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

Good day, and welcome to the Hansa Biopharma Autoimmune Deep Dive Guillain-Barré Syndrome Conference Call. [Operator Instructions] Please note this event is being recorded. I would now like to turn the conference over to Hitto Kaufmann, Chief R&D Officer. Please go ahead.

Thank you. Good morning and good afternoon, everyone. My name is Hitto Kaufmann. I'm the Head of R&D at Hansa Biopharma, and Hansa Biopharma is welcoming you and thanking you for dialing in to our virtual event, Autoimmune Deep Dive Guillain-Barré syndrome today. I'll have the pleasure of guiding you through this about 1 hour of presentation and question and answers. And at the very beginning, I'd like to introduce you to the 3 exciting speakers we have lined up for today's webcast. First of all, Dr. David Cornblath. He's a Professor Emeritus for neurology at the Johns Hopkins University. He is also joined by Dr. Simon Rinaldi from the University of Oxford. And then last but not least, from the Hansa Biopharma team, Elisabeth Sonesson, who is speaking on behalf of our therapeutic area, autoimmunity. Let me quickly give you an overview of today's agenda. We will start with a brief introduction to Hansa Biopharma and our core technology. And I will then hand over to David Cornblath to give the audience background on Guillain-Barré syndrome before Dr. Simon Rinaldi will talk about the results of the 15-HMedIdeS-09 single-arm study we recently conducted in this therapeutic area. Elisabeth Sonesson will then take it one step further and show the results of our indirect analysis to IGOS real-world comparator group. After that, we will have some time for Q&A. Some of the questions have already been submitted by many of you, and this is a great opportunity to thank you for these submissions. So what you see on the next slide is the strategic focus of Hansa Biopharma based on these first-in-class IgG cleaving enzymes. We have developed them and are developing in 2 key areas. One is to use these enzymes to enable therapies such as enabling a transplantation of kidneys for the highly sensitized kidney patient population. And at the same time, we are developing the same principle to enable therapeutic application of systemic AAV gene therapies in those patients who can currently cannot get access to them because high levels of anti-AAV antibodies. Further than that, and in focus for today's discussion, we have conducted a number of clinical studies in rare autoimmune diseases with an acute onset and IgGs being the driver of the pathology such as anti-GBM and GBS. Beyond our lead drug, imlifidase, we have also conducted initial studies with a new low immunogenic version of an IgG cleaving enzyme called HNSA-5487. And to recap a little bit how far we have gone with this therapeutic principle, I'd like to summarize that imlifidase as Idefirix is conditionally approved in Europe for desensitization in kidney transplantation. We have so far a safety database, including more than 200 patients. And we have to be able to supply this commercially scaled manufacturing fully established. We have a number of catalysts in 2025 that we are looking forward to, including the Phase III readout of our ConfIdeS study in the U.S. to aim for application and approval of this treatment for kidney transplant patients in the U.S. We have another Phase III route coming up for anti-GBM, and we expect first data in the space of gene therapy in our collaboration with Sarepta and Genethon. On the next slide, you see a brief summary of the technology and the benefit that we hope to convey using IgG cleaving enzymes as intravenously applied drugs. These enzymes can rapidly deplete IgG across all 4 subclasses of IgG very specifically and very efficaciously. And as you can see on the right side of the slide, it's a simple, specific 2-step cleavage mechanism that disassembles IgGs across the bloodstream, but also in the extravascular space just below the hinge region of the antibody. We have also established the same principle for 5487, which is the next-generation IgG cleaving enzyme. So within hours, we can remove pathogenic IgGs and can reduce them to less than 5% reliably. On the next slide, you see how we have translated this technology into an attractive pipeline. What you can see here the ongoing late-stage studies for kidney transplantation, including our post-approval efficacy trial in Europe. But you also see that we are approaching a real exciting readout in our first clinical studies in collaboration with Genethon and Sarepta to prove, hopefully, that we can desensitize these patients and enable AAV-based therapies. What we are focusing on today is the role that IgG cleaving enzymes such as imlifidase can play in diseases such as the autoimmune rare condition anti-GBM and the focus of today, the autoimmune disease Guillain-Barré syndrome. With this, I would like to hand over to the first speaker, Dr. David Cornblath, to give us some background on Guillain-Barré syndrome. Thank you.

