Good morning, everyone. It's my pleasure to welcome you as well to our conference call this morning on our top-line phase II-A data. We're thrilled to share these data with you, and we're very happy that we got to this point. So we will dive right in. Before we do so, just two notes here: I will be joined by our Chief Medical Officer, Dr. Camilla Chong. Dr. Chong will present the data in chronic spontaneous urticaria, and I will present the data on hidradenitis suppurativa. We're also thrilled to have with us, for the Q&A session, Professor John Ingram. Professor Ingram is not just a treating physician that is passionate about HS treatments and knows a lot about that, but he's also one of the key opinion leaders and really key scientists driving the field forward in HS.
As a former editor in chief of the British Journal of Dermatology, also very well versed in the scene, and we're really thrilled to have him with us for the Q&A session. So with that, we'll dive right back, right into the, presentation. So please, next slide. So we'll be making forward-looking statements today. next slide, please. And please, please take note of the disclaimers. These are important disclaimers on the forward-looking statements. we will also be showing you for comparative, illustration only, some data, that, were presented by, and reported by other companies. So this is, for illustrating purposes, and comparative analysis only. Next slide, please. So just on the mechanism, as a reminder, we have a small, oral compound inhibitor of the C5a receptor, sometimes referred to as C5aR1.
The C5a receptor is a known and validated target in an immunoinflammation field, and obviously, it's part of the complement system. A small, you know, inhibitor of this receptor has certain advantages. It has a deep tissue penetration potential, which acts then in the side of where the inflammation really takes place, in this case, the skin. Also, it's not really dependent on how much C5a is being produced. With that in mind, it's important to know that you cannot simply block the C5a receptor with upstream inhibitors because C5a can be produced by various pathways, particularly through enzymatic cleavage on the cellular level in the skin, but also in different tissues and also in the blood. To block this pathway, you need a targeted inhibitor. Next slide, please.
We have previously, shown, data, and this is from our phase I study here, that, indicated that INF904 has best-in-class potential. And this is, really based on a very differentiated PK profile, next to the reported comparator, which is a marketed drug, Avacopan. And you see the data here, as a reminder, on the upper right corner. So at the same dose already, we reach a tenfold area under the curve increase and a very differentiated ability to block the receptor and really have a tighter control over the signal. Why is this important? Because ultimately, we believe, and some of the data today shown will hopefully make that point again, that with that, we can explore efficacy to a much higher extent, and, eventually, this will lead to higher efficacy signals in clinical studies and in clinical application.
I just also want to remind you that by now we have, including the data we present today, about 180 human subjects exposed to the drug with no signals of safety concern. Next slide, please. So, this was a PK and safety study. So we will start with PK and safety. PK at this point is very preliminary. You see that on the, the right side, we plotted, a compiled, PK data, in green HS and in blue, from the, CSU study. but the illustration here is, is not complete. You see the number of subjects, indicated underneath the figure. The point we're trying to make is it's very differentiated from the marketed comparator. Already at week one, we have a multiple higher exposure for both indications across, the three, tested doses in HS and the two tested doses in CSU.
And even if you see the plotted line here from Avacopan, from its approval data in ANCA-vasculitis, reaching at 13 weeks steady state, even if you compare that, we clearly, exceed that, sometimes by multiple. And so we just wanted to also let you know we started with 60 mix BID, and that was based on the knowledge that 60 mix BID is actually covering the signal quite well. In our phase I studies, we've been able to demonstrate that. So we believe 60 mix is a clearly active dose, but we wanted to explore efficacy upwards, which in skin disease is particularly important as, oftentimes, when first tested drugs are underdosed in this. Next slide, please. So safety, very high level. You find more details in the appendix with the concrete listings. There are no signals of safety concern detected in either of the arms.
there's no reported SAEs in either of the arms, so no severe adverse events. And there are just three adverse events of mild grade one nature reported in two patients in the, HS cohort and one, particularly also mild grade in the CSU cohort. So very, very, clean safety profile so far, and we're really happy to report that we have no signals of safety concern. Next slide, please. So with that, we jump into the HS dataset, and, I'm thrilled to be able to be presenting this to you for you today. We have 29 patients as depicted here below that we will be showing, you today that have reached the end of treatment at week four, and out of these 29, 25 have already reached the end of study, which is week eight, so four weeks later without dosing and without, additional visits.
the other four remain, and have not reached that endpoint yet, but, in the study. Please also take note there's one patient in the low dose group, 60 mix, and one patient in the medium group, 90 mix, that is still, finishing up treatment and data entry, so they are not included in this. The high dose group, therefore, is complete, but the other two dose groups each missing one patient that is still, that are still in the treatment phase. Next slide, please. So just as an indicator, again, this is the setup. the color coding will be consistent throughout the deck. So yellow will be the 60 mix BID group, pink is the 90 mix, and red the 120 mix. You see here the four-week dosing, intervals. Again, dosing is every day BID with four visits after the baseline visit.
Another four weeks, as I mentioned, no dosing and no visits where the patients are just coming back one more time for a safety and efficacy analysis, at so-called end of study week eight. Next slide, please. With that, we are showing you here the baseline of the three groups, 60, 90, and 120 mg, and below that is the combined data of all three dose groups. You will see that they're, overall pretty balanced, and in line with previously reported and conducted HS studies, maybe highlighting that on the AN count, which drives an important regulatory endpoint, the so-called HiSCR. The AN count is the highest in the 120 mg dose group and the lowest in the low dose group. There's a difference that is noticeable.
The dT100 is between three and a half roughly and four and a half in line with other studies. Also, the severity score indicates that the high dose group is the most severe with the so-called IHS four score. And then maybe also noteworthy that we have a few prior biologic experienced patients and a slightly higher BMI, body mass index on the upper right in the low dose group. Next slide, please. We will now show you the lesions first and then the scores, and we start with the driver of the HiSCR, the so-called AN count. Just as a reminder, abscesses and nodules are two of the inflammatory lesions. The third one is the draining tunnel. Abscesses and nodules come and go all the time, so they fluctuate a lot in the patients.
They can go up and down by over 50% in lower count patients, and that's very normal. And you see on the upper left side here how the average in the each dose group is composed with respect to the nodules and the abscesses making the AN count altogether. And as you can see, the high dose group is the most severe one. I should mention that in green, we always depict the compiled data of all three dose groups. When looking at that, we would like you to appreciate first that you see a very consistent overall reduction, and this is week-by-week data, so high granularity in the absolute reduction of these counts. Now, you see that, you know, oftentimes there's a lot of zigzagging, there's flaring patients, so just one flaring patient can cause a lot of zigzagging in this curve.
