Okay, welcome everybody. I'm Douglas Tsao, Senior Analyst at H.C. Wainwright & Co. We are thrilled to have Hansa Biopharma with us, represented by the company's new CEO, Renée Aguiar-Lucander. You know, these fireside chats are only 20 minutes, so we have a lot of ground to cover. Renée, maybe as a starting point, just provide a quick overview of the company and your sort of core technology and what you're trying to accomplish.
Sure. So, Hansa Biopharma has a novel and proprietary platform for enzymes that basically are focused on IgG cleaving. The company really has been a pioneer in this area and is today really a global leader. There is a commercial activity ongoing in Europe, so the product is approved for use in desensitization for highly sensitized patients for kidney transplants. We're also looking at desensitization in the area of gene therapy. There's also other kinds of enzymes coming off of the platform. We're looking at autoimmune, kind of like monophasic IgG-mediated autoimmune diseases as well. The company now has two Phase 3 trials that are due to read out shortly between now and the end of the year. One is a randomized study in the U.S., again of highly sensitized patients in terms of kidney transplant.
One is an ultra-rare autoimmune disease called anti-GBM, which is fundamentally a nephrology-oriented kind of rare disease.
Renée, I think it'd be helpful to orient you for the audience just in terms of IgG reductions. Can you just provide some perspective on how rapid as well as how deep they are, just given we hear a lot about IgG with various degraders or as well as the FCRS?
Yes. This enzyme called imlifidase, there's maybe a 15-minute infusion and within two to four hours, you will basically have reduced IgG below 5%. This is a very, very rapid and effective kind of IgG cleaving. It cleaves the actual IgG in two places and completely, very, very quickly and rapidly. That also means that you can actually stay in these levels for around a week. It's in nobody's interest to keep IgG levels suppressed longer term at those levels. Those obviously come with the risks. This is really focused on rapid and effective IgG cleaving.
As you noted, we are now nearing the Phase 3 data for the U.S. kidney transplant study. Maybe just share some perspectives in terms of your expectations and the company's expectations in terms of that data, as well as what that might mean for the commercialization in the U.S. and how that commercial launch might differ from what the experience has been in Europe.
Sure. Obviously, this is a Phase 3 trial that's randomized. It's 64 patients, 32 patients would be randomized to the active arm, which basically means that they will be given imlifidase. There is an organ allocated and those patients will be transplanted. The control arm, and this is actually something that the agency spent a lot of time on, it was very difficult to come up with how do you define something where actually today those patients have virtually no other alternatives and really remain on dialysis for a very long time. Because of their very high levels of antibodies, finding a matching organ is a real, real, real difficulty, a real challenge. The control arm is basically just defined as standard of care or the practice of medicine. In that case, you can be on the waiting list as a highly sensitized patient.
The probability of getting an organ is very low. In that kind of control arm, it's really kind of whatever the physicians might be able to come up with as a solution. As we know, the vast majority of these patients unfortunately stay on dialysis for a very, very extended period of time.
It's been conditionally approved in Europe for a number of years, and you've made a lot of progress as a company in terms of commercialization. What is the reason or what gives us some optimism that the U.S. launch might be a little faster than the uptake that we've seen in Europe, which is a bit of a distant star?
Absolutely. I think this is a huge difference actually, because obviously in Europe, this was really something where the company ran a kind of small Phase 2 trial. There were two centers really kind of participating in that trial. In contrast, what we have in the U.S., apart from it being a very kind of controlled and randomized trial, there are about 24 centers in the U.S. that are participating in this trial. You are going to have a much, much higher kind of level of comfort, experience, etc., across the U.S. These centers represent almost a little bit over 20% of all transplants that are done today in the U.S. Some of these centers are obviously very high volume, very important centers in the transplant community.
I think we have some really, really outstanding key opinion leaders, primary investigators, participants in this trial, which obviously today will have a lot of experience and expertise in terms of how to carry this out and seeing the actual outcomes from the clinical trial. I think that is a very big difference from in Europe, where you had a very small data set, very few centers, and a lot of uncertainty actually to how this would work. In Europe, since the approval, you have had a lot of patients being treated in real life. There is also a lot of real-life experience in Europe. That is being shared as well at conferences, at meetings, etc. We know that this drug works. It has been used in Europe now in many patients. I think that also kind of helps.
