InflaRx N.V. ($IFRX)

Good morning, everyone. Thank you for standing by, and thank you for joining our conference call this morning to discuss our recently announced effort to pursue izicopan for AAV and other renal diseases. [Operator Instructions] Please note that today's call is also being recorded. [Operator Instructions] I would now like to turn the call over to Niels Riedemann, CEO and Founder of InflaRx. Niels, please go ahead.

Thank you, Jan. Ladies and gentlemen, good morning, and thanks for listening in. It is our pleasure to be sharing with you our recent prioritization here on the renal space, particularly in the ANCA-associated vasculitis. So may I please ask to forward to first slides. Please take note of the important notice and disclaimers. We will be making forward-looking statements. We are a public-listed company. So I appreciate your taking note. Next slide, please. So we're excited about our new molecule izicopan which is an oral inhibitor of the C5a receptor Kibana really. It's a C5a/C5aR pathway is a critical driver of inflammatory cascade, both angles, C5a ligand and its main receptor C5aR, both validated targets from a clinical, both and the regulatory and commercial perspective also in ANCA-associated vasculitis. So there's promising clinical data with C5a antibodies, vilobelimab and [ PDB1 ] as well in the sense of ANCA-associated vasculitis that I want to flag here. So this -- the recent regulatory scrutiny are related to a marketed comparator, our copartners provided InflaRx with a clear and present opportunity with its next-generation C5aR inhibitor, izicopan. So we believe that we have improved significantly on certain shortcomings, if you will, or certain areas where improvement could take place with our molecular, izicopan, and we believe it has best-in-class potential for mainly 3 reasons. We have a very fast onset of action, and that needs to coverage of the receptor right away as far as our PK/PD analysis goes in humans. So far, we have a very clean safety profile, no detected safety signals of concern, and we have properties that make drug-drug interactions and particularly potentially liver tox less likely, and we will go into this a little bit. And we also have potentially more convenient dosing, but also the possibility to still to go to once daily dosing. So we're excited because this molecule can address different markets and potentially here, first, the ANCA-associated vasculitis market, which is currently believed to be $1.3 billion peak sales estimate and given our properties, maybe we can expand on this market even. We see use of this particular molecule across the broader I&I space, but particularly also in the renal arena particularly in aHUS, IgAN, C3 glomerulopathy and some others. And we are also intending to provide first proof of concept in due course here in these indications. So we have a strong IP position. This is our molecule, composition matter is issued, and we have really an issue situation already in various jurisdictions, particularly in the U.S. and Europe and other areas. Next slide, please. So before we go into it, just as a short reminder, because we oftentimes get the question, why don't we just take upstream complement inhibitors. You are all well aware that there are very successful molecules in the complement world on the level of C5 inhibitors, C3 inhibitors, factor B and others. And one of the reasons really is that there's different ways to generate C5a. There is a path from the complement pathways, but there's also a direct leverage mechanism through all sorts of enzymes that are present in various inflammatory diseases. And that these envelopes directly outside the reach of the mechanisms of these other drugs. So you can generate full-length biologically active C5a to large amount even in the presence of these inhibitors in human blood. We've shown and in published this. Therefore, if you believe the great body of work of over 6,000 publications on clinical -- preclinical research around the C5a receptor and the ligand C5a to be meaningful in the I&I space, you may appreciate that a target inhibition is really what you need to control the pathway. That brings us to izicopan, our oral C5aR inhibitor, which may be applicable in multiple inflammatory indications and which has shown a very good control over the signaling pathway here in its first Phase I studies and also in the Phase IIa study. Next slide, please. So I want to come back to the point of the best-in-class -- potential best-in-class properties of izicopan. And I want to slot this into 3 areas, particularly. So we designed this molecule to give us a different plasma presence from the one reported for the marketed comparator. You see on the upper right side, our -- in blue, our human PK data from the Phase I study. And please note, it's not a head-to-head study with avacopan. This is just a reported Phase I data from a plotted in this graph, but it gives you a visual that at 30 mg, which is the approved dose BID for avacopan, if you take a single shot of 30 mg and compare it to izicopan 30 mg, you see this as the order line above it, you already have a 10x area under the curve increase in PK and a higher peak, 3x higher peak and just a very different plasma presence. And why is this important? Because we believe this reads through to receptor coverage and speed of onset of action, and we have