So we were very happy to see a very consistent move, and you can see this is exceeding eight total, abscess and nodule counts already at week four in the high dose group. So why is this important? How does it comp? Next slide, please. We have done a lot of comparator analysis that we will share with you in which we compiled the data, that have been reported for successful DARCs and graded the average of that. And you will always find in blue completed and successfully conducted phase III data sets that, are averaged, and in gray, phase II. In this case, for example, it was just one drug in phase II, povacitinib, and we then report the best reported dose. And in phase III, of course, the, the doses that have, eventually then also led to a, an approval.
and you can see the corresponding, placebos are always in the dotted lines. So blue is phase III, gray is phase II. So you see that the green line of all doses here compiled is just on, on, on par with the reported successful, drugs here. but the red line is clearly exceeding this. and, the other thing that we can learn from this, orientational comparison is that the placebo ability to reduce the AN count is across the different, across the different, studies that we looked at, always in the range of minus two and a half and minus three and a half. Now, that is not unimportant because they drive the high score. As a reminder, the key criterium is a 50% reduction of the AN count from baseline.
So if you have a baseline of six counts, you need to lose, for example, three nodules, and you reach that criterium, 50% reduction. But if you are coming from 30%, you'd have to go down to 15% . And if you see that the average placebo makes about two and a half to three and a half points, you can already kind of see from that that this is oftentimes driven and, and drives response in the low count patients. So the low count patients provide a lot of noise, and they can drive placebo response rates in that score. Next slide, please. So looking at draining tunnels, we had mentioned previously in guided, the markets that draining tunnels are an interesting lesion as we can see them as an indicator lesion. Why? Because historically, they're very low responders, response rates for placebo trials.
So the draining tunnels are more consistent, less fluctuating. one, one draining tunnel can produce up to a liter pus per day. Just want to let you know that a draining tunnel is what you see to the outside, but this usually means if you, for example, drain large, large, milliliters of up to a liter of pus from one draining tunnel, that there's a big underlying large inflammatory lesion in the deep skin that produces an inflammatory lesion that produces this, this pus. And so reducing draining tunnels, is a remaining unmet medical need, but it's not easy, and it's usually not done by placebo responses. So here you see the same picture, different doses, different, again, the, the high dose performs the best.
And on the right side, you see, something that was created recently by calling dT100 , meaning how many patients that have draining tunnels at baseline are now completely draining tunnel free. I just want to remind everyone we're talking about four weeks of treatment. So at four weeks in the high dose, we have half of the patients already draining free, and the average around 30%. Next slide, please. How does it compare? pretty impressive in my eyes. as you can see, the placebo from the phase III trials, by the way, I should have mentioned always underneath you, you find all the trials, all the data that went into the curves. In this case, it's adalimumab, sicokinumab, bimekizumab, povacitinib. So everything that was recently reported here, is in there. And you see placebo has very little reduction of the draining tunnels.
And you see the, the compiled successful drug data here. They reach about one, a bit over 1.3 point reductions overall. And you see, no matter whether you report on all patients or only on those that have draining tunnels at baseline, which in this case makes a difference between dotted red, dotted, solid red and green, there's a very steep initial decrease that, that, that we can note here for our drug INF904. So next slide, please. So how does that funnel into the high score? We now looked at the lesions. The lesions are part of high score. I should mention reduction of draining tunnels is not rewarded and not looked at in the high score. You should just not have increases. So as we explained, there's a lot of noise in the high score.
There's ups and downs, and usually you don't get granular weekly data as we can show here. But again, we were, we're very, happy to report that this is moving upwards step by step, with reaching about 38% in the higher dose group already at week four. And then remarkably, when we took the patients off drug, those 25 that reached the end of the study, the, the, the additional four weeks off drug, the response is deepened. Now, obviously, the denominator is just 25, not 29 here, but the high dose group is complete. So that 63% you see there is no changing anymore. The other two groups, have still a few patients coming in, so they could still change to a higher or a little bit lower level. But the point is that response is deepening. and, we of course looked into how can that be explained.
First of all, we can confirm that the preliminary PK data at the end of the study, so four weeks off drug, do still show active drug levels in the range above the IC50 of the drug. So where there can be a blocking ability still from the plasma levels being, estimated. so that's one thing we want to note, but also the mechanism does provide for a change in the inflammatory environment in the skin, meaning you will have less of certain immune cells moving into the skin over time and being activated in the skin, and that can also have a carry forward effect. On the right side, you see something that we created to illustrate how high score moves overall.
And so for this is the, it's the pooled data, and we said, like, you know, knowing about the variability in small data sets, how can we depict and create confidence that there is a movement towards a higher high score rate? And the way we did that is we created this stacked bars here. We're looking at high score 30%, then high score 40%, high score 50%, and high score 75%. And we said, look, you know, if, if, if without the, you know, with knowing about the variability over time, these stacked bars should get higher as more patients move into the next response level. And obviously, if you're at high score 40%, maybe you need to lose just one or one, one, one nodule or one abscess, and you're already in high score 50%. And this is exactly what we see here.
These stacked bars, they extend, they get larger, and we're, at a high score 75%, then at, 24%, at, week eight, which again, is, is something that we wanted to depict. So next slide shows you then how that compares. So again, depicting the phase III studies, you, first of all, you see visually that placebo is not so much differentiated, and we know about that problem. Very recently, we got reminded again that placebo response rates do play a role. I want to mention again that can be mitigated when looking at the baselines in different ways and how you control not to have too many low AN count patients in your placebo group. But we are right on the blue trajectory line, obviously with some variability and obviously with the high dose again performing better.
But, I would say clearly we are in the range that we can check the box in high score, and have the fantasy that that may even move higher over time and that needs to be proven out in future studies. Next slide, please. So the last remarkable point here in the HS data set is really the pain scores, NRS30, meaning on the pain scale from zero to 10, you get a ground score. You will notice in the baseline that this was roughly between six and seven. So these patients are highly impacted by pretty intense pains. And it's, it's rare that you have a consistency in small data sets because this, you know, individual score, which is a patient reported outcome, has a lot of variability.
But you see a consistent improvement alongside the lesion improvements that we've been showing you, in the pain up to a pretty remarkable level in, in average over 65% and 75% in the high dose group. Now, that is important. We defined high score, NRS30 as having at least a 30% reduction from your base score and at least a two-point reduction, which is a bit more stringent than some others used. A recent, competitor read out, a different way by saying we just want to show you patients that have at least a three-point reduction. So the NRS30 was not part of that, but we also applied that logic and the lines did not change by chance.
