence of preformed antibodies against the viral vectors. And the prevalence of those varies between the type of vector and can be as high as up to 70% in a population. So why is this important? If we start to the far left, you have a virus vector with the gene you want to use for your gene therapy. And as you can see here, it's covered by antibodies. And this means that it can't be entering the target cell. And this is, of course, where our enzyme cleaving our IgG cleaving enzymes come into play. We can use the technology to cleave the antibodies and thereby inactivate them and, in this way, enable the gene therapy treatment to work to enter the cells and be exposed. This concept was recently proven and published in Nature Medicine. And if we start from the left, this is a mouse model where we have the black line showing mice with preformed antibodies against AAV vector 8. The mouse was then treated with gene therapy aiming to express an enzyme and you can see the level of enzyme on the y axis. The mice with antibodies did not express any enzyme. But if you look at the red line, you have mice with preformed antibodies who were treated with emliphidase prior to the gene therapy treatment. And as you can see, those mice express the enzyme to the same level as mice without antibodies, which are shown in blue. The next figure shows nonprimates. And here, we have the coagulation factor VIII. The black box shows primates with antibodies who were treated with gene therapy aiming to express factor VIII. The blue shows primates with preformed antibodies pretreated with Imlifidase prior to the gene therapy treatment. And finally, to the right, this is a figure showing that emliphidase can cleave antibodies against viral vectors Manuel? Thank you, Lena. So turning our focus back on the gene therapy companies. The current focus of the gene therapy companies are disease areas within neuromuscular diseases, bleeding disorders and metabolic disorders. And there is a reason for that. Here you find a lot of non or sorry, monogenic diseases and you can target liver and muscle and nerve tissues to effectively transfer the gene therapy into those tissues for expression. A monogenic disease is a single gene disease where you have a single error in a single gene being the direct cause of the disease progression. So turning to more specifically to the specific indications and the ongoing programs here. This illustration, we demonstrate the programs, the indications and the development programs right now in development where we believe that immunofitase has a significant potential to add value for these patients and these gene therapy companies. Approximately 30% of the patients in these programs are excluded from treatment due to pre existing neutralizing antibodies. And to the right you have SMA which is an indication being treated by Zolgensma, the approved product from Novartis. Slightly to the left in late clinical development, we have the hemophilia opportunity, hemophilia A and B pursued by companies like Spark, Pfizer and Takeda and UniCure. We also have Duchenne muscular dystrophy being pursued by Sarepta and Pfizer for instance. And there's a long list of additional indications being pursued as we speak where this could potentially serve as an important enabler for additional gene therapies. All in all, we look at a couple of 100,000 patients that potentially could benefit from this treatment, the different gene therapy products. And these numbers that we show here in the beach are the prevalent patient populations and that's really important in gene therapy development. When you develop a potentially a 1st in class and a best in class gene therapy product for a product that you're supposed to use potentially just once to basically cure these patients, obviously the prevalent patient population is going to be very, very important and being able to access those patients. Beyond the monogenic diseases, there's also in early clinical development, some non monogenic indications being pursued, like in indications like congestive heart failure or neurological diseases or chronic inflammatory disorders. Here gene therapy serves the purpose of mitigating or interrupting disease pathways in more complex diseases like congestive heart failure for instance. And if gene therapy demonstrates to actually work in these types of indications, gene therapy will help millions of patients potentially. So in July of this year, we were very happy to announce a collaboration with U. S.-based Sarepta Therapeutics. The collaboration gives Sarepta the exclusive right to develop and promote Imliferase as a pre treatment ahead of gene therapy in Duchenne muscular dystrophy and limb girdle muscular dystrophy. Sarepta is a leader, a world leader in these indications and in the development of gene therapy for these indications. Into the collaboration, Hansa provides our intellectual property, all the craftsmanship around the IgG cleaving enzymes that we are developing. We're providing the right of reference to the clinical data that has been generated to date with the immuniferase. We provide of course access to GMP grade immuniferase for the clinical studies and eventually hopefully a marketed product. Sarepta, through the agreement Sarepta will do all necessary preclinical studies to enable clinical studies. Sarepta will do the clinical studies with immuniferase as a pretreatment ahead of the gene therapy treatments in with their specific products. Sarepta will be responsible for all the regulatory interactions based on the clinical data. And eventually Sarepta will promote the combination therapy or the pretreatment regimen. The arrangement or the deal was associated with an upfront payment at $10,000,000 to Hansa. Hansa has the potential to receive up to $400,000,000 in milestone payments. And we're also entitled to royalties on the incremental gene therapy sales enabled by the Imiphase treatment. On top of that, Hansa is going to sell immuniferase into the market and book the sales on