various data to support this belief. And particularly, we also are able with our formulation to updose very highly up to 240 mg, you see here, safely without safety signals of concern. And that may be important to explore the full bandwidth of efficacy if you think of tissue presence of this because remember, PK and PD so far in complements mostly measured in the plasma influx. So that was our starting point, but we quickly learn that our molecule is very differentiated on other areas as well, particularly potentially to improve safety profile. So far, we have over 180 humans exposed and a very clean GLP toxicology study package, including 9 months nonhuman primates. We also have done studies to further characterize the molecule in seen that deliver enzyme CYP3A4, which is important to clear and metabolize chemical drugs like avacopan and our own drug, but also like other drugs, including corticosteroids, may be inhibited by certain drugs particularly within the label of avacopan as a time-dependent inhibitor. And we have recently shown that we are not a time-dependent inhibitor, in fact, we have explored this to very high concentrations and believe that we are not inhibitor of this mechanism. We also show a differentiated profile in metabolic stability. So all these indicates that we have a molecule that may not have the liver tox issues that are in the label in our market comparative. And we also may have a dosing advantage. We have 30 mg per capsule as opposed to 10 mg for the comparator. And we still see the potential for once-daily dosing according to our current modeling of our Phase IIa data that we recently got. So we're really excited about this differentiation last but not least, from a patient's perspective on the lower right corner, you see again, this was not a head-to-head study. This is just plotted in the graph. These are the data that avacopan approval data in ANCA-associated vasculitis, where it's mentioned that it takes 30 weeks to reach steady state. And you see here some data from our early Phase IIa study, different diseases in HS, hidradenitis suppurativa and in CSU, chronic spontaneous urticaria. But you see that we tested 60 mg BID, 90 and 120 in these studies. And already at 60 mg BID, we have a multiple of that plasma presence right off the bat. So we believe that we may have a faster onset of action with our drug. Next slide, please. So I want to speak now a bit about ANCA-associated vasculitis. Next slide, please. This is a rare disease that typically is an auto inflammatory -- autoimmune style disease. There are certain antibodies directed against neutrophil features that excite these cells and other cells, but particularly when finding these neutrophils, they involve various orders because they involve the endothelial cells in the vasculature which can affect all organs on the right side you see typically most affected all in the renal is the kidney. So you see here that the glomeruli in the row A, B, C and also the small vessels G, H and F for complement factors. So complement is activated in the kidney and that drives, but also in the vasculature of all organs and that can drive damage. The [ orphan drug ] market. I mentioned already that it has a large market potential. We also want to just mention that there are different subtypes that tax that usually studied in multicenter studies are called MPA and GPA. There are certain differences between these 2, but I want to -- in the interest of time, not go into that detail right now. However, the current treatment medical needs are clear, there is an induction of remission treatment that usually entails either [ psychophosphamide or rituximab ] in combination with very high-dose corticosteroid treatment. This is a very toxic treatment for the patients. The patients suffered dramatically from the corticosteroid use, and there is a high unmet need to get the patients as fast as possible in remission and of the rather toxic high-dose corticosteroid drugs. And then there's also a remission or a maintenance therapy, which is usually done with rituximab and which is unit then initiated. There are also some other drugs that are usable according to standard of care that is usually initiated after you achieve remission. Next slide, please. So the next slide, please. The mechanism just one back, please. Thank you. So the mechanism here is very interesting and included both C5 and C5a receptor. I mentioned these antibodies you see there on the right lower corner, that are directed against features of the neutrophil and actually excite complement right on the surface of the neutrophil, which is covered with C5a receptors and get that immediately excited puts out oxilate [ radicals ] enzymes undergoes [ nephrosis ], induces vascular damage really that can enter a vicious circle because with the damage, there's a lot of coagulation initiated and microangiopathy happens so to speak, and more C5a is released because of these mechanisms and because of these enzymatic activations that I mentioned earlier. So that's the vicious cycle. And clearly, C5a and C5aR are believed to be drivers of the disease. Next slide, please. So let's look at the market a little bit together. Indeed, I mentioned that the global market for [ TAVNEOS ], avacopan, our marketed comparator have been suggested to be roughly $1.3 billion at peak sales. You see a graph on the right side. And