So no matter how you look at the data, they're really in the comp that it's shown, they really kind of, stand out in as much as they're very consistent and they're showing a very, very large improvement in very early in the first four weeks. And that's maybe a line in line again with treating the inflammation in the skin. Next slide, please. so this is less of a, efficacy demonstrations, like more of a comparator slide. We mentioned, that we think we have a best in class potential drug that showed that is shown and supported by our phase I data. And I think this supports it again because Avacopan was used in HS in a pre-sizable study, roughly 120 patients per arm. And you see this is the data that are reported on clinicaltrials.gov about this study.
And you see that, for dT draining tunnel, this was plotted out over the time phase, phase of 12 weeks. And you see how we compare next to their approved dose, 30 mix, which did not really separate from placebo. And on the right side, you see a bit of an apple and pear comparison, our data at week four and their data at week 12. And when looking at AN count that drives high score, you see that there is a signal in Avacopan, maybe even a dose response. Again, you see that placebo is within the range I mentioned to all of you between two and a half and three and a half. but there, there is a signal in Avacopan, maybe not as strong as a signal as bimekizumab can do, maybe up to seven or so at that time point or even over seven.
but, it's just reaching this very late and it's not very impressive, but we have reached this already in average, at week four and clearly exceeding with our best reported dose at, at week four. Similarly, this, the pain scores that I already illustrated, there's a clear difference. so we believe this is another good indicator that, that the drug is very differentiated and has activity away from the marketed comparator. Comparator. Next slide, please. So with that, we, we conclude here. So we believe that this, data here show a biologic-like efficacy in the first four weeks, with the end counts and high score responses. We see the high score responses deepening four weeks off drug, and we have an explanation for that. And that's a very encouraging signal.
We see fast and deep reductions in dT, and that really is very differentiated from reported placebo and also compares favorably to the phase III drugs. and also we showed you a very consistent reduction in pain in the backup. You will also find data on dermatology life quality index, which are equally impressively re, like improved already at week four. So that's in line with the lesion reductions. And I mentioned safety there was that we don't have a safety signal of concern. And with that, we think we deliver to the market here, a very interesting, a very differentiated mechanism of action, that, is an oral. And, we are very excited to, to take this drug further in this indication. With that, I'm done with my part.
I'm, I'm happy to hand over now for the CSU part, which also shows, clearly very interesting signals and an active drug. And I would, like to hand over to my colleague, Camilla. Would you be so kind and take it from here? Thank you.
Thank you, Niels. I'd be delighted to, take the, CSU part of our presentation. But before I present results from our CSU, study, I would like to take the opportunity to acknowledge, the late Professor Marcus Maurer from Charité Berlin, who really persuaded and collaborated with us in this, to embark on this CSU study because he really believed in the crucial role that C5a plays on not just the mast cell, but also the underlying inflammation. And we are grateful that, his hospital continued to work with us and is in fact one of the sites in, in this particular study.
So for the purpose of today, I will be presenting 30 evaluable patients who have completed treatment up to week four. And out of those, we have 23 right now who are, have data at end of study. The remaining seven are still ongoing, and we also have an ongoing, three. Next slide, please. As Niels have shown you, the, the study design is fairly similar except for CSU. We do not have the 90 milligrams group. We have the 60 mg and 120 mg BID. We also have Arm 3, of which we try to enrich the 120 mg dose group with patients who have previously been treated with anti-IgE and who have either had incomplete or no response, and also those who present with low IGE, more indicative of the type two B endotype.
These patients have four weeks of treatment, and then from end of treatment to end of study, no drugs are dosed. So basically they have a dose, dosing free period, but we follow them up. with that in mind, I'd like to show you in the next slide the UAS, first of all, baseline characteristics. so as you can see, the mean age of these patients are around 44 years old, predominantly female with quite severe, moderate to severe CSU at baseline and also poorly controlled disease. On average, they have had CSU for at least 3.5 years. We have, a group of patients who are anti-IgE experienced, but predominantly anti-IgE naive.
In the next slide, please, I will share with you the UAS seven results at week four, of both our doses, 60 mg achieving a UAS seven reduction of just under - 14 and the 120 mg group at -8 . On average, we achieve an end of treatment results of around - 10.4. And I've mentioned earlier to you from week four to end of study treatment where they have no drug being dosed, the effect on the 60 mg group continues to deepen down to - 16.3 with a more modest, decrease overall on average between the two doses. Next slide, please. Now, how does this compare with other phase II studies that we are aware of, who have progressed from phase II to phase III? And here we took on average the placebo rate, which is, around - 6.3.
But if you look across the active treatment, whether it's Omalizumab, Remi, Rilza, or Baso, the clinical activity range that you see here is from - 9.1 all the way to - 20. So clearly, UA, we do achieve with the 60 mg group UAS seven reduction with it, which is within the range of therapies that have moved into phase III and is differentiated from placebo. How does this compare with phase III data? In the next slide, please. We also see fairly similar placebo range, which is perhaps slightly more at minus seven, but a clinical range which is also interesting that starts from - 8.5 all the way down to - 19.
Now, those of you may remember that Dupilumab at week four, do not achieve substantial reduction in UAS seven, but takes just that little bit longer to get to the clinically impactful UAS seven later on at week 24. So in the next slide, what I hope to show you are the UAS seven reduction in some of the subpopulations that we've looked at. So on the left hand side, you will see patients who have more severe CSU at baseline. So in other words, CSU patients who have UAS seven score of 28 and above. And here you do see that the 60 mg group, have a much deeper reduction of UAS seven at - 15.4 and also a little bit more with 120 mg group at just under nine. in addition to that, we looked at a group of patients, albeit the numbers are very small.
We have three patients who presented with angioedema at baseline, very severe angioedema at baseline. And here you can see that the reduction is around - 18.7. In addition to these two subgroups in the next slide, please, we also have patients who have low IGE at baseline. And those of you may remember that some of these patients are more indicative of the Type IIb endotype and they're more difficult to treat. Here the UAS seven reduction is around - 12, but bear in mind that the placebo rate taken from Remi and Baso data, phase II data at week 12, placebo average is around - 3.8. So it's a lot more differentiated here in this particular group of patients. Next slide, please. And this is, disease control as measured by UCT seven.
I'm pleased to say that all three doses achieve a four-point improvement or more in UCT score. And those of you may know that a UCT score that is minimally clinically impactful difference is two points and above. And here all both doses achieve more than four points. And on the right hand side, you will see that UCT indicates at least 30% of patients achieve good disease control at week four. So next slide, please. So in summary, I hope I've shown you that our 60 mg dose clearly achieves efficacy within the clinical activity range observed from phase II and phase III studies. And in some subpopulations, particularly those with more severe disease at baseline, those with angioedema and low IGE patients, the reductions are more substantial. INF904 also shows good improvement in disease control.