Hitto, thank you, and good morning, good afternoon, everyone. I'll be speaking about Guillain-Barré syndrome. If I could go to the next slide. And then the next slide, please. In this slide, what I've tried to do is summarize a large body of work on Guillain-Barré syndrome that's taken place, particularly over the last 20 or 30 years when the last update in therapy was made in 1990. Essentially, like many neuro autoimmune disorders, GBS is an autoantibody-mediated neuropathy in which complement fixing, IgG1/3 subclass antiganglioside antibodies are induced through the mechanism of molecular mimicry. This usually follows an infection. In particular, this is well known for campylobacter jejuni, but follows many other infections and infections precede about 2/3 of patients with GBS. These antibodies are then directed against epitopes on peripheral nerves. And depending on the specificity of the antibody, this will determine the clinical spectrum of the disorder. This results in geographic variability depending upon the population and the preceding event. But in essence, all GBS worldwide follows this relatively simple straightforward plan. So GBS, in essence, is caused by these autoantibodies, which are contained in the IgG fraction of blood and then affected at the tissue level by complement. There are 2 current therapies: plasma exchange, which everyone knows, works by removing IgG and complement, although on a relatively slow 2-week basis; and IgG, which works -- IVIg, which works for multiple mechanisms, including interfering with autoantibodies and reducing complement. Next slide, please. What we now have come to realize is that the acute phase of Guillain-Barré syndrome is quite short, probably about 2 weeks where all the activity takes place that is the nerve fiber injury that leads to paralysis. As mentioned before, this follows an infection and the development of autoantibodies so that there are now based on previous work, multiple mechanisms to target. If I could have the next slide, please. Let me provide background on the unmet medical need. This slide is from a natural history study done by Professor Richard Hughes in 1988 in Southeast England. And the point I'd like to make is that in those days, if there were 100 patients with GBS, 13 died or 13% was the mortality. As you see in the box, 21% were left bed bound, unable to walk or unable to work. And if you look now in the 2000s, what we've done substantially is reduce the mortality mainly. It's now down to 3% to 7%, depending on which part of the world you're in. But again, 15% to somewhere up to 20% of patients experience long-term impairments and reduced mobility, and that's the unmet medical need that remains over the last 40 years. Next slide, please. So there are now, however, opportunities for advancement in treating. As I mentioned, treatment hasn't changed. And now we know that we can use targeted immunotherapies based on evolving knowledge. This evolving knowledge is parallel, as I mentioned, to multiple neurologic autoimmune disorders where we can now give drugs that will target the pathogenic mechanism at early stages. We'd like it to be given within 2 weeks. We'd like it to have a rapid administration and onset of action. And because GBS is GBS everywhere in the world, we think the clinical benefit would be across the entire spectrum of disease. Obviously, patients would like all the targeted treatments to have minimal side effects. On the next slide, which is borrowed from Professor Hugh Willison in Scotland, is a simpler way of looking at this. GBS pathogenesis starts with, as I said a preceding infection. There's B cell activation leading to plasma cell activation, leading to autoantibody production, complement activation and tissue injury. And we now know that we can specifically target at multiple ways. We could deplete B cells, seems rather a large ask; we could deplete plasma cells, again, with lots of side effects; or we could move more directly to antibody removal or destruction by imlifidase or the anti-FcRns around; or we could inhibit complement at any one of a number of sites. Next, please. What I'd like to do is set the stage for what Elisabeth is going to talk to, and that's the comparative study using the International GBS Outcome Study or what we all call IGOS. This is a large prospective cohort study run by Professor Bart Jacobs in Rotterdam, where over a number of years, 2,000 patients in over 160 hospitals with the entire spectrum of GBS were collected prospectively and followed as shown in the right panel for 3 years. On the next slide, this is the data that's currently available within the IGOS database. There's extensive clinical database, including the demography, antecedent events, neurologic examinations and patient reported outcome measures. There's treatment and clinical response known. We know about diagnostic investigations, in particular, neurophysiology. And we have an expanding number of biomarkers that are being integrated into this database, including the BIC5 infections, the glycolipid antibody arrays characterized by Professor Wilson in Glasgow. We have nerve biomarkers such as NfL, and we're working on proteomics and GWAS data. On the next slide, please. This is how we can use the IGOS database. If a company does a Phase II or III trial and wishes to compare themselves to Western controls, we can take the large IGOS database shown on the far right and from it, take out individual data points that match those seen in the Phase II or Phase III trial. There are then 2 ways statistically to make comparison. One, which you'll hear about today is the matching-adjusted indirect comparison or MAIC method; and the other, which you've heard about before from Annexon is so-called propensity matching. Both of these are well-established techniques in which a company can make a go/no-go decision about moving forward. And with that, I'd like to turn it over to Dr. Rinaldi.