I want to mention that the mechanism of action has been well established in major markets. When you think about what U.S. physicians think there was a recent survey about from 21 U.S. treating physicians that treat a lot of ANCA patients in -- they typically like the C5aR inhibition and initiated treatment during the major flare phase and then continue treatment for 6 to up to 48 months. And the real reason why they give the drug according to the survey is almost all of them say for glucocorticoid reduction, I mentioned that need already, but also some mention for renal function preservation and generally for all in preservation. There are concerns about the tox profile and some recent reported liver tox issues. But also physicians say that they monitor for it, and it is decently under control, at least comes from the U.S., and we've heard similar from European physicians. When asked for product X with our profile, they see a potential strong share from new AAV patients, but also some switching promoted in the year that they believe that currently, they treat roughly about 15% and mean it could go up to 55% and then up to almost half, 45% here may also switch over. So this is highly encouraging for our product development and next slide, please. So how do we get there? What's the -- we call it the rock to boat scenario. So how would the label look like? Ideally, you would like to have a steroid reducing a rapid taper enable. So that's part of your label, which is not currently the case for our competitor. And ideally, you demonstrate early benefit, early reduction of proteinuria and improvements in eGFR, both signals were present for avacopan I should mention and then also potentially improve the time to remission. That's something that we believe our drug may show. Additionally, of course, ideally, a clean label, ideally no liver tox on the label. And then last but not least, convenience, lower capture intake or even once daily dosing. You see corn here how important steroids reduction is for certain physicians. This was an interview from an external research we conducted. On the right side, so the overall development role is like trying to increase the signal data to placebo, especially during the early major flare phase. Now how do you get that done from a study design aspect? You want to enroll patients fast. You don't want to mandatorily taper them down to a certain level, which was previously done in studies, which kind of preselected a bit better patients because they were already out of the out of maybe out of -- or to a certain extent, already doing better. And then you can enrich for patients that have severe renal impairment. We got that recommendation from various experts in the field. They believe that you can go early and go to very severely real impaired patients. Obviously, another idea would be to fix the remission induction to rituximab in combination with corticosteroids. And I mentioned also, of course, you would like to have an aggressive rapid steroid taper paper in your treatment arms to demonstrate that you can do that. Next slide, please. This is really presumably the current planning stage of a Phase II trial. We have a base case scenario in which we do a Phase II or we call it Phase IIb trial, but the 2 trial followed by a Phase II much like the development path that [ ChemoCentryx ] back then did with avacopan, however, we are putting the studies, if you will, together, but we're also trying to rein some of the feedback that we gathered from earlier interactions between [ ChemoCentryx ] and the agencies, particularly the FDA, as this was published in the approval documents. So you see here placebo standard of care arm with a general standard GC tapering approach, GC stands for glucocorticoids and then a drug approach instead of placebo with the exact same underlying treatment to establish signals of efficacy. And then the third arm would then just go to rapid taper to say that when you're at the taper, you do not differentiate from the signal that you have detected in arm 2. Now this will be a 26-month week readout because we won a 6-month endpoint for the renal endpoint of eGFR. We may or may not go to 52 weeks and to treat out to get more data, but the unblinding would take place after week 26. As far as endpoints, the first Phase II is a safety endpoint descriptive nonpriority for BVAS 0, BVAS the score used, Birmingham vasculitis activity score, used to see if you get into remission and when it's at 0. But we also want to really focus our secondary efficacy on the early criteria. We believe there's good reasons to believe that there's a good delta early. This was visible with treatments on C5a reduction inhibition just as much as the avacopan at week 4. We will look at eGFR, a signal of renal function at week 26, and we also invested time to remission time to BVAS 0, amongst other secondary incomes. Next slide, please. So once we selected that and assuming that the efficacy determined comes with or without the rapid steroid tapering, we would then go to Phase III approach just very similar to what you would be familiar with from the approval trial, except again, we would probably adjust according to the signals detected in the first trial. So there's a scenario on where we go to a noninferiority on BVAS, paired with a superiority, which could be different. In this case, for example, eGFR be it 