Thank you for the introduction, and thank you very much for your interest in Hansa Biopharma. Before I start, just the usual warning that my presentation today contains forward-looking statements, and as such, you should take appropriate caution. For those of you who are not familiar with Hansa Biopharma, we're a commercial-stage biotech company listed on Nasdaq in Stockholm, and we sit on top of this very versatile and flexible immunology platform that has allowed us to advance into three broad therapeutic areas: transplantation, autoimmune diseases, and gene therapy. In transplantation, we're currently in a commercial stage in Europe, and we're running a pivotal phase III trial in the U.S. In autoimmune diseases, we've generated very, very solid proof of concept in two diseases: anti-GBM and Guillain-Barré syndrome, and we're currently running a phase III in that space.
We're also getting our next-generation enzyme called Hansa 5487 ready for moving into patients, based off of very promising results in our first-in-man trial. Thirdly, we're also active in the gene therapy space, where our focus is on pre-existing and neutralizing antibodies against the AAV vectors commonly used across many gene therapy programs in development or on the market. Our platform consists of IgG cleaving enzymes. The most advanced is called imlifidase. This is what is on the market in Europe under the brand name Idefirix. We have the lead compound from our next-generation program called the NiceR program, and this is Hansa 5487, also now getting ready to move into patients after very promising results in the first-in-man trial, as I said. Both of these enzymes, and indeed all of our enzymes, share the characteristic that they target specifically IgG.
They do not cover other immunoglobulins, only IgG, and they cover all four subtypes of IgG. Unlike certain other therapeutics like IgG degraders and so on, they act by essentially decapitating the IgG molecule just below the so-called hinge section, as you see here, creating then a F(ab')2 and an Fc component, and thereby rendering the molecule inactive. That happens extremely fast and leads to a very, very solid reduction in IgG. Essentially, in a couple of hours from a 15-minute infusion, you see IgG levels drop below 5%, essentially down to non-detectable levels, and then they stay down there for approximately seven days or so before gradually bouncing back, and then within a month or so, you're back to normal.
This is very, very unique and highly differentiated from other approaches like IgG degraders, FcRn inhibitors , plasma exchange, and so on, where it takes at least a week or so to get down, and then the starting or what you get down to is something like 30%, 35%, 40% of the starting level. This is completely different. We're, as I said, currently active in three broad spaces: autoimmune diseases, gene therapy, and transplantation. If you only look at those programs that are the most advanced, it's really a very, very significant patient universe that we can target. This is just looking within the autoimmune disease space at anti-GBM and Guillain-Barré syndrome here, looking at up to 20,000 cases annually that are hospitalized and have a very high degree of unmet medical need.
In the gene therapy space, just looking at the programs that are currently at an advanced stage, namely those that are partnered with Sarepta in the DMD and limb-girdle space, as well as the one that's partnered with Généthon in Crigler-Najjar. Again, we're talking about north of 10,000 patients, and a significant proportion of those will have neutralizing antibodies above a certain titer level, making it impossible for them to actually benefit from typically life-saving gene therapies. In the transplant space, looking at highly sensitized patients that are having a very hard time getting access to compatible donor organs, we're also looking at just in the U.S. and Europe, certainly north of 10,000 patients, up to 20,000 patients, including then also not just kidney transplant patients, but other solid organ transplant patients like heart and lung transplants.
With a price point current in Europe of around $300,000 and expecting a significantly higher price point in the U.S., this is a very, very solid and significant commercial opportunity just looking at where we are right now. Of course, there is a very broad universe of additional indications that we can access with our platform. If we look across the IgG space, many, many diseases within autoimmune diseases certainly are IgG-driven. Even though IVIG is currently used in many of those, plasma exchange as well, and some other therapeutics, the problem is that they do not work very, very fast, and they do not get the pathogenic IgG autoantibodies down to a very low level very, very fast. There is a high degree of unmet medical need.
