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

Hello, everybody. I think it's now 9:00. So we're going to try and kick off reasonably on time. And I want to welcome you all to this Capital Markets Day for Hansa. I'm going to introduce a little bit of the people who are here. But first of all, obviously, you should pay appropriate cost, take appropriate caution and refer to any kind of regulatory filings. There will be kind of forward-looking statements made during this presentation. So this is the agenda for the day. And I'm truly delighted that we've been able to bring you such a distinguished panel of experts who are here to share their insights and experiences. We'll cover the top line data from our European confirmatory study. The recently presented data at ATC, our Phase III ConfideS study. And then we will also have very exciting outcomes from real-world experience in France, reflecting what dedicated physicians have achieved there with Idefirix, who is conditionally approved there. We'll follow up with insights and viewpoints from the experts in the field of ALA profiling, crossmatching and delisting. It is a critical component of transplants. And I will tell you that having had the opportunity to sit through quite a few sessions at ATC that delves into the details of this. I'd say it's an intriguing complex and fascinating in its science in its own right. And then we will actually thank our KOLs and move over to our kind of U.S. prelaunch activities, pipeline and finish off with some general Q&A. So in terms of the panel that you will be seeing today, it is a panel consisting of Dr. Kamar -- Nassim Kamar from the Telus University, who is here to kind of share that dedicated group of physicians results of real world. We have Dr. Matthew Cooper, who's from the Medical College of Wisconsin. Chief Transplantation Director, solid organ transplants there. We have Roslyn Mannon, Vice Chair, Research and Professor of Medicine, Pathology, Microbiology and Immunology at the University of Nebraska. And we also have Dr. Annette Jackson, Chief of Clinical Transplantation, Immunology Research Director Clinical Transplantation Immunology Laboratory, long titles from Duke University. So thank you very much all for coming. We are great, greatly, greatly appreciative of your time, and we look forward to you sharing your insights and expertise with everyone in the room and online. For those of you who may not be familiar with Hansa, so we have a novel first-in-class IgG cleaving enzyme. It's from a proprietary technology platform. It cleaves all classes of IgG, both intravascularly extravasculary. It does so very efficiently, very rapidly. And so within 2 to 6 hours of an infusion. You really used IgG by over 95% from baseline. And so what we are doing mainly with these technologies, we're addressing rare and orphan indications. We're in the area of desensitization, both in terms of enabling transplantation. And obviously, as you know, this has been mainly kind of kidney transplantation and we're also looking at enabling gene therapy dosing. So this is really for those patients who have antibodies against the AAV vectors. And then we have another kind of enzyme that we call 50487 that we're taking into rare autoimmune diseases. And we have a Phase II trial, which was conducted with imlifidase. It's a proof of concept. And we're now in conversations with the FDA with regards to starting a clinical trial with 5487 in Ganbare syndrome, which we hope to basically be initiating before the end of this year. In terms of imlifidase, imlifidase is here in the U.S. It's not an approved agent. We basically read out the Phase III trial data in September of 2025. We filed our BLA. There is an ongoing FDA review with the PDUFA date of December 19. It is, however, conditionally approved in Europe under the brand name of IDEFIRIX and so as you might have seen recent press releases also, we have recently entered into an out-licensing agreement with SERB Pharma and that transaction is presently going through regulatory review in Europe, including kind of the FDI review, which is a foreign direct investment and we hope to see that transaction close, hopefully during the month of July. But that is obviously depending on the time line for that review. So with the kind of -- with that kind of out-licensing transaction, we've created a very strong financial position for the company. and a clear focus in terms of both the kind of the precommercial activities that we're doing in the U.S. and the actual pipeline activities in terms of rare autoimmune diseases, and obviously, the gene therapy area, where we hope to kind of continue to develop that partnership and collaboration during this year. But in terms of this actual transaction, it was an upfront payment of EUR 110 million, which significantly increases our cash position. There is another kind of milestone payment upon acceptance by EMA of the filing for full approval, which we're targeting to do in Q4 of 2026. This will obviously also mean that there are going to be some savings in terms of kind of the commercial infrastructure that we have in Europe. And also as SERB will become the market authorization holder, they will also take over responsibility for our clinical trials that are ongoing in Europe. So this really puts the company in a situation where we have a very significant runway irrespective of an approval in the U.S., but obviously, an approval with significantly extend that runway and actually provide a potential path to profitability. We're also going to use some of the proceeds of this transaction to delever the company, there is some prepayments kind of going from our '27 kind of scheduled -- mid-'27 scheduled payment that will be brought forward to the closing of the transaction. And so this is something else that we will balance kind of the capital structure of the company. So we're very excited about this, and I think this will really kind of enable -- 2 things. I think it will enable really kind with serves kind of experience and expertise in Europe to really kind of provide the best kind of basis for access to patients for IDEFIRIX in Europe, and for any further development of that asset in Europe. And it will enable Hansa to really kind of focus on the U.S. and enable us to do a robust kind of commercial launch, obviously subject to approval. So this is really kind of the pipeline that we have. So obviously, as I've just said, an approved product in Europe a product that actually our expecting [indiscernible] towards the end of this year. We have a couple of collaborations in the gene therapy space, which we're hoping to expand to further kind of collaborations this year. And then we have, obviously, the GBS trial, which I mentioned previously. So there are a couple of people here. This is kind of our management team, and I think actually many of them are in the room here today, and you will hear from some of them in their kind of presentations. We have Dr. Richard Philipson, who is our Chief Finical Officer. We have Maria Turnstone, who is our Chief Operating Officer and also President of the U.S., who will be taking you through some of the parts of this agenda. So with that, I'm not going to bore you anymore of the kind of corporate overview because that's clearly not why you're here. I'm very well aware of that. So I will leave that and I will actually kind of start the whole section and ask for us to kind of really talk to the people and hear from the people that you're here. to meet. So thank you very much for your attention. Thank you for coming. And I'm going to hand over to Richard Philipson. Thank you.

Thanks very much, Renee. So it's my pleasure to kick off the data presentation part of the meeting this morning by talking to you about our study that we have conducted in Europe which we call the postauthorization efficacy and safety study. So this was a controlled open-label post-authorization, efficacy and safety study. So this was a study that we agreed with the European authority as a commitment to convert our initial approval through to a full approval for imlifidase in Europe. So the objectives of this study that we conducted, the primary objective was to determine the 1-year graft failure free survival in highly sensitized kidney transplant patients, pretreated within [indiscernible] a positive crossmatch against a diseased donor into a negative cross match. So that was the primary objective. Secondary objectives, again, from an efficacy point of view, evaluated up to 1 year after transplantation were to assess kidney function, patient survival and graft survival. And of course, safety was also an important part of the study. So I'm going to move on and explain to you the design that we used for this study. And the study comprises 3 different cohorts. But it's very important to understand that there is no randomization in this study. And there is no statistical comparison between these 3 different cohorts. So I'll explain the 3 cohorts in turn, if we start at the top of the schematic. So this was the imlifidase treatment group. And in this treatment group in a fashion that we have used in many of our clinical trials, we identified patients who are highly sensitized and we're unlikely to be transplanted under the kidney transplant scheme within Europe. And these patients were entered into a prescreening stage in the study. And at that point, a prescreening patients underwent delisting of unacceptable antigens. And I think later on in the morning, that will be discussed in more detail. So I'm not going to go into that in huge detail now. That process of delisting. However, through doing that, it essentially opens up the organ pool for prospective recipients. So it allows them to have an increased likelihood of receiving a donor organ offer. If they receive a donor organ offer, they then enter into a screening step if they're crossmatch positive to that donor organ offer and they meet other required eligibility criteria, then they then move through to being included into the study in terms of receiving treatment with imlifidase that in treatment with imlifidase converts the patient from Crossmatch positive to cross-match negative. They then proceed to transplantation and have followed up for 12 months. So that is the approach to patients who are entered into the imlifidase treatment time. So moving down the schematic, we then have the 1 of the 2 noncomparative reference groups. So the first one in green is the noncomparative concurrent reference group. So this reference group comprised 50 to 100 patients who are enrolled at the same sites that we're enrolling patients into the imlifidase treatment group but these were patients who were cross-match negative to the donor organ offer. And these patients were then entered into this cohort. They went through some screening and then were transplanted with the Crossmatch negative donor organ and were then followed up for 12 months. And the intent of this non-comparative concurrent reference group was essentially to understand better the performance of the sites who are enrolling patients in the study in terms of a more usual transplantation setting. And then finally, there was a noncomparative historical reference group, so these were patients who were randomly selected from a registry in Germany. There were 100 patients randomly selected from that registry from 2010 onwards. And again, these patients were sensitized but not to the level that was seen in the imlifidase treatment group the cross match negative to donor organ offers, and we collected data from that historical reference group, again, for the purposes of understanding better the historical outcomes of patients who are transplanted who had some level of sensitization. So just to summarize again, those 3 separate cohorts. And again, just to emphasize, there's no statistical comparison between these different cohorts because they do include different patient populations. Nevertheless, across the 3 cohorts, they all enrolled male or female patients, aged 18 to 75 years with an ABO compatible disease donor aged 10 to 70 years. But then moving across the different cohorts, you'll see that for the imlifidase cohort, they were highly sensitized and with a CPRA equivalent of 95% or higher. The noncomparative concurrent reference cohort was not sensitized -- noncomparative historical reference cohort was sensitized but to a lesser degree than to a lesser degree than the imlifidase cohort. Imlifidase cohort, they were cross-match positive to a donor organ offer, whereas for the other 2 cohorts, the reference cohorts, patients or cross-match negative to the donor organ offer. And then for the noncomparative historical reference cohort, these patients were selected from the registry based on transplantation in Europe in the period 2010 to 2017. So I'm now going to move on and talk about the disposition, demographics and exposure. And because we have rather limited information relating to the historical reference cohort when we compare that with the other 2 cohorts for the purposes of this presentation. I'm only going to present data from the imlifidase cohort and the concurrent reference cohort. So if we look first at the disposition of the 2 different cohorts for the imlifidase cohort, 51 patients accepted a donor organ and were dosed within lipids. Of those 50 were transplanted. One patient, it was not possible to transplant them because of technical surgical reasons. So we have 51 patients in the safety analysis set and 50 in the intention to treat analysis set for the lifts cohort. And of those completed the trial, 3 early terminated. And for the concurrent reference cohort, we had 63 patients enrolled and transplanted and of those 57 completed the trial and 6 early terminated. So in terms of demographics, you'll see that the age in the imlifidase, mean age in the cohort, 50 years, slightly older in the concurrent reference cohort, about 56 years. Around 40% of patients were female. And of those female patients in the imlifidase cohort 60% that had a previous pregnancy. And again, sticking with the imlifidase cohort. The majority of patients were white, 78% and then 12% were black with the remaining patients of other races. In terms of the concurrent reference cohort, again, a similar distribution in terms of males and females and fairly similar in terms of rates. So again, continuing with the baseline characteristics of the population, all patients in the imlifidase cohort or on dialysis at the time of transplantation. And it's really noteworthy to see that the mean years on dialysis, nearly 9 years, 8.7 years was the mean number of years on dialysis and the majority of those patients were receiving hemodialysis and again, it's interesting to note that in terms of the number of previous transplants, nearly 40% of patients in imlifidase cohort had received 2 or more previous transplantation slightly different pattern in the concurrent reference cohort where you'll see that the majority of patients, nearly 90%, 88.9% had not had a previous transplantation when they're receiving a matched donor organ offer. So in terms of exposure, the vast majority of patients only required one dose of imlifidase. It is possible if you don't see cross-match conversion after the first dose to give a second dose of imlifidase and 4 patients, 8% required a second dose for crossmatch conversion. So now I'm going to move on and talk about the efficacy and safety outcomes of the study. So here, we see the primary endpoint, and it's important. I must emphasize that the primary endpoint only applies to the imlifidase cohort. And this is an endpoint of graft failure-free survival. So it's a composite endpoint of graft failure and patient survival. And you'll see that for the imlifidase treatment arm, there were 5 events over the 12-month follow-up period. So the graft failure free survival estimate at 1 year was 90%. And for reference, in the concurrent reference group. Again, there were 5 events in that group and the estimate of survival graph failure-free survival at 1 year was 92%. So that was a composite outcome endpoints for the primary end point for the imlifidase treatment arm only. In terms of patient survival, so one of the contributing outcomes for the composite. There was one death in the imlifidase treatment arm with a survival estimate 1 year of 98%, and there were 2 deaths in the concurrent reference cohort with survival to of 96.8%. In terms of craft survival, the other component of the composite then for the imlifidase treatment arm, there were 4 events in the imlifidase arm resulting in a survival estimate in terms of graft survival at 1 year of 92%. And for reference, in the concurrent reference group, that survival estimate of 1 year was 95.2% based on 3 events. So in terms of kidney function, this was estimated using eGFR, estimated glomerular filtration rate and 1 year, the mean eGFR in the imlifidase arm was 51.6 mls per minute. And in the concurrent reference, cohort in patients who received a matched donor organ offer. The eGFR was a touch higher at 55.9 mls per minute. So then finally, in terms of safety. So this just provides a summary of the safety that we saw in the study and for obvious reasons, I'm only presenting data for the imlifidase treatment arm. And all patients and these are treatment emergent adverse events. So these is a summary of events in the first 30 days after enrollment in transplantation. So all patients experienced at least 1 treatment-emergent adverse event, but of these very low number were considered possibly or probably related to treatment. Around half of patients experienced at least 1 treatment-emergent serious adverse event and 13 patients experienced at least 1 adverse event of special interest. And those are infusion-related reactions that occur within 48 hours of imlifidase treatment. All events resulting in interruptions, so a pause or discontinuation of imlifidase dosing and superior or serious infections within 30 days after enrollment. So those are what we term adverse events of special interest. And as I say, around 25% of patients experienced at least one ASI. In terms of treatment-emergent adverse events leading to study withdrawal or death, there were no events in those categories. So in conclusion, this was a well-run trial, more than 90% of patients completed the trial. The demographics and baseline characteristics were exactly what we expected to see in terms of a kidney transplant population. I think we can say that in terms of these headline data, efficacy outcomes at 12 months in imlifidase-treated patients were excellent graph failure-free survival was 90%. Patient survival was 98% and graft survival was 92% with an eGFR of 51.6 mls per minute at 12 months. And the treatment was generally well tolerated with the safety profile consistent with previous clinical trial experience, and there were no new safety findings. So with that, I will hand over now to Dr. Cooper, who's going to present the outcomes of the Phase III ConfideS study.