Thank you, David. Hello, everybody. I'm Simon Rinaldi. I'm an Associate Professor of Neurology and Honorary consultant neurologist in Oxford. And I was one of the PIs on the study that I'm going to present an overview of today, which is the pivotal Phase II study of imlifidase in patients with Guillain-Barré syndrome. Next slide, please. So this was an open label and fairly simply designed multicenter trial, which took place in the U.K., France and the Netherlands. Patients were screened, and we were looking to include patients with severe GBS defined as being unable to walk 10 meters without assistance. And actually, as we'll see on the next slide, patients who were, in many cases, more severely affected than this. They needed to be diagnosed with GBS according to standard criteria and within 10 days from the onset of weakness to have early disease. Following screening, they were given on day 1, a standard infusion of imlifidase and then standard of care treatment with intravenous immunoglobulin was started on days 3 to 7, and that was a standard dose of 2 grams per kilogram of IVIg over 5 days. And then outcome measures were assessed, including disability measures, the GBS disability scale, which we've heard -- briefly mentioned before. Their strength was measured over time and also the requirement for mechanical ventilation or intensive care treatment was recorded. Next slide. So if we look at the included patients, we know that 3 were excluded, but of the remaining 27, they had fairly typical features of GBS, a median age of 60, slightly more males than females. And as I said before, they were severely to extremely severely disabled. So the majority were bedridden or chairbound, unable to stand, unable to walk even with assistance at disease onset. The MRC sum score measures their strength across 6 pairs of muscles with maximum score of 60. And you can see they had a significant reduction in strength at disease entry as is typical for GBS with a median MRC sum score of 42 and a mean of 39. As per the inclusion criteria, this is early in the disease process that the patients were included, so 4.5 days on average from the start of onset of weakness. And you can see that they also had in 44% of cases, cranial nerve involvement, so weakness of facial muscles, eye movements swallowing and so on. Next slide, please. So this slide shows that imlifidase did what it should do under these circumstances in that the levels of IgG were very rapidly reduced. So you can see pre-dose, if we normalize to 100%, IgG levels were normal, and they fell very rapidly to almost undetectable by day 2, remain suppressed at day 3. IVIg is then started as a standard of care. And of course, the primary ingredient in IVIg is exogenous immunoglobulin IgG. So the IgG levels then returned essentially to normal by day 4 and became super normal on day 5 in keeping with the treatment with IVIg. So in summary, the imlifidase rapidly reduced total IgG, including removing pathogenic IgG related to the disease process. IgG levels were then restored by the standard of care intravenous immunoglobulin, which, of course, shouldn't contain disease causing pathogenic autoantibodies. Next slide, please. More importantly, of course, is looking at what happened to the patients following the imlifidase and then standard of care treatment. And this graph on the bottom left shows the first 7 days following treatment in terms of what happened to their strength as measured by the MRC sum score. And the takeaway here really is that even by day 1, there was an observed increase in strength, which continued to improve across the course of the first week. And you can see by the end of week 1, patients had regained about 10.7 points on their MRC sum score, which is just over halfway back to normal from where they were on average in terms of the weakness following the onset of GBS. And you can see then there's a steady further increase to week 26 following that initial rapid increase in strength across the course of the follow-up period. If we then, on the next slide, look at what happened to disability in terms of the GBS disability scale, you can see week by week, there's a steady improvement in the number of patients, the proportion of patients who are improving by 1, 2 or 3 grades in terms of the GBS disability. But I think, again, the important takeaway here really is just how many patients improved quickly in terms of the disability. So in week 1, over half of the patients have improved by at least 1 grade, 30% had improved by 2 grades and even a small proportion has improved by 3 grades. And you can see as we step through the weeks, proportionately more and more increase with greater magnitude of improvement on average as time goes on. So really a fast improvement in functional status here as early as week 1, over 50% improving, and that improvement then continues and increases as time goes on. Next slide, please. We can also look at this data in a slightly different way, and that's looking at patients who are returning to minimal levels of disability. So able to walk with a GBS disability scale of 2 or less or able to run with a GBS disability scale of less than 1. So you can see, again, in week 1, almost 40% of patients regained the ability to walk after imlifidase and standard of care treatment. And by week 26, it's around 85% of patients who are able to walk independently. And indeed, 10%, 15% in week 1 are actually able to run with minimal levels of disability, rising to 60% by week 26. So again, the takeaway here really is there's a fast return to independent walking and some patients really improving very rapidly indeed. And the mean time to return to independent walking was 16 days in this study. It only took 6 days on average for patients to prove at least 1 grade in their GBS disability scale. So again, evidence of rapid improvement in strength and disability across different measures as shown in the preceding data. If we go to the next slide, we'll just briefly summarize the safety outcome data, which was positive in many ways. There were no major side effects. There were a few treatment-emergent adverse events at the time of the trial medication in 25 out of the 30 participants, but none of these led to withdrawal or treatment discontinuation. There were no changes in vital signs or in terms of heart rate as measured by the ECG, and the complications were largely those that one would expect in GBS patients treated with standard of care in any case. So no major concerns in terms of the safety data either. If we move on to the final slide of my section, which is just a summary. What I've shown here, I hope, is clear that imlifidase produced a rapid fall in endogenous IgG levels as it should do. This was associated with a rapid improvement in strength and disability in the patients who were treated with this medication, and the infusion was well tolerated and appears safe in combination with the standard of care. So thank you for your attention. And I will now hand over to Elizabeth Sonesson, who's going to look at the IGOS comparison. Thank you.

