Hansa Biopharma AB (publ) (HNSA) Earnings Call Transcript & Summary

Ladies and gentlemen, welcome to the Hansa Biopharma Q3 earnings calls. [Operator Instructions] Today, I am pleased to present CEO, Søren Tulstrup. Speaker, please begin.

Thank you. Good afternoon. Good morning. Welcome to the Hansa Biopharma conference call on the results from the first 9 months of 2021. I'm Søren Tulstrup, CEO of Hansa Biopharma. With me today, I have our CFO, Donato Spota as well as our Head of Investor Relations, Klaus Sindahl. Today, we'll review the overall progress and highlights of our business in the most recent quarter and provide a preview of our near-term milestones. Our presentation should take around 15 to 20 minutes. And after that, we'll take your questions. Please turn to Slide 2. Please allow me to draw your attention to the fact that I'll be making forward-looking statements during this presentation, and you should therefore apply appropriate caution. Please turn to Slide 3. Hansa Biopharma's transformation into a fully integrated commercial stage biopharmaceutical company has become a reality this year, and we are on track to deliver on our key objectives for 2021 as well as on our strategic priorities to build tomorrow's Hansa. Throughout the year, we made significant progress advancing our clinical, commercial and corporate strategy with solid progress in our efforts to build and advance the pipeline of valuable drug candidates for rare immunologic diseases, while in tandem introducing Idefirix in Europe as a new transformative therapy that brings hope to the thousands of highly sensitized patients across the continent who are currently waiting for compatible kidney transplant. During the third quarter, we made good and steady progress with the commercialization of Idefirix in Europe. As we have discussed before, Idefirix represents a paradigm shift in the transplantation ecosystem, and as such, there is much foundational work to do in establishing it within the system. We made important advancement towards obtaining market access in a number of key markets and funding has now been secured in the first 3 countries. In total, we have now submitted Health Technology Assessment dossiers in 10 countries. These dossiers are an important component of successful product launch, asset support pricing and reimbursement, the achievement of which is obviously critically important for subsequent market penetration. The submitted filings include data demonstrating the uniqueness of Idefirix from a clinical perspective, various country-specific demographic data sets to define the eligible patient population based on the drugs approved label as well as proposed pricing based on the overall value proposition. Recent assessments in Sweden and Germany concluded that Idefirix would be a cost-effective and potentially even a cost-saving drug versus standard of care, which is a rare event for orphan drugs. At the end of August, we participated in the 20th edition of the European Society of Organ Transplantation for ESOT Congress, which was held in Milan, Italy. The ESOT Congress was the first in-person event post COVID, and the Hansa team had a strong presence, which included a sponsored symposium. One of the key outcomes from ESOT was the formation of a new work stream with leading transplantation or key opinion leaders to advance clinical guidelines in transplanting in compatible kidney transplant patients. The new ESOT work stream is expected to be a key driver for harmonization in approach to transplanting highly sensitized patients and to ensuring positive outcomes for patients and transplant programs. We will later discuss in more detail how we track progress towards commercial success and which metrics to look for as the company advances its commercial launch strategy in kidney transplantation. In the U.S., we have now initiated the first site in San Antonio, Texas for recruitment of patients to our randomized controlled clinical trials in kidney transplants, the so-called ConfideS study, and we expect patient enrollment to commence in the fourth quarter. Initiation of ConfideS is a significant milestone in our efforts to access the important U.S. market. The new trial will enroll 64 highly sensitized patients with a cPRA score of 99.9% or above, representing the group of patients with the highest unmet medical need. We expect to enroll patients at 12 to 15 leading transplantation centers across the U.S. and that the U.S. trial will generate valuable experience at these key clinics ahead of a potential approval and commercial launch in the United States. Looking beyond transplantation, we have now initiated discussions with the FDA on our anti-GBM program following the successful completion of Phase II, which demonstrated very encouraging clinical data in the first area outside transplantation for Imlifidase. As previously guided, we aim to achieve alignment with the FDA on the regulatory path forward in anti-GBM later this year. In our ongoing Phase II programs for GBS and AMR, we've seen patient and recruitment accelerate as new centers were initiated during the third quarter and we are on track to meet our target of completing enrollment in both studies towards the end of this year or first half of next year, as previously guided. Further, I'm also pleased to announce a new study in 12 patients in the U.S. to assess whether Imlifidase in combination with other therapies can optimize patient outcomes in highly sensitized patients with donor-specific antibodies rebound and antibody-mediated kidney transplant rejection. The study will be run at New York University Langone Transplant Institute and is expected to commence this next year. Lastly, I also want to highlight that Hansa Biopharma was recently awarded certification as a Great Place To Work for the second consecutive year. The certification as Great Place to Work reflects our successful efforts over the past years to not only build and maintain a high-performance team, but also to create a rewarding and stimulating workplace for our employees. Please turn to Slide 4. As I said initially, Hansa Biopharma's commercial launch activities are progressing as planned. Our goal is to have a positive impact on patients as we work closely with the transplant community to reshape the area of desensitization and integrate Idefirix into clinical practice as a new standard of care. With this novel therapy, we're paving a new path in changing the transplantation ecosystem to accommodate transplants for incompatible kidney patients, and we do this in a very focused way, clinic by clinic. We're taking very strategic approach as Idefirix is the first and only approved drug to enable kidney transplants in highly sensitized patients in the EU or in incompatible with a deceased donor and the long-term market uptake for this innovative product is highly dependent on successful early experiences in key early adopter clinics. We measure