Good day and welcome to the Hansa Biopharma Autoimmune Deep Dive Guillain-Barré Syndrome conference call. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on a touch-tone phone. To withdraw your question, please press star, then two. 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 one hour of presentation and questions and answers. At the very beginning, I'd like to introduce you to the three exciting speakers we have lined up for today's webcast. First of all, Dr. David Cornblath. He's a professor emeritus of neurology at Johns Hopkins University. He's also joined by Dr. Simon Rinaldi from the University of Oxford. Last but not least, from the Hansa Biopharma team, Elisabeth Sonesson will be 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. 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 15H-MetIDAS S09 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. 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 two 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. At the same time, we are developing the same principle to enable therapeutic application of systemic AAV gene therapies in those patients who currently cannot get access to them because of 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.
To read a little bit how far we have gone with this therapeutic principle, I'd like to summarize that Immifidase, as Idefirix, is conditionally approved in Europe for desensitization in kidney transplantation. We have so far a safety database including more than 200 patients. We have been 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 ConfideR 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 readout 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 four subclasses of IgG, very specifically and very efficaciously. As you can see on the right side of the slide, it's a simple, specific two-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 a next-generation IgG cleaving enzyme. 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. What you also see is 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.
Thank you. Good morning, good afternoon, everyone. I'll be speaking about Guillain-Barré Syndrome. If I could go to the next slide. 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. Infections precede about two-thirds of patients with GBS. These antibodies are then directed against epitopes on peripheral nerves. 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. In essence, all GBS worldwide follows this relatively simple, straightforward plan. 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 two current therapies: plasma exchange, which everyone knows works by removing IgG and complement, although on a relatively slow two-week basis, and IgG, which works—IVIG, which works through 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 two 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.
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. 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 bedbound, unable to walk, or unable to work. If you look now in the 2000s, what we've done substantially is reduce the mortality mainly. It's now down to 3%-7%, depending on which part of the world you're in. Again, 15%-20% of patients experience long-term impairments and reduced mobility.
That's the unmet medical need that remains over the last 40 years. Next slide, please. There are now, however, opportunities for advancement in treating. As I mentioned, treatment hasn't changed. 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 two weeks. We'd like it to have a rapid administration and onset of action. 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 a set of preceding infection. There is B-cell activation leading to plasma cell activation leading to autoantibody production, complement activation, and tissue injury. We now know that we can specifically target it multiple ways. We could deplete B-cells. Seems rather a large ask. We could deplete plasma cells, again, with lots of side effects. We could move more directly to antibody removal or destruction by Immifidase or the anti-FCRNs around. We could inhibit complement at any one of a number of sites. Next, please. What I would like to do is set the stage for what Elisabeth is going to talk to. That is 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 three 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 report outcome measures. There's treatment and clinical response known. We know about diagnostic investigations, in particular nerve physiology. And we have an expanding number of biomarkers that are being integrated into this database, including the big five infections, the glycolipid antibody arrays, characterized by Professor Willison 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 two ways statistically to make comparison. One, which you'll hear about today, is the matching-adjusted indirect comparison, or MAIC method. The other, which you've heard about before from the next slide, 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. 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. 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 Immifidase in patients with Guillain-Barré Syndrome. Next slide, please. This was an open-label, 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. Actually, as we'll see on the next slide, patients 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 one a standard infusion of Immifidase. Then standard of care treatment with intravenous immunoglobulin was started on days three to seven. That was a standard dose of 2 g per kg of IVIG over five days. Outcome measures were assessed, including disability measures, the GBS Disability Scale, which we've heard briefly mentioned before. Their strength was measured over time. Also, the requirement for mechanical ventilation or intensive care treatment was recorded. Next slide. If we look at the included patients, we know that three were excluded. Of the remaining 27, they had fairly typical features of GBS, a median age of 60, slightly more males than females. As I said before, they were severely to extremely severely disabled.
The majority were bedridden or chair-bound, unable to stand, unable to walk even with assistance at disease onset. The MRC sum score measures their strength across six pairs of muscles with a maximum score of 60. 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 was early in the disease process that the patients were included, so 4.5 days on average from the start of onset of weakness. 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.
This slide shows that Immifidase did what it should do under these circumstances in that the levels of IgG were very rapidly reduced. You can see pre-dose, if we normalize to 100%, the IgG levels were normal. They fell very rapidly to almost undetectable by day two, remained suppressed at day three. IV Ig is then started as a standard of care. Of course, the primary ingredient in IV Ig is exogenous immunoglobulin IgG. The IgG levels then returned essentially to normal by day four and became supernormal on day five, in keeping with the treatment with IV Ig. In summary, the Immifidase 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, should not contain disease-causing pathogenic autoantibodies. Next slide, please.