Thank you, Simon, and thank you to both of you for your excellent presentations. So now we've just listened to the outcome of the single-arm trial with imlifidase followed by IVIg. And if we move to the next slide, please. To enable adequate decision-making at Hansa, we have performed a contextualization of the results from patients receiving imlifidase followed by standard of care versus data then from patients treated with only standard of care. And the method, as we heard before by Dr. Cornblath that we choose for this project was MAIC and that stands for matching adjusted indirect comparison, and it's a well-established statistical method for comparing 2 different data sets. Next slide, please. So Simon Rinaldi just presented the baseline characteristics for the patients that were included in the imlifidase plus IVIg trial. And in this slide, we also see the baseline characteristics for the patients in the IGOS cohort. So we can conclude that the cohorts were very similar on most parameters. However, one important prognostic factor differs significantly, and that is that the imlifidase IVIg cohort had a substantially larger proportion of patients with preceding diarrhea, and we know that this is an indicator of poor prognosis. You can also see a small difference with respect to initiation of treatment versus onset of symptoms. And additionally, the 1509 cohort was slightly worse when it comes to MRC sum score at baseline as compared to the IGOS cohort. Now these differences, they are all accounted for in the statistical method used for comparison, and I'll try to explain that in the next slide. So when applying the MAIC method, you use weighting, and this refers to an adjustment or a balancing of the data from either 2 different groups or studies in order to make them more comparable. And therefore, you account for the differences between the 2 groups. And by doing the weighting, you give more importance to certain individuals or certain data points in the 2 groups to ensure that the comparison is done as fairly as possible. Now after the weighting is done, the outcomes of the 2 cohorts can be compared in a more accurate manner than by using a naive comparison. So in the current study, the weighting was done using the most important prognostic factors for outcome in GBS, and that includes days from onset of weakness to start of treatment, the age of the patients at baseline, the GBS disability score at baseline, whether there was cranial nerve involvement and what the MRC sum score was at baseline as well as preceding diarrhea. So looking at the baseline characteristics that I showed in the previous slide, all these differences will be adjusted for in the method. Additionally, sensitivity analyses were performed to assess the robustness of the results to changes in the covariate selection. Next slide, please. Now if we turn to look at the outcome from the MIC analysis, we can conclude that we see a statistically significant difference in all of the evaluated endpoints. And just to remind you, it took a median of 6 days to improve by 1 grade in GBS disability score in the 15-09 trial that you can see in the top orange bar. And this is 3 weeks earlier compared to what was observed in the IGOS cohort. And the median time to reach independent walking was 16 days in the trial, and this is 6 weeks sooner as compared to the IGOS cohort. And in the next slide, we will see the proportion of patients that were able to walk at week 1, week 2 and week 4 in the 2 cohorts. And in the orange bars, you can see the MAIC adjusted values from the 15-09 trial and the blue bars shows the IGOS cohort data. And what we can conclude is that it's a statistically significant larger proportion of the patients treated with imlifidase and IVIg that are able to walk at all 3 time points compared to the IGOS cohorts that received only IVIg. As you can see, the difference is most pronounced at 1 week. And over time, the difference between the cohorts become smaller, but it still remains statistically significant. And as you may remember from Professor Cornblath's presentation, the natural cause of GBS disease is that most patients do recover over time and that the treatment window is really in the first 2 weeks following onset of weakness. And the major benefit for patients treated with imlifidase and IVIg, if this data holds up then in a randomized controlled trial, that is that patients will improve much earlier, meaning that they can be discharged from the hospital and come back to normal life faster than with current standard of care. Next slide, please. So this slide concludes the presentation. And as we have heard, GBS is an acute autoimmune neuropathy. And there's really been no advancement in the treatment of patients with GBS in the last 30 to 40 years and the unmet medical need remains very high with currently no approved FDA -- or FDA-approved treatment, I'm sorry. So what we have shown is that imlifidase followed by IVIG results in rapid and sustained benefit in patients with severe GBS. The median time, to repeat again, to return to walking was 6 weeks sooner compared to the external cohort. And further, the median time to improvement by at least 1 grade on GBS disability score was 3 weeks sooner in patients treated with imlifidase followed by IVIG as compared to the IGOS IVIg group. And with that, I leave the floor back to you, Hitto, and questions from the audience. Thank you.