launch progress using a set of key commercialization metrics, which directly impact future adoption and sales of Idefirix as a new transformative therapy. Securing appropriate pricing and reimbursement at the right price level and on label is one of the key metrics for the rollout of Idefirix. We are on track to secure funding market by market in Europe as indicated by the recent successful completion of HTA assessments and negotiation procedures in the first of the early launch countries, namely Sweden, Finland and the Netherlands. Further to this, we've initiated additional HTA and reimbursement processes across 7 countries, including United Kingdom, Germany, Norway, Denmark and Israel and most recently also in Italy and Scotland. By year-end, we expect to have completed HTA filings in all of the 5 largest European markets as HTA dossiers are being prepared for submission in France and Spain during the fourth quarter. I also want to highlight that we have now submitted marketing authorization applications in both Switzerland and Israel and that Idefirix has received status as a priority medicine in Poland, which potentially will lead to accelerated access. On the clinical side, we've been working with a number of priority centers to ensure and optimize their clinical readiness as a number of new compatible patients are being identified and prioritized for kidney transplantations in the coming period. So far, 9 clinics are considered clinically ready to take on highly sensitized patients for a compatible kidney transplant and we continue to work closely with an additional 9 centers across Europe on their preparedness through training, key opinion leader engagement, protocol drafting and logistics. In relation to the awareness and interest metric, we have been extensively engaged during the recent quarter, especially after the easing of COVID-19 restrictions as exemplified by our significant presence at the European Society of Organ Transplantation Congress, which was held in Milan, Italy in August. At this congress, we held a very well attended symposium entitled a road map to Transplant for the highly sensitized patients, hosted more than 30 key opinion leader meetings with our combined commercial and medical teams and had 2 oral presentations in support of Idefirix. We are very pleased with the great interest from key opinion leaders throughout the Congress. And 1 of the key outcomes from ESOT was the formation of a new work stream leading transplantation key opinion leaders to advance clinical guidelines to include incompatible kidney transplant patients. The new ESOT work stream is expected to be a key driver for harmonization in the approach to transplanting highly sensitized patients and to ensuring positive outcomes for patients and transplant programs. Now please turn to Slide 5. Turning now to our clinical programs in antibody-mediated rejection in Guillain-Barre syndrome where patient recruitment in the 2 Phase II programs has been accelerated during the third quarter, driven by the initiation of additional recruitment centers. In the AMR trial, 7 patients were enrolled during the third quarter, which takes the total number of patients up to 19 out of a target of 30. Since July, we have increased the number of access sites in AMR from 7 to 12 and expect 2 additional centers to be opened in the fourth quarter. With the current pace for patient enrollment, we are well on track to completing recruitment towards the end of this year or by first half of next year at the latest. We expect to announce the first data readout from the AMR Phase II study in the second half of 2022, as previously guided. In the GBS trial, we have now enrolled 14 patients out of a target of 30 patients. During the third quarter, we have added 1 additional center and expect 2 additional centers to be initiated during the fourth quarter. As previously guided, we expect enrollment in the GBS trial to be completed towards the end of this year or by first half of next year at the latest, with the first data readout in the second half of 2022. Enrollment into both of these studies is ongoing under a risk-based side-by-side approach given the volatility of the situation we are facing related to COVID-19, our guidance assumes no further escalation of the COVID-19 pandemic, potentially forcing trial centers to reprioritize patient recruitment or even shut down again. Moving on to our anti-GBM program, where dialogue with the FDA has now been initiated regarding the regulatory path forward towards a BLA in the U.S. The dialogue with the FDA is expected to conclude later this year, as previously guided. Similarly in Europe, a constructive regulatory advice meeting was recently held with BfArM. Hence is now preparing for a dialogue with EMA around the regulatory path forward towards a marketing authorization application in Europe in anti-GBM. Last year, very encouraging Phase II data was presented in anti-GBM demonstrating that 2/3 of the anti-GBM patients enrolled achieved dialysis independence 6 months after treatment. As I mentioned earlier on this call, we've just initiated the first center in our new ConfideS trial in kidney transplantation in the U.S. at the San Antonio Methodist Hospital in Texas. The U.S. trial will target 64 highly sensitized patients with a cPRA score of 99.9% and above, representing the group of patients with the highest unmet medical need. We expect to initiate additional centers in the coming months, aiming at 12 to 15 leading transplantation centers across the U.S. As previously communicated, we expect to complete enrollment in the second half of 2022 with a 12-month follow-up on eGFR completed by second half of 2023. Results from the trial are expected to support a BLA under the accelerated approval pathway in the first half of 2024. Please turn to Slide 6 and a summary overview of our pipeline. As depicted on this slide, thanks to continued progress over the past few years, we have developed a broad clinical pipeline in both transplantation and autoimmune diseases. In addition, we have exciting preclinical projects ongoing in cancer and antidrug antibodies as well as in the very promising field of gene therapy, where our partnership with Sarepta is assessing Imlifidase as a pretreatment to Sarepta's gene therapy programs in Duchenne and Limb-Girdle muscular dystrophies. Preclinical development is progressing according to plan. And upon successful completion, we expect Imlifidase to move into the clinic as a next step. Beyond the partnership with Sarepta, Hansa is also engaged in a preclinical collaboration with argenx, which is also moving forward according to plan. The focus of the argenx collaboration is to assess the potential benefits of combining Imlifidase with efgartigimod argenx's FcRn inhibitor. With this overview, I will now hand over the call to Donato, who will take us through a review of the financials for the first 9 months. Donato, please?

