Good morning and welcome to the Hansa Biopharma Presents phase II Trial Data in GBS and Indirect Treatment Comparison Conference Call. Today, all participants will be in a listen-only mode. Should you need assistance during today's call, please signal for a conference specialist by pressing the star key, then zero, on your telephone keypad. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one, on your telephone keypad. To withdraw your question, please press star, then two. Please note that today's event is being recorded. I would now like to turn the conference over to Mr. Søren Tulstrup, President and CEO of Hansa Biopharma. Please go ahead, sir.
Thank you, everybody. Good morning, good afternoon, and welcome to this call on the positive results of our phase II study and comparative analysis of imlifidase in patients with Guillain-Barré syndrome. I'm Søren Tulstrup, President and CEO of Hansa Biopharma. With me today is Hitto Kaufmann, our Chief R&D Officer. On today's call, we'll first review and discuss the results of the study and analysis, and then take your questions during a Q&A session. Next slide, please. Before we start, just the usual warning that today's presentation may contain forward-looking statements, and you should therefore apply appropriate caution. Next slide, please. We're very excited to share and discuss today the positive results from our phase II trial and comparative analysis of imlifidase in patients with Guillain-Barré syndrome, as announced yesterday by a press release.
Usually preceded by infection or other immune stimulation, Guillain-Barré syndrome is a serious, acute, rapidly progressing, and paralyzing attack by autoantibodies on the peripheral nervous system. Thousands of patients are hospitalized in the U.S. and Europe annually due to a GBS attack and need intensive care. The majority of patients have severe symptoms resulting in the inability to walk unaided, and a large proportion of patients need respiratory support. With current standard of care, i.e., IVIG and plasma exchange, the recovery generally takes many months, and patients often suffer from permanent nerve damage. The mortality rate has been reported to be as high as 7%. Due to the hyperacute nature of a GBS attack, it is critically important to halt the attack as quickly as possible and within the first week of the attack.
There is currently a high unmet medical need for therapies with a significantly faster onset of action than current standard of care, and we believe that imlifidase, with its ability to very effectively cleave and robustly reduce IgG-based autoantibodies within hours following a single infusion, has the potential to transform standard of care in GBS patients. Please move to the next slide. To set the context, GBS is one of more than 80 autoimmune diseases that have been identified, and IgG is a significant factor in many of these. Clinical guidelines call for fast and effective reduction of IgG in the acute stage of the disease. While a range of IgG-reducing therapies and interventions are being used in an effort to achieve this goal, current approaches have significant side effects, have a slow onset of action, and limited efficacy. For many conditions, there are no FDA or EMA-approved treatments available.
As I just said, we believe that in this situation, imlifidase and other of our IgG-cleaving enzymes have the potential to transform standard of care for GBS and other of these diseases. We've been very encouraged by the strong proof-of-concept data generated earlier from a phase II study of imlifidase in anti-GBM antibody disease, also known as Goodpasture syndrome, and we're currently running a pivotal phase III control study in this disease that has been fully enrolled and will read out next year. Today, we're equally excited to share the results from our phase II trial and comparative analysis of imlifidase in patients with GBS, and for this, I now turn over the call to Hitto Kaufmann, our Chief R&D Officer. Hitto, please.
Thank you very much, Søren. Hello, everyone. My name is Hitto Kaufmann, and in light of the high unmet medical needs Søren has described, and in my role as the Head of R&D at Hansa, I'm particularly delighted today to share more detail with all of you on the positive results of our recent phase II study in GBS. The presentation is actually having two chapters. The first one, where we will share more detail on the outcome of the phase II single-arm of the 1509 study, where we are evaluating a single dose of imlifidase of 0.25 mg per kg ahead of IVIG. In the second part, I will show you the results of an indirect treatment comparison with the so-called IGOS real-world comparator group, also treated with IVIG as the current standard of care.
Here, we will look at the efficacy of imlifidase in combination with IVIG versus IVIG alone. Next slide, please. This is the first chapter on the phase II results. Next slide, please. Thank you. Here you see the summary of the exciting results on the phase II. As I said, an open-label single-arm multicenter study across the U.K., France, and the Netherlands. We included patients that have severe forms of GBS, characterized by a GBS disability score of three and higher. For those of you who are interested, the slide on the bottom gives you the exact definition of this disability score. We included 27 patients who were initially treated, as discussed, with imlifidase, followed by IVIG.