Thank you very much, Elisabeth. So far, we have covered 3 topics in our presentation, hoping that they were helpful to the audience, starting by getting a good understanding of the disease biology and the evolution of treatment in GBS. Then Dr. Simon Rinaldi summarized the data of our 15-HMedIdeS-09 Phase II trial, a single-arm trial in GBS. And then at the end, Elisabeth put these data into context of our comparison with the IGOS database with a quite some exciting outcomes as I hope we could have convinced you.

Now we have time to answer questions. And the way we would like to do this today is start with picking the most representative questions of all the questions you have all submitted to us. And thank you for these submissions because they helped us really in preparing this event today. So let me start with one question that we got in many variations, and that is, what is the current treatment paradigm for patients diagnosed with GBS? And I'd like to pass this question on to Dr. Cornblath to summarize the clinical practice for us.

Thank you. Currently, in North America and Europe, IVIg is used in about 80% of the cases with the rest getting either plasma exchange or a combination of IVIg and plasma exchange, in particular, in those who are severely impaired and do not improve with one course of treatment. However, in the rest of the world, both of these treatments are generally unavailable so that, in my view, a single injection drug that would be safe and efficacious would be a vast improvement in GBS care all over the world.

Thank you, David. The other answer that we -- other question, sorry, that we got was about the unmet need in GBS treatments today. Dr. Rinaldi, could you answer this question for us, please?

Yes, of course, Hitto. Yes, I mean, GBS occurs in 1 to 2 people per 100,000 each year. So that equates to around 150,000 cases of GBS annually worldwide. And David touched on, there is a standard of care, IVIg or plasma exchange. Actually, neither are FDA approved in the U.S. IVIg is the only approved therapy in the EU. But actually, even despite treatment, the issue is that patients typically continue to progress after treatment has been started and perhaps for several days and occasionally weeks more. And they don't rapidly recover by and large. They spend prolonged periods of time in hospital, in rehabilitation units, and slowly recovering. So really, even despite treatment, 20% have residual disability, 5% still die from their disease, and the vast majority have very prolonged hospital admissions and journeys through rehabilitation. So there's a really -- there's a need for a more efficacious and a more rapidly acting therapy in GBS to really improve this patient journey.