There is a real-world experience, which is kind of rare that in the U.S. you have Phase 3, but you actually know how that works in real life. I think that really kind of helps as well. I also think that in terms of everything that has been learned in Europe, including working on the guidelines, really having the clinics being ready to do this procedure, all of these things are learnings that we have now we can take and apply in the U.S. I think we also have a team in the U.S. finally that is very experienced. This team really kind of has been there, done that before. I think also from that perspective, it is slightly different from Europe. There are many, many different aspects as to why we feel very confident about the fact that the U.S.
launch is going to look very different from the way that the European launch did.
When we think about the, you know, one of the things that has affected the European launch is the organ availability, right, and allocation in those rules. I think this has been something that a lot of investors have struggled with, just sort of understanding the rules around allocation. I'm just curious, from your perspective, do you think the rules in the U.S. are appropriate in terms of prioritization of patients and allocating organs to facilitate or take advantage of that greater awareness?
I think the answer to that is yes. The reason is also that in Europe, if you think about it, you may not, you don't even have organ allocation systems on a national basis. You can actually have them on a local basis. The amount of variability and differences and variations that you actually have to deal with in Europe with all of these countries, if you actually even go down on local levels, is actually very challenging. It's not like you have a rule in Europe for organ allocation. In the U.S., you have a central organ allocation system that, you know, at least you know kind of what the rules are, how to operate it, and what to do with it. I think in Europe, this has caused an additional kind of complication.
Also, in some parts of Europe, you have a group of countries that will collaborate around kind of the whole organ allocation. It can become quite confusing as to how to kind of deal with that. I also think that there are some, you know, in certain kind of European countries, you've had a very kind of conservative approach. There's been some, you know, there's been some issues several years ago with transplants, et cetera. That's kind of spread throughout the entire system. Again, you have very varied kind of approaches to how these different countries will kind of look at organ allocation.
As I noted at the beginning, you joined the company about four months ago. I'm just curious about changes you might have made or expect to make in terms of the European commercial operation. When do you think we might start to see the fruits of any sort of commercial changes?
Yeah, so one of the most important things actually that I did is I brought on board, you know, a highly experienced person, Maria Törnsén, who actually then both is President US, but who also has a very extensive experience from running commercial franchises in Europe, particularly in rare diseases. I think that experience and expertise, we've had about two months or so that we've been able to kind of look at the European operation, look at how it's organized, how it's measured, what we can do. I think also when you come into kind of a new, you know, new kind of organization, you have an ability to really kind of, you know, turn over all the stones, look at things in a slightly different light.
I think we've identified, you know, quite a lot of things that we believe is going to be able to make a very significant difference to the way that the European commercial operation operates. We're going to probably start rolling that out now kind of in the next weeks or so. I think we will be, we'll be in a position that basically, you know, this should all have been kind of implemented and done by the end of the year. I would actually expect us to have a, you know, significant improvement in terms of kind of visibility, management, and kind of, you know, market kind of, yeah, market predictability with the caveat of the fact that, you know, we can't do anything about, you know, if there's no, if there's no local reimbursement, we can't fix that, you know, overnight.
If there's no, you know, if there's an organ allocation system issue, we can't fix that either. I think we can fix what we can control. We think that that's going to kind of enhance and improve certainly the European commercial operation starting next year.
As we noted at the top of the conversation, you have another Phase 3 study ongoing in anti-GBM disease. That is a sort of, I guess, almost ultra-orphan opportunity, just very rare. I'm just curious if you could help people understand how you see that opportunity, especially within the sort of landscape of other opportunities for which imlifidase could have clinical utility.
Sure. Obviously, this is a trial that was already kind of fully recruited and ongoing as I joined the company. You know, anti-GBM is, I mean, first of all, obviously, it's an ultra-rare disease, but there's really nothing approved. For these patients, this is a really devastating disease. A lot of these patients within six months, the majority of these will have no more functioning kind of kidney, will have no more kidney function and will be on dialysis. This really is a bit of almost like an IgG storm that gets triggered. It is a monophasic disease, but it's really very serious. I think the fact that we can help in these rare diseases to really kind of do something for patients who today really have nothing, there's nothing approved and nothing to do, I think that that is important.
