Good morning and welcome to the Hansa Biopharma Virtual KOL event. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations and fireside chat. As a reminder, this call is being recorded and a replay will be made available on the Hansa website following the conclusion of the event. I'd now like to turn the call over to Renée Aguiar-Lucander, Chief Executive Officer of Hansa Biopharma. Please go ahead, Renée.
Thank you very much, Tara, and welcome, everybody. Thank you for attending this webinar on our recent phase III trial data and for the discussion to follow. Obviously, a very special welcome to our highly distinguished guests, Professors Montgomery from New York Langone and New York Langone Transplant Institute, and Professor Cooper from the Medical College of Wisconsin. Thank you both for taking time out of your very busy schedule to share your insights with us here today. Next page, please. I refer you to the fact that we may be providing forward-looking statements in this presentation. I ask you to refer to our documents on file. Next page, please. This is the agenda for this webinar. The presentation will take a total of about 15 minutes. It'll be followed by around a 25-minute discussion with our distinguished guests, after which we will open up for Q&A.
I will now give a very brief introduction to those of you who may not be that familiar with Hansa. Hansa's built, and next page, please. Hansa's built around a novel, unique, and first-in-class IgG cleaving platform with a lead product candidate in imlifidase, as well as a next-generation enzyme, 5487. And imlifidase is extremely efficient at cleaving IgG both intravascularly and extravascularly and reduces IgG by over 95% from baseline in just two to six hours from administration. It's highly selective with no identified off-target activity and is therefore very well adapted to address situations such as acute flares or exacerbations. Next page, please. The platform is uniquely positioned really to treat these serious immune-mediated diseases or challenges due to this very rapid IgG reduction.
In comparisons to FcRn, for example, these enzymes do provide this immediate and significant reduction that allows for both a faster and deeper impact on IgG. Obviously, antibody levels will recover after about a week from that kind of deep reduction. Next page, please. Hansa is really presently pursuing some key rare indications where there are significant unmet medical needs. This includes desensitization before kidney transplantation for highly sensitized patients, as well as desensitization for patients eligible for gene therapy but who might be excluded due to high levels of antibodies against AAV vectors. Finally, we have also generated highly promising phase II data in IgG-mediated autoimmune diseases such as anti-GBM and Guillain-Barré syndrome. We are planning to read out top-line data from our randomized control phase III trial in anti-GBM later this year.
We recently read out kind of positive phase III data in our randomized control US kidney trial with a p-value of 0.0001. We plan to file a BLA before the end of this year with the FDA and building out our commercial presence, which we already have in Europe, based on a conditional approval for highly sensitized patients. We have a cash runway into 2027 following a successful capital raise recently. Next page, please. In terms of the actual kind of market opportunity with regards to kidney patients, highly sensitized patients in the US face great difficulty in finding a matching organ due to their high levels of antibodies. There is a significant unmet medical need, which imlifidase hopes to address. Today, there are about 100,000 patients on the waiting list in the US.
About 15% of those, about 15,000 or so, are categorized as being highly sensitized, which is then looking at a so-called CPRA score of above 80%. In the study that we conducted, we conducted this in the very, very highly sensitized group with a CPRA score of over 99.9%. There are about 7,000 patients with a CPRA score over 98 and about 3,500 patients today on the waiting list with a CPRA score above 99.9%. Against this backdrop, obviously, these patients stay on the waiting list much longer than the average kind of patient on the waiting list. It can be up to seven years for these highly sensitized patients.
We do know, obviously, that the community is really looking for a solution for these patients because, obviously, as we know, staying on dialysis for extended periods of time is a very difficult situation for a lot of these patients, obviously. Against this backdrop, I'm going to hand over to Dr. Richard Phillips, who's our CMO, who will take us through the results of the ConfIdeS trial and get some insights from our guests in the discussion to follow. Next page, please. Richard, over to you.
Thanks very much, Renée. Before we move on to the discussion with Doctors Cooper and Montgomery, I'm going to start by presenting a short summary of the efficacy and safety outcomes from the ConfIdeS phase III study. This was an open-label randomized control study evaluating kidney function at 12 months as measured by estimated glomerular filtration rate, or eGFR, in highly sensitized kidney transplant patients treated with imlifidase prior to transplantation compared to a control group. I'll begin by just presenting a brief summary of the study design. Patients considered potential candidates for the study were consented and entered a pre-screening period. One or more of the unacceptable antigens were delisted from the patient's HLA profile to increase the likelihood of the patient receiving an organ offer. When an organ offer was received, patients entered screening and underwent a final evaluation of eligibility.
Eligible patients were then randomized to the imlifidase arm or the control arm in a one-to-one ratio. The period of follow-up in the study was 12 months from the time of randomization. Patients randomized to the imlifidase arm accepted the organ offer and were treated with imlifidase. If treatment resulted in cross-match conversion from positive to negative, then patients were transplanted and entered follow-up. Patients randomized to the control arm either accepted the organ offer, were treated with non-approved desensitization, and then proceeded to transplant, or the organ offer was rejected and the patient waited for a more compatible organ offer or offers later in the 12-month follow-up period. A total of 64 patients were randomized in equal numbers to each either treatment with imlifidase or the control arm. There were 32 patients in each arm of the study.