And I'm also pleased to say that the drug was well tolerated and did not result in signals of safety concerns. So we are also grateful, for the continual support that we are getting from Professor Martin Metz, successor to, Marcus Maurer, and further exploration into, potential CSU program will be, discussed in and provided at a future R&D event together with, and also, HS. So with that in mind, we would like to also now, we are thrilled to have with us Professor John Ingram that I hope have joined us, to start our Q&A session. And in order to do that, perhaps I, we can kick off by asking Professor John Ingram that in his view, in your view as an expert and treating physician in HS, what is your impression of the data?
And perhaps related to that first question, what do you believe matters to your patients and to you as prescribing physician when it comes to measuring progress and/or improvement? So those are the two questions. I don't know whether John.
Yeah, we're still waiting for, for, for John. so what I can do is, if you could just hold that thought, Camilla.
Okay.
Run through some of the questions we have, we received and, and then, and then address him when, when he gets on board. so, just quickly, you know, at this time, we'll, we'll start the Q&A session as we wait for, for, John Ingram. You may ask a question a few ways. One is you can raise your hand, using the, icon below the presentation window, and then we'll, we'll get people individually.
You can also use, the chat, the Q&A button below the presentation, and I'll read those questions, out loud. So, with that, we've got the first question, from Steve Seedhouse at, at Cantor. Steve, if you could accept the, the invitation to unmute and go live and you can ask your question.
Great. Yeah. Thanks so much. good morning. congrats. Obviously, in the really encouraging data here, I wanted to ask a few questions. First, I believe the study, according to the clinicaltrials.gov entry, enrolled across, quite a lot of, of sites in the U.S. and Europe. Just hoping you could comment on maybe the distribution of enrollment across those sites, particularly in the HS study. start with that question.
Sure. Yeah. Niels, I think you could take that. I think you need to unmute perhaps or, or no.
No, you're good. Sorry.
Yeah, I'm, I'm on, I'm unmuted.
And, Camilla, you try, I mean, if I say something wrong, but I, we had, that's right. We had a bit, below 30, study centers. So I think 28 actively recruiting in the two arms. Not every center recruited in both, in each arm, obviously. but we had a good distribution. The, like roughly 40% of the patients in the HS arm came from the U.S. And then, I think the largest side recruited four patients. So there was no single center that recruited like a majority of patients or so. So very well distributed over maybe a, a, a like a total of maybe in the range of 13 to 15 sites in HS and, and, similar, similar site like level in, in CSU. I, I'm assuming you, you were most interested in where HS was recruited, but, happy to, to give you more color in CSU as well.
Camilla, I don't know if you could speak to the, the site distribution in CSU.
Yeah, absolutely. So, so similar. We have our U.S. sites as well as, Western European sites coming from Bulgaria, Germany, Poland, Greece, and, and also Georgia.
Great. thanks, thanks for that. Just mechanistically also, Niels, I mean, nobody's been studying compliment longer than you and also, HS. Curious if you could comment on the, like the draining tunnel data, the pain data, and maybe also the, the DLQI data are sort of where the most profound effect you see is. is that what you expect with the mechanism here? Like what, how, how is that fitting into the sort of hypothesis of this, this mechanism in HS?
Yeah, absolutely. Great. great question. Thanks, Steve.
So maybe noteworthy before I go into answering directly that the C5a receptor expression has been found to be increased in various immune cells around all three types of lesions, abscess nodules and draining tunnels, and in all stages of the disease, like in early stage one, two, and three. Now, you know, early system is more like a chronicity kind of thing rather than a severity thing. But what I'm trying to say is the receptor expression is up regulated in different cell types. now we've always been pronouncing the role of neutrophils in this disease as it's a, the clustered into the so-called neutrophilic skin disease bucket. And obviously they do play a big role, particularly in draining tunnel and abscess formation. And, and why is that? Because, you know, C5a, induces natosis in these cells and, and the production of granular enzymes and also of oxidative radicals.
So if you think about the impact of natosis has been implicated in the last few years more and more by the experts, the HS experts to be driving and also not just driving like draining tunnel, you know, existence and path formation, but also the, the actual development of draining tunnels. So the natosis angle is an interesting one and we really cater to that. On the other hand, there are different other cells like immune cells, like, you know, monocytic cells, histiocytes that show a strong, expression and they, they also modulate the inflammatory environment. So when thinking into pain, if you change the inflammatory environment, you may work on, you know, like two different angles.
I mean, there's, there's certainly the, the pathogenic pain, if you will, like the destructive, like tissue destructive angle of neutrophils and other cells that will cause, you know, certain dendritic cells or certain receptor like just to be damaged and, and causing pain. And then there's also potential direct angle, into the nodeception of pain that has been described in the literature. but on a more kind of high level, if you do change the cellular component and the activation status of these cells in the skin, you, you actually what you are expecting is not just to be active on draining tunnels or their formation, but to over time particularly also move abscess and nodule counts further down, further down, further down, because you're kind of taking away one of the driving factors of the disease, which is really the immune cell driven inflammation in the skin.
So that's why we are so encouraged and we, we do believe it works on all three lesions. There's data in, in the appendix as well on the total inflammatory burden of disease, which is the AN dT count. And also there are clearly and, and differentiated, movement from any placebo ever reported. So I would say, you know, the pain is the most impressive one 'cause it's, it's an integral part of the disease that is oftentimes not well addressed. but at the same time, I would not focus that we're just working on draining tunnels. I mean, we're really working on all three lesions and that, that was the belief that drove us back into the disease. we all had made our experience, like we' re recently all made experience again through another big readout that high score can be very difficult because particularly controlling placebo responses.
And we have a good idea now why that is. We've done a lot of modeling. So I, I paused here. I could go on and on as you can see, but I hope I addressed part of it by really the immune cell composition in the skin. Yeah. No, I appreciate that perspective, Niels. Just one last quick one for me. The step, the, IGE experienced Arm 3, of the CSU trial, just an update on the status and the timing maybe of when you might have data from that. Thanks for taking the questions. Yeah, absolutely. I will hand this over to Camilla. Camilla, do you wanna take the CSU part?
Absolutely. our Arm 3 is, challenging as you know, with this particular patient group.