This is also for us, obviously, also kind of in terms of call point, is mainly kind of a nephrology-oriented disease. The way I look at it is obviously, you know, we will have the kidney data Phase 3 readout first. The plan really is to file for approval on the kidney data. Basically, as we have that approved, we would then file an sBLA for next kind of product, which I also think from a commercial perspective allows us to kind of roll out the kidney, you know, get to know all of those kind of, you know, hospitals, nephrologists, et cetera. I think obviously give us the time to also really try and assess, are there kind of specialist centers? Do we need to kind of slightly expand kind of in order to kind of, you know, deal with anti-GBM?
Really the way I look at it is like a year later, we might have another product, very, very similar call point. I think that is really something where we need to just work with education because there's nothing been anything approved and how you find these patients in time because it's a very acute disease and you really need to treat them right away. You need to treat them very much exactly with this type of a profile of drug where you do something immediately and you really reduce down the IgG very rapidly.
That's obviously what we've seen in the Phase 2, you know, extremely kind of, you know, promising Phase 2 data where, you know, compared to kind of real-world evidence, kind of historical data, you would expect kind of patients to maybe 18% to 20% to have a functioning kidney whilst in the Phase 2, it's like 67% had a kind of functioning kidney at the time. We're very hopeful that we're going to be able to do that. That's how I look at the opportunity.
Renée, that study enrolled much faster than I think the company expected. I think you noted that a lot of that enrollment took place in Europe, just given the fact that they are more aggressively screening for anti-GBM disease than in the U.S. Does that mean that perhaps Europe is a better market in the early going for that indication?
I think that it's kind of in that way, it's kind of called an easier market potentially because you do have the anti-GBM as part of a standard panel. You do have an opportunity. You don't have to go look for it specifically. It is kind of part of just a different way of diagnosing. I do think that at the end of the day, this is also something where patients with this disease, I think we just need to educate the market and educate the patient or patient organizations to become aware of the fact that this is actually very, very simple to find. I think that's really more where we need to kind of spend our time.
You sort of noted that you intend to get approval, file the BLA in kidney transplant, file an sBLA in the U.S. What's the regulatory strategy in anti-GBM disease in Europe?
Yeah. In Europe, what we're really kind of the driving force really from a regulatory perspective in Europe is that we're going to, we're expecting the full data from the 50 patient kind of PAS study. The open study where actually the 50 patients have been transplanted across Europe is due to read out in the middle of 2026. There again, I mean, we're going to have to kind of deal with, look at this in terms of how do we deal with this in a kind of filing, having two filings going at the same time. I do think that we'll probably end up going for the full approval in Europe first of imlifidase rather than pushing that off and kind of doing the anti-GBM. I think that that's probably what we're going to have to do.
We'll also obviously engage with regulators at the time and see what their kind of advice to us is under the scenario.
One of the other sort of data sets that I think has gotten people's attention is Guillain-Barré syndrome. Maybe sort of frame, you know, sort of what, from your perspective, what some of the key takeaways in terms of the data, in terms of the outcomes and the efficacy that imlifidase generated. How does that fit into the broader strategy in terms of development of the portfolio?
Yeah. GBS again is kind of a monophasic IgG-driven, you know, IgG-mediated kind of autoimmune disease. There's really nothing approved today in GBS. This is a kind of, we'll say, more normal rare disease. It's not ultra rare. Obviously, it's a, in that way, it's a larger kind of patient population. We do know that a lot of these patients do say they have to be on mechanical ventilation. A lot of them still kind of have issues in terms of being mobile, not been walking, et cetera, after extended periods of time. I think in GBS, what we've shown in that kind of Phase 2 trial was obviously again a very, very significant difference versus kind of what you could expect with standard of care. This was run in Europe, and it was run with standard of care in terms of taking into account IVIG.
I think that in terms of the data that we saw, we actually just presented it at the ESOT, the European kind of organ transplant conference in the UK about a month ago, six weeks ago. I must say that the actual kind of KOL response was quite overwhelming. I think that also we're just in the middle of doing quite a lot of market research in a variety of different autoimmune diseases. As we talk to kind of KOL specifically about GBS, I think that that is something that they are very, very impressed by the data that they've seen. Obviously, because there's nothing approved, there is a significant medical need. It's also clear that they're very kind of focused on safety for this patient population.
We've had a really kind of positive feedback, both kind of in real world and interactions with KOLs, as well as in some of the market research that we've looked at. I think that this is a really kind of important and, you know, exciting kind of opportunity for the company. Since I've only been here for four months, there's only so much I can do in that period of time. Actually, one of the things that I have kind of done is, you know, we needed to just take a broader look at the kind of portfolio and also looking at the fact that we have HNSA-5487.