Okay. Okay. Good morning, everyone. Can you hear me okay? People just don't seem happy. It's -- we're in New York City, it's beautiful. If you're a German or from Ecuador, it's a great place to be. Taylor Swift is coming soon. So I'm really thrilled to be here. The folks from Hansa keep thanking me for being here. And we just had our national meeting in Boston a past couple of days where this data was presented and I keep telling them if ever knowing that this was going on and I wasn't invited, I'd be upset because I have the opportunity to explain to all of you why I believe, and I think our experts believe that this is, if not one of the most exciting things that has happened in our field in a long time. And I realize that there's a lot of competing things going on right now, but if I could steal your attention for about 15 or 20 minutes just to explain exactly why I think this data is so important. I'd really appreciate it. And then we'll have the opportunity to hear from some of our additional experts and hopefully answer some of your questions. So as I said, I'm the Chief of Transplant. I'm a surgical -- I'm a transplant surgeon, the Director of our adult and pediatric transplant program in Milwaukee, the gray hair gives it away. I've been in this field for about 26 years. I trained at Johns Hopkins, the turn of the century where treatment and finding answers for highly sensitized patients was really a big focus of our program. Leaders in the field, a gentleman by name of Robert Montgomery, Lloyd Ratner, we had outstanding HLA leaders. And we had just this tremendous collaboration and I actually thought naively that we would have an answer for this years ago. And as I said, we just finished our national meeting, and we come back year over year, and this still is a problem, trying to find opportunities for people that really through no fault of their own developed HLA antibodies and it has prevented them the opportunity to receive the gift of life. And again, to me, like I said, this is so exciting that we really now have a better answer than the standard desensitization, which we'll talk a little bit about or even worse telling people that you're just not going to receive another transplant because most of these are repeat transplants. Some are not because, as Richard mentioned, there are a number of women who are sensitized simply from pregnancies. And for that reason alone, they're unable to receive a kidney transplant. And I think all of us would find that to be really unpalatable, particularly here in the U.S. So again, a little background with some numbers. highly sensitized patient has a little bit of a different definition depending upon who we're talking to. But the data clearly shows that the numbers of individuals with a CPRA that C is important, calculated panel-reactive antibody. Why is that? Because the United States has determined in order to receive prioritization. So individuals who are 100% sensitized have national prioritization. So it's a big country, but in order for those individuals to receive an opportunity, which the data would say is about 10 and maybe 300,000 offers, one in 300,000 grasp that number. that, that may be the only opportunity that the way that they could do that is through national prioritization. 99% is a little bit less than that, but still has prioritization. But in order for those people to even receive that recognize that they have to have a calculated PRA meaning we put in there unacceptable antigens. And my colleague is going to talk more and more about that in order for them to gain the prioritization. And if we don't do something to help them even get an organ offer, even this opportunity doesn't exist. But if you look at the numbers, they're still well over 3,500 patients in the United States with a calculated PRA of 99.9%. So truly a needle in a haystack for most individuals to receive the opportunity of a disease stone of transplant in the United States. And again, that inability to match them has become a significant barrier for patients for certain, for sure. So as mentioned, this is the drug of interest. Imlifidase is a degradating enzyme really a novel desensitization treatment cleaves intra and extravascular immunoglobulin into both an Fc and FAB fragment. What's important is this pharmacokinetics curve is something that we've all become very familiar with. So the ability to be able to rapidly cleave and decrease antibody allows patients -- I need this to. Okay. So now we're to fishing it here in a different way. So it allows patients to be able to reach their opportunity to get to the operating room to transplant because the season or offers, time isn't on our side. We often have less than 24 hours in order for someone to be transplanted. And so we truly need this rapid declination of antibody in order for patients to be able to accept offers and to proceed to the operating room in a safe manner. We do appreciate that there will be this rebound. And if you examine the clinical protocol, the need to be able to prepare for this by also introducing interventions such as antithymocyobulin, anti-CD20 and IVIG is very important in the protocol. But again, we know this something that we can see in clinical trial data. And so we prepare for this, and you'll see that the outcomes, including development of donor-specific antibody and its effect on the graph, were negligible. So again, appreciating this PK is incredibly important to the success of this protocol and again, something that our PIs are very much aware. So a little bit different setup than what Richard shared from the trial in Europe. This was a trial that had a comparative control arm to it. It was, quite frankly, if having the opportunity to discuss this in great detail, a challenge to help identify what that comparative group was because that in order for most patients to receive a transplant with this high level of sensitization there really isn't a great option. We have options, namely things like plasmapheresis, IVIG and all those things that I mentioned. But the ability to convert to a negative cross-match for most patients utilizing standard desensitization therapy has been very unsuccessful and very unrewarding. But that was our control group, and I'll talk more about that. The prescreening piece, as Richard mentioned, is also critical here, in order for patients to receive any offer at all. As I mentioned, the need to be able to delist some of those unacceptable antigens and for our teams to be ready for that rebound and assure that patients not only met standard inclusion exclusion criteria, but they were ready in understanding that this was going to be an effort on both of our parts but something that they recognize the best opportunity to receive a transplant. Organs were offered to patients based upon, again, that national allocation scheme, and they were randomized 1:1 to either receive imlifidase or to be in the control arm. The control arm was that the centers had to identify what their standard desensitization protocol would be when they were offered that particular organ. The decision was either to reject that organ offer or wait for a more compatible we're going to offer within a 12-month period. You'll see that there were patients that were transplanted in that control arm. We're going to talk a little bit more about them. I'll skip a little bit to the chase, again, almost an apples and oranges comparison even for those patients that were transplanted in the control arm, which I think is very important. And then patients that were randomized to the mulifidase arm. They underwent the treatment. We demonstrated a positive to a negative cross match. They proceeded to transplant, and then we followed both of these groups out through a year. So a little bit different than what we saw in Europe because there was a control arm and I think that provides for some meaningful comparative data. This is the results that we presented, excuse me, that Dr. Montgomery presented at the ATC, the baseline and characteristics, demographics of our patients were comparable. I'll show you some of that. The primary endpoint was eGFR at 12 months, and we had key secondary endpoints, which were the dependency for dialysis, for patients that either received the transplant or that in the control arm were unable to move forward with their operation and of course, patient survival. The other key secondary endpoints, not only the graft, but also the incidence of delayed graft function, meaning that it takes time for that kidney to start working, delayed graft function in this instance is defined as a need for dialysis within the first week following their operation. The development of antibody-mediated rejection the development and identification of donor-specific antibodies, the effect of both of these on the function of the graph thereafter and of course, the appropriate safety profiles that are concurrent with this controlled trial. This is that demographics slide that I promised you to orient from left to right, these are the [indiscernible], 32 patients in the control. Now as I get older every year, my definition of old changes. But this to me, this is a young cohort. So these are our average patients 45 years old. This isn't individuals who are saying their sixth or 7 decades and we perhaps consider that as maybe too old for transplants. Again, old is sort of your own definition. But these are often individuals, if I steal all the way down here, to the incidence of patients who have been either transplanted or have been on dialysis. The average time of dialysis for patients in the olympidase arm is 7.3 years. I ask you to take a second to consider what it means to sit on a waiting list for 7.3 years with all of us saying that your answer for your greatest survival, both in years gained and in quality of life is with a transplant, and they're waiting on average 7.3 years. difficult conversation to have with our patients. Again, the majority of patients in milifidase arm were female, recognizing again that one of the #1 sensitizing events for our women is pregnancies. In the United States, a little bit differently, the predominant characteristic of race where these were predominantly African-American patients. Here in the U.S., the incidence of end-stage renal disease is highest among our African-American patients. they unfortunately don't have the same representation on the disease [indiscernible] less and they don't get the same rates of transplants. All of that is a problem that is further accentuated by the highly sensitized nature of these patients. And so again, this provides another opportunity for a social economic disadvantaged population, which we also think is very important. I mentioned the time on the wait list. If you look at the percentage of patients that are retransplants as Richard showed in Europe, some of these patients, I should mention I was fortunate to be a PI in this trial. I transplanted a woman who had her third transplant and another woman who had a fourth transplant. So again, most of these individuals would probably never have an opportunity, had this clinical trial not been available to them. You look at the level of combined antibody, mean fluorescence intensity. That's a significant exposure of very broad, both type 1 -- both Class I and Class II antibody. So a significant immunoglobulin burden to overcome. If you look at the ischemia times, we recognize that in order, even for a national priority to it takes some time for that organ to come from point A to point B. Sometimes it's going from Pacific to Eastern Time zone. That provided us even some opportunity to help get this protocol up and going, but still appreciate that prioritization adds to some of the complexity of this clinical trial. And I think it further accentuates the outstanding outcome that we saw in this recipient population. Again, to sort of cut to the chase, if you look at the estimated GFRs at the 1-year time point, the purple is the imlifidase arm, the orange is the control arm a truly statistically significant difference in EGFRs, 51.5 intelipidase group, 19.3% in the control group with a difference of 32.2 million per minute between the two. I'm a simple surgeon, but that P value is pretty easy for me to understand. So I can recognize this group is highly statistically significantly improved by the treatment of imlifidase versus the control. Again, many of which not -- weren't even able to achieve the opportunity to get to the upper in room and receive their transplant. Again, that -- the dialysis dependency that again was one of our significant end points. The incidence of needing dialysis was certainly much less imlifidase arm versus the control arm, 5 patients versus 17 patients. This is the stages of end-stage renal disease, Stage 5 and dialysis down here. What I also want you to appreciate is the folks that were in the study arm, some had absolutely outstanding outcomes with their treatment, outstanding outcomes, that, again, I don't think any of us perhaps would have predicted. We certainly wouldn't have expected that they would have gotten a transplant and this result was, again, extraordinary and one that we are very hopeful for and expect to see more of that with this drug moving forward. Survival and adverse events. Survival was excellent, and I apologize with survival was excellent in both of our arms, 97% in lipids. We did lose one patient secondary to a nonrelated incident, as you can imagine. These patients are sick. They come with a lot of comorbidities, #1 and #2 diagnosis for end-stage renal disease being diabetes and high blood pressure that doesn't necessarily go away after transplant. And so unfortunately, we lost one patient secondary to a nonrelated event. The adverse events and the significant adverse events we're really what we would expect in this patient population, as I just described, very few, if any, were related to drug administering. [indiscernible] discontinued due to an adverse event and there were no new safety signals that were identified as well, again, all very positive sign going forward. donor-specific antibody. As I mentioned, if you look at that pharmacokinetics curve that we saw in one of the earlier slides, the recurrence of antibody was not surprising to us. And in fact, it was a conversation in the investigator's meeting prior to dosing anybody within lipids that there needed to be a strategy to be ready for this I would also say what I've always loved about transplant is not only the team opportunity, but this really provided an opportunity for us to phone a friend, right? So I would be calling my friends here in the front row saying, "Listen, this is what we're seeing. What have you done? This is what we have found successful, let's share it with the other group." And so while the incidence of donor-specific antibody was much lower in the olipidase arm with this expected rebound all our investigators and our teams collaboratively we're able to get on this very quickly and you can see at year 1 that the development and the incidence of donor-specific antibody was not critical nor did it affect the outcome of these patients. So again, being prepared, being ready, recognizing that this has an opportunity for patients, but that rebound is expected is something that our teams are prepared for. When you look at, as I said, the result in AMR and its effect on the eGFR at 12 months, I'll point you over to this right side of the slide. These are the folks who received imlifidase. These are our control groups. The individuals who developed AMR are in the dotted lines, and those without AMR are in the purple lines, and you can really see that negligible changes in their EGFR even with development donor-specific antibodies. So again, I think mass is the takeaway is that even the development of donor-specific antibody isn't the failure. We, again, are not surprised by this, and it doesn't mean that we should be fearful of providing this therapy, recognizing that we have therapies available the investigators, the specific way in which DSAs and AMR is treated was not mandated in the protocol. And so investigators treated based upon center practice. And so there were various ways and again, you can see that, that met with great success in the outcomes at EGFR at 1 year. So perhaps went a little fast. I have lots of information more I would like to share to you, but I'm certain there'll be plenty of questions going forward. But our conclusions in this randomized trial here in the United States that, like I said, was just presented nationally at the American Transplant Congress, demonstrated that 1 year, the desensitization with imlifidase was associated with clinically meaningful, more than just statistically significant. Why is that important? We have a lot of things that are statistically significant that show perhaps a change in eGFR of 1 or 2 or 3 mills per minute but this is clinically meaningful. We're talking about individuals, number one, who perhaps would never get transplanted, not only were they able to get transplanted. They had a clinically meaningful eGFR at 1 year off of dialysis, enjoying a life free of a machine ability to get back into life, have, again, the experience as well with all of us look forward to Taylor Swift's wedding is coming. So I think again, all this is an important piece that we want to be able to offer our patients. It resulted in a higher successful transplant rate, the 1-year dialysis dependency again, apples and oranges compared to the control arm despite the development of donor-specific antibody and incidences of antibody media rejection, the ability to identify that early and to treat that resulted in no graphs being lost and was well tolerated with a safety profile that was again not surprising or concerting to our PIs and when the data was read out to the entirety of the organizations. And as a concluding sentence I'd say, if approved, I'm going to be positive and please say when approved because I would be remiss if I didn't say that I believe that this is truly the greatest opportunity that is currently facing us here in transplant in 2026. Like I said, I had the ability to see a lot of changes in transplant over 26 years, things like the laparoscopic donor nephrectomy, things like paired kidney exchange, those were all interventions that allowed us to find transplants through increased complexities. This is truly an intervention for patients like we've never had in the past. And if we think of everybody here is having equal opportunity to receive a kidney transplant, this now levels the playing field for some people otherwise may not. And so I think, again, this is a highly effective therapeutic option for highly sensitized patients to receive a successful kidney transplant. These are our investigators, not only those that were able to randomize but additional PIs at the participating centers. I want to thank all of them I want to thank our patients as well. So one of the conversations that we've often had is like who do you need on the team to be able to perform this and while it does require a true multidisciplinary team, many of individuals like you'll see here today, physicians, coordinators, financial individuals, people that deal with the patients on a regular basis our coordinators but it really involves the patient as well that we can't forget. Many of these people come to us seeking an answer better than dialysis. They come to us saying, I've either been transplanted before and I've been able to enjoy being off of dialysis and I've been able to see my kids graduate from college, be able to watch my daughter get married. And I want to see that again. And now we have the ability to have a better conversation with them about what options are available. For the longest time, we'd have patients that would come to us with a high level of antibody, and we knew that the odds were highly against them because the data, which, as I presented before, says that their opportunity of receiving a negative cross-match kidney was few and far between. Now I'm more comfortable and confident and excited about the opportunity to say, we now have this therapy that's available for you that gives you the same opportunity as everyone else coming in here. And I think everybody deserves that. And so with that, I will get off the stage and pass things off to our colleague, Dr. Kamar, who's going to talk about his experience in France. We had some prewords here, and I think he had some pretty exciting data to share with you. So thank you for the opportunity. I think you have handed here.