So we would like to, take, take a, you know, a, a review by the end of November to see how far we have got with that. but those numbers are difficult to come by. we, we will, we will announce the progress in, in due course. So no clear guidance yet when we expect that to be fully closed out. But, yeah, it's been proven very difficult. As you can, probably appreciate, Steve, one of the challenges in these smaller trials is if you provide like a four-week treatment outlook for patients with a chronic disease, it's not necessarily appealing for many of them. So it's not so easy to get patients on board. but, yeah, we don't wanna create excuses either. This arm is recruiting slower. and it's, that's probably why it's usually just looked at retrospectively in the larger studies.
But we're doing our best on that one. Yeah.
Thank you.
Great. Thanks, Steve. so we do have, John Ingerman, but I, I do wanna have one question for, for Camilla, a very important one. And I think in our case, a very, easy and, and fast answer. So that's related to, the use of antibiotics in the HS, study. If you could, give us, a sense of, of how that was, yeah, used.
Absolutely. I'd be happy to take that. So first of all, patients are not allowed to have, systemic antibiotics during the course of the study. And, and I'm pleased to say that no, no patients actually took it. so therefore we didn't have any patients who were on systemic antibiotics. we did allow any patients who were previously stabilized on tetracycline-like, drugs to come into the study.
But I'm once again pleased to announce that we didn't have any such patients either.
Great. And Camilla, if you want to address John and, and, get, get our insight from him.
Absolutely. So Professor John Ingram, thank you very much for joining. And, we are delighted to be able to have you here to, perhaps give your perspective as an expert and, treating clinician in HS, your first impression of the data that we presented so far. And then also, a leading on kind of next level of question is, you know, what do you believe matters to your patients and to you as a prescribing physician when it comes to measuring progress and, or, you know, improvement?
Thanks, Camilla. And yeah, it's a pleasure to join you. it's for me, I'm a clinical academic, so I, I have, two clinics a week and I do HS surgery.
And it, you know, those key issues for our patients, I think the early data is addressing. it's, we have of course these three lesion concepts around inflammatory nodule, abscess, and draining tunnel, and all three are important. the, probably the, the, the, the lesion type that's been most difficult to treat has been draining tunnels. and that's where I think some of the additional focus is at the moment. and one of the issues there is that they can drain continuously for weeks or months. So an abscess might last 10 days and be acutely painful. It may give a, a pain score that's gone from zero or one out of 10 to 10 out of 10 for that 10 day period, but then it will resolve. A draining tunnel, will, carry inflammation typically for a very long term, you know, sort of, as I mentioned, months, quite routinely.
And that produces drainage and odor and, stains clothing and limits a, a person, and will be painful. So they'll, they'll have that pain continuously. So, you know, I thought I, it was, it's very encouraging to see the data that, that you have around, within four weeks. I think we should be mindful that this, this is very short term data in that we have seen in, in treating our patients that if a, a targeted therapy is gonna work, it often works quite swiftly. So this data probably does represent a, a, a demonstration of the, the mode of action being pretty effective in targeting HS inflammation. And that's not a surprise to us in HS. We've always felt that compliment was an extremely good target for HS therapy. the innate immune system is such a big component of HS.
And we've seen, as, as Niels has already mentioned, that, you know, those links, you know, with neutrophil biology, for example, where, you know, it's all part of that pathway, and interleukin one and so on. So, so this is very congruent with our thinking. We've been looking for a, you know, a, a molecule that, is effective against this target. and the early data is encouraging. And I think, you know, we look at the, the overall lesion counts and they are greatly reduced. And, and I think importantly the, the draining tunnel count in particular, and that then is complemented by the patient reported outcomes in terms of pain is the key, symptom of HS is followed by drainage and fatigue. Those are the three actually that, that patients most, value in terms of improvement. And then the overall concept of quality of life comes in.
So that's the, you know, the DLQI you've seen here, some, substantial changes from baseline. The, the DLQI minimum important difference of four points is probably a bit low in HS if, to, to be very, you know, direct about this, that, our patients need more than a four point decrease, but it's a pretty good start to, to at least attain that. And we can see here that, you know, for example, on the high dose, we get a, DLQI mean score reduction of 10 points. And that's the, those are the kind of figures that we really have been looking for in HS because if you have a DLQI score of between 20 and 30, you, you know, you're gonna need it below 10 to really, demonstrate that clinically meaningful change as well as the minimal important difference. So the data, is of course week four.
We would anticipate deepening of response going to week 12 or 16, primary endpoint of most phase III trials. But beyond that as well, although often it's observed case data, you'll see at least maintained, if not deepening of response beyond week 16 up to the sort of one year mark. So, this is, encouraging, very encouraging early data.
Great. Thanks. Thanks, Professor.
Thank you, John.
So we do have a few other questions. Again, it's a reminder that, if you could limit to one question and one follow-up, that would help us very much. We also have now Ryan at Ray J. Ryan, if you could accept the invitation to unmute and ask your question.
Hi there. Congrats on the data. Question for me is, is the 120 mg dose looking like the go-forward dose, given the safety and efficacy data so far?
And, and are you thinking about less frequent dosing cadences given the magnitude of the continued HISCR50 response that you saw? I have a follow-up. Thanks.
Yeah. Niels, I think you can. Yeah. Talk about you and, Camilla.
Yeah. Happy to take that. certainly we, that, that's, that's one route we are contemplating right now, just given that, that it's performing the best on, on every angle of, of the dataset. But, we, we are still doing some, PK, workup. We have not yet gotten all samples in, as you can see. And we will also do simulations that will further inform us. Now, what to your second part of your question, you know, yes, we, we do see potential, ability to mo maybe move this to once daily dosing, but not maybe not right away.
We're trying to assess this right now because we've seen, as you know, like when we take patients off drug after we've loaded them for full four weeks, that, we, we saw quite a good continued response after we've taken them off drug. And the, the, the, the preliminary levels we see at week eight, four weeks after stopping of dosing, are encouraging. So maybe, maybe we can after full loading, you know, in, in like also look into once daily dosing. So that's, that's something that will come out of the simulation work. So we, we can't fully answer it, but, certainly we're not currently planning to go higher than 120 mix. That's clear. But, we're also trying to assess, the, the, the abilities in between 60 and 120 for, for sure.
Got it.
And then, regarding, potential prioritization, you know, how are you thinking about prioritizing, upcoming clinical studies and, and clinical progression for HS and CSU based on this dataset? and, and do you anticipate a, a meaningful target dosing difference between these two indications at this point? Thanks.
Y eah. Very good question as well. I just, I just take it in the interest of time. certainly there like we, we, we judge both datasets as warranting to, to forward the development. Our, our key interest is in probably also a market that is, you know, very interesting just from the medical need, which is HS. And, and, and, and I think the data clearly warrant that. So there will be, an, an initial focus here to move forward with HS.