I just talked about the number of patients, but you can also look at the size of the IVIG market, and it's currently in the $20 billion range, and it is expected to grow to north of $40 billion by 2032. It is a very significant opportunity we're looking at here. These are the three broad therapeutic areas that were present then. I mentioned them before. In autoimmune diseases, there are more than 80 known autoimmune diseases. Many of these are IgG-driven, and many of them don't have any approved therapies on the market at this point in time, and even those that have, as I just said, have a high degree of unmet medical needs. Within gene therapy, there are hundreds of gene therapy programs in the clinic currently.
Many of these are using AAV vectors to get the healthy gene into the cells, but many patients, because they've been exposed to these AAVs before, have relatively high levels of neutralizing antibodies, and therefore there's a very significant opportunity for us here. Up to one in three people have too high titers, depending on the specific AAV vector and the specific gene therapy and the specific disease population. Within the transplant area, just looking at kidney transplants, kidney transplants are essentially standard of care for patients on dialysis. A significant proportion of those patients on the waitlist, because they have had a previous transplant or blood transfusion or multiple pregnancies, have had their immune system primed to such an extent that they're highly sensitized, and that makes it very difficult for them to access a compatible donor organ.
If you're extremely highly sensitized, you're more likely to die waiting than actually be transplanted. This is a snapshot of our pipeline, and as you can see, it's rich and pretty mature. The most advanced project is with our first-generation enzyme, imlifidase, at the top of this slide. As I've mentioned before, we're already on the market in Europe. We got approval based on four phase II trials with a total of 53 patients that were transplanted. In 100% of these patients, even though they're extremely highly sensitized, imlifidase was able to enable a kidney transplant with a non-compatible donor organ and with an outcome measured as graft survival at six months that is similar to what you see in the broader population, 94% graft survival. Really, really very encouraging.
We are currently running a post-approval efficacy study in 50 patients in Europe, very close to being fully enrolled, and we should have data from that trial in the relatively near term. This will then qualify us to get full permanent approval in Europe and potentially over time also a broader label. In the U.S., we are running, as I said initially, a pivotal phase III trial in 64 highly, highly sensitized patients. They have what is called a CPRA of 99.9%, meaning that 99.9% of available organs would not be a good fit. When they get a donor organ offer that is non-compatible, they have then been randomized to either desensitization using imlifidase or standard of care, which essentially is to wait, hoping against hope that another organ that is compatible will be offered within the 12-month period.
What we're measuring is eGFR at 12 months, and a patient will only have an eGFR measured, of course, if that patient is not on dialysis or has been transplanted. Even though it's only 64 patients, it's highly powered to show benefit in the imlifidase arm. This study will read out over summer, at the other end of summer this year. We're looking very much forward to that. In the autoimmune disease space, the most advanced project is in anti-GBM, a relatively rare disease. We're looking at maybe 1,500 patients or so in the U.S. and Europe, very, very serious. Two out of three patients using standard of care plasma exchange. There is loss of kidney function relatively quickly after the onset of the disease.
We have generated very strong proof of concept in a phase II trial with 15 patients where all of those patients that had not progressed to dialysis were able to be kept off of dialysis, and even some of those that had progressed to dialysis were able to be taken off of dialysis. Really, really encouraging results. We are now running a phase III in 50 patients. It is a controlled trial on top of standard of care plasma exchange versus standard of care. That study will also read out over summer, very similar timeline to the kidney transplant trial. Second in line in autoimmune diseases is Guillain-Barré syndrome, and I will talk about the results there, but we recently communicated very encouraging phase II trial results, and we are getting ready to take that into phase III.
There is an investigator-initiated trial in ANCA-associated vasculitis focusing on a subset of these patients, those with acute respiratory syndrome, very severe situation, and that's being run in a clinic in Germany in 10 patients, and we have, I think, one-third enrolled at this point in time. In the gene therapy space, I already said that the most advanced projects are in DMD, where imlifidase is in the clinic ahead of Elevidys, so Sarepta's DMD gene therapy, and we expect data from the first patients at some point this year. It's also in the clinic in Crigler-Najjar with Généthon. Again, the first patient has been enrolled, and we expect data from that first patient also later this year. That's going to be very exciting, kind of POC in these patients with high titers of neutralizing antibodies.