We saw rapid overall improvements on the functional status of the patients, including an expedited muscle recovery, a fast return to independently walking, which is a key parameter to monitor the progress of recovery of GBS, and improvement by at least one grade on the GBS disability score that I just mentioned. And we could show that the median time of patients to have at least one grade of improvement is just six days in our study. On top of that, we saw a median time to independently walk down to 16 days. We looked at the two key data points at week one and week eight, and if you look at week one in our data set, you see that 37% of patients were able to walk independently.
On the critical parameter of measuring muscle strength, which is called the MRC sum score, we saw a significant improvement of 10.7 points at week one. If you look at the data at week eight, we saw that 67% of patients were able to walk independently, and that means that they have reached at least a disability score of two, and we saw 41% of patients that regained the ability to run, which brings it down to disability score of one; 37% have improved by at least three points at that point in time on the disability score. The responses we saw were durable, as in 63% of patients were able to run or had no functional disability at the six-month time point. Overall, the administration of imlifidase was safe and well tolerated. Next slide, please.
This slide briefly shows that the experience we have with imlifidase across multiple clinical studies was clearly demonstrated here as well. It cleaves all classes of IgG very rapidly and very profoundly, as you can see here, looking at the overall IgG normalized to predose amount of IgG, and you can see that as soon, obviously, as the IVIG treatment is applied on day four and five, IgG levels go up again, and I just wanted to remind everyone that our safety data set for treating with imlifidase goes way beyond that study, and more than 200 subjects have been exposed to imlifidase so far. Next slide, please.
As already announced, we particularly looked at the so-called MRC score, which measures the strength of the muscles of the GBS patients, and you can see here very early on in the studies, post-starting the study, we saw a significant increase of 10.7 points on that scale, so the higher you are on that scale, the more you have recovered your muscle strength, and that increase continued over the duration of the study. Next slide, please, so here is the detailed analysis of the really important GBS disability score, and you see three columns measuring the patients that have improved, A, by at least one step on the disability score, B, by at least two steps, and C, by at least three steps, and you see those data for week one, two, four, eight, and six months.
You can see, for example, looking at least one step of improvement, that already at one week, 56% have improved by at least one step on that scale. If you look at week eight, that's already 78%. There's also a significant improvement if you look at just the patients that have improved by two steps. That is, after two weeks, already 44% and 63% after week eight. After a while, especially after four weeks, you also see a number of patients that have basically reduced the severity of the disease by three steps on the disability scale. Next slide, please. Here we look at the same points in time at the ability to walk and the ability to run, which is a key readout for GBS, and it is the functional translation of muscle strength and coordination.
So if you look at first at the ability to walk, then you see again that the patients had a 37% ability to walk already at week one, going up to above 80% in week 26. And if you take it one step further and look at the ability to run, which means it translates to disability score one, you see that after 15% able to run at one week, this goes up above 60% after 28 weeks. Now, these improvements are very encouraging. How do they compare to what is known from previous studies, which is summarized on the next slide?
What we have done here is we have taken data from published studies that are at the bottom of the slide, and we have compared in terms of imlifidase plus IVIG versus IVIG, the median time to walking, which in our study, as I told you, was 16 days, compared to the literature that told us in IVIG alone, it was between 50 and 55 days. We also looked and compared the median time to improvement, which you see is also very different in our study, down to six days versus 22 to 30 days. Now, just to cite Professor David Cornblath here, the early improvements observed by imlifidase in GBS patients are remarkable. Let's move on to the real contextualization with the IGOS database.
IGOS is standing for International GBS, and it is containing more than physicians and researchers from more than 120 clinical centers across the world. Please move to the next slide. First of all, it is worth mentioning that we have very closely collaborated with the researchers and clinicians in the IGOS consortium, and we have made sure that the clinical protocols are very much aligned. On top of that, if you look at the group of our 27 patients in the phase II, and you look at the 754 subjects we included from IGOS, you see that across many parameters, the patient groups are very much comparable in terms of age, gender, but also in terms of baseline MRC sum score.
What we have applied with statistical rigor is a propensity score weighting using all available parameters for IGOS that had IVIG treatment compared to the imlifidase followed by IVIG treatment in our active treatment arm. We weight the data to match external control prognostic variables, and I will show them on the next slide. This is generally considered a valid approach to contextualize data when a direct comparison is not available. Please move to the next slide. As I told you, we have taken great care to weight the data using so-called prognostic variables, and at the top of the slide, we have listed examples of those prognostic variables in GBS, such as age, the GBS disability score, the cranial nerve involvement, or the MRC sum score that I talked about before. What are the outcomes of that comparison?