But it's, that is not to say that we've looked at the, CSU data a lot and we feel there's a clear differentiation to placebo. Obviously, there is the ability to move forward into a deeper response with also targeting not just the histamine slash mast cell angle, but also the angle in like tissue inflammation, which is going on in that disease as well. So there is this clear wish to further progress it. And we think this is a pipeline and a product, potential that we have in our hands. So, while we focus maybe initially to drive, start NHS, there's clear, clear, I would say support internally and also clear wish to move it forward in CSU, but also beyond in some other indications. We mentioned previously the renal space, peripheral neurological space.
And as you probably appreciate, there's, there's renewed interest here in, in the area through a recent deal, but also through a marketed drug that's bringing real sales. So from, from that angle, we, we, we clearly see this potential. Thank you.
Great. Thank you.
Thanks, Niels. And then for those, that are queued up, we, we, we do offer Professor John Ingram, to answer your questions in HS if, if, that's of interest to you. So, let me, so Camilla, this one's for you. It's regarding, you know, the, the data we saw in the CSU arms. And I'm wondering if you can give us your thinking, on what we might be seeing there in the context of other successful drugs and, and, you know, target coverage and, and things like that.
So I, I think what's encouraging about CSU data is that the 60 mg group, a bit like in HS as well, you, you see efficacy with 60 mg. we cannot fully explain why we see the modest, decrease with 120 mg in CSU. We do know that, you know, that there are a couple of patients who seem to, skew the results because of, flare in, in one particular patient, in particular. But, you know, I, I, I guess I like to bring your attention back to the development in Omaluzumab, right? the 600 mg group actually ended up having, worse UAS7 reduction than the 300 mg. Now, you know, it's early days. And as Niels mentioned, we will be doing further PK analysis as well as PK simulation to really try and understand, the efficacy that we should be, focusing on.
But I think, you know, we come away being very encouraged that 60 mg show good efficacy.
But, if I may add, Camilla, and also to the earlier question of Ryan, the 60 mg group, particularly also in CSU provides for, for, for, I mean, it's preliminary PK data, but it provides for a real, good and high exposure as well. So from, from that end, it's a vi like just to, like to basically reiterate what you just said, that, that promotes that 60 mg is a viable way forward too, right? And you just basically also said, in other words, we, we don't fully know yet whether there's an inverse dose response here or whether that is just a matter of sometimes in small trials, you, you may have a few patients having a large impact.
And when you look at larger datasets, that may not be the case anymore. But yeah, that being said, like 60 mg is, is viable from an early PK look, right?
Exactly.
Great. We've got a one question from, Katherine Dellorusso from LifeSci. Katherine, please, accept the, unmute request. Katherine, I think you might be live. Go ahead. Try. Okay. so we'll go next to Andreas Ropko. Andreas, if you could, accept the, the invite.
All right. Great. Thanks, guys. a couple of technical difficulties here. anyway, congrats on these results. two questions for us. thinking about the, the phase II-B in HS, would you be interested in including an active comparator, in, in that study and, and maybe some of the additional comments around, potential, dosing arms there, duration, primary endpoint? I know you showed a couple of, very interesting data points there.
And then, just in CSU, we, you saw, consistent responses across, low IgE, high IgE patients, and also strong effects in severe and angioedema subsets. So do you plan on kind of enriching the phase II- B 3 study, for, for a subset of, of, of those patients? And, could you use a baseline IgE as a predictive, biomarker? That's, that's for us. Thanks.
Okay. Maybe I jump in first and then come back in time for, thanks, Andreas. Lots of really important questions, clearly. I think, you know, for the HS part, we, we haven't yet fully done the, the simulations on PK, but we anticipate maybe at least two, maybe three doses moving forward with placebo. your question was, do you, do you want to put in, or do we plan to put in a comp, like an active comparator?
I know that has been like, I think once or twice been done before, but, if we do so, we haven't fully excluded this possibility. What I don't necessarily like, if you have a certain power, assumption and if you like to do like a certain study just to put a smaller arm in, because I wanna come back, like a lot of people judge like, like efficacy on high score and in small datasets that can be very deceiving, right? The problem with that is, again, if you have two datasets that look in mean baseline and end count the same, they can be very differently distributed in terms of the question is how many low end count patients you have. When I say low is maybe below 10 in the, in the placebo arm.
and if you by chance, you know, are in that, in that noise, those types of things can score results. And so if you have two non-comparable datasets, that's something we would want to avoid. So if we did put in and it's not finally excluded that we will put in a comparator, it's just maybe less likely in my eyes, but it's, it's possible. We'll also do work with experts to discuss that. we would, we would then put it in at the same size and not as a small arm, if that makes sense. And so to the, to the other questions, I think in CSU, I'll definitely hand over to Camilla here in a second. but yes, I mean, we, like we are very encouraged by some of the findings in the more severe subgroup. Why?
Because when we discussed this with our expert, Professor Metz, at the Charité, he mentioned this angle that I mentioned before. If, if you're not just treating histamine from mast cells and clearly the receptor is expressed on mast cells, but, if, if you are also changing the environment, that may have, a different impact longer lasting. and he reiterated two things. The one thing is if you treat that tissue inflammation, that may be particularly important for those that have a very inflammatory phenotype. And, you know, talking about angioedema, if you think about how many patients have angioedema history, it's roughly 40% according to literature. So that it is a sizable subgroup that could be of interest, but we haven't like made that dis decision yet. But, I hand over to Camilla to give more color or, or her, her thoughts on, on, on moving forward in CSU.
Yeah, sure. I mean, currently lots of, great ideas, coming our way and also in discussion with, Professor Martin Metz. I mean, I think we would look at the group with, so-called, you know, who have more inflammation and those who are indicative of, you know, Type IIb endotype, low IgE. But I would say, you know, we still have Arm 3 ongoing, and I think results from that would also help inform in our planning for phase II- B. So, so I think we could potentially enrich, but enriching this group with low IgE will also take longer, and that's been our experience. So it's possible, but also in terms of timing, it will take potentially longer.
using baseline IgE as a potential biomarker, I mean, I think baseline IgE is informative, but I'm not sure if it's a perfect biomarker because, as you know, if we wanted to go fully for Type IIb , endotype CSU population, we also need to think about potential other tests like, you know, basophil stimulation tests, BAS and BRAF and so on. these are not commonly done in a lot of, hospitals. So, you know, it's possible that we may want to think about sub-studies to really see where else we can enrich, right? And how else we can enrich the population. So all things are possible, you know, and, and it's still ongoing. So hopefully more to come at a future R&D day. Thank you.