immuniferase. Now we turn to Lena again, who will describe a bit more about Sarepta's efforts in these two indications. So like Emmanuel just said, we're working with mainly with 2 indications in cooperation with Sarepta. The first one is a monogenic disease, which causes muscular weakness, and the disease develops normally around the age of 3 to 5. It's only in boys. And by the age of around 11, they are usually dependent on a wheelchair. The disease progression leads Sarepta has shown a promising 2 year data from an open label study in 4 patients, And they are now conducting a placebo controlled study with 41 patients, and results from that is expected in Q1 2021. The other indication we're working on with Sarepta is limb girdle muscular dystrophy Type 2E. This is also a rare disease causing severe muscle weakness. And in this, it also develops in early childhood. And in this indication, Sarepta is now conducting a study in 6 patients. And the results from the 18 months follow-up for this study are very promising, both in terms of efficacy and safety. And in both those indications, there is about 15% of all patients who possess preformed antibodies to the treatment. So those can't be included in the gene therapy treatment program without removing the antibodies. Thank you, Lena. And as concluding remarks, I want to point your attention to the potential values that can be unlocked by Hansa joining forces with many of these gene therapy companies. We can enable more gene therapy for these patients that have these diseases. That could potentially also mean that Hansa can enable repeat dosing in gene therapy. We can potentially this can provide a competitive edge for the gene therapy companies obviously which ultimately will generate potentially more sales for the gene therapy companies. Hansa will be able to book more sales by the pretreatment regimen and ultimately we are hoping that this will of course lower overall treatment costs. Thank you very much. Thank you both, Emmanuel and also Lina for that very thorough presentation. We've got probably around about 25 minutes or so for a Q and A now, 20, 25 minutes. We've got a lot of questions that have come in. I'm going to try and group them a little bit, but I'd like to invite certain sorts of to come up and join me on the stage here so that we can maybe start with some of the more corporate questions that have come in and then we can take some of the R and D questions after that. So maybe if we start, we've had quite a few questions about the patent situation. So perhaps you could talk to us a little bit about the patent family and how robust you feel the patent situation? Sure, absolutely happy to do, though. So we have very solid patent protection around the amyloidase and also the other enzymes. Just looking at amyloidase, we have 11 patent families covering medical use and dosing, and they last well into the 30s, mid-30s, with also patent term extension opportunities and so on. And then clearly, in addition to that, we have orphan drug designation for certain indications, right, which is also providing exclusivity and exclusivity around data usage and so on. So we have very solid IP. We've also had quite a lot of questions about pricing, considering there are so many indications that we've talked about today. So how will you handle that going forward? Obviously, in kidney, there's already a bit of an indication, but how will you look at it in terms of the other indications as well? Yes. So obviously, we will have different products, if you will, for different indications. But given the fact that very often it is the same molecule, there is interrelation there. So that's certainly something that we have thought through very carefully. As we set the price also for early indications, we do consider the impact on subsequent indications. That's clear. That's a complexity that is typical for all companies that are launching different products based on the same molecule. So there is a way to go about that. So picking up on the fact that I think you gave guidance of a launch in Q4. When are you expecting to book first sales? And also perhaps you could talk about how many hospitals, how many regions, countries you think will be online by the end of this year and maybe by the end of next year? Yes. So the time to first commercial sale really is, of course, dependent on getting market access, right? And Henk talked to that, what we have in place, and we've made much progress. And so from that perspective, we're certainly ready to move on in a number of countries very soon. Then the question is, when do we actually get the 1st patient on board and have the 1st commercial sale? And that really is dependent on initiating the sender. Again, we have made much advance here in terms of talking to the centers and enabling them, but they also need to identify the 1st patient and an organ has to become available. And then you have, of course, the COVID-nineteen situation. So it's difficult for me to predict specifically when we will have the 1st commercial sale. But clearly, we are launching the product this year, and then we'll see when the 1st commercial sale is booked. As far as how we stack up the different countries and how you'll see that progress, again, it's difficult to say. It really depends on, again, of course, getting access to the country to the extent you need national level reimbursement and the individual center. As Henk talked to, we consider this much more of a center by center launch than a country by country launch. So we do expect that we'll have certainly a number of clinics initiated in the very near term, very important centers of reference. And as they generate positive experiences, not only will they start using the product, but they will act as reference centers for other centers. So what we S shaped curve. We're really focused on not generating massive sales early on. I mean, we probably could have a very fast uptick given the fact that a lot of patients are pre identified. They're on a waiting