Thanks, Simon. Let's maybe switch to questions that are centered around the role that imlifidase or IgG cleaving enzymes in general could play as a therapeutic option in this disease. So one question that we got was, what role do you think imlifidase could play in the treatment of GBS? I would suggest, Simon, you start and then maybe hand over to David.

Sure. I mean I think -- as I touched on in my answer to the previous question, I think the fact that this rapidly reduces IgG levels and has a rapid effect is really a critical advantage over current therapies. I think the other thing is that it gets into the tissues and cleaves IgG at the site of tissue injury within the nerves. And so it's essentially cutting this disease off of the knees in the very early stages. And so therefore, I think this is a rapid induction therapy that will be used as early as possible in GBS and potentially arrest the disease process very effectively and provides big advantages over the current standard of care in that regard.

Thanks, Simon. I would add that to me, this is a very impressive Phase II study and builds on this idea that I mentioned of targeted immunotherapies, which will be coming rapidly in all of neuroimmunology and will rapidly become the future in GBS as well. What's also impressive here is the comparison to geographic similar group from Europe and North America, where the age, geographic location and severity is similar and very strongly, in my view, suggests that imlifidase could become the standard of care with or without IVIg. To build on what Simon mentioned about the results of improvement quicker is that these result in enormous potential health care costs, that is people getting out of the ICU, getting out of the acute care hospital, getting out of rehab and getting home much sooner mean immense savings for the system.

Thank you, Simon. Thank you, David. Highly appreciate it. Let's move on to the questions that are more forward-looking for this development program that we are currently conducting. So one question we got is, in your opinion, what are clinically meaningful endpoints in a Phase III trial in GBS for potential treatment option? So may I suggest, David, that you continue answering this question and then pass on to Simon.

Yes. So I think the clinically meaningful endpoints for those that have been used here, that is time to improve 1 grade, time to independent walking. But if one looks and thinks about GBS as a slowly improving disorder, what one would hope is that regardless of the primary endpoint chosen, it's that all the endpoints, the primary and the secondary would all be going in the same direction and compared to a comparator group or placebo or standard of care control would improve quicker.

Simon, anything you'd like to add?

Yes. I mean I agree with that. I mean the GBS disability scale has been a standard when things like meta-analysis have been done in the past. And each of those points on the GBS disability scale is clinically significantly different than an improvement. So I think that would be a mainstay. I think this idea of -- we need to bring in this idea of the benefit of rapid improvement as well. It's not just where people end up, how they've got there, the journey taken 2 years down the line, if patients have recovered walking, there's no difference. But actually, if one recovered walking at 1 week and one took 6 months, that's a big difference that you need to capture. So I think some idea of the journey, the area under the curve potentially for these measures is also important, not just the long-term final outcome here.

Great. Thank you both. Obviously, we got quite some questions on the treatment context -- on the data contextualization that we have conducted with our Phase II study and the IGOS database. And I would say the question that summarizes this best is, can you discuss the IGOS study and how the population in that study compares to Hansa studies? I initially would like to hand this over to Elisabeth.

Thank you, Hitto. Yes, as we heard, the IGOS study is the largest real-world database based Guillain-Barré syndrome data. And the study was performed over 12 years, and it included in total 2,000 patients across 5 continents. And so starting with these 2,000 patients in IGOS database, we excluded patients to use in the contract registration, we excluded patients that were missing substantial outcome data. We excluded patients that were treated with PLEX because we wanted to compare ourselves to IVIg. And then we applied relevant selection criteria that was essentially the inclusion/exclusion criteria of the 1509 trial, and that ended up then with 754 patients that were treated with IVIg and that were also closely matched with terms of the study population based on the most important inclusion criteria from the 1509 trial. And those criteria included stuff like patients should be above 18 years old, they should have a confirmed GBS diagnosis, they should have GBS disability score 3 or above, and they should have had the onset of weakness within 12 days prior to diagnosis. There was no geographical selection done to the cohort. And you could see during the presentation in the demographics table, the 2 cohorts were fairly similar in terms of disease severity and MRC sum score at baseline. And then the weighting procedure used in the prognostic factors, as I explained, resulted in 2 very balanced cohorts that were suitable for the comparison. And maybe, David, you want to add something to this?