Great. Great. Thanks for taking my questions and I'll, I'll hop back in the queue for someone else. Thanks, guys. Congrats again.
Thank you, Chris. we do have a question in, in the chat. Niels, this is for you related to, you know, some interest, right? In, in, in the C5aR mechanism in, in recent weeks. And, and, you know, given where we are with the product profile, where you see, where we see potential avenues of, of further development outside of, of HS and, and CSU. Some, may perhaps some, some low hanging fruit on, on that.
Yeah. Great question. So first of all, I wanna reiterate, I think these data further support that we may have a best in class asset here in our hands just upfront. the C5aR as a target is really well researched. There's a lot of studies. C5a, C5aR, over 6,000 publications, in PubMed, and the target is really indicated in many inflammatory diseases, particularly many autoimmune and autoinflammatory diseases.
there have been over the last, you know, couple of decades, lots of efforts to drug this target, but it's, it's a tricky target. C5a, we know really well is a tricky target, but C5aR, it's also not easy because, that's the big contribution back then from chemocentrics who got acquired by Amgen for 3.7 billion some years ago, is they found that allosteric binding site inside the pocket of the receptor that when you target that and your drug gets in there, then you can really evoke a complete blockade of the signal. so that, that, that, that discovery was important. The cyclic peptides in previous history, they all had toxic side effects. They were good blockers, but toxic. and so the, the chemical ones, it was difficult to target, as I mentioned. However, targeting that allosteric binding site means your drug is very lipophilic to get in there.
And then becomes a formulation issue. And that's really where we worked like several years on. Can we find an angle to get to that same allosteric, binding site, but with a, with a, with a formulation and a drug that has a better PK and therefore like blocks that much better in the human system, in the in vivo system? And that's where our drug is differentiated. So recent, activities, there was a recent, Biogen, I think agreement with a, with a, with a small company that has a, that's very, very early. We don't know much about that product. That's been about, I think it's, it's a couple of years away from even IND filing, so we can't really say too much about it, but I think that further indicates there's interest. So long story short, target is well known.
if you can drug it and you have a drug that, fulfills our requirements, I think it's a, it's, it's a very interesting pipeline and a product potential. And, I come back to my first sentence. I think we, we now have a best in class target drug in our hands and we are really excited to move it forward.
Great. Thanks, Niels. Katherine, if you can hear me, we'll, we'll try you again. I think your, your mic should be working.
Yes. Thank you. And I apologize for the technical difficulties here. This is Kate on for Sam Sletsky. I'll be quick here. did you happen to measure C5a levels in the studies and was there any correlation between patients who responded better, to those with higher C5a baseline levels?
Katherine, really good question. I just jump in. We don't have this data yet.
We have though in previous times not seen that the baseline C5a levels, which are elevated, in, in HS, for example, clearly, and also have been reported to be elevated in CSU, they're not necessarily a good patient by patient like indicator whether your drug works or not. And that has to do with a lot of intraday variability about how much C5a is produced, but also with a simple fact, if you have low C, if you have very high C5a levels, you know there's complement activation going on. There's no other way. But if you have low or not, not elevated C5a levels, that can be just because you've, you can't exclude that complement activation is going on because there's so many receptors around that you may just not see the elevation yet because they're soaked up by the so-called big sink.
So our historic experiences that, that C5a levels are not necessarily a good initial guidance. obviously, this drug, just reiterating, it doesn't block C5a, it goes to the receptor, so it wouldn't be a PD marker for our drug either. But, but we don't have the data in yet. We do measure C5a levels and we can probably say more at a later time point.
Great. Thanks so much.
Sure. Thank you.
Thanks, Kate. also we now have Will at, Leerink. Will, you can ask your question.
Great. Hey guys, thanks for taking my question and congrats on the data today. Really great to see. So just one question on the, the pain data for NRS30.
It seems like there's a flattening of response between week three and four, but then on high score and some of the other endpoints, even draining tunnels, we see a really nice improvement between week three and four still. So I guess just curious what you make of this dynamic and is there anything here that we should appreciate as we, we dig into these data a bit more? And then I have a quick follow-up for Professor Ingram. Thanks.
Yeah, absolutely. Good question. I mean, for the 75 mg group, it looks like this, but I wanna reiterate 75%, NRS30 and the two point reduction. No one has delivered that at, at week 12 or 16 ever. So maybe, maybe it is real that we don't see much more than we see already week between week, three and four.
So we will get more granularity on week eight data to make that point. We don't have that yet. but if you look at the dose groups below the 120 mix, they seem to be still moving. So is the 75% NRS30 response the highest we can get to? I cannot answer that yet. but if it was, it was, it would still be at least to me pretty impressive, and, and, and very differentiated from the rest. So sorry, I can't give you more at this point in time, but we, we may have more over time. yeah, I think the author had a question for, for, Professor Ingram.
Yeah. Great. Thank you so much for that, Niels. Appreciate it. And yeah, just for you, Professor Ingram, appreciate your time today.
I guess just quickly thinking about the, the evolving treatment paradigm in HS, it's, it's seen a lot of, you know, recent data sets over the, the past 12 months or so, but when we think about INF, I mean, I could see it being a very valuable second line option for people who, you know, failed biologic therapy, but then it's with this really rapid onset of action here. It seems like it could be a very valuable first line option as well, so just curious to get your preliminary thoughts on how it might fit into the treatment landscape, assuming these data are replicated in, in future studies. Thank you so much.
Hey Will, yeah, I think I was also gonna comment on your pain question as well, because some of that flattening until week three to four may in part reflect that you have to attain that at least three point reduction in pain. And when baseline means are around six or so, it may be that, you know, to some extent you kind of produce that rapid improvement. Then there's a bit of residual pain, for example, from chronic scarring as well in HS. So maybe that some patients it's quite hard to get their pain scores down, you know, to complete, sort of, low levels because of that scarring too.
But in terms of, of where, you know, INF might sit in terms of, you know, the treatment pathway in HS, some of this will depend on the delta really, in terms of comparison with, for example, anti-TNF biosimilars. you know, the, the payer will, be mindful of that. If we, there's a demonstration of improved efficacy beyond those biosimilars, then the cost benefit equation may allow, you know, to be the, the first, targeted therapy. What we've seen, of course, in recent times is that phase III results, there, there's, there's nothing that's a, a substantial improvement above, say, Adalimumab, biosimilar or Adalimumab in the pioneer studies in terms of its high score 50 attainment. And so there's probably then payers might consider this, you know, subsequent target therapy to be second line, after, the, the biosimilar on cost grounds.