Yes, I'm not sure to be as nice as you did, you have been in Broadway yesterday, and we saw it. So thank you very much. It's really my pleasure to be here and try to share with you some real world data on the use of imlifidase. We have the change in Europe to get imlifidase approved by EMA, and we have now the opportunity to use it in a large number of patients and I'll show you how it works and how it changed the game. It has been said earlier by Matthew in Europe. When it became available in Europe and has been approved by the e-mail we decided in France to try to have a national guidelines. And the national guidelines were set up by the [indiscernible] of transportation [indiscernible] of nephrology dialysis and transplantation and the Society of Easter compatibility. We wanted to have national guidelines to have homogeneous population to share the same criteria for using this drug and we try to have also a registry in order to obtain all this data and to be able to analyze this data and to present you this is what I'll present you today. So in October 2025, we had identified 143 patients who are eligible for the -- according to our guidelines. I'll go through the guidelines later on and 62 have been transplanted. And I'll -- 47 had a follow-up of more than 3 months present you the results of this 47 patients. You have just to have an update. Currently, we have 82 patients transported in France using imlifidase, and I have already 16 patients in my center who have betas what to do with this drug. And if you want in the Q&A session, I can give you some feedback on these patients and how they feel, how they are very happy because those are -- as has been mentioned earlier, patients that you see at the outpatient clinic every year or every 2 years, they are listed and they do not get any offer. And every 2 years, I ask you, doctor, do you have something new for me, should I stay on dialysis? What should I do in the future? Exactly the same question that Matthew had. And every 2 years, we have -- I'm sorry, I have nothing new. You have to stay on The dialysis. And hopefully, you will have a kidney which will be [indiscernible] compatible 100%, which it's quite impossible. Otherwise, you have to stay on dialysis. And now we have completely changed this policy, and we are able to offer them another opportunity to get a transplant and to get a kidney and they are living again, they are not on dialysis anymore 3 times a day, a week. So these are our eligibility criteria that we have decided for our patient. First of all, we have decided to have a patient with of more than 98%. Matthew, the discussed earlier the CPRA, how can we calculate it? And why did you choose this level because the -- we looked in France for all the patients having over 80, and we look for the possibility to get the transplant in France. And over 98%, it was very difficult, 99% nearly impossible and 100%, it's really impossible to get the kidney inference. So we decided to include only the patients who are above 98%, those below 98% were able to get a transplant. Initially, we have decided to have patients less than 65 years old. So it was a new drug. We were a bit afraid of the safety concern, now we are updating our guidelines, and we increased the age to 70 years old because I show you, we did not have any safety concerns with this drug. In order to have an equity between all the patients on the waiting list, we decided to give the opportunity to have imlifidase only the patients who are on the waiting list for at least 3 years. You will see there are much more than 2 years on the waiting list for these patients. Initially, we decided to do it only for 2 previous transplant, but finally, we did the force transportation also with imlifidase, and finally, the most important point is how to delist the antigen and how to do it. So first of all, we selected the patient. We did 1 to 10 dilution in the lab. And when the MFI or the level of the antibodies decreases, we were delisting these antibodies and the patient get a transplant. Secondly, with this -- we had to turn a positive to a negative cross match to get the transportation -- it was not acceptable to do it with a positive crossmatch and the patients who have given one single dose of imlifidase, 0.25 milligram per kilo. And when the post-imlifidase crossmatch was negative, the patient had undergone the transportation. With respect to the other immunosuppression, the patients were able to get rituximab either before the transportation or after the transplantation few sectors use it before. But since we didn't know how long the patient had to wait on the waiting list, we decided to do it after the transportation and the large majority of patients, only 2 or 3 patients get it before the transportation. When the patient show up when you have an offer for the patient, he comes to the hospital. We gave him immediately the MLP days and waited to 4 to 6 hours to get the second sample and to look for the second cross match. And at the same time, we've looked for -- with a single antigen for the antibodies we are able to follow all the antibodies before and after. And one, it was negative, the patient went to the operating room, and we started the immunosuppression at day 4 because, as you know, mits clearing the immunoglobulin. So we cannot give bit immediately at transportation. We gave it at day 4, we gave also IVIG and ituximab and afterwards, they have emetic immunosuppression quite classically with tech NPA and steroids. So for the 47 patients that we have grafted as it has been shown earlier in the U.S., the majority were young. The mean age was 48 because you can see -- for instance, in France, the mean age of the transport patient is currently -- so they are 10 years younger, which means that the patients are quite young and not able to get a transplant. The majority were females and not mail because you know that the majority can get immunization by the pregnancies. You can see that 2 out of 29 patients have been pregnant before and 77% of this patient had a previous transplant. So we are dealing with young people, some of them I can give you an example of one of my center. He has been transported when he was 6 years old. He lost his graft and he was highly sensitized and he was still waiting -- under waiting. This year he was now 26 or 27 years old without getting any transport because he was highly sensitized. The median time on the lysis was 10 years, quite similar to the one observed in the U.S., 10 years, patients who are waiting without having any offer for transportation. At the CBR, according to our inclusion criteria was 98% on only 4 patients. The majority were at 99% or 100%. With respect to the DSA before imlifidase, the median number of DSA was 4 going up to 8 DSA quite a lot. And the immunodominant DSA, which is DSA with the level the most important, the highest level was 10,000 going up to 17,000. And the sum of DSA went up to 70,000 with a huge amount of the assay against the kidney. What about the patient survival. Only 2 patients died during the follow-up. The first one died with a functioning graft from a septic shock at 1 month after transportation and the second 1 was a young patient from my center. She was 38 years old. She was undergoing a third transplantation. She had a large number of comorbidities and the main problem that didn't have any vascular access to gate dialysis. So we knew that it was a very bad candidate for this treatment and for the surgery, but we didn't have any choice except to have a compassionate use of imlifidase to get her a transplant otherwise, she had to die because you were not able dialysis to undergo dialysis, not any vascular access. Unfortunately, she presented a multi-organ failure and the operating group since we started the transplantation. So it was not related to [indiscernible] was not related to the acuity injections. You did not present a rebound. And unfortunately, we remained in the intensive care unit for nearly 3 months and it at 3 months. And of course, the kidney was not functioning after 3 months of ICU. So only 2 patients died during the follow-up. So the patient survival was 96% and this was the so rough loss that we observed. We did not observe any other graft loss among all the other patients. None of them lost had a graph because of antibody-mediated injection or any other side effect related to the use of MDs or immunosuppression. With respect to infection, so the profile of the fraction is quite similar to the one observed in classical kidney transplantation. We have UTI, 1/3 of patients. You all know that Nearly 90% of kidney transplant patients will present a urinary infection within the first 3 years. So it's quite common to have 4% of UTI. We have some BK viremia, 17%, but only 2 patients presented PAN, BK virus associated nephropaty. Nevertheless, none of them have lost this graft and 8% present CMV infection. What is also quite usual. So we didn't have any real concern regarding the infection. And this is why we extended to the age of the -- of eligibility of the patient because we were a little bit afraid in the beginning and finally, no safety concern. What about the risk of antibody [indiscernible]? As it has been said earlier, we know that when we give imlifidase, we will have a decrease in the donor-specific antibodies rapidly within a few hours but we also knew that some of the patients will have a rebound of the antibodies before. It's around 60% to 80% of the patients. But we knew that the patient will have a rebound, and we were prepared for the rebound. We're prepared to do whatever we need to do in order to treat the rebound and to treat antibody-mediated rejection. So 34% of the patients presented on antibody-mediated rejection episode than the first month after the transplantation. And we have some few patients who developed another ABM later on between month 6 and month 12. All our patients had surveillance biopsies. They get a first biopsy that has been performed before discharge. So between day 7 and day 15 or for cause in case of any rebound of the antibody, but also they have surveillance biopsy at month 3 and month 12. I will not present you the data here, but I can tell you that the results are much better at 12 months than 3 months than at 1 month because finally, we were able to treat correctly the antibody-mediated rejection since we were prepared for the antibody immediate introduction we are able to treat it. So the patients who are treated with different strategies, mainly apheresis to remove the antibodies, but also eculizumab, so anti-complement blockade, especially in the early phase, and daratumumab with CD38 [indiscernible] antibodies, especially in the later phase after the transportation. So with respect to the patient who presented antibody-mediated rejection in the early phase, the majority received steroids. Nearly all of them had Plex, plasmapheresis, [indiscernible] an additional dose of rituximab in some patients in some patients, it was also given because it was already planned at day 7. 80% received eculizumab and 25% were given daratumumab. What was really, really striking was the kidney function of this patient at 1 year. The kidney function was really very, very, very good I present here the creatinine level, I could present also the EGFR. The EGFR is around 55 to 60-milliliter per minute. It was very good. And as it has been shown in the study we presented earlier, we did not have any difference between patients who experienced an AMR and those who did not experience the AMR. So patients who experienced the AMR, they were correctly treated and kidney function completely recovered. And I'm not showing the data here, but the patient didn't have any proteinuria and on the surveillance biopsy, we have a decrease of the activity index and the chronicity index was increasing very, very slightly. So if you compare the results of our history in France to the results of the initial trial Phase I/II trials, all the data were pulled in 1 single cohort that the data were published in the American no transportation at 5 years. And our study, of course, the follow-up was shorter than the 5 years. The 1 month AMR incidence was 28% in the initial study, it was 34%, so quite similar in our -- so it's only 1 patient difference. And our experience 5 years, the sensor graft survival was 82% at 5 years. And in our study, it was 98%. And I can give you some data that will be published. If we look for the iBox prediction at 7 years, it was more than 90%. And the EGFR was 15%, our credit level was 1.2 million and the -- we had an acceptable safety profile. So not any problem regarding the safety. So in conclusion, at 12 months, very good kidney function, very good kidney survival. We know that nearly 40% of the patients will develop an AMR during the first year, but we know how to treat this AMR. And when we treat correctly the AMR, we do not have any graft class. We even have a very good kidney function similar to the patient who did not present. And as I said earlier, the profile was the safety profile was good. This is onen very important point because when you have the patient at the outpatient clinic, when we discussed initially with the patient telling them that we have a new drug that works very well. And the main concern was not losing the graph in Italy was the safety profile because they were wondering what will happen if you are giving me an additional drug, what will happen? And initially, some of these patients declined to participate to the protocol and said, no, start with some other patients, and we have some results, you can call me back and I'll come back and we'll be -- I'll accept or I'll decline. And I can tell you that all the patients who told me this came back 1 year later because now we have some patients at 4 -- nearly 4 years follow-up and all of them accepted to be in the protocol and all of them accepted to receive MDs, some of them have been transplanted and they are still texting me telling me, "It was wonderful, I had accepted 2 years before because I had 2 additional years of dialysis." And currently, they are not on dialysis. And currently, in my center, I told you we have transported 16 patients, and I have nearly 20 patients waiting for a transportation again with MDC days. Here are all the centers in France who accepted to participate to our national guidance. I think one of the strengths of our registry that we are all able to work together, all centers according to a single protocol according to the same guidelines to the same inclusion criteria in order to have a homogeneous population and to be able to provide some robust data. And thank you very much, and I think it's time for a coffee break.