More importantly, of course, is looking at what happened to the patients following the Immifidase and then standard of care treatment. This graph on the bottom left shows the first seven days following treatment in terms of what happened to their strength as measured by the MRC sum score. The takeaway here really is that even by day one, there was an observed increase in strength, which continued to improve across the course of the first week. You can see by the end of week one, 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.
You can see then there is 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 is a steady improvement in the number of patients, the proportion of patients who are improving by one, two, or three grades in terms of their GBS disability. I think, again, the important takeaway here really is just how many patients improved quickly in terms of their disability. In week one, over half of the patients had improved by at least one grade. 30% had improved by two grades. Even a small proportion had improved by three grades.
You can see as we step through the weeks, proportionally more and more increase with greater magnitude of improvement on average as time goes on. Really a fast improvement in functional status here, as early as week one, over 50% improving. 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. That's looking at patients who are returning to minimal levels of disability, so able to walk with a GBS Disability Scale of two or less, or able to run with a GBS Disability Scale of less than one. You can see, again, in week one, almost 40% of patients regain the ability to walk after Immifidase and standard of care treatment. By week 26, it's around 85% of patients who are able to walk independently.
Indeed, 10%-15% in week one are actually able to run with minimal levels of disability, rising to 60% by week 26. The takeaway here really is there is a fast return to independent walking. In some patients, really improving very rapidly indeed. The mean time to return to independent walking was 16 days in this study. It only took six days on average for patients to improve at least one grade in their GBS Disability Scale. Again, evidence of rapid improvement in strength and disability across different measures, as shown in the preceding data. If we go on 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.
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. The complications were largely those that one would expect in GBS patients treated with standard of care in any case. 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 have 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. The infusion was well tolerated and appears safe in combination with the standard of care. Thank you for your attention.
I will now hand over to Elisabeth 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. Now we've just listened to the outcome of the single-arm trial with Immifidase, followed by IVIG. 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 Immifidase, followed by standard of care, versus data from patients treated with only standard of care. The method, as we heard before by Dr. Cornblath, that we chose for this project was MAIC. That stands for matching-adjusted indirect comparison. It is a well-established statistical method for comparing two different data sets. Next slide, please. Simon Rinaldi just presented baseline characteristics for the patients that were included in the Immifidase plus IVIG trial.
In this slide, we also see the baseline characteristics for the patients in the IGOS cohort. We can conclude that the cohorts were very similar on most parameters. However, one important prognostic factor differs significantly. That is that the Immifidase IVIG cohort had a substantially larger proportion of patients with preceding diarrhea. 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. Additionally, the 1509 cohort was slightly worse when it comes to MRC sum score at baseline as compared to the IGOS cohort. These differences, they are all accounted for in the statistical method used for comparison. I'll try to explain that in the next slide. When applying the MAIC method, you use weighting.
This refers to an adjustment or a balancing of the data from either two different groups or studies in order to make them more comparable. Therefore, you account for the differences between the two groups. By doing the weighting, you give more importance to certain individuals or certain data points in the two groups to ensure that the comparison is done as fairly as possible. Now, after the weighting is done, the outcomes of the two cohorts can be compared in a more accurate manner than by using a naive comparison. In the current study, the reweighting was done using the most important prognostic factors for outcome in GBS.
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. 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 MAIC analysis, we can conclude that we see a statistically significant difference in all of the evaluated endpoints. Just to remind you, it took a median of six days to improve by one grade in GBS disability score in the 1509 trial.
You can see that in the top orange bar. This is three weeks earlier compared to what was observed in the IGOS cohort. The median time to reach independent walking was 16 days in the trial. This is six weeks sooner as compared to the IGOS cohort. In the next slide, we will see the proportion of patients that were able to walk at week one, week two, and week four in the two cohorts. In the orange bars, you can see the MAIC adjusted values from the 1509 trial. The blue bars show the IGOS cohort data. What we can conclude is that it is a statistically significant larger proportion of the patients treated with Immifidase and IVIG that are able to walk at all three time points compared to the IGOS cohorts that received only IVIG.
As you can see, the difference is most pronounced at one week. Over time, the difference between the cohorts becomes smaller, but it still remains statistically significant. As you may remember from Professor Cornblath's presentation, the natural course of GBS disease is that most patients do recover over time and that the treatment window is really in the first two weeks following onset of weakness. The major benefits for patients treated with Immifidase and IVIG, if this data holds up in a randomized control trial, 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. This slide concludes the presentation. As we have heard, GBS is an acute autoimmune neuropathy.