I think the main thing to add, Elisabeth, is that this cohort started by Bart Jacobs, as I mentioned, essentially took everybody who had GBS who went to a study hospital. So the cohort includes pediatric patients. If someone wanted to compare it to young people, it includes people with mild GBS. And right now, I think if I get the number right, it's somewhere around 40 papers -- academic papers have been published from the GIOS cohort. There's an online site that people can look at to get further details. But it's a rich database that's getting richer all the time with the addition of these biomarkers.

Great. So that was great color to this topic here. I think now would be actually a very good time to switch over and open the lines for questions. Hopefully, our presentations and initial Q&A have given the audience a good background to ask further questions beyond that. I'd like to ask the operator to open up for questions, please.

[Operator Instructions] The first question today comes from Suzanne van Voorthuizen with Kempen.

This is Suzanne from VLK. I have one for HNSA. Can you put the imlifidase GBS program into context of the broader pipeline for the assets? How do you see the opportunity in this indication relative to other settings in terms of commercial potential, for example, compared to kidney transplantation and anti-GBM? And secondly, when should we be expecting to hear more about the potential Phase III plans and how they will crystallize?

Thank you, Suzanne. Thanks for this question. I'm happy to take this question. First of all, at this point, we're simply very excited about the data so far that in context of anti-GBM and GBS, we have now already 2 -- data for 2 acute IgG-driven indications that show that this rapid interaction, as was described to do is potentially very helpful to patients. Obviously, as a company strategy, we have to be very focused and very targeted and we are currently reviewing the best possible options, for example, for GBS. The great news is that the data provide us with options that should not, in any way, I would say, deter our focus on bringing the imlifidase to the market in kidney transplantation as planned. Everything around GBS is currently under review. And sometime soon, later this year, we will inform more about timelines for the next step, which obviously would be a Phase III study.

The next question comes from Douglas Tsao with H.C. Wainwright.

I was just curious if maybe you could help us understand the sort of how you're viewing the relative contribution of imlifidase in GBS relative to IVIg? And do you think it's possible that we could get comparable efficacy or meaningful efficacy with imlifidase alone?

Great. Thank you for that question. Maybe initially, I would hand that question over to Elisabeth and then also for Simon to make more comments in light of the data that we have today. Elizabeth?

Yes, thank you, Hitto. Yes, I will start. Well, the data we have presented today is obviously from patients treated with imlifidase followed by standard of care as this was the first pilot study in this patient population, and it was not considered ethically, what do you say, ethical to remove standard of care when you don't know anything about if your compound will work or not. With that said, maybe imlifidase would work on its own, and we have not studied that any further. But as you see, you also asked how imlifidase could compare to IVIg. And I think that as we have alluded to during this call is that imlifidase has this very fast onset of action. Within hours, you will see the effect by cleaning all the IgG, both, as Simon talked about, IgG already causing the injury to the nerves and in circulation. And that will happen very quickly, and it's very targeted as opposed to IVIg, where the onset is very slow and you often see patients still deteriorating while they're still being treated with IVIg. But I think that both Dr. Cornblath and Dr. Rinaldi are better to speak to that. So I hand over.

Yes. Simon here. If I make a couple of comments. I think that increase that we're seeing in strength and disability in the first week is very likely all due to the imlifidase. It's very unlikely that the IVIg started at day 3 there is contributing significantly to that. And of course, when we compare to IGOS and against IVIg alone treated patients is a much greater improvement. I think the key as to whether it could be a monotherapy is how long will that effect last and the effect of imlifidase outlast the duration of disease activity otherwise. As David said, actually, the majority of the nerve injury happens within probably 10 days to 2 weeks of onset of illness in GBS. So if we're starting a treatment 4 or 5 days and that lasts a week, that might well be enough to cover all of the periods you need to cover to turn off the disease activity as the immune system resets in the background. This is a monophysic disorder. The damage lasts for a certain period of time and it goes away. There's a bit of variability in that, though, of course, and some patients may have a disease activity that lasts a bit longer and is not completely covered by imlifidase. They may require a second treatment or may require a subsequent treatment with a different modality. But I would imagine for the majority, a single treatment with imlifidase probably will cover as long as is required to provide essential complete benefit from the disease, and you wouldn't have to give anything else after.