Thank you very much. We will just take a short leg stretch 10 minutes leg stretch, and it's -- coffee available for you. We would like to see you back in the room within 10 minutes. [Break]

Okay. Hello, everybody. Hope you had a nice little stretch and got some coffee, and we'll continue on with, again, some more of our discussion today. So good morning. I'm Jennifer Leonard. I am the Senior Director of U.S. Medical Affairs for Hansa Biopharma. I'm joined on the stage with 2 great colleagues and experts Dr. Roslyn Mannon from the University of Nebraska Medical Center; and Dr. Annette Jackson from Duke University. So as a transplant nephrologist as well as an HLA laboratory director, they bring complementary perspectives to kidney transplantation. And so today, they're going to help us further understand the unmet need of the highly sensitized patients and also provide some information and speak to the significance of the data that you've seen today. So thank you, both, for joining us today. I'd like to start with you, Dr. Mannon. So let's think about broadly about the highly sensitized patients themselves. So one thing that can be difficult for people to comprehend is and fully appreciate is how challenging it can be for these patients to be transplanted. So can you help us understand what life looks like for a patient with a high CPRA level and what prolonged time on dialysis really means to these patients.

So hopefully, you can hear me properly. Being on dialysis is a very -- it's a challenge. I think there's a misunderstanding in the community at large that dialysis is forever that you don't have to worry about a transplant that you can live on dialysis, but the median survival in the United States on dialysis, all comers is only about 4 years. And so you can imagine that we lose people on our waiting list over time because of death on the waiting list. And so it is like supporting and life sparing, but it is not the solution for kidney failure. These patients undergo for hemodialysis in general in center in the United States, about 12 hours of treatment, 3 days a week, 4 hours at a time. You have to sit in a chair, you're often anticoagulated. There are large fluid chips and electrolyte ships so that many patients coming off treatment don't feel the ability to do work household chores, take care of their children, walk the dog. I mean it's -- and that's just some of the restrictions. They have a prohibitive fluid intake and they have a prohibited dietary intake. So they can't eat a cheese -- they can't eat pizza, for example, or they can't drink a diet Coke. Some of the simple things we take for granted, taking trips even out of town is impossible unless they prearrange. And though there are more people on home hemo than used to be at the beginning of my career. Most patients are on in-center treatment. The outcomes may be a little bit better between [indiscernible], but that's just some of the restrictions individuals have.

Okay. Thank you, Dr. Mannon. And so -- now let me turn to you, Dr. Jackson. So many people in the room may not understand the role of the HLA Laboratory Director as it relates and it belongs within the transplant program, right? So could you explain your role and how your expertise contributes to the decision-making across the transplant team? .

So we in the laboratory are behind the scenes. However, we're very interwoven into the transplant team. And we play a role at the time that the patient becomes eligible for transplant, we receive blood samples, we HLA type them. and we begin screening their sera for HLA antibodies. Antibodies deemed high level and high risk are listed in our national database as avoids or unacceptable. That means if a patient has a high HLA-A2 antibody, all donors that type as an A2 are disqualified for that recipient. And that is what listing unacceptable antigens means and that these listing of unacceptable antigens is what's used in the calculated CPRA, so the more high-level antibodies that patient has, the higher CPRA, and what that means is that the donor pool shrinks. And so with our 99.9% CPRA patients, there's very, very few donors that are deemed eligible or compatible with them. So we screen patients while they're on the wait list, at time that a donor becomes available, we actually type the donor and we look at compatibility. Is this a safe transplant? Is there donor-specific antibody toward this donor and we're a 24/7 365 operation. And so the surgeons will call us to get a thumbs up. do we go to the OR? Is this the best donor that this patient is going to get? So we do cross match testing at that time. And all of this goes into a risk assessment to determine whether they move forward with that donor and what immunosuppressant regimen they may use for that donor. And then once the transplant happens, we're not done because we go on to screen these patients post transplant for any preformed donor-specific antibodies or any new donor specific antibodies that may arise. And because we alert the team, the moment we see a Ryzen antibody or a new antibody and then they can start antibody-mediated rejection therapy. And so we are tight with our transplant colleagues. We support not only kidney transplantation, but my lab supports heart, lung, liver, pancreas, and we also screen for our bone marrow transplant recipients that have blood cancers. And so we're a very busy operation, very dedicated to our teams. And very intricate, I think, to the whole transplant process.

Yes. So I think your laboratory is crucial to everything from identifying the appropriate donor through the monitoring process. And so again, you're an integral part of the transplant team at the center. So let's stay on topic a little bit with you. So I want to talk again a little bit about the patients, but specifically looking at our ConfideS study and those enrolled in ConfideS. Those are the most difficult to transplant patients. So can you help us understand what this patient population, how difficult it is to identify a compatible donor? And then I also want to take it one step further. Is there a need for patients that necessarily may not have a CPR of 99.9%, is there a further need for those patients as well?

Our review of the transplant waiting list has identified, and I believe Dr. Cooper mentioned this, that the people that are waiting with these high CPRA are non-white and they're primarily and there's a large number of women. And so it's really an unmet need, as Dr. Kamar mentioned some of these patients will not get an offer. And as Dr. Mannon mentioned, it really became real to me when one of our highly sensitized patients was transplanted. She got married, and she was able to go on a honeymoon. And I had never realized that they could not ever take a vacation. And you saw these are young patients, and they are not in dialysis for a very long time through the prime of their life actually. And so finding opportunities for transplant is really crucial for this patient population. And this trial really showed that we can break down that barrier. So should this I hope that we would be able to use this drug for many patients. I'm organ-agnostic. I support all transplants, and I know our thoracic teams would love to get their hands on it. If we do not find a donor quickly for our heart and lung failure patients, they die. It's very cut and dry. I also think it would open the window for living donor transplantation. Many patients have a living donor that is willing to donate a kidney to them, but for whom HLA antibodies block that transplant. And so I believe there is a lot of opportunity, and I believe the safety profile from this trial in the European trial may open up many more opportunities.

Okay. Thank you. One more build on that question. So I did ask about the CPRA -- like -- so say you have -- do you see any need like outside of that tight population, again, the ones we obviously know need or at the most highest need of an agent such as imlifidase. We saw this in the comfitis trial. But are there patients? Is there any patients outside of that 99.9% window that you would foresee also not receiving offers and would have a need for [indiscernible]

I mean their HLA antibodies block donor offers. If we eliminate HLA antibodies, we open up the donor pool. And we can transplant our patients faster, and we can better match recipient and donors better. There's also blood group in equities. African-American and Asian patients are more likely to have a B blood group, and they are transplanted at a much lower frequency because there are fewer B donors. And so this is added on top. If they also have HLA antibodies. There's a great in equity there. And so this drug really opens up the playing field for these patients so that we can find acceptable donors to which we can successfully transplant.

Perfect. Thank you. Thank you for expanding on that, Dr. Jackson. So Dr. Mannon going back to you, you've had a chance to review the ConfideS results. More importantly, we're not involved in the ConfideS study. So I'd like to understand your reaction to the data and how do you think that the findings will be perceived by the broader transplant community?

So I've been in the field longer than Dr. Cooper, but I invest in a lot more facial care products here. So -- but in all seriousness, I mean, I think we were very excited going back in history to the mid-2000s with John Hopkins group doing desensitization like that just didn't exist when I was in training in my early faculty years. And I was at NIH, I had an opportunity to invite them even pair donation was another evolution. And again, though that is a partial solution to this issue, we still have a large number of incompatible individuals on these payer donation list. It's a challenge. The therapy since 2000s are the same. Plasmapheresis, IVIg, rituximab, OBL, maybe we got opportunity with eculizumab. But again, the drop in antibody is so incredibly dramatic and very predictable, and we didn't see that with Plus and IVIG. And even though we had protocols when I was at UAB of the treatments and then we were measuring DSA and then repeating it again because certain individuals are very hard to remove antibody successfully or tamp down with IVIG in its magical way. So I think that seeing this dramatic drop and the transplant rate in these people on diseased donation, which is very challenging. This isn't prepared living donation, where we know the specificities. This is really a challenge in trying to get a donor out of the pool to match these individuals at least with some confidence. It's just -- it's a game changer, I think. And I don't -- I think everybody that I ran into at the study in the American Transplant Congress was similarly impressed and really happy to see these findings and moving this field forward, we have no FDA-approved agents right now in this space. And this is probably the most dramatic clinical shift that I see.

Okay. Thank you. Let's kind of stay on the ConfideS study a little bit more because I think just to understand and discuss a little bit around the primary endpoint. So for those that know have the clinical background and you as a transplant nephrologist. Can you explain why renal function at 1 year is such a good surrogate endpoint for long-term outcomes and why the difference that we saw in our eGFR endpoint is so clinically meaningful?

So there's it's impressive estimated GFR rates. If you looked at all the seas donation around the country and looked at 1 year function, 55, 57 is really good. greater than 90 is almost unheard of in a disease donor. Again, our donor pool in the United States is now more heavily weighted to older individuals but individuals with other health issues. And we're pushing the donor pool as hard as we can. Some of these individuals had delayed graft function. So we would anticipate worse function, but yes, they did quite well. the disparities between the 2 groups are in the control group, the ability to control and measure and anticipate recurring AMR is not as, I think, as controlled as it could be because -- it's just -- we use these therapies that are not particularly effective, where it's imlifidase use. It was very well anticipated. And I think the French data though you're not asking about the French data really show that there's a management strategy. The other thing is the AMR events had really no impact on GFR. That's also quite important to recognize. And you could debate why that is. It's probably the close attention but when you see that level of GFR at 1 year, it usually correlates well with better long-term graft survival. It's part of this multi composite endpoint that we refer to as Ibox that's also under review right now as an end point, but many of us would trade or left arms, but not as a surgeon for an EGFR that that's good. And again, when you think about one kidney, that GFR of 60 as sort of like the target because you're never going to be back to 100% the kidney may high purchase fee and get a little bigger, but it's pretty impressive that you would see a GFR that that's well controlled. And again, we have many patients who've had standard transplant unsensitive where their GFRs of 1 year are not as superior.

Thank you. Thank you for that explanation. So Dr. Jackson, we've heard a lot about delisting antigens today in the room as a strategy for expanding donor opportunities. So first off, can you explain what delisting means and how does the process work for those in the room? .

So as I mentioned, we're testing these patients sera for HLA antibodies. And we determine which antibodies are at high level. for which we should not do a transplant across those antibodies due to early antibody and severe antibody-mediated rejection. What we did in the confides trial was we delisted them anyways. We -- these are patients for whom if we don't delist, remove some of the HLA antibodies as avoids, they will not get donor offers. So the goal was to move them down to 99.5%. We know at that, that's kind of the magical number with the number of donors available in the U.S. that these patients will start to get donor offers. And so we took off of voids, even though they would be cross-match positive and then offer -- allow these donor offers to come in. And that's at time of randomization, then we decided do we move forward or not. And imlifidase because it is so powerful and it's so reliable, it allowed us to move forward. with those crossmatch positive transplants.

So technically, like those antigens that you delist are like your -- would you say those are your lower risk?

Yes, we delist from lowest risk to higher risk. But at time of randomization, only 3 of the controls were transplanted when they had that first donor offer because the risk was too high when they learned that they were -- their patient would not get imlifidase. So that, to me, is the true story of this trial is that nearly all of the imlifidase randomized patients were transplant and when that first donor offer came in, only 3 of the controls moved on to transplant because the risk was too high using standard approaches.

Thank you. Thank you for that. So Dr. Mannon, it's a little more complicated question or complex. But there is considerable variability across transplant centers and their willingness to desensitize and proceed with HLA incompatible transplantation. So how would you categorize in your own words, the current landscape in the U.S. with regard to this?