Two patients randomized to the imlifidase arm did not proceed to treatment. In one case, the organ offer was refused. In the other case, the patient withdrew consent to be treated with imlifidase. The overall rate of completion of the study was excellent. A total of 58 patients, or just over 90%, in the study completed the 12-month follow-up period. The treatment groups were balanced with respect to sex and age. Overall, there were almost equal numbers of males and females in the study, and the mean age of the study population was 45.3 years. The treatment groups were also balanced with respect to race and ethnicity and representative of a highly sensitized kidney transplant waitlist population.
With respect to the primary efficacy outcome, at 12 months, mean eGFR was 51.5 mL/min in the imlifidase arm compared to 19.3 mL/min in the control arm, with a statistically significant and clinically meaningful difference between the two groups of patients of 32.2 mL/min with a p-value of less than 0.0001. This outcome reflects the excellent graft survival that was observed in the imlifidase arm. When looking at two of the supportive analyses of the primary endpoint, these provided outcomes consistent with the primary analysis. When we performed an analysis of 12-month eGFR using a non-parametric test that does not assume normally distributed data, the outcome remains statistically significant. Similarly, when we look at 12-month eGFR in patients transplanted based on organ offer at randomization, again, the outcome remains statistically significant. These supportive analyses of the primary endpoint give us additional confidence in the robustness of the primary analysis.
Also of note, a key secondary endpoint of dialysis dependency at 12 months was statistically significant with a p-value of 0.0007 in favor of imlifidase. In terms of the safety outcomes of the study, the tolerability of imlifidase was good. There was a low incidence of infusion reactions, and no infusions were interrupted due to an infusion reaction. Infections observed in imlifidase-treated patients were typically not related to treatment. The adverse event and serious adverse event profile of imlifidase reflected a population of patients undergoing kidney transplantation, with most serious adverse events considered unrelated to imlifidase treatment. I'd now like to move on. Following the conclusion of that presentation, I'd like to move on now and open up the discussion with Dr. Cooper and Dr. Montgomery. Perhaps I can open this discussion with you, Dr. Cooper.
I think it would be really helpful if you could first please describe what receiving a kidney transplant means for patients with end-stage kidney disease who are on dialysis, particularly in terms of the clinical outcomes, the quality of life changes, and the long-term prognosis.
Thank you. First, let me start by saying I really appreciate this opportunity to be here. Twenty-five years into the practice of transplant, I can say this is one of the most exciting potential opportunities that I've seen in my entire career. It is also a privilege to be here with Dr. Montgomery, who was one of my attendees when I started in this field. It is, again, very exciting. To answer the question, when describing to patients or to anyone who is interested in hearing about the kidney transplant and end-stage renal disease, I describe dialysis and transplant as the pure apples and oranges comparator. They really should not be in the same sentence. Individuals, in some of the data we've shown, will wait for years for a kidney transplant. Many of them will not receive a transplant.
They'll continue to suffer the complications associated with what brought them to end-stage renal disease, most often this being diabetes and high blood pressure, increased risk of peripheral vascular disease, of strokes, and of heart attacks. The ability to receive a kidney transplant, albeit in these highly sensitized patients, waiting sometimes for up to eight years, I think most data would show, it is a really life-changing experience for them. Dialysis patients will tell you that their entire life revolves around either presenting to a dialysis center, three times a week for four hours each session, home dialysis or home peritoneal dialysis. All of that requires a significant demand, a significant change in lifestyle, challenges in holding a steady and regular job, inability, for instance, to go on vacations, all the things that probably you and I may take for granted.
The transplant really gives people the opportunity to return back to life. The data would show about the five-year survival on dialysis is around 45%. The survival with transplant, again, is so much better. The early data in the imlifidase trials, we'll talk about, begins to show those same statistics. I think that this is really revolutionary for individuals who come to our transplant programs looking for an opportunity better than dialysis or the fear of dialysis. For the longest time, the numbers and the percentages, and we can get into CPRA, would show that their opportunity for sensitized patients in identifying a suitable candidate donor organ is almost limited to really to none. This is a major change for us. It gives us a different way to converse with patients.
It gives us hope to be able to tell people when they come to us that we're going to give them every opportunity to have a life free from dialysis. Apples and oranges, dialysis to transplant, highly sensitized are options in the past to what we have with imlifidase the same way. Very, very different.
Thanks very much. I think that really paints the picture of the transformational impact of undergoing a transplant for patients who are on dialysis. Perhaps turning to you, Dr. Montgomery, again, thinking of that kidney transplant setting, now turning our attention to highly sensitized patients, can you just take a moment to describe how highly sensitized patients waiting for a kidney transplant, how these patients currently manage, what their treatment options are for desensitization, and what the unmet needs are for these patients? You're on mute.