Thank you, Søren. Please turn to Slide 7. As Søren outlined, we are on track to achieve our key 2021 objectives through continued progress across our business and pipeline activities. Revenue for the first 9 months of 2021 grew to SEK 18.5 million, including SEK 6 million in product sales and SEK 10.4 million in revenue recognition under the Sarepta agreement. Please turn to Slide 8. We continue to invest in the Idefirix launch and our pipeline in accordance with our operational and financial plans. For the first 9 months of 2021, SG&A expenses amounted to SEK 224 million compared to SEK 140 million for the same period last year. The increase is in full support of our objectives to develop Hansa into a fully integrated biopharmaceutical company and as such, primarily reflects our expansion of commercial activities, including investments in the territories, marketing, market access and supply chain activities related to the launch of Idefirix in Europe. Our investments in R&D amounted to SEK 163 million for the first 9 months of 2021, which is about the same level as for previous year. Investing in R&D and our pipeline activities across all of our therapeutic areas remains the key priority for Hansa as it supports long-term value creation for the company. The net loss for the first 9 months of 2021 was SEK 385 million compared to SEK 315 million for the same period last year. The increase is primarily driven by an increased activity in ramping up our commercial activities and developing Hansa into a fully integrated company. Please turn to Slide 9. Cash flow for operating activities amounted to minus SEK 365 million for the first 9 months of 2021, which compares to minus SEK 194 million from the same period last year. The increase should be seen in the context of the USD 10 million upfront payment received by the Sarepta in July last year under our license agreement with Sarepta. As of September 30, 2021, Hansa's cash position, including short-term investments, amounted to SEK 1 billion corresponding to approximately USD 115 million. Our solid cash position and projected run rate, we expect Hansa to be financed into 2023 as previously guided. I'll now hand back to Søren to give his final remarks.