So I think we have about 220 approved transplant centers that are partners in the Oregon procurement transplant network, [indiscernible] that are supported by CMS and under regulatory review by CMS. The number of sites that you showed listed based on PI was what about -- they represent the sites that typically support desensitization. Desensitization strategies require a dedicated HLA lab director who is familiar with this -- the more advanced techniques, which are no longer serological but molecular, the ability to monitor 24/7 and work on the weekends to monitor these patients. It requires a committed transplant pathologist, you really cannot use an off-site service though they exist. And you have to have a dedicated team, you have to have surgical support and importantly, medical support, transplant nephrology. And you have to have people that are experienced that understand, recognize the patterns, look at the numbers, and it's a day-to-day interaction. And you have to have a good floor to do it. But the other issue is you have to have a risk threshold. You saw the frequency of AMR, the intensity of treatment. Many programs are very risk averse right now. We are under intense scrutiny by [indiscernible]. This is really makes whether it's the surgeon or nephrologist depending on your program, accepting an organ, very closely watching. We watch our numbers every month. We do strategy me we have a quality meeting. We look at our expected graph loss, expected patient in graft loss. And I think programs are quite risk-averse now, probably more than they ever have been. I think one of the reasons some centers don't do desensitization either as they just feel like we haven't advanced the field enough that it's the same old, same old, and I came from a center where we did standard desensitization. We kind of drifted away from it because we didn't have these kinds of agents. And the story of the control arm and ConfideS is really kind of the real-world experience in experience centers. So I think that as centers see this data, they're starting to say to themselves, we've got these people on the waiting list. And Dr. Cooper knows because I just referred him to someone. I think we are trying to figure out as a community with an agent that we can trust and predict the outcomes, getting -- we have the regular elements, we have the required amounts for transplant. But can we build a little bit more extra in terms of the support to take the risk and hopefully get people off our waiting list that would otherwise die. I mean there is a metric for death on the waiting list. We're all very familiar with it. It's a challenge to tell a patient, we're not going to list you. But if you're waiting -- if you're in your 60s and waiting 3 or 4 years, your likelihood of survival on dialysis even if you have been scrutinized through all the testing, it becomes very difficult at the time of transplant. The vascular disease is a real challenge as well. And so our job is to get the waiting list to 0. We have 90-some-odd thousand people waiting for a kidney this year. will transplant maybe 28,000 of those. Those individuals keep staying on and staying on, and then we have graph failures over time. And the list just keeps growing and growing and growing. I hope that answers it, but if you want me to focus down, let me know.

Thank you. No, I think you did a great job addressing that because there is a lot of variability, and I just wanted people to understand what could be the cause among or why there's such variability. But we can kind of stay on that topic because you mentioned Dr. Mannon and Dr. Cooper mentioned, I think everybody has kind of mentioned that there's been a failure to advance the science to help to treat these patients, right? So today, currently, there are no approved therapies for desensitization in the U.S. So I'm going to focus this question to you, Dr. Jackson. So from the perspective of someone who is responsible for monitoring donor-specific antibodies and immunologic risk, what are the challenges associated with these experimental desensitization strategies that are being used today? Well, what do you see? What are the problems?

I would say, and I believe this has been mentioned by other people that the other form, the other modalities of desensitization result in very heterogeneous responses by the patient. I've been had the privilege to work at Johns Hopkins and to see many -- a lot of data on past and current methods of desensitization and patients have different responses. My research lab is now researching why that is, why women with 8 pregnancies maybe recalcitrant to desensitization. And the ConfideS trial confirmed that imlifidase is -- we get a homogeneous response and in medicine, if you can predict with great certainty what is going to happen, it allows you to prepare. We knew that these high-level antibodies would be eliminated, and we could go to transplant in the absence of donor-specific antibodies and that they would stay away for the safe window when, in fact, the body is most inflamed because there's a lot of inflammation with transplantation. HLA expression is upregulated and therefore, having this window without any antibodies is likely the reason why the endpoint was so good. But then we also knew that the antibodies would come back, but we were prepared, we were monitored. The minute we saw any upward movement we told our clinical teams and then they could immediately start mitigating that antibody. And so it is the known that makes this drug completely different from any other desensitization modality. It's really important to know what's going to happen and now to be prepared. And I think the confides trial went very well because of that.

And I think we kind of alluded to this a little bit in some of your previous answers, but I'd like to kind of maybe go back to this and kind of reiterate this point. for you, Dr. Jackson, but the work doesn't stop when the transplant is completed, right, post-transplant monitoring is essential for the success of that organ and the best possible outcome. So can you describe how the HLA laboratory collaborates with the broader team to not only monitor the patients in the post-transplant process right or that period of time but also manage at risk.

So over time, at time of transplant, we discuss risk. And then post transplant, we monitor for the return of HLA-specific antibodies to the donor. That is really crucial. You have to keep your eye on the prize, and we have to keep control of this immune response. And so our lab get serum every other day, and we turn around testing its stat testing. If we see -- as I mentioned, if we see any uptick whatsoever, talking to clinicians directly get another serum as soon as possible. And it's really staying on top of that immune response that has allowed the great successes. And so -- we work very collaborative within the ConfideS trial. I think [indiscernible] a friend. We had monthly meetings, and I really think there was a harmonization with the way that the HLA labs were supporting their teams that led to great success. And I think it makes us ready should the drug be approved and I guess -- as we're going to conclude our discussion, I want to give both of you the opportunity to talk about what are the most important messages that you'd like to convey to the audience today and with regard to our discussion with regard to the data that was presented. So Dr. Mannon, I'll turn it over to you first.

And this is really a revolution and solution. The current strategy is utilized in the control arm, which varies slightly from center to center because unlike the French American transplant centers, all think they know what to do better. But it is also a point to recognize that we can come together. And one of the reasons there is this variability and post-trade management of these patients are pre is the effect of Dr. Jackson mentioned that you may -- the protocol says 6 pre-transplant dialysis or fares and dialysis alternate days, pre-op and you're giving [indiscernible] it's that the DSA, the donor specificity remains positive. And so then you're plexing again and again. But emblifidase is a total, totally different story. Go back to that figure where you see the drop in donor-specific antibody and then the return days later, that is very anticipated. We could not do that with Plex IVIG and all of our other strategies even with fullest immunosuppression, rapid ATG, a levels, the whole 9 yards. And so that opportunity I see is a major change, plus the opportunity to expand into live donation where you have an incompatible payer and you can -- and that was really the way [indiscernible] was first done. It was done on living donor payers because we were learning how to do it 20 years ago. But that was 20 years ago. Some of you may not have been born then and we were doing the same thing. So I just am very -- I'm excited about it as a study participant recognizing that this could really change the transplant field in my opinion.

You kind of [indiscernible], everything I had to say, I would say it is giving transplant opportunities to people who have no transfer opportunities in the prime of their life. The fact that it works, we know how it's going to work. It's predictable. I would say that is the most important thing about this drug. It is predictable, and it allows us to be ready to battle the immune response once the DSA is refilled into the circulation and the opportunity to move out toward living donation. As I mentioned, many of these patients have living donors our number of disease donor organs is not keeping up with the number of patients that need a transplant. So being able to transplant patients using living donors is really a tremendous opportunity to close that gap. And so to be able to expand it beyond what we used for in the ConfideS trial, I think, is very exciting.

So hopefully, we'll -- I guess we'll have to see. Fingers crossed. Obviously, going through the regulatory process now. So we'll just have to -- we'll have to see how things work out. But again, but thank you, your insights, your expertise on these questions that I have for you today. I'm going to defer -- are we going to have some questions for experts now or is it later? . Okay. So thank you, everyone, for kind of paying attention and listening to our discussion today. And hopefully, we can answer some questions for you later in the event. So thank you.

So thanks very much. We now have all of our 4 guests here now to participate in Q&A session. And we're going to open up the floor to questions. But perhaps before we do that, I think we've heard some really valuable insights from doctors Jackson and Mannon. I would like to just give the opportunity, firstly, to Dr. Cooper, following your presentation of the results from the ConfideS study, I wonder if you could just take a moment to reflect on what particularly stands out for you from the data that you've presented?

Yes. Thanks, Richard. So first off, thank you to Roslyn, that was outstanding. I took a bunch of notes that I'm going to use back when I speak to my group also. I think all of us have said similar things that -- for those of us that have the really the privilege of sitting in front of patients on a daily basis that you really want everyone to have -- what you know is the best answer for end-stage renal disease is an opportunity. And we didn't -- we don't have that right now. There's a number of people that I know before they come to my clinic when I'm reading their past medical history, and I see that there are repeat transplantation that perhaps they've had several pregnancies many of our patients have blood transfusions because of the anemia associated with end-stage renal disease. I know that they're going to come back with folks like a net telling me that, yes, this is a 100% sensitized patients. And I'm worried when I'm beginning to have that conversation, my positivity kind of gets blend a little bit because I know it's going to be different for them. To me, this opens up a whole new opportunity. The conversation is very different and the results demonstrating that not only can I get them transplanted, but I can promise them an eGFR as Dr. Mannon said, that rivals really any organ out there that predicts their long-term success. I mean, it just opens up a whole new window for not only those patients but for patients that are less sensitized and I equally agree with living donation, growing up with doing a lot of these desensitization for living donations and some of the really difficult scenarios we found ourselves won would be so much nicer to tell people we have an opportunity sitting either right next to you or with a disease donor or allocation system that we've ever had in the past. So the fact that we get them transplanted the fact that they have outstanding outcomes, the fact that we can predict what we're going to see and have interventions to treat that. Well, I'm really excited about what the future holds.

Thank you. I will open up to questions from a floor in a moment. I promise. But before we do that, I would also just like to ask Dr. Kamar after you gave an excellent presentation on your own experience with the use of imlifidase, but perhaps, again, you could just take a moment to reflect on what you've seen Dr. Cooper present in terms of the confides data and how you sort of -- how you think about those data that you've just seen in the clinical implications of those data?

I can say I am just wondering how you don't have imlifidase yet the ConfideS showed clearly that you will be able to transplant some patients who are not able to get any transplant. I will not repeat what I had already said earlier. We have some patients that are crying even in the outpatient in because they do not have any access for transplantation. And when you have not any possibility, and I agree what has been said earlier, we start several these strategies and none of them is really functioning. And this is the first time that we have something that works. And the COVID study showed clearly that we are able to transplant patients with some good results, some good kidney function at 1 year that it can be predicted for the long term. . So you have -- we have now the opportunity to keep these patients. We will not treat all the high desensitize patients, but we'll be able to treat a proportion of these highly sensitized patients. And based on our experience in France, for me, it's completely changed at the outpatient clinic when I have a highly [indiscernible] compared if you have nothing to do. And I fully agree that we have to open also the use of [indiscernible] because we are declining some donation because of the lake of any robust strategy, and we know that it's a quite important kidney that we are taking from [indiscernible]. So if we have a good drug to use it, it will be wonderful. So the ConfideS study is just confirming that this drug is working very well, and we will be able to take out of the [indiscernible] few patients and a large portion of patients with very good kidney function and good outcome, but we have to be prepared to all what will happen after the transportation, and we know how to deal with this.

That's very helpful. So I'm now going to open up to questions from the floor. And we also have questions online. So we'll try and do a little bit of a mix. And so we'll ask members of the audience to ask questions to try if possible to give everyone an opportunity to ask questions, and we will also turn to Maria to call out some of the questions online. So without further ado, I see someone's got a microphone in their hands. You're first.

[indiscernible] Dr. Jackson, I was curious to hear how [indiscernible] move patients down to 99.5%. Is that what you expect to do commercially, there's that balance of, well, you can desensitize them, but you want them to still stay prioritized. Or how do you see that kind of evolving assuming imlifidase approval? And then Dr. Mannon, you talked about how you maybe got away from desensitization because of the troubles and lack of reliabilities with imlifidase availability, do you foresee maybe bringing back desensitizing the clinic?

I think that's the easier question. So I'm going to interrupt you because that was when we thought about strategies like this, we were worried about allocation and the allocation scheme is dependent on [indiscernible]. So I think a lot of programs don't do this because they don't have reliable agents. And I'll reiterate again that the standard protocols, pre- and post-transplant are good, but they're not great. And you saw some of the things that are being used now off-label because of either AMR or the notional. I'm [indiscernible] we used to call it the kitchen sink. . I mean we even did splenectomies 10 years ago because you were trying to get this DSA down. And can you imagine you've been on dialysis. I came from a center were like 10-year weight. And these people, it was very challenging. You did a transplant, you were dialyzing them, you were [indiscernible] them. So I see this as really shifting how the standard program incorporates this, I see this as becoming a standard therapy across the community. And it's -- I mean, I really do -- I believe that it's not that I'm crazy because I am pretty tough in my program and around the country in terms of our expectations, I think that's an important change how programs will see and they've got good examples now. And we've got programs in this country that have had success. Will we ever be unified by the 13 or 14 centers everybody thinks they know more than all of us, right, Matt. And -- but I think they'll have -- it's true. But I do think we have examples now where we can protocolize therapy pre and post. We couldn't do that before because of the responsiveness of patients being very variable with [indiscernible], a little this, a little of that [indiscernible] mean we put all these patients on preop immunosuppression for a couple of weeks to make sure they could tolerate the higher doses before we even did the Plex IVIG and there are some proportion of patients that don't like it.