First, I just want to say hello and thank you all. It's great to be here today to talk about something that I think is extremely important for our field, and particularly for a group of patients that, when I started working with these patients in the 1990s, were essentially warehoused on lists with really no hope of getting a transplant. You probably know that in 2014, we had a change in our allocation system that gave extra points, priority points, to patients who were highly sensitized. Just to sort of get a nomenclature sort of wrinkle that I think a lot of people don't understand out of the way, if you're greater than 99.5% sensitized, you're referred to as being 100%, right? We round up to 100%. If you're 99.5 % or less, you're 99%.
I think the important thing is to really focus on this group of patients. These 100%ers are actually quite different in terms of how much the new allocation system, which is not so new anymore, has helped them. We did a study published in 2019, Schinstock et al. in Clinical Transplantation, which really looked deeply at this because I think what happened was with the new kidney allocation system, most groups stopped doing desensitization because they thought that we had a solution to this problem. In fact, when you really look at what's happened to these patients who are 99.5% and above, you will see that there really has not been a transformative change in their access to organs. This is particularly true for the patients who were included in this study. The FDA felt strongly that we should look at the most disadvantaged patients.
These are the patients who are 99.9% or above. As mentioned earlier, this is about 3,000-3,500 patients. On average, these patients will receive one organ offer every 10 years, so 0.1 offers per year. Really, for these patients, the likelihood of getting a transplant is ridiculously low. If we drop down in each of the categories below that, down to 99.5%, you do see that the transplant rate increases a bit. If you look at that whole group, the waitlist mortality at five years is 50%, and that has not changed. In fact, anybody with a CPRA of greater than 98% has had no improvement in waitlist mortality. Half the patients are dead at five years. The other sad thing is we used to transplant a lot of these patients with living donor transplants, and we do not do that anymore.
Only 1.4% of the patients who are 99.5% or above got living donor transplants, the best quality transplants. In conclusion, what I would tell you is really things have really not changed for this group of patients. That is what's so exciting about this opportunity because we have the first drug that has been approved for getting these patients transplanted. You can see that when you receive this drug, there's close to 100% chance that you're going to get a transplant. That is a dramatic difference.
That's very helpful. I think we've kind of painted the picture of the many positive impacts of kidney transplantation and the very limited options there are for highly sensitized patients and how long they do remain on the waitlist waiting for a transplant. Maybe we can now turn to the results that have been presented today. I'd like to ask each of you in turn what your key takeaways are as a transplant surgeon and clinician working in the field of kidney transplantation, what your key sort of takeaways are from these data. Perhaps I could start with you, Dr. Cooper.
Yeah, thanks, Richard. Dr. Montgomery outlined the problem extremely well. Like I said, having the privilege of working together at Johns Hopkins at the turn of the century, trying to care for these patients with the non-approved, and I think that's the right word, non-approved desensitization techniques that were available at that time, it was a very, very difficult road to travel with the patients. That's an important piece. We as clinicians want to do everything we can to provide patients the opportunity when they come to us. Desensitization with interventions such as pheresis and plasmapheresis and IVIg were very challenging and required significant follow-up and an appreciation that there was a high risk of complications, including antibody-mediated rejection. Certainly, as mentioned, that was the only option, and we felt necessary to provide patients with that option.
The results of this current study now allow me to say that there is a much better option for these very complicated patients that, while still requires very close follow-up of these patients, and we can't ignore the fact that these individuals have a breadth of antibody that demands close follow-up after the successful procedure, at the same time also gives us a much clearer pathway into the operating room and immediately thereafter. When I first look at the data, as mentioned, these are a group of patients that before the numbers of transplants would have been close to zero. As our data demonstrates, the patients that were randomized to this arm of the trial, in fact, did receive a transplant. Number one, that's hope.
Number two, we have now one-year data that demonstrates not only are patients being transplanted, but the outcomes of those transplants are consistent with others who have received a deceased donor organ and with an eGFR that is comparable. We are not substituting poor outcomes for just the ability to transplant. We are not only transplanting, but we are seeing patients receive the benefit of that organ. While these are "early data," one-year outcomes, there is, I think, significant data and significant publications that would say utilizing that one-year eGFR is predictive of at least medium-term outcomes. I see this data as incredibly positive. It is something that, again, I am very excited when individuals who come into my clinic, oftentimes having one, two, maybe three transplants, let's recognize that one of the highest levels of sensitization is women with pregnancies.
When I see those individuals come to my clinic, and before I would panic, like, "Now let's see what their CPRA comes back," and I may have to have a totally different conversation with them about their opportunities. I do not feel I have to think that way anymore. I have something that regardless of what that antibody level comes back, I am able to give them, I think, hope for which perhaps they have never felt in the past and may have been to other centers where they have given them that message. I am encouraged by the fact that people are transplanted. I am encouraged by the outcomes at one year, certainly a very, I think, a safety profile, which is non-conserving to me. Like I say, this is an option which I never had before.
Again, I'll reiterate, this is an incredibly exciting intervention that in my 25 years, I've never seen anything like this.