If I could just add one comment and that would just be a safety concern that is if your IgG -- if you're acutely ill with GBS and your IgG goes down to 0, you'd have to decide if you'd like to be in the hospital with no IgG. And so there may be a role for a more maintenance dose, that is a dose that would bring you up to a standard level, but not for safety, but not necessarily a super physiologic dose that we use in current treatment.

If I may just add one small comment to that. I think that we have talked a lot about the efficacy data and what we see in the trial. But I think also an important finding in this trial is that it is safe to treat GBS patients with standard of care IVIg following imlifidase. That's also a finding from the trial.

Very good point. I hope we gave a rich answer to your question. Thank you for the question.

The next question will come from Matt Phipps of William Blair.

This is Eric, on for Matt Phipps, William Blair. Just 2 questions. So first, you mentioned the importance of targeting that first 2 weeks, but also the potential of imlifidase across the rest of the disease. So I'm just curious how wide do you think the window for treatment might be with imlifidase? And do you think it could be used throughout the rest of the disease process outside of that initial 2-week window? And secondly, I was just wondering how often do patients have recurrent GBS? Or if they have an acute attack, how likely are they to have another one? And so do you think GBS would make sense as a potential development indication for HNSA-5487 given its redosing potential?

Great. Thanks, Eric, for this question. Let me tackle it. Let's first hand over to the clinicians, Simon and David, to answer your -- the first part of your question on, is there another phase of the disease where treatment with imlifidase could be helpful. And I will later comment on 5487. Simon, could you start?

Yes. So recurrent GBS is rare. Studies quote a recurrence rate of 5%. But in practice, it seems much less than that. So it's not usually a concern. And certainly, when it happens, it happens many years later, it's not an acute one. What you can see is what I call treatment-related fluctuations, i.e., a percentage of patients, maybe 10% to 15% will be treated with standard of care, they'll improve and then they will worsen again as that treatment wears off because it's a short duration within a few weeks. And those are the patients who have a slightly longer than 2-week disease activity so that the treatment doesn't quite cover the full length of their active disease and then they redeteriorate. But again, both of those are uncommon. And -- but there is, therefore, an indication in some patients for further rounds of treatment.

Great. David, anything you would like to add on this one?

No. Thank you.

Great. Yes. So the second part of the question also touched on 5487. And maybe let me use it in a few sentences to summarize where we are with 5487. First of all, it's -- again, it's an IgG cleaving enzyme. So far from everything we have done has very comparable efficacy, very comparable specificity and a lower immunogenicity. That's how we developed [ 5487 ]. In terms of stage of development, we have conducted a Phase I study in healthy volunteers so far to show that in this group of patients, it was safe and well tolerated and at the same time, did some experiments in serum samples from these patients to evaluate how well we can redose in light of another response that was very encouraging. We have not yet finalized our strategic thinking around the question of could HNSA-5487 play a role in a disease such as GBS. And obviously, as it was mentioned before, we are currently not assuming that GBS would require repeated treatments in close proximity to each other. At the same time, 5487 is an attractive option for Hansa across the board. So that includes autoimmune diseases, but also other antibody-related diseases in general. And we will, during the course of the year, update more on this as we go along.

There are no further audio questions. I'd like to turn the call back over to the company.

Thank you very much. So this leaves me with a couple of concluding remarks. First of all, I would really like to thank everyone who dialed in, who has provided questions before the call and also now online. That was really great to see so much interest in our webcast today. Secondly, I would really like to thank the 3 speakers today to give us more background on the clinical, I would say, characteristics of GBS, on the treatment paradigm currently and how it emerges in the future, hopefully and also thank you for presenting our clinical data in our GBS development program so far. Hopefully, we could convey why at Hansa, we are so excited about the data that we have in hand today. It is simply because after so many years of no change in standard of care in this really severe neuro-autoimmune disease, we can see data emerging that hopefully, at some point, can help the patients that really need improved treatment options. With this, I'd like to close today's call and today's webcast. And again, thanks, everyone, for dialing in.

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