There is a third partnership, which is with Ask Bio and Pompe disease, and that's still at the preclinical stage. Our next-generation program called the NiceR program has its lead candidate also in the clinic. Very good results from the first-in-man study were communicated in the autumn of last year, and we're getting ready to move that into patient population, namely myasthenia gravis patients, and we expect to start that trial towards the end of the year. That's what we're working towards. We have a very exciting year ahead of us. 2025 really promises to be very data-rich with two phase III trial readouts and other programs moving forward and the first readout from patients in the gene therapy space. In autoimmune diseases, Guillain-Barré syndrome will publish the full results from the phase II study, and as I said, prepare for initiation of a phase III.
Anti-GBM will get the data over summer. The same is going to happen with imlifidase and kidney transplantation, similar timeline, as I said, and then we have the gene therapy programs with several readouts this year as well. Let me briefly talk about some results within autoimmune diseases. I think I mentioned already it's a very significant opportunity for us, and we've generated solid results so far. If we look at the Guillain-Barré syndrome results that we communicated from the phase II trial in the autumn of last year, actually was in December, so more like winter. Guillain-Barré syndrome obviously is a very, very serious disease impacting maybe north of 20,000 patients that are hospitalized in the U.S. and Europe on an annual basis, follows a viral infection, and quickly leads to an attack on the peripheral nervous system . Very serious standard of care is IVIG.
Even with IVIG, the mortality rate is up to 7%. A very significant proportion of the patients end up in respiratory support, 30%-40%, and unable to walk, and it takes a very long time to recover and get out of the hospital. There is a high degree of unmet medical need. What we saw in the phase II trial, which was a trial where we put imlifidase on top of IVIG standard of care, and then in a second step, we compared to a patient registry called the IGOS database. What we saw was that in the single arm, there was a very rapid overall improvement in functional status, including expedited muscle recovery. 37% of patients were able to walk independently at week one, very, very significant proportion, and two-thirds were able to walk independently at week eight.
63% of patients were able to run or had no functional disability, meaning that they had a GBS disability score of less than one at six months, and overall, imlifidase was seen as safe and well tolerated. Importantly, we also did this comparison to patients in the IGOS database that had received IVIG, and what we saw was really, really encouraging. Essentially, patients were able to walk independently six weeks earlier than if they had only received IVIG, and this is essentially really what you want to see. You want to see them improve on this very important functional parameter, and you want them out of the ICU. You want them out of the hospitals as quickly as possible.
That's very encouraging, and as I said, we're preparing now to commence a phase III trial, which is going to have a real control arm, of course, not a patient registry alone. Looking then at the first-in-man trial with our next generation, 5487, which is an enzyme that is less immunogenic than imlifidase, and therefore is being developed for repeat dosing scenarios. What we saw in this trial where we put it into 36 healthy volunteers was that the efficacy mirrored what we see with imlifidase, highly, highly efficacious, very, very well tolerated and safe, PK/PD as expected. Then what we did is we took samples from these patients at different time points where obviously the antidrug antibody levels and IgG levels were different.
We performed experiments with imlifidase to see if we could cleave through the ADAs, and that certainly was possible, month six, month 12, meaning that we really think this product can be redosed and can be targeted to be developed for, let's say, myasthenia gravis, where you have exacerbations and crises and so on with this kind of frequency. Very encouraging results with 5487. In gene therapy, I think I talked about the overall initial focus being pre-existing neutralizing antibodies. Of course, in a second or third step, there is also going to be neutralizing antibodies appearing after the first administration of the gene therapy. It looks like many gene therapies will have to be administered several times, but initially we are focused on pre-existing neutralizing antibodies, and we currently have three partnerships: Sarepta, Généthon, Asklepios. I mentioned this. We have not outlicensed imlifidase. We will book all sales.