Here are the four parameters that we used for this comparison. First of all, the median time to return to independently walking was overall six weeks sooner in the active imlifidase arm compared to the control group and had a statistically significant improvement. The median time to improvement by at least one grade on the GBS disability score was three weeks sooner, with an even higher statistical significance. Then looking at the likelihood to walk independently, we saw a 6.4x higher likelihood when initially treated with imlifidase ahead of IVIG versus the IVIG control group at week one, and we saw more than four times likelihood to walk independently at week four, again, when you compare our phase II active arm with the control group from IGOS. Those were really exciting results that were the results of that treatment comparison.
On the next slide, you will see a summary of both data disclosures. On the left, and I'm not going to go through this again, you see the main data points that we disclosed on the phase II study. I'm just going to reiterate one point here, and that was a median time to independently walk of 16 days. And on the right, you see the summary that was the results of the comparison with the IGOS control group. And again, I'm not going to walk through all of them again, but I wanted to point out one data point here. So if you look at one week after treatment, it is 6.4x more likely that patients can walk independently than the initial treatment with imlifidase ahead of IVIG compared to IVIG alone. With that summary, I would like to hand over back to Søren Tulstrup.
Thank you very much, Hitto. The results shared today from our GBS trial add to the mounting body of evidence showing the significant potential clinical benefits generated by fast and robustly removing pathogenic IgG via our unique IgG-cleaving enzymes. As I said earlier, we're very encouraged by the positive data from our phase II study and comparative analysis of imlifidase in GBS patients. We believe the demonstrated ability of imlifidase therapy to get patients to recover significantly faster than standard of care IVIG alone, including regaining the ability to walk independently, could bring significant value to GBS patients and providers, and we now look forward to discussing the results with regulatory authorities and the broader scientific community. With this, I'd like to conclude the presentation and turn the call back to the operator for Q&A. Operator, please.
Thank you. We will now begin the question and answer session. To ask a question, you may press star, then one on your telephone keypad. 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 it, please press star, then two. At this time, we will pause momentarily to assemble our roster. And today's first question comes from Christopher Uhde with SEB. Please proceed.
Hi there. Christopher Uhde from SEB. Thanks for taking my questions. I have a few. The first are around sort of just trying to get a sense of the robustness of the data. So first of all, did you have any deaths in there? Because I know normally we'd expect to see about 5%, correct?
I had that all for you, Hitto, so thanks. Yeah, Hitto, will you take this one on the robustness of data?
Yes. I mean, first of all, it's important to note we have 27 patients. So with regard to death, anything we would see would not be statistically relevant. However, it's important to say that we did have a very low number of patients that required ventilation and no deaths in the study.
Okay, great. And then so can you talk a little bit more in depth about how you selected the patients from the IGOS pool? So I mean, what kind of steps did you take to limit potential bias from the MAIC method? And how many patient candidates did you consider out of the total? What geographies especially did you consider, given there's obviously geographic differences in the types and outcomes of GBS? And then what about the eight-week and 26-week endpoints, given long-term outcomes are, of course, the most important here?
Hitto, do you want to take this one? Hitto?
And excuse me, Mr. Kaufmann, your line is open. This is the operator. Mr. Kaufmann, you may want to check if your line is muted at your end. It is open to the conference.
Okay, so in the meantime, I think we move on to the next. I can say that what we did when we did the matching is this is not a patient-by-patient matching. This is looking at an average, and obviously we took into account a range of different factors when selecting these patients, and we can get back to you with a specific number of patients, Christopher.
I appreciate that. Thanks. I guess I'm moving on for now until he comes back into the addressable market. What can you tell us about that? Because I understand you did severe—oh, is Hitto on? Sorry. I understand you had severe patients there, which is just a proportion of the total number of patients. Obviously, it makes a big difference to where we come out to in terms of forecasting. So how should we think about this? How would you define severe? What's likely to be the addressable market in your view?
Well, as I said, you know.
Sorry I was muted.
Sorry, I'll take this one on the severity. So there are thousands of patients that are hospitalized, right? And when you get into a hospital, it's critically important that you try to halt the progression of the disease as quickly as possible. And as I said, you really want to have an impact in week one. So essentially, all those patients that are hospitalized, you would want to take a therapy that has maximum impact as quickly as possible. So there is a very significant opportunity here looking at, again, the number of patients that are hospitalized with GBS. And Hitto, I don't know if you heard the former questions by Christopher on robustness.
