Morning, everyone. Thank you for standing by, thank you for joining our conference call this morning to discuss our recently announced efforts to pursue izicopan for AAV and other renal diseases. During this today's presentation, which will take about 45 minutes in total, all participants will be in a listen-only mode. Please note that today's call is also being recorded. We'll have a Q&A session, followed by the presentation, where you can ask written or audio questions. Please note that you can only ask questions while you are logged in online. As I said, we'll be done in about 45 minutes this morning and get you on your way. I would now like to turn the call over to Niels Riedemann, CEO and Founder of InflaRx. Niels, please go ahead.
Thank you, John. Ladies and gentlemen, good morning. Thanks for listening in. It's our pleasure to be sharing with you our recent, you know, prioritization here on the renal space, particularly in the ANCA-associated vasculitis. May I please ask to forward the first slides? Please take note of the important notice and disclaimers. We will be making forward-looking statements. We're a publicly listed company, so I appreciate your taking note. Next slide, please. We're excited about our new molecule, izicopan, which is an oral inhibitor of the C5a receptor. It's a C5a and C5a pathway is a critical driver of inflammatory cascade. Both angles, C5a, the ligand, and its main receptor, C5aR, are both validated targets from a clinical both and the regulatory commercial perspective, also in ANCA-associated vasculitis.
There's promising clinical data with C5a inhibitors, vilobelimab and PDB1, as well in the sense of ANCA-associated vasculitis development that I want to flag here. This the recent regulatory scrutiny related to a marketed comparator, avacopan, has provided InflaRx with a clear and present opportunity with its next generation C5aR inhibitor, izicopan. We believe that we've improved significantly on certain, you know, shortcomings, if you will, or certain areas where improvement could take place with our molecule, izicopan, and we believe it has best-in-class potential for mainly three reasons. We have a very fast onset of action and that leads 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 with 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 in a bit. And we also have potentially more convenient dosing, with also the possibility to still to go to once-daily dosing. 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. You know, given our properties, maybe we can expand on this market even.
We see use of this particular molecule across a broader I and I space, but particularly also in the renal arena, particularly in IgAN and C3 glomerulopathy and some others. We are also intending to provide first proof of concept in due course here in these indications. We have a strong IP position. This is our molecule. Composition of matter is issued, and we have really an issued situation already in various jurisdictions, particularly in the U.S. and Europe and other areas. Next slide, please. 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's very successful molecules in the complement world on the level of C5 inhibitors, C3 inhibitors, factor B and others. One of the reasons really is that there's different ways to generate C5a. There is the path from these complement pathways, but there's also a direct cleavage mechanism through all sorts of enzymes that are present in various inflammatory diseases. These enzymes can cleave off C5a directly and outside the reach of the mechanisms of these other drugs. You can generate full length biologically active C5a to large amounts, even in the presence of these inhibitors in human blood. We've shown and published this.
Therefore, if you believe the great body of work of over 6,000 publications, on clinical, pre-clinical research, around the C5a receptor and the ligand C5a to be meaningful in the I and I space, you may appreciate that a targeted 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 sickling pathway, here in its first phase I studies and also in the phase II-A study. Next slide, please. 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 three areas particularly.
We designed this molecule to give us a different plasma presence from the one reported for the marketed comparator. You see here on the upper right side, our, in blue, our human PK data from the phase I study. Please note, this is not a head-to-head study with avacopan. This is just the reported phase I data from avacopan plotted in this graph. It gives you a visual that at 30 mg, which is the approved dose, B ID for avacopan, if you take a single shot of 30 mg and compare it to izicopan 30 mg, you see this is the borderline. Above it, you already have a 10x area under the curve increase in PK and a higher peak, 3 x higher peak, and just a very different plasma presence. 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. Particularly, you know, we also are able, with our formulation, to up those very highly, up to 240 mg a year safely, without safety signals of concern. That may be important to explore the full benefit of efficacy if you think of tissue presence of this, because remember, PK and PD so far in complement is mostly measured in the plasma impact. That was our starting point, but we quickly learned that our molecule is very differentiated on other areas as well, particularly potential to improve safety profile.
We have over 180 humans exposed and a very clean GLP toxicology study package, including 9 months non-human primates. We also have done studies to further characterize the molecule and seen that the liver enzyme apparatus, 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 it's in the label of avacopan as a time-dependent inhibitor. We have recently shown that we are not a time-dependent inhibitor. We have, you know, explored this to very high concentrations and believe that we are not inhibitor of this mechanism. We also show differentiated profile in metabolic stability.