26 or 52 or time to BVAS 0. And scenario 2 would be to directly power for superiority if any of the end points allowed to do so. So that will be determined only when we have the data. Currently, the planning is that will be roughly 150 to 170 patients per arm. Obviously, that needs to be adjusted once we have data and do a statistical planning. Just as a rough idea, the Phase II study is what we have here currently fully financed. We see the financing reading through 2029 right now. So we believe we cover -- we will cover the readout of that Phase II study that I introduced to you in the slide before. Next slide, please. So there's also an aggressive approach, if you will. We also plan to go to the FDA given the recent environment, regulatory environment to see if there is a more expedited path with this new drug. Now we can't promise, but we certainly want to make a push. We have certain ideas how to do a seamless Phase II/III registrational trial approach. Obviously, that would entail going back with some data after the Phase II part to the FDA. But if the FDA, the agency was amenable to it, we would certainly try to discuss this with them and potentially that could reduce the time to commercial market significantly. Next slide, please. So last but not least, I want to share with you a bit of the excitement around the real indications that we will also investigate in a more open label fast fashion so that we have data to come as early maybe as next year and in the next couple of years before the ANCA vasculitis readout. Next slide, please. We are particularly focused on 3 renal indications, and we have a network that includes center s that are very, very familiar with these indications and with complement inhibitors in this indication. I want to speak very briefly. You don't have to go to go through the entire slide, but why have we selected aHUS, IgAN and C3G. Now all 3 have in common that there is an approvable accepted endpoint, which is more or less a biomarker endpoint. I will explain to you the TMA response for aHUS in a second. But you probably are familiar with the surrogate marker protein urea reduction in IgAN as well as in C3G, both will be then followed by -- with an eGFR stabilization as confirmatory endpoint. So that's an interesting environment because proteinuria reduction is something that was seen in these indications also with avacopan before, and I will show you the data in a minute. And in aHUS, that is actually a relatively rapid response that you could already men early and we sure that, too. So all 3 indications have an interesting biomarker approval that has been at least in IgAN and C3G have shown to be present in early studies with avacopan. And in all 3 indications, there are complement inhibitors already improved. However, we may see a big advantage to have a drug that you don't need vaccination with because we don't inhibit the membrane a tech complex, the arm of the component system that if you block it, can cause serious infections, including meningococcal and meningitis. And we have an oral drug that may be an advantage on some of these indications. And so let's look into it real quick together. The next slide, please. So aHUS, atypical hemolytic uremic syndrome. Next slide please, is an interesting indication. You know that this was one of the first indications were Alexion's drugs, [ Soliris and now Ultomiris ] have seeked approval with this TMA response, you find that definition below that, that means you normalize the platelet count, you normalize the serum LDH levels and you improved the serum creatinine by 25%. If you reach all 3, you call the TMA responder, and these are small open-label trials that have led to approval based on this end point of these complement inhibitors. Now some say, okay, is there really -- these are actually pretty interesting large markets, given the high price in this real life threatening disease. However, next slide, please, you may argue, well, isn't that a MEK-driven disease, which is in the front of minds of some people we've spoken to. However, Well, the answer from us is, well, that's not really entirely clear if it's a MEK or a C5a-driven disease or if it's maybe even predominantly see C5a-driven disease. Why are we saying that? Now there experiments done with avacopan on the right side, you see that they use treated patients with aHUS and use the serum before treatment and after to excite platelet endothelial cells. And then they saw when you excite these cells and then you let blood flow over, you all a sudden see platelet aggregation, which is one of the hallmarks of the disease. Except when you do that with the treated serum, you see that also below in the graph, you're almost back to normal levels. So the red bar is basically control where you don't excite these cells. The bar in the middle is the one where you give the serum of the sick patients that actually leads to platelet aggregation and then the one with the treated serum. Now we have -- and on the right side, sorry, I should have said that, the MAC formation is not affected. Now we have confirmed this with very similar experiments with our antibody, vilobelimab that blocks the ligand C5a and with our new molecule, izicopan, the oral C5a/C5aR inhibitor. And so we believe that C5a/C5aR seasonal may actually be 1 of the key drivers of vascular damage in this disease. And we would love to