list. So unlike my experience from, for instance, Shire, where we had to troll the entire universe to find and identify these patients, they're already there by name. We know where they are. But you have to identify the right patients and generate good experiences early on. Then you'll see a very solid uptake over the lifetime of this molecule. And as I said, we certainly consider this molecule to have blockbuster drug potential. So we're laser focused on generating great positive experiences in the right patients, in the right centers early on. And this is what I think people should stay focused on. This is what we are focused on. And then as we see sales take up, it will be more easy to make projections. I promise you, we will come back to the pipeline, but there were a couple of questions about expenses, which I think we should just cover. So in terms of Donato talked about accelerating R and D expenses, but can you talk a bit about the expense base in the coming years, also including SG and A or maybe separating out, see if there's going to be an increase across the board or can you talk a little bit about that? Well, clearly, there will be an increase across the board, right? I mean, we are a small team at this point in time. Certainly, compared to, let's say, U. S.-based benchmark, this is a very, very small company. We have a lot to invest in. I hope everyone can see that this is an imminently investable platform, and there are many growth opportunities. We talked about them specifically here. So clearly, you'll see R and D expenses go up. You'll see commercial expenses go up. You will see some uptake also in the SG and A, overall, broadly speaking, including other expenses, right? So that's what you should expect. And I think the chart provided by Donato kind of indicates for the different categories how we see that play out over the coming years. And of course, as always, we have got a question or a number of questions in about fundraising in the future. I know you talked about the idea of a U. S. Listing, but have you got any other plans on fundraising in the future? So we're very happy to be in a situation where right now we are well funded for the coming years. There is no urgent need for us to raise additional capital. So we can really focus on executing on the many different opportunities we have. Having said that and having spent quite some time in the biotech industry, you should always be open to raise capital when there is an opportunity. And I think we can just look around and see what is happening. You don't know what is happening what will happen going forward to the external environment. So that's something that we, of course, remain focused on and we're ready to do if we think it's necessary and there's a good opportunity. But certainly, it's great to be in a position where there is no urgency that we don't need to raise capital in the short run. If we turn now to idipforyx and the U. S. Launch, but before we talk about the plans to try and get the drug to the U. S, we also had a question about Japan and whether you've got plans of how you're going to develop the Japanese market eventually? Absolutely. So we are looking at the entire globe. And again, based on my experience in other companies, you should not forget Latin America, for instance, and Asia Pacific, huge opportunities in different countries. Now you asked specifically or someone asked specifically about Japan. In Japan, there is actually not a huge opportunity in the transplant business. The Japanese, for a variety of reasons, are not really prone to do that currently. So that's not a key priority for us. But within the autoimmune disease space, there are many, many opportunities, and we're already engaged. We're talking to specialists, key opinion leaders in Japan. We're putting in place the next steps to get regulatory potential approval. There are different statuses that you can get like Sakigake designation and so on. So we're looking at Japan also as a significant opportunity, but primarily for the autoimmune disease space. So going back to the U. S, I know you've been having discussions with the FDA. We did get some questions in asking, have you got agreement with the FDA? And the trial design, a bit more meat on the bone than you said earlier. Yes. So as I said, we have overall agreement with the FDA around the path forward, and we need to run a randomized controlled trial where we compare using amylifidase in one group against standard of care in the U. S, which for these highly, highly sensitized patients that we're talking about really is to remain on the wait list, hoping against hope for a compatible kidney to become available. But there are certain things that you can do. And so this is the trial that we will conduct. It is limited in scope. So we talk about approximately 45, 50 patients. So it's not a typical Phase III type trial. And I don't want to go into all the details. We have submitted a draft study protocol. Dialogue with the FDA around finalizing this study protocol. And once we have that in place, we will set up the centers. It's going to be a bit more than what we've done in the past in the U. S, so we'll reach out to a broader group of centers. There is enormous interest, I would say, in participating in this because there is a real unmet medical need in the U. S. So we have great contacts to some of the leading centers in the U. S, and I'm comfortable that once we get the green light from the FDA, and the FDA right now is a little bit underwater, as you can imagine, due to the COVID-nineteen situation in the U. And other things. But we are dialoguing with them once we have the green light. As I said, we will set up these centers and move ahead. And you talked before about how in Europe, they're a very dedicated center, so you know the patients. Is that the same in the U. S? Or would you look for a partner? No, it's the same in the U. S. So we have excellent connections to these centers. A number of these centers already participated in our