So the CPRA question. So when we detect antibodies that we want to avoid, it goes into a CPRA calculation, the higher the CPRA number, the more allocation points they get, patients that are 100%, so 99.5 rounds to 100. They are at the top of the list. They get the most allocation point. So if there's 10 patients buying for the same donor the person with the highest CPRA will have the higher allocation points. And so we want to reduce their CPRA to 99.5%, but we want to leave them there so that they get all the allocation points. reducing from 99.99% down to 99.5% opens up donor opportunities. We've seen it in our data that there's enough donors if we lower the CPRA to that. The CPRA is really you take the whole national donor pool and the higher the number the Mart squeezes. And these patients really need a specific donor a specific donor that our clinical team will say, okay, I'm willing to transplant that. We may delist 20 antibodies and 1 donor offer may come up and the patient may have 10 antibodies to that donor. We may pass on that 1 because the next donor will come up, they have 1 antibody toward them, and we'll go with that. So the more donors we have available, the better we can select the right donor for the right patient. So that's our strategy, get them to 99.5% to let the donor offers roll in and then we can select which donor is best.

Thanks very much. So do we -- we've got someone here and yes, we'll go where the microphone is.

[indiscernible]. Dr. Kamar, I'm just curious because, obviously, you have been used imitates quite a lot, just given the availability commercially in Europe. But obviously, your view seems to be much greater than what we've seen across the Europe where it is available. I'm just curious when you talk to colleagues if you get a sense of why some of them have been much more hesitant to use it, I know access and reimbursement is part of the equation. But even within France, it seems like you are probably one of the more, if not the top user, probably very close to it and what might sort of explain some of that variability? .

It's a very good question. First of all, nearly 50%, 52% of the centers of on trends are currently using life days. I can say the big centers that have all the facilities that are used to deal with desensitization are using imlifidase. The other centers who are not still using imlifidase are the centers who are not used to have all the management together with the immunologist because we have discussed delisting. When we have to delist, we have to decide which antibody with the list because we would do the list everything in order to get to the priority. So this require a meeting every month just to discuss the imlifidase patients. And so it's not available in all centers, all especially in small plasma centers, I'm not able to do it. Secondly, when we start using it, there's a risk Initially, we had the risk to start because it was a new drug. And some of them are waiting to get the feedback, our published data, so they will be prompted to use it. This can explain why there is some centers using it in France, some other are not using it. Nevertheless, within the last few months, the number of centers is increasing. There are very few centers not using it. With respect to the difference in Europe, this is probably related to the reimbursement system, the access to all facilities. There are -- we had a meeting with [indiscernible], Germany, Spain, Italy, Belgium and France 2 days ago. And we were discussing these issues. The majority were took more time to have their guidelines. So the Italian guidelines will be published soon. the German guidelines were published 2 weeks ago and [indiscernible] in immunology. So they were a little bit late compared to France, but I'm convinced that within the next year, all of them will have that guide that is published, and all of them will move forward. In addition, we would have some published data. The PAS data will be published, the confides will be published our French data will be published, so probably it will increase. This is just the timing to start.

And if I could just ask a follow-up question. I'm just curious in terms of your clinical experience, what were some of the aspects of the methods that you learned or some of the most important learnings that really let you sort of unlock the clinical potential of the drug. What we learned that initially, what we learned is to work together with the pathologists with the immunologist and very closely, otherwise, we cannot do it. Secondly, we know that you need to have facilities to do [indiscernible] if we have early bound and to use some off-label drug, if you want. This was the main point. And my first patient, when we transplanted our first patient with imlifidase, he did not experience any rebound, any ABM, nothing at 3 years now, we have 0.7 milligram of cretimine level. . So just this first patient, I received a text from all the colleagues and my side telling me. So we can use it to everybody because we have the good experience with the first one. So what we learned now that we have -- we can use it. We may have ABMR. I show it, and we have really to be careful in the monitoring. Looking for the DSA every other day, it's mandatory. Otherwise, you cannot do it. Being able to do [indiscernible] once you have the rebound and to go of the treatment. This is what unlocked its use, and we have more and more data and so the payers in France so that we are -- have good results and we present our data to the biomedicine agency showing them that it's not -- I'm not completely stupid. We are doing some good job. We have some good data. We have good kidney function. And so we have the support to continue.

I'm going to add to that. So the focus has been on efficacy, but as a nonuser or no experience. When we first heard about this agent presented, [indiscernible], we were worried about risk people were asking him, do you think people are going to get meals afterwards? Are you going to lose your protective immunity. I mean people are still vaccinated from diesels in transplant. But that wasn't a joke. I mean we -- there was clinical experience in Phase I in safety, but I think you can see that the post-transplant data presented those -- they may seem astonishing to you, BK viremia and all that. Those numbers are not any different than standard. And I think that, for me, was important to see because I just did not want to have some were dealing with opportunistic infections and loss of their protective immunity. I did a lot of tolerance trials in the past, and that was always a challenge was we had to do proactive monitoring for TV and other -- all the vaccines that we got as kids had to be monitored because it was an expectation by the institutional review board for patient safety. And we're not -- that's not an issue here. And that's, I think, a comforting feature that we now recognize.

If I could add one additional thing. Other desensitization modalities, the question is, can you bring these antibodies down? That's the uncertainty, imlifidase eliminates that. The antibodies will be down. And then we just control them as they come up. It's much easier to control an antibody when it's on the rise and it's low level, we can get ahead of it, if you will, it's very hard to bring a high antibody down with the other modalities. And so that perspective, that is a flip in perspective that clinicians have never had before. And so I think -- that's what's exciting and will be revealed in these publications. .

Okay. I think we've got a question over here. We'll take one more question here, and then we'll go to one from online.

[indiscernible]. I had a question on the confides results on the untreated or control arm, were there patients were well balanced at baseline, were there any differences in the patients who did get transplanted in the control group versus the ones who did not or was a just a transplant not avail or [indiscernible] not available?

So the data we showed the total groups. And the answer to your question is, is the patients that were transplanted, the 15 patients that were transplanted within the trial. They were well matched to the imlifidase patients as well. repeat transplants, highly sensitized. The data, as I said, once it's published, we are working on that draft right now. We're really excited. We hope to get that published soon, will also include the fact that some of those patients that were transplanted in the control arm did very poorly, which is, again, I think the demonstration that the other option that's available outside of imlifidase is not really a good option. So in some of those that made it to the operating room and went forward with the operation and still had a close follow-up those outcomes were still poor specifically to what Dr. Jackson mentioned. They went in with a high level of antibody and those patients struggled. The providers struggled to care for them and their outcomes were reflected in the network.

So Maria, we have a question online?

So we have a few questions online that are sort of similar in theme, and I'm going to address them to a couple of you. So the first question is really around how do you see imlifidase being used in the U.S.? Will it be used as part of standard of care? And how do you think about incorporating that into your transplant protocol should the product be approved? Will it change? How you think about how you manage patients after transplant? And I'll pass the second question for you to think about Dr. [indiscernible] in the ConfideS study, the CPRA was 99.9%. Clearly, in France, you have guidelines pointed to 98%. So maybe you can talk a bit about like how do you use the product in that population as well in France.

People are looking at me. So I'm [indiscernible]

Maria, do you mean standard of care for [indiscernible]

For desensitization.

It would be desensitization.

So I would say, yes, I see it being a standard of care, not standard of care for everyone, but for the highly sensitized patient. But I don't -- will it ever be one where maybe your CPR is 50 and you got a living donor and they're a little incompatible. Would it might be -- it might potentially go that way. When people get comfortable Think of a drug approved in 2011. It goes, no, by no name. It's an infusion. That drug had low uptake. The reason our center had a high uptake as we were in the studies, it's used a lot now. And so you just have to get the transplant clinician comfortable, and I think they'll see this data. And maybe I'm crazy, I actually see it being utilized even when your PRA is not that high, but maybe you're incompatible and people say, let's just go because we have a prediction of how we can do with that donor.

I agree and add a few extra points that -- so bringing some of that additional data that we talked about earlier, patients don't have a huge window when they're waiting for their transplant, right? The average survival on dialysis is not good. And so if we don't give people, the opportunity, perhaps when they get that once in a lifetime chance that they have their unacceptable delisted. They get that offer and we don't utilize this drug, they may never get another offer again. And so I believe that, yes, it will be utilized in that fashion for well beyond the inclusion that we saw in ConfideS. I'll add that, and maybe this was inferred in one of the previous questions, it's -- it will take some time to get out there. Quite frankly, as I said, we've had decades of solutions that weren't very palatable to the clinician. And so I think many centers and many leaders in this field, they become a little bit apathetic and are going to take a little bit of time to get reengaged here. you get people like us on the stage. It won't take long with a couple of pompoms and the ability to share this. But when people see this data and begin to, I think, anticipate really the ability to transplant. But in the past, we've used this word untransplantable. I think it's going to become standard of care pretty quickly well beyond with what we saw in the ConfideS trial.

And when we think about -- when we think about safety, no one has mentioned -- I'm not the MD, but since no one's mentioning this, I'm going to bring it up. Plasmapheresis removes clotting factors. And the need for plasmapheresis prior to going to an operating room and removing clouding factors, yes, we have fresh frozen plasma, but -- this is like 25 plex in 2 hours without the problem of CAD ion and clotting factors. So the safety profile is much better. .

I'll be brief because I'll start having PTSD with how we used to treat these patients. So we would routinely consent patients sharing with the expectation that we most likely would need to go back to the operating room potentially for a bleeding. We would, in the middle of the night and have to run back to do a splenectomy, as Raj mentioned, because of a tremendous rebound in antibodies. The only way that we could get on this, we thought was removing the spleen, and it was a very, very difficult process for the patient and for the providers. So you get to the operating room much more confidently with a much better safety profile which is the beginning of what we should expect in a successful outcome if you can go into the much more comfortably with a better safety profile.

And these patients need biopsies. I mean, we know there's some clinical antibody media rejection as your data pointed out. And it was always a challenge to say because I'm doing the biopsy and though I'm pretty skilled the nerve racking aspect. In fact, sometimes if the accounts are really concerning, you would send them to the OR for laparoscopic biopsy. I mean that's another invasive procedure that requires general and you've got these people that are just beat up. I mean it's a lot to sustain. These aren't well-trained athletes going for a transplant. These are people that have been on dialysis Three, 5, 7, 10 years with other comorbidities.

Okay. And Dr. Kamar?

Yes, with respect to the difference between the CPR and France and the CPR in the U.S., it's just a problem of the denominator because the number of donors and the recipients are not the same. There are nearly 23,000 transportation in the U.S., 29,000, they are only less than 4,000 in France. So the number of donors is exactly not the same. And the CPRA is calculated according to the panel of the area where you live. So this is why you have to calculate the threshold according to your country. In France, we did the job, and we looked -- we have observed that below 98%, you have access to transportation, no problem. 98 to 99 very few nearly nothing and 100 is absolutely nothing. This is why we opened it to 98%. Probably if you do it in another country, it depends on the volume, it could be a bit different.

Okay. Thanks very much. So maybe we'll turn back to the audience in the room.

[indiscernible] from Jefferies. Looking at the Phase III data and your clinical experience, you said anything to read on specific patient it's like retransplants [indiscernible] those patients benefit the most from the imlifidase treatment.

Fair question. So as you can see, we had a very -- even within the inclusion exclusion there was a pretty heterogeneous group with some having one transplant, some having 2 and 3. I think what is an important piece to recognize is the dialysis vintage that these patients had as well. So many of them, diabetes and high blood pressure, the significant vascular disease that came along with that these patients also had to have an extensive workup that demonstrated that technically we could do that operation because sadly, there's individuals who lose their transplant candidacy, simply because of the throes of the comorbidities that again, the dialysis population sees. But again, the application is broadly diverse. I think there's patients who regardless of cause of kidney failure, regardless of the true level of sensitivity and maybe Dr. Jackson wants to speak more specifically about Class I versus Class II antibodies because it was different for really everyone that I saw the data in my patient population. Like I said, I transplanted to patients that otherwise would have never received a gift of life without this intervention. Both were so incredibly broadly sensitized with the dilutions, we were able to reduce both Class I and Class II antibodies. That's, again, otherwise, I wouldn't have been able to get them transplanted. So I think it's nearly applicable across the board. As you can see, it's all antibody. It's not just specifically one or another. It's really that predictability, and I love that line. I wrote that down. The predictability allows the possibility that really got us to that transplantation because all the other therapies, to your point, there were some that we knew [indiscernible]. We have more problems with one class versus another. This is nondiscriminatory. It really allows something we've never seen before.

Perhaps I can add just one point. We have a paper currently under revision and with our colleague from Barcelona and some centers in France, and we try to look for a reality factor of rebound, for instance. We did not observe any effect for the moment based on our data on the repeated mismatches on the Class 1 or Class 2. There are some other factors. So we need more data and more patients probably will be able to predict the rebound. But currently, with the available data and the one that could be published soon, don't have any impact on the rebound.

And I would just say that the patients on the wait list that are nonwhite, they have -- they don't have common [indiscernible]. So these are patients with uncommon phenotypes that become sensitized to common antigens, common antigens that are in blood products, for instance. And so they will never find a well-matched kidney because they have unique HLA phenotypes. And so this is really the only option for them. .