There has really been no advancement in the treatment of patients with GBS in the last 30 to 40 years. The unmet medical need remains very high, with currently no FDA-approved treatment. I'm sorry. What we have shown is that Immifidase followed by IV Ig results in rapid and sustained benefit in patients with severe GBS. The median time, to repeat again, to return to walking was six weeks sooner compared to the external cohort. Further, the median time to improvement by at least one grade on the GBS Disability Scale was three weeks sooner in patients treated with Immifidase followed by IV Ig as compared to the IGOS IV Ig group. With that, I leave the floor back to you, Hitto. Questions from the audience. Thank you.
Thank you very much, Elisabeth. So far, we have covered three 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 15HMS IDAS09 phase II trial, a single-arm trial in GBS. At the end, Elisabeth put these data into context of our comparison with the IGOS database with quite some exciting outcomes, as I hope we could have convinced you. Now we have time to answer questions. 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. Thank you for these submissions because they helped us really in preparing this event today.
Let me start with one question that we got in many variations. That is, what is the current treatment paradigm for patients diagnosed with GBS? 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 questions 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. Thank you. Yeah, I mean, so GBS occurs in one to two people per 100,000 each year. That equates to around 150,000 cases of GBS annually worldwide. 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. 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. They do not rapidly recover, by and large. They spend prolonged periods of time in hospital, in rehabilitation units, slowly recovering. Really, even despite treatment, 20% have residual disability, 5% still die from their disease. The vast majority have very prolonged hospital admissions and journeys through rehabilitation.
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 Immifidase or IgG cleaving enzymes in general could play as a therapeutic option in this disease. One question that we got was, what role do you think Immifidase 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've 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 of 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. It is essentially cutting this disease off at the knees in the very early stages. Therefore, I think this is a rapid induction therapy that would be used as early as possible in GBS and potentially arrests 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 a geographically similar group from Europe and North America, where the age, geographic location, and severity is similar and very strongly, in my view, suggests that Immifidase 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 healthcare 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 appreciated. Let's move on to the questions that are more forward-looking for this development program that we are currently conducting. One question we got is, in your opinion, what are clinically meaningful endpoints in a phase III trial in GBS for potential treatment option? May I suggest, David, that you continue answering this question and then pass on to Simon?
Yes. I think the clinically meaningful endpoints are those that have been used here. That is, time to improve one grade, time to independent walking. 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 a placebo or a standard of care control would improve quicker.
Simon, anything you'd like to add?
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. Each of those points on the GBS Disability Scale is clinically significantly different than an improvement. 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, it's how they've got there, the journey taken. Two years down the line, if patients have recovered walking, there's no difference. Actually, if one recovered walking at one week and one took six months, that's a big difference that you need to capture. 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. Thank you both. Obviously, we got quite some questions on the treatment contextual and the data contextualization that we have conducted with our phase II study and the IGOS database. 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's studies? I’ll initially would like to hand this over to Elisabeth.
Thank you, Hitto. Yeah, as we've heard, the IGOS study is the largest real-world database based on Guillain-Barré syndrome data. The study was performed over 12 years, and it included in total 2,000 patients across five continents. Starting with these 2,000 patients in the IGOS database, we excluded patients to use in the context of the study. 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. We applied relevant selection criteria that was essentially the inclusion-exclusion criteria of the 1509 trial. 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.
Those criteria included stuff like patients should be above 18 years old. They should have a confirmed GBS diagnosis. They should have GBS Disability Scale score three or above. They should have had the onset of weakness within 12 days prior to diagnosis. There was no geographical selection done to the cohort. You could see during the presentation in the demographics table, the two cohorts were fairly similar in terms of disease severity and MRC Sum Score at baseline. The weighting procedure used in the prognostic factors, as I explained, resulted in two very balanced cohorts that were suitable for the comparison. 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. The cohort includes pediatric patients. If someone wanted to compare to young people, it included people with mild GBS. Right now, I think, if I get the number right, it's somewhere around 40 academic papers have been published from the IGOS cohort. There's an online site that people can look at to get further details. It's a rich database that's getting richer all the time with the addition of these biomarkers. Thank you.
Great. 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.
As a reminder.
Sorry. I'd like to ask the operator to open up for questions, please.
As a reminder, to ask a question, please press star, then one on your touch-tone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star, then two. The first question today comes from Suzanne [audio distortion] . Please go ahead.
Hi there. This is Suzanne from FieldGate. Thanks for taking my questions. I have one for Hansa. Can you put the Immifidase GBS program into context of the broader pipeline for the asset? 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? Secondly, when should we be expecting to hear more about the potential phase III plans and how they will crystallize? Thank you.
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 data for two 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. 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 Immifidase to the market in kidney transplantation as planned. Everything around GBS is currently under review.