Thank you, Donato. Please turn to Slide 10. Hansa Biopharma's transformation into a fully integrated commercial stage biopharmaceutical company has become a reality in 2021, and we continue to demonstrate solid progress in our clinical, commercial to corporate strategy including significant progress in our efforts to build and advance a pipeline of valuable drug candidates for rare immunologic diseases. Looking at the milestones ahead. We expect to announce the first patient enrolled in the U.S. ConfideS trial during the fourth quarter, following the initiation of the first recruitment site in Texas. As discussed, results from the trial are expected to support a BLA under the accelerated approval pathway in the first half of 2024. In addition, as also discussed, we aim to conclude our dialogue with FDA on a regulatory path forward for our anti-GBM program later this year as previously guided. In our 2 Phase II programs in AMR and GBS, we've seen an acceleration in the enrollment rate for new patients following the addition of more centers. At the current pace and assuming no further escalation of the COVID-19 pandemic, we're well on track to completing recruitment towards the end of this year or by first half next year at the latest, as previously guided. Following completion of enrollment, we expect to announce the first data readout from both studies in the second half of 2022, as previously guided. With regards to our NiceR program for repeat dosing scenarios, we expect IND-enabling tox studies to be completed in 2022. Upon successful completion of these studies, we expect to advance the NiceR program into clinical studies. We look forward to keeping you updated on our progress in advancing our mission to bring life-saving, life-altering therapies to patients with serious rare diseases while generating long-term value for our shareholders and society at large. Please turn to Slide 11. And with this, we are now ready to take your questions. Operator, please begin.

[Operator Instructions] The first question from Christopher Uhde from SEB.

So you've been guiding expectations lower for over a year, I guess, giving everybody plenty of time to get used to the idea. But your negative gross margin on Idefirix, not only in Q3 but also from obviously -- but also from before -- for the whole year, I mean, looks like a possible signal that demand has not met internal projections. So would you please comment on how your expectations may have changed in the past 12 months? And at what level your assumptions have changed? Is demand a factor here at all? Or is it just access? And how confident are you that sales will finally start again in Q4?

Thanks, Christopher, for that question. So no, our internal forecasts have not changed. This is due to the fact that, obviously, when you produce, you need to produce pretty big batch sizes, and we want to make sure that we have product available in any -- under any circumstances. The last thing we want is to not to be able to supply market wide. But our internal forecasts are totally consistent over the past year. And so there's been no change in that. And we're confident that, as I said earlier in this call, that we've had a good start to the launch. We're seeing very, very solid progress versus the key launch metrics, and we certainly expect this to pick up and follow the S-shaped launch curve that I've been talking quite a lot about over the past year or 2.

Okay. Perfect. Sort of just another follow-up question. Do you need to add manpower experience to your market access marketing or medical affairs teams to get that pickup to happen? Do you feel that you're adequately staffed there?

Well, I'm very pleased with our market access team that really has done a fantastic job of getting market access programs going. We may need to staff up as we spread out geographically. But at this point in time, we have the capacity needed to handle the submissions as we've submitted on 10 different countries, and we have ongoing discussions in many of the key countries. As far as medical and commercial staff is concerned, there will be some additions as we get into specific markets. Currently we have the core team in place. And overall, it's a low double-digit number. They're doing again, an excellent job in the key markets, interacting with the clinics. But of course, over time, as we get access to additional countries, there will be some additions at the front end.

Okay. Appreciate that. If I could just ask 1 more before getting back in the queue. Desensitization with previously available methods has gone out of favor to some extent over the years. What's the latest feedback you get from across the nephrology community around Idefirix being the answer to desensitization needs. And I guess when it comes to the ESOT work stream, can you give a little bit more background? How is that related to guidelines? What are the steps you need to take to get into guidelines?

Yes, sure. So you're right. I mean desensitization has not really been at the top of the list in Europe for a number of years for a variety of reasons. So this is also why we're stepping into what is somewhat of a virgin territory here. But overall, I would say the feedback and the reaction to Idefirix has been very, very positive throughout Europe. I have also interacted with quite a number of key opinion leaders over the past year or 2. And I would say that we definitely see a high degree of interest. Obviously, that should not be taken as a signal that you'll see very, very strong uptake in Italy. But I'm really, really pleased with the interest that we are seeing. You mentioned the ESOT guidelines. And as I talked earlier on this call, we're very happy that our work stream, a formal work stream has now been formed within the society, to put in place European-wide guidelines for desensitization of these highly sensitized patients because that will be very helpful going forward. It's not necessarily short term to get started. We have direct interaction of course, with key clinics and national societies, but it will be helpful to have European-wide guidelines. And again, just looking at the discussions that took place at ESOT in this team that has been set up, I was pleased with the degree of consensus that we need to do better in Europe here and there is much more to be done and that the society has a key role to play. So the next step will be, obviously, to get this work stream going and then to have the guidelines submitted for publication at some point in not too distant future, I would expect.