Yes. I'm very sorry. For whatever reason, I couldn't unmute my phone, but I will take the first question happily. So first of all, it's important to note if you go back to that slide that the patient population between the IGOS study and our arm was very, very comparable, also with regard to the prognostic criteria. And that also are the criteria that are relevant for the geographic distribution. So there only had to be minimal weighting performed, but we did weight our data versus the control group. And this is important to note. The method that we used is a method that doesn't include patients. So all patients are included in that study. So that's a different approach. For example, when you do individual matching up of patients, that's not how that contextualization is working.
If you look at the key factors, the prognostic factors, the two groups, the 27 patients from the 1509 study and the IGOS group, it's very, very comparable.
Okay, great. Sorry, and then what could you tell us then about the sort of geographic spread compared to your study?
Yeah, it's also very comparable. And there are also some markers that, depending on which part of the nervous system are attacked by the antibodies, that are geographical difference, for example, between Asia and Europe. And again, those markers are very comparable between the two groups, which is a great measure of having the same type of geographic distribution. And also, if I heard the second question, I'd like to comment on that one as well. So in GBS, almost all patients proceed to three and above, three, four, and five. And in our study, we included three, four, and five. So that's essentially the 6,000 to 8,000 patients every year in the U.S. that we would treat with imlifidase if that would be confirmed.
Okay, thanks. That's very helpful. And then last question, what can you say about the next steps in the design of a potential pivotal study?
The next step here is obviously to, of course, discuss the data with regulatory authorities and the broader scientific community. Clearly, we would need to run a phase III control trial. The design of that is something that we'll be able to discuss more when we've had that dialogue, right? Hitto, do you want to add to this?
Great.
Clearly, as you said, the next step is a study that compares imlifidase and IVIG versus an IVIG control arm in a phase III trial.
Great. Thank you so much. I appreciate it.
Thanks, Christopher.
Today's next question comes from Douglas Tsao with H.C. Wainwright. Please proceed.
Hi, good morning. Thanks for taking the questions. I guess I'm just curious. I know a competitor recently ran a study involved severe to moderate patients. And I'm just curious, is there any significant sort of distinction between those sort of classifications of patients? And how does that potentially affect the market opportunity when you think about phase III, sort of including somewhat different patients than what were in phase II? And congrats on the data. Thank you.
Thanks very much for that question and the c ongratulations, Doug. I mean, obviously, we cannot comment on the specific competitive trial there. This is a trial that was a placebo-controlled trial, and we haven't seen any, of course, comparative data here. Overall, the patients are looking at a variety of parameters that are different. It's difficult to comment on that. I don't know, Hitto, if you want to add to this.
Sure.
Well, I guess. Søren.
Yeah, well, I'll let you comment. Hitto?
Okay, Hitto.
So in terms of classification, I think it's important to stick as much as possible to the GBS disability score. That's the real precise definition. And so we talk about severe GBS patients when we talk about three, four, and five. That's, to our knowledge and also in our discussions with KOLs, the key definition of severity.
I guess, Hitto, as a follow-up to that, I mean, would they see an opportunity for imlifidase in patients with lower scores? And I'm just curious in terms of sort of how you view sort of this was obviously done in combination with IVIG. Do you get a sense that you could have efficacy as a standalone therapy? Thank you.
Yeah, thank you. Two excellent questions. First of all, I can definitely not exclude that imlifidase is also helping patients with a lower degree of severity. However, unfortunately, GBS almost always manifests as a severe acute disease to start with. So almost all patients that reach the hospitals with GBS diagnosis are three and above. So even if that may be a possibility, remember, patients that are in this score at two can independently walk. So I would say in terms of the key addressable patient groups, it will be three and above. The second part of the question was about standalone treatments. At the moment, the way clinical studies are designed, and I think that's, I would say, the standard in the community right now, is to have IVIG treatment setting in at a later point in time.
Obviously, as you can see from the comparison, the key effect that we see in our studies is very likely attributed to imlifidase. It is also thinkable at some point in time to dose imlifidase a second time and to prolong the time with the very low levels of IgG, which will certainly be part of development considerations or even post-market development considerations.
Okay, great. I'll jump out of the queue. Thank you.
Thank you.
The next question comes from Matt Phipps with William Blair. Please proceed.