test this because we can test as relatively early. And if successful, we could potentially introduce later an oral drug into this space, which doesn't need vaccination. Next slide, please. IgAN, next slide, please, is rare or a pretty large rare disease, if you will. So there are quite a few patients for being a rare disease. It's one of the larger renal diseases. And this is also a disease which involves the kidney and complement activation, in this case, also an antibody-mediated industry. So without going into all details, there are complement inhibitors, one is approved, which is the factor B inhibitor. It's an oral inhibitor, which has shown proteinuria reduction followed by eGFR improvement. And very recently, just a couple of weeks ago, Alexion's trial, AstraZeneca trial, the readout with [ ULTOMIRIS ] with the anti-C5 antibody and also shows a significant proteinuria reduction, which was a Phase III clinical study. Next slide. Now with our drug work, we believe there's a good chance. Why would we believe that? Because avacopan was tested in this disease. You see here, these are just 7 patients preselected went into the short-term treatment of only 3 months, but you see in the center graph that proteinuria measured by urinary protein creatinine ratio greatly reduced for being such a small patient group. So certainly, they look like a signal that's kicking in after about 8 weeks of treatment, and also, there were signals of less inflammatory markers in the kidney in the urine, I should say. So clearly, early signals, but in line with the role of complement and very encouraging to test this further. Next slide, please. So we come to the last indication, with C3 glomerulopathy. C3G, nex slide, clearly another complement-driven renal disease. In this case, slightly different mechanism, like predominantly involving the alternative parts, but in the end, usually, all parties are excited through that. And again, an interesting case, this is a more rare but also very interesting disease with a very high unmet medical need. And here, you know that the former [indiscernible] drug, [indiscernible], was approved for proteinuria reduction followed by eGFR improvement. So also the role of complement well established. The next slide, please. Now would the C5aR inhibitor approach work? There are early signals of efficacy, again, generated back then with avacopan. This was a trial of actually 22 patients for each group, so not even that small for being such a rare disease. And again, you see a nice separation between the placebo and the treatment curve on UPCR, so on proteinuria. And also you see the eGFR differentiation after time of treatment, which is typically 26 weeks. The first time where you see it better. So there is a common thread, next slide, please. There's a common thread in these indications where complement inibitors are improved, where the regulatory pathway is clearly established on signals that have been seen with C5aR inhibition. So we're very excited to test this and to put up a study in which we can improve early growth concept to maybe then roll out into more serious development should we see a good signal. We think that can be done relatively fast and cost efficient, and this is what we are planning here to do going forward. Again, I mentioned we have an expertise in that work last but not least with these clear endpoints and the differentiation of our molecule, this could be a very interesting expansion into the renal disease. So last but not least, next slide, I want to also talk about hidradenitis suppurativa. I'm excited. We have guided the market that we would have interesting discussions with the FDA, and I'm happy to say that because we had an interesting Phase II readout that we hold a biological like activity just in 4 weeks of treatment, the pretty deep reduction of draining tunnels and significant improvement in pain. We went back to the FDA and concluded our discussions, and we think we majorly move with the agency over the years. So they acknowledge the importance of draining tunnel as a major contributor to HS disease, which is really a big thing that changed the position there and is supportive of a new endpoint in HS, the so-called hidradenitis clinical response score, which could be validated in the Phase IIb trial and potentially used as a new primary endpoint of pivotal trials. Now why do we suggest that this would be the first endpoint that actually includes in a meaningful manner, the DT reduction, draining tunnel reduction into an endpoint and thereby we hope and we believe it may help to control placebo response rates much better than the old endpoint, given you need, of course, have a drug that meaningfully moves all lesions, including particularly the draining tunnels. And you can see the details. So we see this as a potential great potential for the future. We would, at this point, only develop this further with the collaborator. But we believe that this field needs new drugs with new mechanisms and we believe that could be an interesting path forward. So we wanted to not withhold this from you guys to make sure that we did progress that quite well. So this remains a potential future upside but cannot be our current focus of development. With that, I'm really thankful for your attention. We conclude the presentation session, and I will hand over now to Jan for the Q&A session. Thank you.