Next question from Dominic Gus from Intron.

This is Dominic from Intron Health. My first question is have any of the centers that took on an Imlifidase patient this year since taking on a second? And if not, then when would you expect them to? Question 2 is just on the quarterly P&L. I was wondering why the cost of revenues were so high this quarter. And finally, question three, just wondering again, whether you received any negative feedback from the first transplant centers that have used Imlifidase.

On the first question -- I'll hand over to Donato for the second. The first question, whether any centers has taken on a second patient, the answer is no. That is obviously something that we're looking at to have repeat business. And when I'm talking about repeat business it is not at the patient level, of course, it's at the center level. But we expect some of the most important centers to have, hopefully, first patient this year and then they will typically wait for a number of months to see the outcome before deciding on potentially doing the second and subsequent patients. On the -- let me take the third question, which was on negative feedback and at this point in time, we do not receive any of that. So far, really good interest positive attitudes and most centers are getting ready to transplant their first patient. And then on the second question, I'll hand over to you to Donato.

Yes, sure. So Dominic, I think your question goes in the same direction as Christopher's question at the end of the day. I mean this is -- looking at the quarter in isolation, this is really an accounting topic mainly. It is -- in that call, we have delivered additional material. And then in this case, you have to do certain tests from an accounting perspective to value that you can show a value not on your balance sheet. And obviously, since we don't have a history of our sales, due basically to a provision, and this is what you see in the accounts on the cost of sales, I think important to note in this context is a few things. A, I think this is completely not unusual in -- if you compare it to similar companies like Hansa who're just launching their first product. And secondly, the material while this is provision -- material has not been discarded or so, and this is obviously still prime material, and we will -- if there's sales, we will use the material to sell it. So it's really just an accounting topic at this point.

Okay. That's great. That's very helpful. I suppose longer term, thinking about COGS, a product like in this day, you would expect the gross margin to be pretty high. I mean, are we looking at kind of north of 85% for that?

We have not guided exactly on what the gross margin is going to be. But generally speaking, I think whatever your interpretation of pretty high is, but we will have a certain healthy gross margin from that product, yes.

Next question from Frederic Gomez from Pharmium Securities.

Two on my side, first on Idefirix. Can you maybe clarify a little bit the way you're going to take in France. Would you go through the normal process to submit the dossier with [ DHS ]? Or would you try to take advantage of the new early access scheme that has been set up in July, maybe to go faster. And another one on the current Phase II in AMR. Just curious about the 30 patients. Will you do a kind of stratification between patients having preexisting DSA and patients who will develop de novo DSA. And what kind of analysis you will perform in this population? Just maybe to understand better the data that you could get and the next pass after the result of the topline from the Phase II.

Well, thanks, Frederic. On your first question, the approach to France. You're right. I mean there's new early access program pathway available in France, which certainly is something that we are looking at. At the same time, even normal route also exists. So we will certainly move forward in France. And I can't say specifically to what extent we'll make the early access program pathway an option that we will exploit at this point in time. But certainly, it's a possibility, yes. As far as the AMR study is concerned, we will discuss it in more detail when we get into next year how will approach it and so on. So if you will have a little patience, I think you'll get more insights there. Was that okay?

I can hear you still.

Yes, I can hear you. I don't know if we just lost.

I think we lost the conference. It looks as if we gotten out of the conference. But I mean, not just -- I mean that's probably a more general problem.

Yes, that's a problem.

We'll go to the next question. Next question from Zoe Karamanoli from RBC Capital Markets.

Apologies if these questions were asked before, but I've missed the start. Two questions from me, please. The first one, on the clinical readiness, you mentioned 9 centers are ready. Can you elaborate a little more what this means exactly? Is that Imlifidase now is included in the clinical guidelines and physicians are aware and willing to use the drug. So the centers basically are ready for the eligible patients. And then the second question, based on your discussion so far with the centers, how much of a hurdle or a need for education is to convince to include the desensitization with Imlifidase. And can you give us an estimate of what you think is the current desensitization rate? And what is your aspiration of how much this can increase in the next 2 to 3 years?