Phase 2 trials. So we certainly will conduct this ourselves. And also outside of this group, we have very good connections. You've met Vincenzo today, who's based in the U. S. We have a team of MSLs in the U. S. So this clearly is a market that we will also approach ourselves. And I mean, just lastly, before we go back to the pipeline, I know it's difficult to say, but the market opportunity in the U. S, obviously, very important. How do you think about that? The market opportunity in the U. S. In terms of patient numbers is similar to the opportunity in Europe. And then, of course, typically what you do see is that in the U. S, the price point tends to be higher than in Europe. So it's a very significant commercial opportunity. So after Adiim's presentation, we had a couple of questions in. One of them was looking at the GBS opportunity. It's a potentially very large indication, but historically, it's been difficult to get approvals there. So how should we think about a registrational trial in that indication? What are the endpoints? Sort of what kind of makeup would that be? So as Achim talked to, the current study that we're running, the Phase II trial, we're putting amylifidase on top of IVIg essentially, and then we're comparing to a patient registry. So there is a comparator there, but it's not, of course, a randomized controlled trial. How that may look like, I think I'd rather have Achim and the team on another occasion. Probably, I don't know if Achim is still here, but this will become pretty granular. Is Achim on the line? And does he want to say something, Achim? But I cannot add much to this. I think very I think important is that we show proof of concept first. So and we are doing this in a match control analysis versus the Argos database. And there are a number of endpoints that will be captured in this proof of concept trial. And this concept proof of concept trial will educate us. And as you said, there have been actually there is no precedence for randomized controlled trial. I think the first or the last trial looking at IVIG was done in the 90s. And currently, there's nothing else out there apart from IVIG and plasma for this. So no drugs, no steroids. So everything in this indication has actually failed. So currently, the field is pretty empty, which is good on the one side, but this is also a challenge in order to design a randomized controlled trial. Thank you. Maybe staying on that indication, we did have a question about the pace of enrollment in both GBS and also AMR. It seems to be going fairly slowly. Was there some sort of inference from the question? So is that because there's a lack of excitement about the treatment? Or is it other factors? Absolutely not. So we actually once we started recruiting patients, we saw a pretty fast uptake, and there's lots of excitement. But then we had the COVID-nineteen pandemic just explode, right? And we took a deliberate decision in order to protect data integrity to put patient enrollment on hold. And it has essentially been on hold for a couple of quarters now. We have now taken a decision, also working with the different external collaborators, to move ahead, right? So we're opening up, but we're doing it on a center by center basis. I mean, we don't want to compromise data. That's absolutely a critical priority for us. So but I would say that given our experience so far, just looking at, for instance, the GPS trial, the patients are out there. And so I'm confident that we'll be able to get this going again fairly quickly and that we can meet the time lines that Achim discussed. On GBS, for instance, I mean, I think it's quite interesting we talk about COVID-nineteen. It seems like the SARS CoV-two virus actually is a trigger, right? So you can think about how that may impact over time if it is the incidence here. So I think we were confident that we can enroll at a reasonable speed. Just turning now to the NICER program. Are there limitations for development in that program? Where are you in the process? When will you announce clinical candidate? Can we talk a little bit about that? The NICE program overall, obviously, this is a key value driver going forward. As it opens up, as we've discussed today, a new universe of repeat dosing scenarios, diseases and scenarios. So we have identified a very promising lead candidate. We obviously also have backups. And we're now moving towards IND enabling tox studies that we expect to complete next year. And then on the backside of that, in parallel, we're doing CMC and so on. We hope to be able to take the lead candidate into the clinic. I can't give you a specific month here, but certainly, we hope that it's going to be in the near term. We've heard a lot of presentations today and Imliferdata is obviously a very versatile technology platform and product we can use. So perhaps you could talk a little bit about how you balance in house development, which obviously leads to costs and maybe working with the academic community. We are already working with the academic community, right, in many different ways. And we certainly intend to continue doing that going forward. As I said, I'm really a firm believer in the ability to access external sources of innovation and leveraging that also. So we will be an open, not society, but an open company and really continue to place ourselves in a very central position versus external partners, including academic institutions. We have a number of leading global academic institutions that we're already working with and lots of interest from others. I just want to check-in a minute, I want to check whether there are any more questions coming in. We've got some more questions here about gene therapy. So maybe we'll turn to that now while we're just checking the status of the webcast. So the deal with Sarepta, we heard quite a lot about that. Can we expect further partnerships in the gene therapy area? We're certainly working on it. There's lots of interest from a broad range of flares, both large and small, and