Okay, thank you. Perhaps turning to Dr. Montgomery, could I also ask for your reflections on the results that have been presented?
Sure. As mentioned earlier, both Dr. Cooper and I got involved in trying to care for these really desperate patients who I've just shown you their outcomes are, without being desensitized and transplanted, are worse than most types of cancer. We showed in a paper that was published in the New England Journal of Medicine that just using plasmapheresis and low-dose IVIg, desensitizing the patients that we could and transplanting them, the difference was an 80% survival at eight years versus a 30% survival if they waited on the list. Most of them, 84%, never got a transplant. We did what we could, and we transplanted about 700 incompatible patients during that period of time, 15 years or so. We saw their lives transformed. The techniques we were using were not approved. In many cases, we struggled to get them paid for.
That did not stop people from all over the country coming and trying to get some shot at a bit of hope. This is an incredible step forward to have a drug that I think, based on these data that were shown today, has a significant likelihood of being FDA-approved for this indication. It is going to be transformative. There is no question about it. I think we will be able to rapidly get those patients that have been sitting for a long time and just clear the patients who are 99.9% from this sort of hellish existence that they have had to live. Very excited about this, very excited about the future with this drug.
I wonder if I could just ask you a follow-up question, Dr. Montgomery. We saw the eGFR at 12 months in patients who received imlifidase. That was 51.5 mL per minute. I wonder if I could just ask you to expand on taking what we see at 12 months, how we see that in terms of longer-term benefits. I wonder if you could just kind of reflect on that and expand on that a little.
Sure. So I think the FDA for a long time really did not accept any surrogate endpoints in clinical trials and transplantation. That really held our field back. There is such convincing data now that endpoints like eGFR, like the iBox, are extremely good at predicting the long-term function. eGFR now is the endpoint that is used in the majority of transplant trials of different new drugs. You might say, "Okay, well, this is a very unusual group of patients whose immune systems are highly primed to be responsive to other people's tissue.
Is it relevant in these patients, or are they going to have a different trajectory after a year? I think the proof that that's not the case, that these patients, that eGFR is going to be just as predictive as any other group, comes from our five-year study of the patients who were treated in the phase 2a trial that we completed quite a few years ago. We were the highest enrollers in that trial. I, of course, continue to see those patients now. There really wasn't a drop-off in graft survival and patient survival after a year in that group. I think you can take this to the bank that what we're seeing in this trial is going to be predictive of the long-term outcomes in these patients.
Okay, thanks very much. Maybe I can turn back to you, Dr. Cooper, and just perhaps begin to think about how you see this treatment being used in clinical practice. Could you perhaps expand on that, how you see it being used and which patients might be eligible for treatment with imlifidase?
Yeah, thank you, Richard. I began to hint at that when I've talked about patients that come into our clinic. Certainly, the inclusion criteria for our trial makes it clear that patients 99.9% CPRA are the individuals that, as Dr. Montgomery said, would benefit the most and sadly have been underrepresented in the transplant populations. The way I think it could be used, should be used, and has the opportunity to be used is that there are other individuals, certainly with perhaps not that degree of sensitization, that could also benefit from this drug. Putting a couple of other numbers together, as mentioned, death on the waitlist is a real thing. It's unfortunately numbers that we don't follow.
We are always excited about the numbers of people waiting for transplant, the numbers of folks that are transplanted, but we often forget the number of people who die waiting for that transplant. The fact of the matter is many patients, including especially highly sensitized patients, often can't wait five years for "a perfect organ" or a compatible deceased donor organ to be available for them. Even with lower levels of sensitization, there are patients at programs that may not ever get a second offer. There has been a lot of data particularly published out of Columbia that shows patients who have an offer refused for them that maybe they never get the chance for that second offer. I think there's a lot of additional patients with lower levels of sensitization that could benefit from this intervention as well.
Now, I think what is important, and to add on to Dr. Montgomery's conversation about long-term outcomes, there does need to be a higher level of concern, a closer follow-up with these patients. Certainly, the one-year data is encouraging, but that does demand the efforts to ensure that we are still following these patients greater than 365 days for instances such as antibody production changes in GFR. We do have, I think, additional molecular techniques that allow us to follow these patients closer. We do have, I think, the expectation that we may need to biopsy these patients more often to identify things earlier than maybe we might have been in the past for non-sensitized patients. I think overall, there's going to be a greater confidence in addressing sensitized patients in transplant programs around the country who, let's be honest, were very uncomfortable approaching these patients at all.
There were individuals who, like I said, remained on waiting lists just expecting for that one-in-a-million organ offer to come that we know never did. Now I think transplant centers will have the ability to really provide access for these patients regardless of their experience in desensitization, that patients, regardless of what they call their zip code, now have access to transplantation. I think that's very important. We often want to say that patients should go to a center that has all this experience. While I don't disagree that there are centers of excellence, Dr. Montgomery's is one of those, there are some patients that just can't travel to New York City or to Wisconsin to be able to receive their transplant.