I'll probably need to have you repeat your second question. But in the meantime, let me just try to answer the first question, which is on what does clinical readiness mean as far as the centers are concerned. And that really means that the centers, key employees, key staff have been ongoing training that we've certainly been involved in very deep dialogue with the staff around how to treat these patients, how to identify appropriate patients, et cetera. So that is a pretty extensive interaction that needs to take place upfront because, obviously, we are as interested in successful outcomes as far the centers and the patients clearly. Second, we also want a specific or not we, but certainly the hospitals, a specific protocol to be drafted and put in place for how to approach all of this. And then obviously specific logistics around how to get the product in and handle the product in a transplant situation. So those are some of the key steps, but we really have a very, very granular protocol overall, if you will, for our own sake to move forward in our interaction with these centers and make sure that they're ready to transplant. So this is really managed at a very detailed level on our end. The second question, if you can just repeat it, it was around how we expected desensitization rates to increase. But can you -- because the audio was a little bit bad, so I didn't get all of it.

Yes, sure. So I'm wondering if the desensitization is part of using Imlifidase. And I wonder so far with the discussion with the centers that you're trying to include it in the clinical guidelines, how much of the hurdle or education the centers need to use it? And if you have [indiscernible] the rate of desensitization so far as a baseline? And what do you expect this rate to increase in the next 3 years with the education that you're going to begin the clinical awareness.

Yes. So reality in Europe is that right now, there is very little desensitization taking place, looking at these very highly sensitized patients and trying to make them eligible for potentially life-saving kidney transplant. That just doesn't really happen because you don't have any approved product, and you don't have non-approved products that are able to get the kind of decreasing in donor-specific antibodies rapidly to enable patients to undergo kidney transplant when a deceased donor organ becomes available with a positive cross match. So essentially, as I said, we're walking into a virgin territory here. And this is also why we need to talk not just about our own product, but the whole field of desensitization. And that is a process which has started. And as I said, we are very comfortable and happy with the progress that we've seen, the reception within the medical societies, including the European Society of Organ Transplantation where they've now created this very focused work stream that will specifically look at guidelines for desensitizing, highly sensitized patients. And this is all in the back of the emergence and the availability of Idefirix as a transformative therapy, right? So this is what is happening at this point in time.

Next question from Christopher Uhde from SEB.

So what's the status of the confirmatory trial that you need for the EU for kidney transplantation. And how important is it to your marketing strategy? That's my first follow-up. And then the next one is, so how much influence coming now to the broader pipeline. How much influence do you have on recruitment rates in the IISs. You've talked about potentially starting a trial for stem cell transplantation and potentially other indications. Given that IISs have so far proven to be a slow way to go, how do you think about what your development strategy would be for any new indications?

Good questions. Thanks, Chris. So first, on the post-approval efficacy study, which is a study we won as a confirmatory trial in Europe. We are finalizing the last steps, and we expect this to be ready to be initiated by the end of the year, essentially. As far as the importance of this study, obviously, we need to run it. It's significant on our side, but it's also a good way to develop experience in some of the countries in Europe where it will take a little bit longer to gain access, right? So that we have the second way of generating hopefully positive experiences in key centers. So that's where we stand with that trial. Your second question is also a good one. You're right, investigator-initiated trials tend to be a little bit slower in recruitment rates and so on. Obviously, as a company have less influence there. So going forward, we will aim to run key trials ourselves but they will be complemented by some of these investigator-initiated studies for certain indications. So it will be a combination going forward.

Okay. And just to be clear, the post-approval efficacy study that will be separate from the FDA -- the study for the FDA.

Yes. That's a separate study. That's a European protocol only. The FDA study is again a separate U.S. trial that we're initiating following good interaction with the FDA. We are aligned on the started protocol and the pathway forward. So that's a U.S. only trial, the ConfideS trial.

Okay. And do you have a rough indication of how many patients you need for the European one?

For the European one, we expect over the years to include approximately 100 patients.

We have a new question once again from Zoe Karamanoli from RBC Capital Markets.

Just a follow up question, probably a quick and very specific. You have so far for the U.S. trial, 1 site active. And the intention is to have between 12 to 15 sites active. Can you tell us how many more sites you expect active by the year-end and by when we should expect to see all sites up and running?