Really, we're in the kind of coming up towards the end of doing that assessment to be able to kind of come back to you with a clear answer as to where exactly do we, where does GBS fit in, how exactly are we going to attack that, and how does that kind of plan look? I probably need another couple of weeks or so to get all the information and the data collected. I think it is a really exciting opportunity. Clearly, I think we need to find a way to take that forward and towards a pivotal trial.
Next month, when you report 3Q earnings.
That's a good target. Why not? Yes, let's try and commit to that.
When you also talked about your use of imlifidase for sort of preconditioning of gene therapy.
Yeah.
We did get some initial data from Sarepta Therapeutics. I think it was in the first three patients. We did see sort of reduction in AAV antibodies. There was some reduction in terms of the dystrophin production in patients. I'm just curious, you know, if you've had feedback from Sarepta Therapeutics in terms of the next steps there. Is that data or what was seen in those initial patients a proxy, do you think, for what might be seen with some of your other gene therapy partnerships with other manufacturers?
Right. This is obviously the first time that we really kind of saw real kind of patient-related data in gene therapy. I thought that was super exciting. I think what we actually, what we can kind of report out on is obviously that imlifidase did exactly what it was supposed to do. It actually did cleave and it did enable kind of the actual dosing of Elavidis. However, I will say that there was always kind of an assumption that this would be a little bit of a two-step kind of proof of concept because you always want to also look at this in terms of is there anything we can optimize, is there anything else we can look at. I think this is very much kind of a normal path of what we're expecting to do. In terms of this, I actually have spoken to Sarepta Therapeutics about this.
I think obviously this is not anything that, this is all the basis upon which we kind of started this trial and that nothing's really changed. I think they see this also as a very positive step forward. I think it's more a matter of kind of from Sarepta Therapeutics' perspective when they'll have the clarity on their own side to kind of move forward with anything else that they're really kind of engaged in. I think from that perspective, we were very encouraged by it. I will say that there is some more data coming out again with imlifidase use in a different vector, different tissue that's going to be presented in Europe in October. That will be much more kind of more data that we're going to be able to see from that partner. We're super excited about being able to kind of share that as well.
I don't think that, I think there will be variations and differences depending on the gene therapy that you're looking at. I think that this is something that we're now in a position where we're getting this data. We're going to get more and more data in more patients in the near term. I think that's really going to set the company up for a super exciting potential opportunity in gene therapy where again, this type of approach is exactly what you need to kind of do.
I guess it sounds like you would say not to overinterpret the results from those first three patients in terms of DMD, in terms of the protein expression, and that might be unique to that product or that indication even.
I think we need to kind of, you know, three patients is a fairly small N. I think we need to be cautious of kind of like overinterpreting that. I also think that we will get some more patients, as I said, kind of over the near term, and we'll see how that kind of develops. I think we're all encouraged by what we saw.
Maybe really quickly, because I think we're out of time, we'll go into stoppage time. You know, HNSA-5487, what you mentioned, maybe just provide some perspective on how that's different from imlifidase and how you're thinking about development with that asset.
Yeah. This has come, so this is an enzyme derived from a different host. This is actually not similar from that perspective, but has a very similar kind of efficacy safety profile that we've seen in terms of PKPD. It just seems to have an even stronger potency, better, higher duration, et cetera. It does have some benefits there for sure. It also has, it's less immunogenic, right, for that particular. It does lend itself to looking at it from a slightly different perspective. In the market research that we've been undertaking and still are undertaking, we've had actually quite a lot of interactions with a variety of KOLs in different indications.
One of the things that's coming back loud and clear, and if you actually look at this whole FCRN space and all of these things where it's a very different approach where you're actually trying to not reduce IgG, or you want to have a certain target level of keep it in a certain level, that I think is having an impact in terms of some of these opportunities out there. I think we are learning a lot in a shifting environment. Once we get all of that data back in, I think that we're going to have a pretty good idea of what is really the right approach and right indication to take this forward in. Clearly, one of the benefits with this compound is that it is less immunogenic.
It's just a matter of identifying really the sweet spot for where does it make most sense from both a patient and commercial opportunity.
Okay, great. With that, we will wrap it up. Thank you very much, Renée.
Thank you.