Hi, thanks for taking my questions. Nice update here. Thanks for the comparison data. Following up, Christopher did try to ask about if you had any comparisons at, say, week eight or six months, and it might have been when Hitto's line was having issues. So I don't know if you have any data comparing that. And then looking at the baselines, it does seem like the mean days from onset of weakness to treatment start might favor the imlifidase arm a bit. But I'm just curious, is that something that then gets propensity weighted when you're doing the analysis to make it closer, or do you think there's an issue there? Thanks.
Hitto do you want me to take it right away?
Yep.
Yes.
Do you want to take it?
So in the first one, sure. The first answer is we have chosen week one and four for the contextualization with IGOS despite having data also for week eight. And the reason is the established standard among clinicians. These two data points from everything we know and from all conversations we have, also from comparing it to other clinical studies, week one and week four are considered the key parameters. And especially in GBS, the damage is done very early. And therefore, clinicians really want to get novel treatment options that, unlike IVIG, act really quickly and show improvements on the disability score and on the ability to walk really early. So that's why we've chosen one and four weeks. We have data for week eight, but they haven't been contextualized with the IGOS control group. Matt, can you just remind me about the second part of your question? Sorry.
Yeah, I was asking about the mean days from onset of weakness to treatment start, just looking at the two arms and then maybe a day earlier for imlifidase. But was there weighting involved in that too?
Yeah.
Weight days that are more similar?
It is one of these parameters that we, of course, consider. Two days difference is actually not a lot. But it is something that was not part of the credible prognostic weighting parameters that we used.
Got it. And then, yeah, just kind of maybe a follow-up on the first question. It does seem like the GBS disease severity is good at capturing early benefit, but maybe struggles to show that or just define a longer-term benefit for those patients by achieving this earlier benefit. And yeah, I guess I assume preventing damage should lead to some long-term benefit. Do you think there's other endpoints or other scales that might be better at capturing that longer-term benefit a patient might achieve if they're able to, if you reduce the disease severity so rapidly?
Yeah. I mean, most long-term problems would be covered to some degree in the disability score. That's why this is the standard. And of course, the assumption at the moment is the earlier you can bring down the disability score, the less you will have long-term effects on the central nervous system that are typically observed. And the disruption of the damage that the pathogenic IgGs do in GBS is, in our view, the key point to intervene.
Got it. Okay. Thanks for taking my questions.
Thanks, Matt.
As a reminder, if you do have a question, please press star, then one on your telephone keypad, and the next question comes from Alexander Kramer with ABGSC. Please proceed.
Yes. Good morning. Thanks for taking my questions. Good afternoon, sorry. Thanks for taking my questions. I have two, and actually, one is a little bit related to the question that Christopher asked before today, and it relates to your ClinicalTrials.gov entry. In that entry, I mean, you have this description that for the data analysis for the IGOS contextualization, you are going to match the data from each patient with up to four subjects treated with IVIG from the IGOS. And I know in the previous questions, we have asked this. We have discussed this today already. But are you going to have this direct matching in a future data analysis? And also, are you planning to publish that?
Hitto, do you want to take that?
Yes. So, yeah. Of course. Yeah. Thanks for that question. That goes back to one of the slides I showed. So we did not do a patient-to-patient matching. Instead, we did this so-called propensity score weighting using all available patients. And that's important to note, which was a very large group, 754 in the IGOS control group and the full 27 patients. So it is a slightly different approach compared to what we initially intended.
Okay. Okay. Thanks.
It is, I would say, it is oriented at what is currently considered a most validated contextualization approach.
Okay. Good. Good. Thanks. And maybe a second question on the timelines going forward now. I mean, you said that you're going to publish the data. And also, I mean, of course, you will have interactions with regulatory authorities. Is this something that you plan to give updates on in 2025?
Yes. We will move forward in 2025 and give updates as appropriate next year.
Thank you. That's it from my side.
Thanks, Alexander.
At this time, we are showing no further questioners in the queue. This does conclude our question-and-answer session. I would now like to turn the conference back over to Søren Tulstrup for any closing remarks.
Thank you, Alfred, and thank you, everyone, for taking the time to call in today. This is an exciting time for Hansa, and we're very happy with the results from the phase II trial in GBS and the comparative analysis. We think this is good news for patients, and we look very much forward to keeping you updated on progress. Thank you very much.
The conference is now concluded. Thank you for attending today's presentation, and you may now disconnect.