This is really an opportunity to provide access for patients that have been, perhaps, their unappreciated lack of ability to receive these types of interventions has gone unnoticed. We are really opening up transplant for populations that really, I think, deserve equal access to therapies like this.
Thank you. That's very helpful. I think turning back to Dr. Montgomery, perhaps it's a related question, but good to hear your thoughts on this. I mean, obviously, we need to go through an approval process for imlifidase, but if it is approved, how do you think it is going to impact the care of highly sensitized kidney transplant patients?
I think it's going to be a game changer. I think the important thing to point out is that we had really good results with plasmapheresis and low-dose IVIg. The problem was it is a totally inefficient way to remove antibody because it only removed antibody from the intravascular space, the IgG. You had to know when the transplant was going to occur because you had to start the treatments in advance of the transplant. Oftentimes, those treatments would need to occur over a period of a week or two weeks. We could only reach the patients that had low enough levels of antibody that this very inefficient way of removing it was capable of getting them to a safe level at the time of transplant.
Imlifidase gets rid of all the antibody in the body within two to four hours. There's nothing that we have had that is anywhere near that. It works across the interstitium, across the vascular space. You don't have to remove it from, like we did with plasmapheresis, remove the antibody from the intravascular space, wait two days for it to re-equilibrate, and then remove a little more. In terms of its ability to get rid of antibody, it is incredible. Now that opens it up to anyone, right? We can get an organ offer for somebody on the deceased donor list, bring them in, give them the drug, and transplant them. That's exactly what we did in this trial. I think it's going to completely change our approach.
I agree with Dr. Cooper that it is going to be something that will really help change some of those numbers that I mentioned earlier. Those numbers are not just about the 99.9%ers. They are really about anybody over 99.5% in terms of their survival rate waiting and so on. I think that we have to do what is right for the patients to save their lives. I think you are going to see this drug really changing the whole landscape in this field.
Okay, thank you. Maybe in the last minute or two, just before we then turn this over to some questions from our audience, perhaps I can ask Dr. Cooper to reflect on that. Maybe you can just, in a minute or two, just kind of tell us how this is going to change your conversations with patients waiting for a transplant.
A minute or two. Important. Again, I'll say that this has allowed me to approach really every patient that I think now who walks into the clinic a little bit differently. As I said, you can't help but be concerned when an individual who has a complicated comorbid history, particularly those, as we're seeing now with the success of kidney transplant, second, third, fourth transplant, multiple pregnancies, you can't help but worry about their access to deceased donor transplantation with the statistics as they are. Now I think we're able to really look at every patient truly as someone who has equal access to a life-sustaining or life-improving organ, as we talked about. Quality of life can't be undervalued in all this. The one thing we didn't and can't spend a lot of time about, there's also opportunities for living donation here too.
I mean, there's individuals who come in with a living donor with which they may be sensitized. In the past, it's almost difficult to imagine. We would say, despite how difficult it was to identify a living donor, you may have to go out and find someone else. Again, some of these highest quality organs now, with the use of imlifidase, they could proceed to transplant. It really shines a light on many more opportunities for patients when they come in. I think I'm able to more positively give people confidence that we have options available for them and not pretend, particularly with the highly sensitized, that they're going to have a very, very difficult time of receiving an organ transplant. It's just, again, a different conversation. Expect to be a very difficult conversation with people when they come.
Okay, thank you. You managed to do that in two minutes. I appreciate it. I think we'll move from a very, very insightful discussion. I'm going to hand it over to Tara, who's going to moderate the Q&A from our audience.
Great. Thank you so much, Richard. At this time, we will be taking questions with our speakers. Please hold for a brief moment while we pull for questions. Our first question comes from Farzin Haque at Jefferies. Please go ahead, Farzin.
Thank you for taking my question. The doctors, both of you mentioned PLEX and IVIg, but curious on your thoughts on where imlifidase fits relative to, say, anti-FcRn agents, CD38 like daratumumab, and other complement inhibitors that could come up as alternatives.
First of all, most of what the drugs that you mentioned are not, they do not reduce soluble antibody, which is what the problem is in patients who are highly sensitized. They are drugs that target plasma cells, which make those antibodies and also can reduce the B cell compartment so that those are not replenished as readily. Those drugs, I think, are going to be important in this story because once we have an approved drug that gets rid of the soluble antibody, that is what puts the organ in jeopardy when you do a transplant, we can start to use those other drugs to prevent any rebound of antibody afterward. I think that is what you are going to see happening over the next few years. All the drugs that we have been using have been off-label. A lot of them are drugs that are used for hematologic malignancies.
Having a drug that's approved, I think, will make some additional trials enabled because the FDA in the past has been really hesitant to combine drugs at all, particularly unapproved drugs in clinical trials. I think you will see clinical trials using some of those drugs that you mentioned that target plasma cells and B cells along with imlifidase to reduce the likelihood of rebound, which occurs somewhere around 40% of the patients will get a significant rebound. This is only going to get better as time goes on. I think the use of imlifidase will only improve. Plasmapheresis and IVIg, as I mentioned earlier, are so inefficient at getting the job done, I think that that's going to disappear.