Thanks, Niels. So yes, we'll have about 15 minutes here for the Q&A session. [Operator Instructions] So we have our first question from Yatin Suneja at Guggenheim.

Yes, can you guys hear me?

Yes.

Perfect. Guys, thank you so much for taking the question, very nice presentation and the overview. So I have a couple, if you could sort of address them. So number one, on avacopan front, right? So there are basically 2 debates. One is on the safety. The second one is on the efficacy. So the question, and I know now you sort of touched on it, but if you can maybe frame for us what gives you confidence that the talks that avacopan has is a compound-specific issue not a class-specific issue, and you do not get that, right? So that's one part. The second part is also on the efficacy. And I think there is some debate if we read a little bit about it that maybe the efficacy is under question. So can you maybe put in perspective in terms of what we have seen on the efficacy front with this mechanism across a number of renal indication like what exactly, because when we talk to nephrologists or rheumatology, the reason they really like avacopan is the data on kidney protection or organ protection, which we don't see it on the label. So I'd love for you to sort of put these things in perspective. And then I have a follow-up after that.

All right. Thanks. Very, very good questions. Thanks, Yatin. We appreciate that. Yes. So let me start with your liver tox question. So we've done a lot of work on our molecule and try to understand where the differences lie. I Mentioned the CYP3A4 inhibition which were not a time-dependent inhibitor. We believe this is very important because this pathway metabolizes a lot of drugs, including our drug, and it's also one of the metabolic pathways on how avacopan and its potential metabolized may get to metabolized. So in a way, if you time dependently start inhibiting this mechanism, you may slow down the metabolization of certain drugs, but also maybe of your own metabolize. So we -- aside from this clear differentiation on CYP3A4, we also looked at metabolic stability. Obviously, these are all preclinical assays that are managed to scout, whether you fall into certain higher or lower level of concern, so to speak, and all chemical drugs can be in these categories. And we've seen a very strong difference in metabolic stability in, for example, the GSH [ trapping ] studies that we recently done had ahead with avacopan's molecule. So there's really an initial big differentiation, which stays over time and like in several orders at the beginning and over the entire time in an order of magnitude when it comes to, like, in this case, the active metabolite formation in this assay. We've done also other metabolic assays in liver microsomes to understand this depreciation. So we came out with the conclusion that our drug, which is very different on the 3-dimensional layer. It has 3 [indiscernible] centers. It is -- it is an amorphous drug and not crystal in a steady state. So it is quite a differentiated drug, but particularly, it's pretty stable in these metabolic assays. So this, including that we have over 108 patients already with very high doses tested, granted only up to 4 weeks, but without any signals of safety concern with no enzyme and GOG GPT elevations in the liver that were AEs or [indiscernible] none of this occurred, plus the fact that we have all this differentiating mechanistic data in the preclinical studies and a very clean overall tox package. We can only say that until today, we have no reasons to believe that we have this concern. That's where our confidence comes from. Now there's no reason to believe that this is an effect of C5a/C5aR pathway inhibition. We have never seen this with our highly potent antibody blocking the ligand. There is like a myriad of research on different C5aR blocking molecules preclinically that actually have been shown to be all in protective in certain diseases, particularly also the liver. So really, there is no reason to believe there's a class effect. We rather believe that this has to do with the molecules themselves and they go into a liver tox signal. So I hope that covers it from all angles that we can cover today. To your second question, is the efficacy question. Yes, there were some questions around that. So I would like to start by the data that I showed you here at the end of my presentation. So very consistently avacopan has shown that it had effect on proteinuria on eGFR improvement on the renal side of the game. So I would argue that this was also present, by the way, in the ANCA vasculitis study. And even though there is regulatory scrutiny around the molecule, and we cannot speak about the details of these ongoing scrutiny situation with the FDA. But from all we understand is that these efficacy signals, they're all there and they're all real, right? Our understanding is that there is a debate around how BVAS was adjudicated at the end of the 52 weeks. So from our understanding, there are various efficacy signals that came out of the study with avacopan. Now we believe we can build on them. We may be able to engage patients earlier, go to more severe renal patients to make these efficacy signals with a faster, potentially faster acting drug more visible. So I hope that covers it. Would we necessarily power for superiority on BVAS at week 52? That's a very tough game as far as we believe that avacopan was tested but not powered for superiority [ as ] that endpoint. So that's a matter of finding the right angle with the FDA how to approach this. But we do believe there are various signals, valid signals of efficacy of avacopan in ANCA vasculitis, and we want to build on them. it.

And then just a quick one. How could you use China as a region to generate data maybe on a faster pace across the indications that you're pursuing?

Yes, thank you very much. That's a very good question. So in the recent years, there are certain areas that have been explored by larger companies like companies like Novartis, AstraZeneca, Alexion and others in the renal space as far as I believe also Roche and others that involve the renal space in China, there is a network that we know very well. We're very well connected to that network and to Professor Zhou, Z-H-O-U, that runs this network in Beijing and Shanghai that can lead to very fast enrollment. The reason why we're knowing so well through our contact there, but we also we developed our BDD001 license molecule that is the vilobelimab IV antibody targeting the ligand licensed to a Chinese partner. And they are in Phase III development. They did a very rapid 100-patient Phase II development within this network. So we know that the enrollment speed can be dramatic there. which we believe we can explore. Obviously, we would not just enroll patients in China, but we could certainly make like benefit from this amazing network that has ample experience not just in ANCA vasculitis ancovusculitis, but also the 3 other indications we mentioned here. So we really try to exploit that speed factor to get faster to data. But I mentioned, we cannot just go to China, so we'll also want to look at Caucasian patients, of course, in other regions.

Great. And then I think just reiterate a bit on the other renal indications we talked about, we think we can start showing some data next year on the IgAN, aHUS and CG3 [ in ] one or more of those next year. Okay. So in the -- moving on quickly, I want a couple of questions we have that were submitted to us in writing. The first one is from Sam Slutsky at LifeSci Capital asking that based on your PK/PD data, what go-forward dose do you envision using for AAV?