In the case of Sarepta, then we're qualified for milestone payments up to $400 million, and we'll also get royalty payments on the sale of Elevidys when enabled by imlifidase. In the case of Généthon, it's more of a research collaboration in Crigler-Najjar, and importantly, we'll get data then from liver tissue, whereas in the Sarepta case, we'll get data from muscle tissue. That is very helpful as we develop imlifidase for broader application in the gene therapy space. Finally, there's the Asklepios collaboration, which currently is in the preclinical stage focused on Pompe disease.
Finally, transplantation, I think I already mentioned the overall unmet medical need, really ensuring access to lifesaving kidney transplant for these highly sensitized patients, and it's a very significant group of patients. We're looking at maybe 15% of the 170,000 patients on the waitlist in the U.S. and Europe that are highly sensitized. We got imlifidase conditionally approved back in 2020, and we have now generated also very positive long-term follow-up data in the patients transplanted as part of our phase II program, showing again that we mirror the slope of the curve in terms of graft survival that you see in the broader transplanted population. That is really very ensuring. We are currently then launching in Europe.
Typically, as you know, in Europe, it takes a number of years to get market access, pricing, reimbursement. We now have access to the majority of kidney transplant patients in Europe at a price point of around EUR 300,000 per patient. What we are seeing is that the key clinics in Europe are also getting ready to use, and they are using the product and with very good outcomes. We have Idefirix-specific protocols in place in 110 clinics in Europe now.
One-third of those have experience, meaning they've tried it in one patient. Typically, they're tried in one patient, wait 6 to 12 months, and then if they're comfortable, they'll try it in a second and so on. Repeat usage is really not in the patients, of course. It's at the clinic level, and we now have repeat usage in two-thirds of those that have had an initial experience, again, indicating a positive experience. In fact, what we've seen in the most advanced market in Europe, which is France, is that the outcome in the commercially transplanted patients is potentially even better, actually, than what we've seen in phase II. That's really very encouraging. Overall, 12 months, 2024 versus 2023, 83% product in-market growth, and we're comfortable that this growth rate is certainly going to stay there for the foreseeable future.
We're getting into more significant growth territory as more and more clinics get repeat usage and line up patients for transplantation. Really, what is kind of restricting growth in Europe is the flow of organs and making sure that the organ allocation systems are tweaked so that these patients have a real chance of accessing organs. The U.S. opportunity is significantly larger than in Europe, not so much in the volume, but in terms of the speed of access. Reimbursement is going to happen much, much faster, of course, than in Europe. You have pre-approval payer interaction, and we're getting ready for that. We also will be in a situation where, thanks to the phase III trial, we'll have north of 20 clinics with experience at the time of launch. That's a factor of 10 versus Europe, where we only had two.
They will actually not just have the experience, but also the protocols in place at the time of approval in the U.S. Finally, we expect a significantly higher price point in the U.S. because the cost of dialysis, which really is a benchmark, is significantly higher in the U.S. compared to Europe. We are looking forward with excitement here. This is the Mafia mugshots , and I think this is probably the last slide. I hope I have left you with an impression that we have this highly versatile, flexible, highly differentiated IgG lowering platform that we move forward really very significantly in three broad areas, and that looking ahead for this year, we are going to have some very, very important and exciting data readouts. With this, I think I am going to close and see if there are any questions.
In the Sarepta study, what do you hope to achieve? [Inaudible]
Essentially, Sarepta has been a situation where they've had to exclude patients with neutralizing antibodies above a certain titer level. What we hope to see is, of course, that we can knock down neutralizing antibodies, that the transduction actually happens, and that the outcome in terms of microdystrophin level impact is similar to what they've seen in the patients that have been included in their clinical trials, and in fact, also what they're seeing in commercially treated patients. It's over the first three months, essentially, do you see a similar slope of the curve there and impact on microdystrophin?
Henrik, do you have any other questions?
Yeah, what increase in the size of the population would that correspond to in the case you're successful?