Sometime soon, later this year, we will inform more about timings for the next step, which obviously would be a phase III study.
Got it. Thank you.
The next question comes from Douglas Tsao with H.C. Wainwright . Please go ahead.
Hi, good morning. Thanks for taking the questions. I was just curious if maybe you could help us understand the sort of how you're viewing the relative contributions of Immifidase in GBS relative to IVIG. And do you think it's possible that we could get comparable efficacy or meaningful efficacy with Immifidase alone? Thank you.
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. Elisabeth?
Thank you, Hitto. Yes. Yes, I will start. The data we have presented today is obviously from patients treated with Immifidase followed by standard of care. This was the first pilot study in this patient population. It was not considered ethical to remove standard of care when you do not know anything about if your compound will work or not. With that said, maybe Immifidase would work on its own. We have not studied that any further. As you see, you also asked how Immifidase could compare to IVIG. I think that, as we have alluded to during this call, Immifidase 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.
That will happen very quickly. It is very targeted as opposed to IVIG, where the onset is very slow. You often see patients still deteriorating while they are still being treated with IVIG. I think that both Dr. Cornblath and Dr. Rinaldi are better to speak to that. I hand over.
Yeah, 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 Immifidase. It's very unlikely that the IVIG started at day three there is contributing significantly to that. Of course, when we compare to IGOS and against IVIG alone treated patients, there's a much greater improvement. I think the key as to whether it could be a monotherapy is how long will that effect last? Will the effect of Immifidase outlast the duration of disease activity otherwise? As David said, actually, the majority of the nerve injury happens within probably 10 days to two weeks of onset of illness in GBS.
If we're starting a treatment four or five days in that lasts a week, that might well be enough to cover all of the periods you'd need to cover to turn up the disease activity as the immune system resets in the background. This is a monophasic disorder. The damage lasts for a certain period of time, then it goes away. There's a bit of variability in that, though, of course. Some patients may have a disease activity that lasts a bit longer and is not completely covered by Immifidase. They may require a second treatment or may require a subsequent treatment with a different modality. I would imagine for the majority, a single treatment with Immifidase probably will cover as long as it is required to provide essential complete benefit from the disease. You wouldn't have to give anything else after.
Simon, if I could.
If I could just add one comment. 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 zero, you'd have to decide if you'd like to be in the hospital with no IgG. 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. I think also an important finding in this trial is that it is safe to treat GBS patients with standard of care IVIG following Immifidase. That is also a finding from the trial.
Very good point. I hope we gave a rich answer to your question. Thank you for the question.
Yes, thank you very much.
Great.
The next question will come from Matt Phipps of William Blair. Please go ahead.
Hi. Hi, this is Eric Kahn from Matt Phipps William Blair. Thanks for taking the question. Just two questions. First, you mentioned the importance of targeting that first two weeks, but also the potential of Immifidase across the rest of the disease. I'm just curious, how wide do you think the window for treatment might be with Immifidase? Do you think it could be used throughout the rest of the disease process outside of that initial two-week window? Secondly, just wondering, how often do patients have recurring GBS? Or if they have an acute attack, how likely are they to have another one? Do you think GBS would make sense as a potential development indication for Hansa 5487 given its redosing potential?
Great. Thanks, Eric, for this question. Let me tackle it like this. Let's first hand over to the clinicians, Simon and David, to answer the first part of your question on if there are another phase of the disease where a treatment with imlifidase could be helpful. I'll later comment on 5487. Simon, could you start?
Yeah. So recurrent GBS is rare. Studies quote a recurrence rate of 5%. In practice, it seems much less than that. It's not usually a concern. Certainly, when it happens, it happens many years later. It's not an acute one. What you can see is what are called treatment-related fluctuations, i.e., a percentage of patients, maybe 10%-15%, will be treated with standard of care that will improve, and then they will worsen again as that treatment wears off because it's a short duration within a few weeks. Those are the patients who have a slightly longer than two-week disease activity, so the treatment doesn't quite cover the full length of their active disease, and then they redeteriorate. Again, both of those are uncommon. 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. Yeah. The second part of the question also touched on 5487. Maybe let me use this in a few sentences to summarize where we are with 5487. First of all, 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. 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 Hansa 5487 play a role in a disease such as GBS?
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. That includes autoimmune diseases, but also other antibody-related diseases in general. We will, during the course of the year, update more on this as we go along.
Got it. Thank you.
Thank you.
There are no further audio questions. I'd like to turn the call back over to the company.
Thank you very much. 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 three 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. I also thank you for presenting our clinical data in our GBS development program so far. 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 neuroautoimmune 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. Again, thanks everyone for dialing in.
The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.