Yes. Thanks for this question. So Sam, good question. So we have not fully concluded this. So this has been taken with a certain care. We have explored so far 60, 90 and 120 mg BID in other indications, right? 120 mg is a bit on the high side, but we tested the drug in the skin disease hidradenitis suppurativa, which usually like meets a lot of truck levels to show these lesions improve. So our current data model suggests that we could move with 60 mg BID. Again, we cannot finally fix it today because we also are looking into switching this to cut and how we best switch it. Our modeling data suggests we can do that. not right off the bat. So expect us to have, at least maybe during the early treatment in the remission phase to the BID, but then potentially switching to [ QD ].

Great. We have another question that was submitted early on, just wanting you to talk about -- also talk about the market potential we see for izicopan in AAV and perhaps also in these other renal diseases that we'll be looking at.

Yes. So I'll start with AAV. I mentioned there are 2 reports. One is actually from Yatin Suneja and then the other one, I showed the market research suggesting that the peak sales of [ TAVNEOS' ] avacopan could be clearly north of $1 billion, maybe up to $1.3 billion. Now we are very encouraged by talking to physicians, and you saw the survey from Sam Slutsky from LifeSci of U.S. physics that currently, they don't have the majority of paints are not on these drugs. So there's a large potential to either put them on the drugs more with maybe a differentiated label or less concerns. So we think that with the profile our drug has, this opportunity could be expanded beyond the $1.3 billion. We can't say how much. We're just saying the initial research suggests that there's space to really expand on it. And that's what excites us. Now on the other renal indications, these are all interesting indications. IgAN is a relatively competitive field, but pretty large markets. So these are certainly really interesting indications as well. aHUS is at a high price point, but it is also in a very large selling indication for rare disease last. And then I think C3G is not fully built out yet. So we don't fully know how large it is. But all of these are believed to be up to above $1 billion by various players. So we're excited because of the profile, and we'll try to capitalize on building it out in the renal space here.

Great. We have 3 questions in the line. I think if we then pretty quickly, we can do them before the time. First one is from Timur at Cantor.

This is Timur on for Steve. So just to follow up on something you mentioned earlier about Phase III design I think the FDA was previously fairly insistent on superiority on sustained remission of sustained remission. So why do you think the FDA would think different by now? And when do you expect to discuss this design with the FDA?

Yes. Thank you, Timur. Yes, absolutely. We want to discuss this relatively soon also to maybe ask for, as I mentioned, for a more seamless approach. We'll see how flexible FDA will be. But just to correct you slightly, they did not insist on that endpoint. They made several suggestions for alternative endpoints, at least from the published documents, including, for example, time to BVAS 0, time to remission and others. So I don't think they were insisting on it, but this is the -- what -- in my understanding, back then, ChemoCentryx came back with to say this is a noninferiority study, but we will test for superiority at week 52. At least this is the order of events that I recall from reading through this very carefully. So there was space to discuss different end points with the FDA.

Great. Let's go quickly to Ryan Deschner. Ryan?

Two questions from me. One, how big of a factor at this point is the potential for avacopan to be forced from the market by regulators? Is it more nice to have or critical? How are you thinking about that as a base case?

Ryan, I may have misunderstood you what potential did you completely refer to? Sorry.

The potential of avacopan being forced [ out of the ] market by regulators?

Okay. Sorry. Yes, it's hard for me to speak. I don't want to speak on behalf of another company. I mean, they made a huge effort to bring this mechanism to ANCA vasculitis patients that really, as far as we understand, suffer dramatically from the current induction remission therapy. I think the language that the FDA used was very harsh. And for all we understand is that what may have happened is according to what was filed by the FDA is that there was no raw data manipulation, but a change on how the BVAS 0 was assessed. Now from my understanding is that had occurred before unblinding that would have probably been okay. but it didn't. So that's probably where the FDA hung up. But again, that's purely my interpretation. I don't want to speak on behalf of any other companies. So I can't say how the likely it is. We just noticed that the language is very harsh.

Is there a program that you're launching is contingent upon avacopan being pulled from the market?

That's a really good question, Ryan. Thanks for that -- definitely not. We discussed this at length with our experts, and we looked at market research. We conducted market research previously ourselves. We are only moving here because we see such a competitive advantage, whether or not the other drug gets pulled, right? We see the drug being decently differentiated. We have an idea how to work this out in clinical trials. And we think we can excite people that are even used to the mechanism with this drug. So we are not contingent on that decision.