you can see it's a pretty rich landscape out there. So we certainly expect that. It's our strategy. It's difficult as ever to predict when and with whom next and so on. But clearly, there is, as I said, lots of interest and incoming in that space. And we know the 2 indications that Sarepta are looking at, but maybe you won't be able to answer this, but can you identify some of the other areas that you think actually could also be really useful there? No, I can't. But I had to try, right? You had to try. Very good. So maybe just talking about the Sarepta partnership, what are the sort of near term development and regulatory milestones that we can expect for that? I know Emmanuel was talking a little bit about it. But are there things that really the market should be looking at in the next term? Yes. So right now, I mean, we have established the infrastructure here. We have a joint steering committee in place. We have joint project teams and so on. Sarepta and us will need to generate additional preclinical data. And so this is essentially ongoing before it can put be put into the clinic. Now as we've discussed, Sarepta has a number of ongoing trials, and there are different ways that you can then integrate the amyloidase component. So difficult to say anything about timing, but I would say that overall in the gene therapy space, given the fact that typically very few patients, as you've seen, are involved, you can move pretty fast. So we'll see. Yes. And maybe you can talk a bit about the competitive landscape as well because it's about one of these buzzwords. We hear lots of buzzwords in this industry and it's like gene therapy has become one of those. So what's the competitive landscape like for Hansa Biopharma? For Hansa Biopharma, I mean, the gene therapy companies obviously has been looking at ways to get around this neutralizing antibody challenge for quite a while, and they really haven't made a lot of progress. I mean, this is why we're seeing this very strong interest in amlividase. But of course, there are other ways that you can deal with this. But I would say that we certainly feel that amylipidase and other of our enzymes that we're looking at clearly has the potential to very dramatic way deal with this neutralizing antibody challenge. Obviously, development timelines are very long in the life sciences industry. And you already said in your first presentation today that Hensa Biopharm has really had to change a lot. You sort of organically develop over the years. So when you look at the future, can you sort of talk about how you see how you can be agile in the future and adapt things? We've seen COVID-nineteen, for example, completely changing how you might commercialize a drug. I'm just wondering if there are other things that you how can you stay agile in the market? Very good question, and it's certainly a key priority of us to stay agile. So one of the ways that you can do that is to really have a very clear focus on the things you want to do and the things you don't need to do yourself. And we have a very clear model here. So we want to partner with sources of innovation externally, but also in certain markets, other players that can bring complementary assets and can take some of the risks. But as I said, it's key for us to remain in control of our key assets from a management perspective. So that is important for us. And just one more question to finish off or very quick question just to sort of wrap up really. In terms of the future, talent acquisition is important and also, of course, keeping the culture as you grow. What are your thoughts about that? How are you going to handle that going forward? Very good question. So I think Hansa has been on a very successful journey so far, and it's obviously critically important for us to retain some of the culture that has brought us to where we are. At the same time, we have to accept that we are growing, right? And so we need to, in certain areas, change the way that we operate. We need to put in place, to a certain extent, a new governance structure, and we're working on that right now. But what is critically important for us is that we have a decentralized setup where we really empower the people at the front end in the laboratories and in the trenches in the markets and so on, as Christian talked to. And this, I think, we're succeeding doing as you can see from our employee survey. Sven, thank you very much. I'm going to pass over to you now to have some closing remarks. We've obviously had a lot of information, and I'm sure there'll be subsequent questions. You can obviously send those into Claus. I expect his details are on the website. So if there's anything that you feel we haven't covered, please do send in those questions. But sir, let me pass over to you now. Thank you. Thank you very much, Rachel. So I hope this has been a productive use of your time today. We certainly have covered a lot of ground, and I want to thank you, Rachel, as moderator and not least, our external speakers who have helped us today. I also want to thank our audience for sending in questions. Hopefully, we've been able to address many of these. But as you said, Rachel, additional questions, send them in, and we'll follow-up in the coming days. I hope that as you leave today, as Asda said initially, you will see that this is a company that has come a long way already. We've been on a very successful journey. We have great momentum and there is a very promising outlook. As we now embark on the exciting journey ahead, we have very, very clear strategic priorities and clear milestones that we want to achieve. And as I said, when we meet 5 years from now, and we're not going to meet 5 years from now, only will we meet before, but when we meet 5 years from now, I'm sure that the Hensa Biopharma will have transformed into a leading player overall in the rare disease space. So thank you so much, and have a nice evening or rest of the day where we are. Thanks.

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