A quick follow-up. You mentioned the variability across the U.S. transplant centers center since techniques, like you're one of the [indiscernible], like how long will it take for the guidelines to update and like formalize it in the procedure?

I've had a crystal ball, I'd probably be doing something different. But again, recognizing that this is a comparator against nothing, and this being the only option -- my expectation is that the societies with which we may seek ASN, NKF, ASTA, STS, I would wish that they're going to jump on this pretty quickly. There are certainly going to be -- we'll use the term centers of excellence that will be the starters of this, and that's an okay thing. We want to have a lot of wins when we first introduced this outside of a clinical trial. So that people can both see the repetition of the data, be confident and then have more friends with which they can call to then expand this to a broader population. But I -- like I said, I expect this to happen quickly because, again, there's really no other good option out there. And people have been thirsty for this for a long time.

So the last consensus we had on AMR treatment was published in transplantation. It was the Transplantation Society, which is the most continent organization that includes Europe and Asia and a bunch of us got together and looked at the evidence and that paper has not been updated yet because we haven't had a whole lot to say. So I foresee that happening as sort of a multinational organization. Some of the societies we're a [indiscernible] guidelines, we're putting our stamp of approval. But I think standard of care protocols will be changed now because the things and the advice provided in that paper, much of it is experience. It's low level evidence, but what appears to work.

Thanks very much. So I think this may be the last question, but please go ahead.

Tom Smith, Leerink Partners. Maybe just first for Richard. I just wanted to ask if there's any update or comments you could give us on the ongoing BLA review. Any color on the exchanges with the agency to date?

Yes. Well, you're quite right. We do have an ongoing review with the FDA. I think that review is going as we had expected it to go. We're not going to give you running commentary of all the interactions between us and the FDA. But I think we'd agree it's going satisfactorily, and we're looking forward to the decision from the FDA on the 19th of December.

Great. And a quick follow-up, if I could, for Dr. Kamar. In case, there were a handful of patients who received multiple doses of imlifidase. So I'm just wondering if you had any experience using multiple doses. If so, how was that experience? Did that end up enabling transplant?

All our patients -- the crossmatch negative and all our patients with one single dose.

Okay. According to the clock, we're out of time. So thanks very much for your engagement in the Q&A, and thanks very much again to our panel. I think there's some really, really insightful comments. Thank you.

So thank you again to our esteemed panel of experts. We're going to now let them actually go and do something other things of useful nature than being here. But we certainly kind of thank them a lot for their contribution. We're now going to actually kind of turn over to some more of the kind of corporate items. So I'm going to kind of hand over to Maria to take you through our kind of launch preparations and market opportunity in the U.S.

Great. So I don't know how to follow that. I thought that was very insightful. I certainly learned a lot, and I hope that all of you did. So my topic is not to talk a bit about how do we prepare the U.S. market? Should imlifidase be approved. As Richard mentioned, we have our BLA on December 19. So there's a lot of activities going on. First, I do have a disclaimer. Obviously, as we know, imlifidase, is not approved in the U.S. So anything that I say is subject to that approval, which, of course, we cannot guarantee but we are very hopeful for that approval. So we've talked about the U.S. market before and how many patients there are right now. We also heard from the physicians that how you define the how to sensitize is not really straightforward. There are different definitions of a high desensitized patients. There are roughly 100,000 patients on the kidney waitlist today -- kidney transplant waitlist in the U.S. If you look at some medical papers, they tend to talk about high sensitized as being 80% and above. But as you know, in France, as an example, 98% is used as a cutoff in their guidelines, and our ConfideS study was in the 99.9%, where we have 3,500 patients roughly today in the U.S. What is also important to note is that this list is growing. We have 45,000 patients added to the wait list and a couple of thousand of those are in that very, very high sensitization from a CPRA perspective. And unfortunately, many patients are just sitting on the waitlist and they die or are removed from the waitlist. As you heard before, there's been no other options for these patients so far. And we also know that they wait for a very long time. The median wait time in the U.S. today is 7 years due to some of the data that pointed to 8 to 9 years in other publications. So many patients waited a very, very long time, and obviously, that is impacting the likelihood of getting a transplant and mortality. Another interesting fact that I think we should not forget is that in the U.S., there are many kidneys that are discarded each year. So we have 9,000 kidneys discarded, and if you look at why are they discarded? Obviously, there are some kidneys that are not suitable for transplantation. They are damaged as part of the surgery or other reason. But 60% of those that are discarded. So 5,000 kidneys are because there's not a recipient located and the list is exhausted. So that is, in other ways, a kidney that has been offered to someone. There is not a match. It goes to a second patient, there's not a match and it continues until that cold ischemic time has run out. So more than 5,000 kidneys are discarded in the U.S. each year for that particular reason. And then if you look at what is the size of that market opportunity? We have not defined a price yet in the U.S. But if you just look at how imlifidase is priced in Europe, we believe that this is a SEK 2 billion market in the U.S. So we have started to launch preparations. We have a very experienced team that we've hired in the U.S. So I have my full established leadership team from market access to medical affairs. You met Jennifer before to commercial and to analytics. They have all launched multiple products in the U.S. before. They have worked in the transplant space. They have worked in nephrology. And we are working 100% to prepare for the potential approval in December. We've also done a lot of market research. So you heard a lot from the KOLs today on stage on what they think about the market and what they think about imlifidase. We've also tested the profile with many physicians and financial stakeholders and with patients blinded to see what do they think about imlifidase. And it's viewed very, very positively, both from a patient perspective and from a physician perspective. As you heard, I think Dr. Mannon mentioned it, like most centers don't do desensitization because these current options that are available are not seen as that effective. And they're quite burdensome, and they're not giving that predictability that Dr. Jackson mentioned earlier. As I mentioned, we have built our leadership team. We have also staffed our medical affairs and our market access team. So they are out in the field today, engaging with clinicians and with the financial stakeholders in the transplant centers. We are focusing on scientific exchange. I think one comment that was quite interesting from Dr. Kamar was just around the availability of data and how he reflected on the fact that they have had a lot of data available in France, but also how that is important for other centers that have not been part of the trial. And as you've seen, we have a lot of data coming out, both from confides from PES and also from some of the French data that hopefully, we'll see published soon. All of that, we believe, will help us as we prepare the market. And then the final piece is around transplant center readiness. So this is a novel therapy that will be introduced to the transplant centers. And we are focused on engaging with the centers to try and understand how they will incorporate imlifidase into the transplant center journey into the algorithm and into the operational aspects of the center. And our initial focus is on those 100 centers that represent 80% of the volume. So from a financial perspective, what do they say about this potential approval? Well, we know from the fact that the majority of patients have Medicare and in our market research that we have done with financial stakeholders, we know that they see that this is a patient burden that they stay on dialysis for a very, very long time. From a Medicare perspective, this will be an inpatient drug that will be covered by DRG codes. There are a few [indiscernible] used for kidney transplant, and the transplant centers also need to do outlier payments. And that is something they do today. If they are using a therapy that is not covered by the DRG, their financial stakeholders will submit an outlier payment to CMS and ask for additional reimbursement. We will also apply for NTAP that stands for new technology add-on payment. We'll do that in October of this year. That is roughly 1-year period until it gets implemented, should it be approved. And we believe that imlifidase has a very high chance of receiving NTAP. The other thing I think is worth noting is that while majority of patients have Medicare, we know that there are patients that are on commercial plans. If you look at an analog such as the CAR-Ts, that's why they saw an early adoption. And in transplant, there are policies with the commercial payers for how to cover transplants. And those policies can be updated and there is also a path towards single case agreements, which is very similar to how the CAR-Ts were adopted when they launched a few years ago. I think we believe that the initial early adoption will come from these high-volume centers that have clinical experience. I think you heard that comment as well from Dr. Cooper just before he left. We see in our market research that they all recognize the value, basically enabling a transplant that otherwise would not occur for these patients. We also see that across all stakeholders in the center is a high sense of urgency because of the high burden of dialysis of patients. We have seen comments in our market research that the fact that imlifidase is a onetime therapy is going to make the operational complexity easier. And we expect, as I said, that the volume will initially come from the centers that have clinical experience. We have 25 confide centers that represent 25% of the volume, and we will see that scale within the large transplant centers and then eventually scale further as we have NTAP adopted. So a bit of a time line on to summer. So we stand. As you know, we presented our data at ATC just a couple of days ago in Boston. We are fully [indiscernible] in the prelaunch activities that I just described. We built out our market access, the medical affairs team or building out a commercial team in Q4, shortly before approval. We are very hopeful for our PDUFA in December, December 19. And should imlifidase be approved, we anticipate that it will be commercially available in Q1 of 2027. So with that, I will hand it over to Richard.

Thanks very much, Maria. So now I'm just going to take a few minutes, just to talk a little bit more about the pipeline that we have. And this is a slide that's Renee showed a little earlier in the meeting. So -- and we spent a considerable amount of time talking about the use of imlifidase both in Europe and in the U.S. in Europe. It has conditional approval. We've read out the PAS study results, at least top line data from that. And we believe those data will, in due course, support a submission to have that conditional approval converted to a full approval. And then you're very familiar with the situation in the U.S. I won't go over that again. We do have other components of the pipeline. We have 2 programs where we're working with an external partner looking at the use of imlifidase in a gene therapy setting, so desensitizing patients who are candidates for gene therapy, but have pre-existing antibodies to the vector being used for -- in those programs. We have a partnership, a relationship with Sarepta in which boys with Duchenne muscular dystrophy received treatment with imlifidase, followed by gene therapy. And we're working with Sarepta to determine the path forward. For those -- for that particular program. And then with Genethon, we have a partnership looking at the use again of imlifidase for desensitization prior to patients receiving gene therapy for Crigler-Najjar syndrome. We've enrolled a patient in that program. And those data were presented in that first patient last -- towards the end of last year, and we expect to enroll 2 more patients into that program this year. There is an ongoing investigator-initiated trial in a condition called ANCA-associated vasculitis. That investigator-sponsored trial is being conducted in Germany. The plan is to enroll 10 patients with ANCA-associated vasculitis and pulmonary hemorrhage. And indeed, that study has completed enrollment of the 10 patients and we expect to evaluate the results of that study over the next few weeks. And then finally, we have a program using our next-generation IgG-cleaving enzyme, HNSA-5487, and that is being taken forward in a condition called Guillain-Barré syndrome, and we hope to agree a development path forward for that program with the FDA later this year. So I'm going to take a little bit more time just to talk a bit about Guillain-Barré syndrome and just give you an overview of the disease. So this is a rare, rapidly progressive monophasic immune-mediated neuropathy. So in this condition, the immune system attacks peripheral nerves. And there is a clear association between Guillain-Barré syndrome and a preceding infection. Many patients will have experienced a diarrheal illness prior to developing Guillain-Barré syndrome. So the disease affects around 1 to 2 per 100,000 patients -- people annually. And in the U.S., there's around 3,500 to 7,000 cases each year. And there are -- because of the preceding infectious relationship, there are some seasonal and geographical differences in the incidence and prevalence of Guillain-Barré syndrome. So as I've said, this is characterized by an acute onset of neuropathy. It affects both sensory and motor neurons. It seems that there's -- so there are auto IgG class autoantibodies directed against gangliosides likely cross-reactive with the immune response generated by the preceding infection. So this condition, which is manifested as a neuropathy, both sensory and motor presents clinically as weakness and tingling in the periphery, in the hands and feet, which rather rapidly progresses and ascends up through the arms and legs to the trunk and then affecting respiratory muscles. And this is a condition that requires hospitalization. Clearly, a significant proportion of patients require some form of ventilatory support. And this progression is rapid. And usually, from a motor point of view, weakness. Most patients reached the peak of weakness within a couple of weeks of developing the condition. So -- and historically, this was considered to be a condition that patients they had, they were supported and they recovered from. I think our understanding of the disease has improved, and we recognize now that many patients don't fully recover from this condition, even if they get over the acute event, many patients are left with some kind of disability and around about 20% of patients are unable to walk independently after 6 months after developing the condition. There are treatments that are used. There are no treatments in the U.S. that are approved, but treatments that are used are intravenous immunoglobulin, IVIg or plasma exchange. In Europe, IVIg is approved for the use of GBS. And obviously, patients are supported and given respiratory support where required. And then we think that around about 25% of patients need mechanical ventilation for days or even months following the onset of the condition. So we have investigated the use of imlifidase in Guillain-Barré syndrome. Our program that we are proposing to take forward is with 5487, but our if you like, our confidence or belief in the use of an IgG-cleaving approach in GBS has come from the work that we did with imlifidase. So in this Phase II study that was run, it was a single-arm study. And in this study, patients were screened and then enrolled into the study. They received treatment with imlifidase. And then following treatment with imlifidase, between day 3 and day 7 after treatment with imlifidase, they also subsequently received treatment with intravenous immunoglobulin, and they were then followed and assessed for essentially 12 months after that treatment, looking at the safety of the treatment, disability status, need for mechanical ventilation and ICU admission. And what we saw in this study is that patients showed an impressive response to treatment, and we'll talk a little bit more about that in due course. So in terms of the number of patients that were enrolled in this study, 30 patients were enrolled, but 27 patients from the analysis set for the study, 3 patients were excluded from the study after enrollment because they were found not to have Guillain-Barré syndrome. So that's not necessary very unusual. Some other conditions can mimic Guillain-Barré syndrome. So I don't think that was an unusual thing to have happened. The analysis set was based on 27 patients. Median age was 60, around about equal split between males and females. We used the GBS disability score to understand the baseline impairment -- level of impairment. And we saw that patients were -- and we required patients to be enrolled with a GBS disability score of 3, 4 or 5. And you'll see the patients were enrolled really quite rapidly after the onset of the symptoms. So the median number of days from the onset of weakness to enrollment was 4.5 days. And you'll see, again, perhaps not surprisingly, quite a significant proportion of patients, just over 50% had a preceding history of diarrhea. And imlifidase in this setting did what was expected in terms of cleaving the IgG. We saw a very rapid cleavage of IgG. And then because of the introduction of IVIg, there was then a recovery of IgG subsequently. And what we saw was a very impressive, albeit it was in a single-arm study, improvement in functional status of patients. The median time to walking independently was 16 days. And most patients improved markedly in terms of their motor function after the treatment with imlifidase by 1 week after dosing, 37% of patients were able to walk independently. And at 4 weeks after treatment, 52% of patients were able to walk independently and 33% were able to run. But what does this mean? Because we recognize this was a single-arm study. So we have then taken the results from that study, and we've compared it to patient data from a very well-respected patient registry called the IGOS database and which is the International Guillain-Barré Syndrome Outcome study. So what we've been able to do is compare the outcomes in terms of change from baseline in the MRC sum score, a measure of muscle strength. And what we can see is a very rapid improvement in patients receiving imlifidase. And when we compare with the IGOS database, we see a very, very different profile in patients with Guillain-Barré syndrome treated with IVIg or plex. And we've also subjected those data from the IGOS database compared with what we've seen with imlifidase. We've subjected that to a statistical analysis called a matched adjusted indirect comparison. And when we've done that, we see statistically significant differences between the 2 groups, recognizing they're not 2 groups in the same study, but we see statistically significant differences in the behavior of those 2 groups in the early part of the post presentation, post-treatment course of the condition. So based on that, as I say, that was with imlifidase, but we believe with our next-generation enzyme, we believe this will have a similar impact on the condition in Guillain-Barré syndrome. And some work with 5487 has already been completed. So we've done a Phase I healthy volunteer study. And what we have seen from this study is that circulating IgG was very efficiently and rapidly reduced by a single dose of the -- of 5487 by more than 95% within a few hours. We saw in this healthy volunteer study, a positive correlation between dose and duration of reduced IgG levels. So in other words, where we gave a higher dose. This resulted in a longer duration of effect. So there's a clear dose response relationship. And there was a significantly reduced antidrug antibody response when compared with imlifidase. 5487 has its origins from a source an infectious bacteria, but it's not a bacteria that typically infects humans. So there is less pre-existing antibodies to this particular enzyme. And it was shown to be safe and well tolerated across all the dose levels tested in that study with no serious or severe adverse events. So we've completed the design of a clinical development program. We are in discussions with the FDA and the intention is to start the clinical development, the clinical aspects of the clinical development program by the end of this year. So with that, I'm now going to turn it over to Renee for the closing remarks.