Yes. So you're right, we expect 12 to 15 centers. It's a little bit tricky to give you a hard number for how many centers we would expect by the end of the year. Obviously, this is an ongoing process. I would expect a couple of more centers to get active in the near future. And that's obviously relatively soon into earnings to the following year that we'll have the bulk of the centers up and running. There is a very strong interest from these key centers to participate. And so I don't think it's certainly not a question of motivating them, but there's obviously a number of steps you need to take them through. So that's what I can say at this point in time.

Okay. So we'll wait for more updates.

We have a new question from Adam Karlsson from ABG Sundal Collier.

Just 1 for me, if I could. Just on the work with the ESOT work stream that you were mentioning in regards to developing clinical guidelines for Imlifidase in the renal transplantation indication. You were saying you hope to kind of complete that work during 2021, as I understand. I'm just looking for a bit of clarification whether that would mean kind of completion of drafting of a potential clinical guidelines or kind of how -- what work needs to be done post completion of this ESOT work stream before there could be kind of clinical guidelines in place that would be implementable broadly in Europe, I guess?

Yes. So the task force has now been set up, as I said, and they're getting going as we speak. Obviously, the next step will be to produce draft that will need to be circulated within the wider community and with initial review and so on. I expect this to take months. And I really can't predict when, obviously, when this will be completed. But if there are not too many discussions and so on, it shouldn't necessarily take very long. Upon completion of this internal peer review, if you will, and agreement on the final version, it will need to be submitted for publication and so on. Again, I can't give you a hard date or a specific kind of status by end of the year. But I expect this to take some months. And as I said, the good thing is that there is clearly alignment within the society that they need to produce these guidelines that they would be helpful. And my reading of the situation is that there is not too much disagreement around how they would look like. But this is a scientific society and as ever, it's impossible to predict what will come out of it. But we are certainly encouraged by what we've seen so far.

Great. Maybe just a second question, if I could. Perhaps a difficult one for you to comment on just now, it was an update that came here during the call that another Swedish company Genovis has entered into a licensing agreement with Selecta Bioscience to develop IgG proteases for use in gene therapy in autoimmune diseases. And I was wondering whether you have any kind of sense of how similar their approaches to what you're hoping to do with Imlifidase in gene therapy and then in autoimmune diseases and whether you can kind of comment on potential similarities or differences between those programs if you're able to at this early stage?

No, I'm not able to comment on that in general words. But I would say that there are obviously a number of different approaches in this space, and we're very comfortable with the unique approach that we are taking. So that's what I can say in general.

Thank you. We don't have any more questions for the moment. [Operator Instructions] It looks like we have no more question by phone. Let's wait a few more seconds. We have a new question from Douglas Tsao from...

I apologize if it was already asked. But just in terms of the targeted centers, that you're in, what's your sort of overall target in terms of the percentage of transplants taking place in Europe over time and certainly in the key markets. I mean, are you going to be covering 90% of the overall transplant volume? Or is that sort of -- or the target can be a little bit longer?

Well, I mean, as we've discussed in the past, this is a very, very concentrated-target audience. So in some countries, you only have 1 clinic essentially doing all the kidney transplants like in Norway, for instance, where there is a center in Oslo. There's 1 center only in Finland. In some of the larger countries, the top 5 or so represents 70% to 80% of kidney transplants. And certainly, we would target the key centers. So we do target centers representing the bulk of the kidney transplants through our efforts. But it's a low number overall.

Okay. Great. And then just Søren. What the time line for actually bringing a center online and fully training them, how long does that typically take from when you first show up to when they're able to use Idefirix?

It's difficult to say at this point in time because most of the clinics that we've gotten, I would say, all of the clinics that we've gotten online, if you will, our clinics that we've interacted with quite extensively over the past couple of years, obviously, in various settings. But that does not mean that it takes several years, obviously, to put them online. This is a very concentrated target audience and we interact for many reasons and have an ongoing dialogue. But it is a process that takes a while because you need to get your consensus within the center. And as I said, you need to take them through training and so on and so forth. So it doesn't happen from 1 month to the next, let me put it that way.

Thank you. We don't have any more questions for the moment. [Operator Instructions] It seems there is no more questions by the phone.

Okay. In that case, thank you so much for your interest. It's been a pleasure to update you on our progress so far, and we look forward to continuing our dialogue. Thanks so much, and have a nice day.

Thank you, ladies and gentlemen. This concludes today's conference call. Thank you for your participation. You will now disconnect your lines.