Any setting that you could think of where you would use that for HLA antibodies or ABO isohemagglutinins, you're going to use imlifidase instead.
Makes sense. One more question. eGFR data is certainly very compelling, but what are your views on the potential impact of the open-label design, heterogeneous control arm for the FDA approval process? Are there risks to it?
I mean, we would have liked to have not seen a control arm, quite honestly. I was involved in the advisory boards and also spoke to the FDA as an expert about this. For these 99.9% patients, I do not think there is a control group that you could really imagine where you would do a transplant without first being able to reduce the antibody burden. The risk of having a bad outcome would just be too great. The FDA felt very strongly about this, and we came up, I think, with the best possible control group.
I think you see the results that for the vast majority of those patients in the control group, there were only three where the team decided to move forward by probably doing a couple of plasmapheresis treatments or whatever their local antibody reduction method was, or they just got lucky with the organ offer, and there happened to be only low-level antibody. I think the data, the fact that this trial was able to be accomplished with a control group, is an extraordinary thing because most people did not feel that there could be a control group for this group of patients.
Just to add, I completely agree. I had the fortune to have three patients that were enrolled in the trial, one of which was at the control arm, and you had a very difficult decision in front of you, knowing, as Dr.
Montgomery described our past history of what was successful but was very, very difficult, very, very challenging, and immunosuppressive in and of itself. There was a number of patients who we had challenges even getting into the operating room. Finding even a control arm is really spectacular, but many of us felt it was unsafe to move forward with the way that the trial was designed. I think what your question asks is, as we've sort of said throughout, that there are patients well below the 99.9% that could benefit from this trial. Not every sensitized patient is going to need this. Certainly, there will be, based upon the genetic frequencies and unavoidable antigens, opportunities for people, but there is a significant number beyond those 32 that receive the drug in this phase three trial that will certainly benefit in a more open-label opportunity for enrollees.
Thank you so much. Super helpful.
I think one thing that people do not realize is that people become sensitized to common antigens. Common antigens are common in the population. In these highly sensitized patients, they are competing with each other for the same rare genotypes because their sensitization is very similar. That is why when you are highly sensitized, it is so unlikely to receive a transplant because these rare genotypes that do become available that could match highly sensitized patients, they are kind of good for everybody. Maybe one person benefits from that.
Great. Thank you.
Great. Thanks for the questions, Farzin. Our next question comes from Tom Smith at Leerink Partners. Please go ahead, Tom.
Hey, guys. Good morning. Thanks for taking our questions and for putting together this really comprehensive event. For both doctors, Montgomery and Cooper, I was just wondering if you could expand on some of your comments regarding the non-approved alternatives here, PLEX and IVIg, and maybe talk a little bit about how often you're using these in clinical practice today and how effective they are in terms of desensitizing patients and actually getting patients to transplant.
I could start, Bob. That's okay. Again, we're actually using it, pheresis and IVIg, that is very rarely at this point, to be frank. The reality and the truth is that the data has shown, yes, to be desensitized and transplanted is better than remaining on dialysis, as I said, apples and oranges. The long-term outcomes have not been as positive as we would have wished or have thought. Quite honestly, I'll be frank saying that I've followed this molecule, I've followed this company for many, many, many years.
Knowing where we were going, where this clinical trial, early phase data, and now this phase three trial was going, I quite frankly have felt more comfortable saying, "I would like to see this drug approved and give patients who are currently highly sensitized on my list the opportunity to receive imlifidase with the data that was demonstrated at the beginning of this presentation." We are using very little of it. Occasionally, with a highly sensitized patient and a living donor with which they are sensitized, we may use a combined paired exchange model and desensitization, knowing, again, that that perhaps is the only way in which they will be transplanted as well. From a deceased donor standpoint, recognize much of which the success of Dr. Montgomery and his program was with living donors and the ability to have multiple sessions. Pheresis IVIg, pheresis IVIg.
We do not have that benefit of time with deceased donor offer. We get a phone call, maybe we have 24 hours before the organ is procured from a deceased donor, it arrives in our operating room, and we are able to perform the procedure. Twenty-four hours is not a lot of time, and it certainly is not how we have been able to demonstrate success in a living donor population. We are doing very, very, very little of it. Oftentimes, it is in combination with a paired kidney exchange and living donor.
Yeah. I mean, I think just as Dr. Cooper said, this worked, plasmapheresis, low-dose IVIg worked well in the right hands and groups that really devoted a huge amount of resources and had great experience. It worked well, but only for living donor, only for patients who had a living donor.
That's only 20% of the transplants in the U.S. every year. That was the big limiter. I have to say, we even stopped doing that for the most part because the thing was that we were very reliant on patients either being self-referred or other doctors referring to us from other parts of the country because these patients are spread out all over all the transplant centers. Once the new kidney allocation system came in, everybody thought we had solved the problem. It was one of the biggest really misunderstandings. We stopped getting patients referred. Yet, they just sat on everybody else's list, believing it's sort of like traveling in the past week.