What we look for now is for a targeted therapy that performs substantially above those levels so that we can advocate that they should be first line as a targeted therapy, and that's where I think there's an opportunity because HISCR50 is not a very high bar. You know, someone might have 20 inflammatory lesions to have that reduced down to say nine or eight is not remission. It's not even minimal disease activity. It's still ongoing active disease, so we are now looking to see if we can get, you know, higher efficacy bars and get increased attainment, and then we could, you know, ideally look to for those new therapies to be positioned potentially, you know, even first line in the targeted therapy pathway.
Excellent. I really appreciate the insights there and congrats again, guys. Thank you.
Thanks.
Thank you, Will.
I think we'll have a couple more questions. I know we're a little bit over time, but trying to cover as much as we can. Our next question is from Dev Prasad at Lucid.
Hey guys, congrats on the data. And just one question from me. So now you have those several patients with the INF904. What's the emerging safety narrative for regulator? And are you any class related concern you are proactively monitoring? Thank you for taking the question.
Absolutely. I may take a first step here. So, yeah, you're right. At this point in time, we have no safety concerns that emerged from all the, and you know, remember we tested very high doses, up to 240 mg in the phase I study. So I think from that end we are good.
We have a preclinical package up to nine months, non-human, GLP, non-human primate tox study, and also no safety signals of concern and no real dose limiting toxicity detected. From that angle, we, you know, we see an interesting opportunity for a safe oral in the future. Obviously, we have to still prove it, but so far it looks like that. Now what are we monitoring? There's no class effect known. I think generally blocking the pathway is, it can be considered very safe. There have been, there was one liver induced toxicity in the Avacopan approvals and there've been some signals since, but that's related to Avacopan in our eyes. It's a very, you know, you know, decent inhibitor of the CYP3A45 liver detoxifying machine, as I call it.
And we have shown preclinically that we are 36 fold less engaging with that enzymatic apparatus. So very likely we, we don't have that problem, which would be great. Are we monitoring anything to, I mean, we are always monitoring safety obviously. And one thing for any immunomodulator is always generally speaking, if you have like an infection risk, for example, over time, and that's also expected by regulators to monitor that. Now that, that will be only looked at in like controlled studies that are longer term dosing. but really, yeah, from that angle, I think that, that covers the question. I don't know, Camilla, if you had additional thoughts on that one.
No, you've covered it. T hank you.
Okay. Thank you.
Great.
One more question, I think, Niels and, I think Professor Ingram, I think a good question for you regarding, just thinking about potential synergies with other mechanisms, in HS, for instance, IL-17s. Clearly it's early days, but we like to speculate on things like that. Niels, I don't know if you had any idea or, John, Doc, Professor Ingram, anything?
I would really defer here to Professor Ingram first, first line, John. I think you are much more positioned to really, I have my biological ideas about that, but I think you as a treating physician, with so much expertise in HS, I think, I'd like to kick that question over to you.
No problem, Niels. Yeah.
And I think, you know, it's a great question because we've seen so far that, that monotherapy is almost a luxury in HS that we've yet to really see, you know, a single agent provide us with, you know, a, a universal minimal disease activity state in our patient cohort. So we're already, using co-treatments routinely in terms of a targeted therapy plus, say, an antibiotic or an anti-androgen therapy. And certainly I'm aware of case reports and colleagues who are, using, two targeted therapy agents, to, manage their most challenging patients with the highest inflammatory burden. So it's very much the case that, we have these multiple pathways in the HS pathophysiology, the inflammatory soup that exists in the dermis of HS lesions. And so of course there'll be safety considerations, there'll be cost considerations when we, combine more than one targeted therapy.
But in terms of reaching those higher efficacy bars, that's certainly a possibility that is already in use. And, you know, we, we're also familiar with, you know, bispecific options and so on. So I think that, that it's a compelling option. but I think of course it's, it's quite a fair way down the road in terms of current, development of, you know, of, of INF and others.
Thank you, Professor Ingram. so one more question, Niels. This one is for you since you, you punted on, this last one. it's regarding, just giving a little more color in what you think we're seeing, with the PK data and, and what we're thinking about the, the end of study portion where we, we saw continued, efficacy in, in many patients even four weeks after, you know, dosing has stopped.
Yes.
So maybe I start with, I mentioned that, we have like, levels detected. That's preliminary. So we don't have all the samples in, but the preliminary one suggesting a range of, plasma presence in the range of, let's say, 50 to 200 nanomolar. And, and that's about where, where like, that's the range to where Avacopan accumulates at week 13. So, that's why we're saying, we still have drug levels that are able to block how much I, I can, I couldn't tell. And that depends, by like patient by patient. We also wanna see if this is like more pronounced in the 120 group versus the others. We have to still see this data to be more granular and get more data in our IC 50 of the drug is around 25 nanomolar, which is pretty much exactly the same like Avacopan.
But our ability to reach a blocking level in, in plasma and in human tissue is, is clearly higher with our differentiated PK and formulation. So that also illustrates that these, these levels are over the IC50. So from, from, from that angle, we are confident that what we see still provides some blocking. Now, clearly not the same level as during full dosing. And the idea is now to do simulation work to understand, what may the half life look after we loaded the tissue after week four? Can that be simulated? Can we, like, how long will we have full coverage of those four weeks? and maybe if after loading is, is a less high coverage enough to continue an improvement, right? These are the questions we right now have. We can't address them all with PK simulations, but maybe some of them.
But I hope, I hope I could give you a bit more color on why we believe there are still active drug levels at the end. yeah.
Great. Thanks. So we, we are out of time, Niels and Camilla. Obviously, thanks for joining us. Professor Ingram, thanks for, for, joining us as well. for those listening in, you know where to find us. You can reach out to us if you have any questions or need anything, any follow-ups. we are available via, via email. So again, thanks to everybody. you are free to drop off.
Thank you.
Thank you.
Bye-bye. Hey.
Hey, so I think there are still 90 participants. I'm not sure if we're off, off or not.
Yeah, I was, I was wondering that too.
Anyways, for, for everyone who's still on, I wanted to say big thanks for all the contributions, all the work, all, but particularly for John, Ingram. I, I know he had clinics this morning, so he was like hard pressed to get in. and he's been very patient with us. So thanks so much, everyone, and the entire team for making this happen. MC service team, you did a great job. I think this went all smoothly. And, yeah, I hope we could cover some analyst question. Obviously, there's only, only that much time, but, hopefully, we can, have discussions now with them after the release here. All right. Big thanks to everyone. I will jump off as well in case you still hear me. hopefully you got the thanks and, we'll be in touch shortly. Thank you. Bye.