Thank you very much, Richard. And so we now have -- obviously, first of all, thank you for taking the time, spending the time to come over here and listen to our experts and to some updates with regards to our programs as well. We do have some time if there are some questions regarding kind of the company or the company's view on some of these things. We're happy to take some of those questions. Maria, Richard and I are happy to do that. And if there are any questions in the room. Yes. you want to come up here?

Matt Phipps, William Blair again. Maria, you outlined some of the market dynamics here. Obviously, NTAP payment probably being an important part of the commercial story. I guess how should we think about the cadence in 2027? Is this pretty limited until you get that NTAP and then it can grow from there? You mentioned maybe some kind of named patient commercial patients potentially like the CAR-T did. But just curious if you could give us some more thoughts on that.

No, thank you. And I hope you can hear my microphone. But I think the way to think about this is in the U.S. today, you have 200 transplant centers and 25 of those are part in the ConfIdeS study. People like Dr. Cooper as an example, we have many centers that have clinical experience. I think that will be a driving factor behind the early usage. And I think what I mentioned earlier is a good analog for us to think about is how the CAR-Ts -- the uptake that they had from approval until they then had the NTAP approved as well. So I think we expect to see early uptake. I think we'll expect to see it in centers that have clinical experience in some of the larger institutions, academic institutions, and they will apply the outlier payments to get that additional reimbursement. And I think you'll see additional boost when you get the NTAP hopefully approved. And that is similar to the way that the CAR-Ts had their initial uptake. And I think another thing to worth sort of noting is that -- we have a mix of Medicare obviously being the majority, but there is also some commercial patients. And I think you'll see an uptick in the commercial segment as well. So -- but that's why we tend to refer back to like the CAR-Ts because it's a great analog if you look at the dynamics when they launched and how sort of MTAP impacted that uptake curve.

Go ahead.

A quick follow-up. Dr. Manon, I think you talked about the protocolization of desensitized patients. How much can you guys help establish that protocol? Because like you said, every transplant center has their own special sauce. Are you guys really going to try to drive that to help get the best outcomes because now you have data across all the European commercial and then the ConfIdeS study?

So I think you're right. I mean what Dr. Manon said is that all U.S. transplant centers in a way have their own protocol for how they treat or not treat patients today that are highly sensitized. The way we think about imlifidase is obviously, as I mentioned, we've hired a market access team, and we've hired a medical team. And their job right now in this prelaunch phase is to go out and engage with the centers and understand who are the stakeholders, what does the protocol look like in every single center out of those 100 centers that we're initially going to target and then how potentially would imlifidase fit into that journey. And I think that is -- that it will be key to success. I don't think that forcing a one model approach to all is going to be successful. I think you need to sort of meet the center where they are at knowing that some centers will have more experience with treating patients, maybe in ConfIdeS, maybe in other trials versus others. I think there will be different sort of journeys to how to get them to incorporate imlifidase in the protocol.

And I would add to that, just obviously, that this is a fairly kind of -- it's a fairly small community. I mean a lot of these physicians have trained with each other in different same kind of -- you can hear that it's like they've been at certain centers. So Dr. Cooper's comment in terms of phone a friend, I think it's actually also going to be very driving in that beginning. I think you are going to have some of those kind of investigators. And I think the protocol that was put in place for the ConfIdeS trial obviously showed great success. So I think that's probably one of the places where they will start building on that existing kind of protocol, but probably kind of like making it more adaptable to kind of real-world use.

A question. So based on the feedback from the KOLs, it should be a no-brainer to be a standard of care, but any insights from these centers and how the initial launch uptick could be?

Yes. It's -- so I guess generally, again, I mean, to Maria's point, I think it is going to be driven by those kind of centers that were part of the ConfIdeS trial or the large kind of academic centers that have some experience and also obviously have the facilities to kind of do this. And then I think there will be kind of that rollout over time to other centers. I will say, though, I mean, again, having kind of been at the ATC, I think that there is a lot of interest. I mean physicians kind of -- they're aware of imlifidase. They've heard about it. It's been kind of talked about for quite a long time. There's a lot of interest, a lot of curiosity and a lot of kind of willingness to kind of learn more until I really understand the data. And so I think that actually puts the team that Maria was talking about in terms of the medical affairs team, it's not difficult for them to get access to these centers at this point in time. I think people are very interested, very curious. They want to learn more. They want to know how do we get ourselves kind of ready to do this. And so I think there's a lot of kind of willingness in the community as far as I can tell talking to having been at this congress for several days. So I think that there is a lot of willingness to do that. But again, I think it will probably in the beginning, be driven by physicians are having some experience with this.

Yes. And maybe I can just add. I mean, like if you look at HSC agenda, there was a lot of topics on desensitization in general. Like every single day, there are multiple sessions on that topic. And I think the other thing is also we do get inbound call. I mean, like as you heard today, there's a high unmet need. We get inbound call questions, both from patients and physicians, when will the product potentially be approved? How can I get access to it? So there's a lot of interest -- so I think -- but as Renee said, like that initial uptake will, I believe, will come from centers that have a bit of experience and have the large infrastructures to manage patients.

And then one more on the pressure testing the pricing assumptions, given the value proposition, clearly higher improved transplant rates, reduced wait list times, like is the EU pricing point reasonable or it can be higher potentially?

I think that we'll have to -- we have been conducting some pricing research, and I think we've been talking to a lot of different kind of stakeholders. And we have not, at this point, kind of arrived at a price in the U.S. I think there's still kind of research that we want to do and complementary kind of information we want to have before we get there. And so I think that will be announced at launch. But I think we are doing, I would say, a lot of work around that to make sure that we price the drug appropriately. Is there something online as well?

We have one question online. For HNZA-5487 in GBS, how do you see the competitive landscape, a realistic market penetration, taking into account that you already know from imlifidase. Is your base case that 5487 will broadly replicate imlifidase like efficacy? Or are you building in any additional benefit in the next-generation profile?

So I guess do you want to start and I can complement?

Yes. Well, I mean, I think from the point of view of the clinical benefits of the treatment, I mean, clearly, this is a 5487 is an IgG-cleaving enzyme. It has some slightly different properties, which we think are advantageous in terms of potency and duration of effect. So I think that's advantageous. But we're obviously confident that the treatment is going to work in a similar way to what we've seen with the use of imlifidase. But we still have to undertake the development of the treatment in the condition. So there's still a clinical development plan that needs to be executed to support that. We're confident that it will work, but we still need to do the clinical work to show that. And as I said, I mean, that's something that we are in discussions with the FDA about in terms of that program.

Yes. And the only thing I would add to that is, obviously, I mean, as Richard was saying, it is significantly less immunogenic than imlifidase. And so I think it's been talked a lot about the ability to redose, et cetera, et cetera. I think that the marketplace has evolved quite a lot in a lot of those areas in the autoimmune space. And so I think once we've actually kind of launched our clinical trial in GBS, as you might imagine, we're looking at a variety of potentially different than other kind of complementary indications as well to potentially take that forward in. But I think we'll -- the first thing that we're really going to focus on is GBS because we think that we have a very high probability of success in that indication. And with regards to kind of competitive situation, obviously, there's nothing approved today. There are obviously other programs that's pursuing GBS. But again, I think a lot of times, what we find is this is a reasonably large indication. It's a rare indication. But obviously, once you start having agents that are kind of considered to be efficacious and safe and approved in these rare indications, you do often see kind of an expansion of that kind of rare area simply because there's now an ability to treat these patients kind of effectively. So I think that as we've seen in a lot of other rare indications, it's unusual that you only have one agent in a rare indication. So I think there's certainly room for certainly 2 or 3 agents in GBS to be commercially successful.

Doug Tsao, H.C. Wainwright again. Just a question. One of the things that we heard from the clinicians was their interest in using imiflidase potentially much broader and sort of maybe not necessarily or is in terms of trying to sort of pump the brakes a little in terms of use certainly in the early days of the product's commercialization in the U.S.

Yes. So, we -- I mean, obviously, we are going to kind of focus our entire kind of effort around the approved kind of the approved indication and the label that we get. It's a bit early yet to kind of know what that label is going to look like. We haven't had those conversations yet with the FDA, as I'm sure you're aware, that happens a bit later on in the process. I would say, however, that, I mean, it is our intention, and I think we've said this before, is obviously, once this drug is approved in kind of an indication in transplant, we strongly believe that, obviously, and you can hear that the clinicians kind of believe that this is an organ-agnostic treatment. And so I think there are kind of certainly reasons for us to go back to the FDA and understand from them what kind of data do they need to see. What would they like to see, what would they need to see in order to potentially then kind of broaden the label. And I think that's certainly something that we intend to do. But I guess for now, we're going to try to focus on kind of getting an approval. I just think it speaks to the fact that, obviously, as you've heard today, is that there is a significant unmet medical need across some of these areas. And I think specifically, I know that living donor has been mentioned several times today. Again, that is not an indication that we have been pursuing from a clinical trial perspective. But again, in the interest of broadening access, allowing for more transplantation to take place. That's certainly something that both from a kind of like socioeconomic perspective and patient perspective might certainly kind of have great benefit. But again, I think we need to kind of go back to the agency to understand what data they would like to see now that they have seen this clinical trial and understand probably more of the profile of this drug candidate. So I think -- anything else? No. Good. Great. Yes. Okay. One last question.

On the -- EU manufacturing in place, can you support the U.S. launch? Or do you need to establish something in the U.S.

No. What we have established for the European commercialization is sufficient to also support the U.S. Okay. So with that, thank you. Thank you very much for coming. I hope you found this to be interesting. And again, even if they're not here, I want to thank our panelists again for coming over and taking the time out of their schedule to do this. And I would invite you all to kind of -- there's some lunch, grab and go if you want to kind of bring that with you. But again, thank you for attending, and we look forward to keeping you updated about our progress as time goes on. Thank you.