Got it. And what gives you the most confidence, I guess, on the efficacy side that you were discussing read-through in terms of avacopan is it what was seen in the clinical trials from that developer? Or is it more the real-world sort of uptake and response from physicians on avacopan?

I think really good question. I think really both, but I want to reiterate that the signal that was there, particularly on proteinuria in the early time point, the reversal of the kidney injury that occurs in a major fare was present also in the Phase II study and in the Phase II whenever the drug was in there. So it's a very consistent signal and I've shown you that is a signal presence in other diseases as well. So the organ preservation by coming in early and helping the patients with this mechanism is a signal that is pretty valid followed by EGFR also in the ADVOCATE study. So I would actually argue that the drug shows efficacy in the disease, clearly, maybe we can improve on it. That's our goal with a potentially better profile block. But we are encouraged by this. Secondly, when we speak to experts and also the research I mentioned, there's really excitement around the mechanism. It's well established. Yes, of course, no one wants to see any tox signals, no one -- ideally, you always have everything clean, but the people use the drug. Nevertheless, they want to reduce corticosteroids even though that's not in the label, but the trial showed that they reduced the intake at least. And so we are encouraged by both, really. We think there are clear efficacy signals that we can potentially improve on. And we believe there is excitement and acceptance of the mechanism in the market already established. So this really prompted us to switch and to really focus on this development here with this opportunity.

And Niels, I think we have time for one more question from Mazahir at Oppenheimer.

So I guess just to -- the first one was really kind of around the opportunity. So kind of given that the agencies proposed withdrawal of avacopan, and I guess, obviously, the clear unmet need that would create. Do you believe that there could be like a credible case here for breakthrough therapy designation? And also, I guess, secondly, like in terms of the FDA interactions and the expedited time line, could you kind of just help us understand what we could expect an update on that conversation? And then secondly is kind of thinking about trial enrollment. And so given -- this is -- regardless of whether avacopan was pulled or not, but just given the uncertainty created, do you think that -- or I guess, maybe refresh, are you seeing any early signals from any nephrologists, rheumatologists about an increased willingness to enroll patients? Have you had any preliminary site activation conversations? and I guess lastly, do you anticipate the current competitive vacuum, I guess, accelerating your enrollment time line? Or could potentially accelerate your enrollment time line?

Yes. Great question. So I'll start with the second first, Mazahir. We think that because the mechanism is so well accepted and not every patient is eligible. This is also an expensive drug. Obviously, you need coverage so. I think that, in and of itself, helps our enrollment. We are not at enrollment stage just to be clear, right? We've just announced the switch here, so we're not there. But of course, if the other drugs got pulled from the market that may create a certain, let's call it, a void for the lack of a better term, that may even put more patients into trials with the exact same mechanism that people feel is active in the disease. So I think it helps us that it is an accepted mechanism in the very first place. And obviously, there may be an additive effect in certain areas of the world. And yes, the other question, when can we expect FDA interactions? Obviously, we're interested to do that as fast as possible, but we also want to do it as smart as possible to maybe having a chance to maybe ignite a discussion on an expedited path. Usually, it takes 3 months to schedule from submitting the request and you need to be having your documents and your ducks in a row that takes a couple of months to work up to. So I don't want to give a concrete month guidance, but it will be a second half of the year endeavor where we are talking to the FDA, as early as 4 maybe as long as 6, 7 months from now is kind of where the current estimate lands, but we want to prepare that well. And then last one, not least, breakthrough. I think for breakthrough designation, you need to have data that show that you're better than a comparator. We don't have data yet with this molecule, so we can technically not file for breakthrough until we have the data. If we had the data, for example, from a Phase II trial, that is the route we could explore.

Thanks, Mazi. So we are at our time unfortunately. I think we will be available over the coming days if anyone has any follow-up. So Q&A session is now over. Niels,, just want to hand it back to you for just a quick concluding remarks.

No, just thanks for listening in. We're really excited as our team, Tom, our CFO, together with Jan, me, will be here available for you guys in the coming days. If you had to follow up questions, we are certainly excited I hope you see the excitement from us. And yes, we will be in touch, and thank you so much for listening, and I appreciate it. Thank you.

Great. We are now done. The conference call is over. Everyone, have a good weekend and a Happy Mother's Day for those who are celebrating.

Thank you.