What I went through two days ago, getting on a plane and then taking us back off the plane and sitting for 17 hours in an airport, that's what these patients do every day of their lives. They get false hope. Sometimes they were told there's an offer, and they come in. I really opined on their life during that 17 hours I was waiting for an airplane. Imagine that being all you do all day, every day. It's a really terrible existence.
Understood. That's super helpful context. Appreciate the insights. If I could just ask a follow-up on, so we think about perhaps that 3,500-patient waiting list for transplant, those patients who are highly sensitized, greater than 99.9% CPRA. Maybe you just help us think through the potential uptake and how imlifidase might be used initially, meaning if approved, how many patients do you expect could get an organ transplant in the subsequent 12 to 24 months because we have this therapy available?
I think it's going to be adopted very rapidly. I think it doesn't require the infrastructure investment that plasmapheresis and IVIg required. I think that people will do this pretty quickly, and patients can get transplanted in their own area, and they don't have to travel. We had a large number of centers that were enrolled in this trial, so they all have experience now. They are going to be probably the first group to just very rapidly start using it and get these patients transplanted. I think it'll be fast.
Certainly. One thing I want to add and give credit to, what it does require is a close working relationship with your HLA lab director. These individuals, in many ways, are unsung heroes of transplant programs in general. In this trial, for sure, it required a close collaboration, the ability to delist unacceptable antigens, as we talked about, to get patients even offers to begin with. It required a collaboration with, again, immediate return once drug was administered to ensure a negative cross-match and then post-transplant to be able to get data. Having that, and that was certainly an encouraging, I think, component of this intervention was to ensure that the HLA lab directors were appreciative of their role and all that. That certainly is going to be something that's necessary for transplants to happen is to have that relationship with HLA.
I think there are probably a lot of patients out there who never get listed who are highly sensitized because people just say it's for you to get listed. So it's probably more than the 3,500 that are who will suddenly have an option.
Super helpful. Thanks for the insights, and thanks for taking our questions.
Thank you for the questions, Tom. Our next question comes from Matthew Phipps at William Blair. Please go ahead.
All right. Thanks for hosting this, and thanks to the doctors for their time and perspectives. Dr. Montgomery, you mentioned, obviously, the FDA wanted to look at 99.9% CPRA, 99.5%. You essentially round up anyways, but also 98% even having very low transplant success rates. I guess, what is a cutoff where imlifidase could really help in your practice? Do you expect maybe your P&T committee or payers to set their own restrictions on CPRA cutoffs? For maybe both docs, obviously, in 2014, with the allocation system, tried to prioritize these highly sensitized patients, giving them more points in the scoring system. Is there something that needs to change in that pointing system with the introduction of imlifidase since you can kind of delist some of that sensitization? Thanks so much.
I mean, I think, first of all, the patients do need to get offers, right? As things stand right now, if you start to delist their unacceptable antigens, you do make it more likely for them to get an offer. The problem is that if we were going to make a change in the system, I think that you would want to not make it less likely for somebody if you delist their unacceptables to a level where they lose that point advantage, then they actually end up not benefiting as much as they could. I mean, I almost think that with this drug, we'll have to see what happens, but that you still would want these patients to see all of the kidneys that are coming available at a national level, right? Because, again, they're searching for that rare genotype.
It's very unlikely they're going to get it locally. I think just wherever you draw the line, giving these patients access to all the organs that they could get a match with is going to be important in addition to having this drug available and not penalizing them if they fall below those advantaged areas. I think we're going to have to rethink the whole allocation system for highly sensitized patients to make it more friendly to being able to use this drug along with it.
Yeah. I agree with Dr. Montgomery. Matt, just to quickly answer, I think, two other questions you had there. I'm an unapologetic optimist, but I also am a realist when it comes to insurance companies. The data would show that it's cheaper to get someone transplanted than be on dialysis. That's always an important data point with which we bring to our P&T committee. With this early one-year data to demonstrate the success of that intervention, I think, is additional value add to the insurance payer. I think in terms of a P&T committee, what this is absolutely going to require is a physician champion, individuals like you see on the screen who are very committed, are able to show the return on the investment for these patients. As an academic transplant center, our job is to find answers for patients who come to us.
I do not at all believe that a P&T committee is going to demand that it only be used at a certain PRA. To your question, I think we have to be responsible in both looking at quality and looking at the financial decision-making around an institution. I do not see that as being a problem as long as there is a champion who is able to verbalize the value add to having this on a formulary.
Thank you for that. I know it's, can I ask one quick follow-up? I know it's a little off topic, but would you look to use imlifidase for the treatment of AMR? That's obviously a, they've generated data there, but it would be off-label. Just curious your thoughts. Thank you so much for my questions.
I mean, so many of the drugs that we use in transplantation are off-label. I think the limiter has always been whether you can get it paid for, right? I think that we would certainly try to help our patients in whatever way we can. If that means they develop an AMR to try to convince our pharmacy committee that it's a drug that will be very effective in treating that, I think we'll have success.