Yes, in the case of Elevidys, what Sarepta has communicated is that in the U.S., it's approximately 20% or so that have too high titers of neutralizing antibodies. It is a very significant opportunity cost for them, of course, and it's terrible for those patients. They have been very good at broadening the label and so on. The uptake so far has been good, but in order to have sustained growth, it is important for them to access a broader range of patients. It may be that the number of—I am just speculating—but it may be that the number or proportion of patients with high titers is even higher in international markets. We will see. Is the objective to reach that 20%? The objective is to reach as many of those 20%. Is that what you think that you can achieve?
Given the profile of our enzyme and what we've seen, right, also in non-human primate models and different disease models where the transduction has worked, yes, we do expect to be able to enable the vast majority of those 20%. I mean, you never know, there might be a few, but yeah.
In the anti-GBM, your competitor is targeting not only IgG, but also IgM. Can you elaborate on how that can impact the profile in terms of speed and durability of the treatment? [Audio Distortion/ Inaudible]
In anti-GBM, I mean, it's really very much driven by IgG, right? I mean, we see the outcomes here, right? I mean, on the key parameters of functionality in GBS patients.
Putting both, you don't really think that you can really add too much of an impact on the outcome? [Inaudible]
No.
Can you talk a little bit more about your opportunity for myasthenia gravis? Speaking about 5487, maybe the clinical trial design from the anti-GBM perspective has been as you're kind of trying to think about? [Inaudible]
Yeah. Obviously, there's been a lot of new products coming into the MG space, right, recently. I mean, none of these are approved for the acute phases, right? It's more maintenance therapy and so on. We think that there is a real opportunity for us to get into that market and target the acute situations when the disease is diagnosed upfront, so induction therapy, and then when you have these exacerbations and crises and so on. That's thousands and thousands of cases on an annual basis.
What we expect to do in our phase Ib trial is to select a subset of these patients, probably not the most severe end because you want to be able to access them and still have them on whatever standard of care, and then see if we can demonstrate efficacy in these patients. Obviously, there's going to be a dose-finding element in this study as well. Can you talk a little bit more about the implication of antidrug antibodies as it relates to kind of the redosing of 5487, maybe what you publicly disclose, I suppose? Yeah, even though 5487 is significantly less immunogenic than imlifidase, there is an antidrug antibody reaction, right, as expected. The question is, how much lower is that than imlifidase? In this, we've seen it's very, very clearly significantly lower in order of magnitude.
What happens over time is that, of course, ADAs decrease. What we've demonstrated is that at different time points that would correspond pretty well with when you need to redose, we can actually have activity and cleave through the ADAs and cleave IgG and have efficacy. Wonderful. For myasthenia gravis, that phase Ib trial, what do you expect to be the timeline of updates? We will have regulatory interaction this first half, and I expect us to be able to give an update on the other side of that. This is where we're heading and so on. The aim is to be ready to initiate this trial in the second half of this year. Wonderful. Any other questions? We have looked at it. It's not one of the most prioritized indications at this point in time.
We've identified NMO and MOGAD and some others.
Maybe to that point, what do you think about the frequency of dosing as you're thinking about different indications?
I mean, it really depends on, again, the frequency of the exacerbations, flares, crises, and so on. Typically, they happen from 6 to 12 months, from maybe 18 months, right? There might be 12 months before they have the next, right? This is what we want to be able to target and have an impact on initially.
As we looked at the phase I healthy volunteer data and you looked at the IgG reduction, what was kind of that curve as you're thinking about timing?
Yeah,
so recovery. Currently, it was you saw ADAs going down and you saw us having with 5487 efficacy at 6 months, 12 months, and so on.
That's what we wanted to be able to do. We're not developing 5487 for maintenance therapy, right? We certainly might be going into that space, but likely not with 5487 because you don't want IgG down to that level for a sustained period of time.
Any other questions? Okay, with that, thank you so much for your time.
Thanks, Stacey. Thank you.