Great. Thank you.
Great. Thanks for the questions, Matt. Our final question comes from Doug Tsao at H.C. Wainwright. Please go ahead.
Hi. Thanks for taking the question. Just to sort of follow up on the point or the question earlier in terms of trying to interpret the data in the context of the placebo arm and how the agency might view that, I guess I have a couple of questions. One, is it fair to say your perspective would be that while there can be patients successfully transplanted using plasmapheresis, IVIg, etc., that is not necessarily a fair representation of sort of the clinical utility just because what imlifidase offers in terms of the speed of onset is so much greater, right, just given the availability of donors kind of often being a last-minute occurrence. That perhaps sort of understates the clinical utility.
The control arm maybe oversimplifies the or the results from the placebo arm or control arm oversimplifies the sort of medical reality that you're dealing with as transplant surgeons.
I'm going to have to drop off because we're after 10:00, but Matt can certainly answer that question well. So I'm going to say thank you and sign off.
Thank you for attending. Yep. Thank you, Bill. I think it's an incredibly insightful question. I'll say I refer back to the primary endpoint. The fact that patients were transplanted in that control arm was a very rare event, and then their outcomes were significantly worse than those that received the intervention with imlifidase. To me, again, demonstrates, as we said before, it was very, very difficult to even identify a potential comparator arm. The reality is that, as stated, it's not realistic, particularly now looking at the data, to say that those are equal options for a patient who is highly sensitized. I think regardless of how the trial was designed and the agency's expectation that we have a control arm, real-world evidence and real-world expectation, I go back to my apples and oranges. Just look at the data.
Very few people got transplanted on the control arm, and those that did get transplanted did poorly. It is not just about getting someone transplanted, Douglas. I think we have to say, how well did they do after the transplant? That is certainly the message that I think the team at Hansa is going to take to the agency, despite the fact that there is a need for a control arm. It, quite frankly, was trying to create something that is not a fair comparator.
I think as a follow-up, it was Dr. Montgomery who said he would have not had a control arm, but obviously, the agency had a different view. I don't know, Dr. Cooper, if you were part of the discussions or sort of heard what the agency's view in terms of wanting a control arm. I mean, obviously, we know randomized controlled studies is kind of the gold standard, but there's certainly exceptions when warranted. What was it that made them think that they would want a control arm, especially given the fact that they probably knew there'd be some heterogeneity?
Sorry, but I wasn't part of those discussions, Douglas, but as you mentioned, the gold standard is the gold standard. There were conversations about looking to use historical controls as the comparator, but I think the FDA, certainly with the importance of how this drug was brought to them and the value add to highly sensitized patients, this was thought, I think, not only to be the best way to study it, but also to provide the scientific community with, like we said, the gold label effort and the comparator was something that they expected.
I guess the final point I would just say is that it sounds like from your perspective, the sort of speed and reliability of treatment effect are sort of the real value adds that imlifidase offers, especially relative to some of the other alternative methods.
No question. The ability to be able to transplant someone within four to six hours is unheard of in this patient population in the past and unable to be achieved in previous non-approved desensitization methods. Again, the success and the reliability of antibody reduction, the ability to get someone through the transplant without evidence of hyperacute rejection. Now we have the data that shows that the follow-up at one year is, as I say, comparable to a non-sensitized cohort. All outstanding pieces along the continuum of care that we provide.
I know we're in stoppage time, but if I can introduce a quick one, a real quick. When we think about the alternative methods of desensitization, you sort of mentioned ours with imlifidase, right, which we know from the data. Typically, how long previously would it take if you were to use IVIg or plasmapheresis? What's that time course that you're looking for to potentially prepare a patient for transplant?
I think it depends upon the level of sensitization. We would often do dilutions to be able to determine the number of pheresis sessions that were necessary. In the living donor scenarios, as we described earlier, we would often demand sometimes three to five plasmapheresis sessions done on an every-other-day basis with IVIg, allowing for the reequilibration and the binding of antibody for the pheresis to be successful. Then, again, at the case donor population, the case donor offer, you'd have the ability to do perhaps one pheresis with the IVIg and maybe add an additional complement antibody, which, again, is demonstrated in multiple clinical trials and found to be unsuccessful. We go from needing sometimes a week of therapy to be able to move forward with transplant to only having 24 hours. It really isn't going to happen.
Plasmapheresis and IVIg.
Doug. I'm sorry. Doug.
Or is it Day?
Doug. Sorry.
Doug. I think we're going to have to kind of actually finish here. I'm sorry because we're actually way over the time. I know that Dr. Cooper also has other things he needs to kind of attend to. I think we're going to have to finish here. Thank you very much to everyone who's listened into the webinar. Thank you so much, obviously, to Dr. Cooper, Dr. Montgomery. I think that your perspectives have been incredibly insightful, really, really helpful. I just want to thank you very much for taking the time.
Yes. Pleasure. Really thrilled for this opportunity, really excited for the future of Hansa and amyloid phase.
Great. Thank you very much.