All these indicates that we may have a molecule that may not have the liver tox issues that are in the label, in our market comparator's label. We also may have a dosing advantage. We have 30 mg / capsule, as opposed to 10 mg for the comparator, and we still see a potential for once-daily dosing according to our current modeling of our phase II-A data that we recently got. 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 a graph. These are the data that avacopan, avacopan approval data in ANCA-associated vasculitis, where it's mentioned that it takes 13 weeks to reach steady state.
You see here some data from our early phase II-A study, different diseases in HS, hidradenitis suppurativa, and in CSU, chronic spontaneous urticaria. You see that we tested 60 mg BID, 90 mg and 120 mg in these studies. Already at 60 mg BID, we have a multiple of that plasma presence right off the bat. We believe that we may have a faster onset of action with our drug. Next slide, please. I wanna speak now a bit about ANCA-associated vasculitis. Next slide, please. This is a rare disease that typically is a, you know, an auto inflammatory, autoimmune style disease.
There are certain antibodies directed against neutrophil features that excite these cells and other cells, but particularly, when exciting these neutrophils, they involve various organs and because they involve the endothelial cells in the vasculature, which can affect all organs. On the right side, you see typically most affected organ is the renal. It's the kidney. You see here that the glomeruli in the row A, B, C are stained, and also the small vessels, G, H, and F, for complement factors. Complement is activated in the kidney and that drives, but also in the vasculature of all organs, and that can drive damage. It's an orphan drug market. I mentioned already that it has large market potential. We also want to just mention that there are different subtypes.
The types that are usually studied in multicenter studies are called MPA and GPA. There are certain difference between these two, but I wanna, in the interest of time, not go into that detail right now. The current treatment medical needs are clear. There's induction or remission treatment that usually entails either cyclophosphamide or rituximab in combination with very high-dose corticosteroid treatment. This is a very toxic treatment for the patients. The patients suffer dramatically from the corticosteroid use, and this is a high unmet need to get the patients as fast as possible in remission and off these rather toxic high-dose corticosteroid drugs. Then there's also a remission or a maintenance therapy, which is usually done with rituximab, and which is usually then initiated.
There's also some other drugs that are usable according to standard of care that is usually initiated after you achieve remission. Next slide, please. Next slide, please. The mechanism just, you know. Oh, one back, please. Thank you. The mechanism here is very interesting and clearly involves C5a and the 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 gets, thus immediately excited, puts out oxidative radicals, enzymes, undergoes NETosis, induces vascular damage really.
It 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. That's the vicious cycle, and clearly C5a and C5a R believed to be drivers of the disease. Next slide, please. 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.
I wanna mention that the market, 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. They typically like the C5aR inhibition and initiate that treatment during the major flare phase and then continue treatment for six to up to 48 months. 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 organ preservation.
There are concerns about the tox profile and some recent reported liver tox issues, but physicians also state that they monitor for it and it is decently under control. At least that accounts for the U.S. We've heard similar from European physicians. When asked for a product X with our profile, they see a potential strong share for new AAV patients, but also some switching promoted. You see here that they believe that currently they treat roughly about 15%. I mean, it could go up to 55%, and then up to almost half, 45% here may also switch over. This is highly encouraging for our product development. Next slide, please. How do we get there? What's the? We call it the rock to boat scenario.
How would a label look like? Ideally, you would like to have a steroid-reducing or rapid taper label that's part of your label, which is not currently the case for our competitor. Ideally, you demonstrate early benefit, early reduction of proteinuria, and improvements in eGFR. Both signals were present for avacopan, I should mention. 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. Last one is convenience, lower capsule intake or even once-daily dosing. You see a quote underneath here, how important steroids reduction is for certain physicians. This was an interview from an external research we conducted.
On the right side, the overall development goal is, like, try to increase the signal delta to placebo, especially during the early major flare phase. How do you get that done from a study design aspect? You wanna enroll patients fast. You don't wanna mandatorily taper them down to a certain level, which was previously done in studies, which kind of pre-selected a bit better patients because they were already out of or to a certain extent, already doing better. 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 renal-impaired patients. Another idea would be to fix the remission induction to rituximab in combination with corticosteroids.
I mentioned also, of course, you would like to have an aggressive rapid steroid taper in your treatment arms to demonstrate that you can do that. Next slide, please. This is really a preliminary 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 II-B trial, but phase II trial followed by a phase III, much like the development path that ChemoCentryx presented with avacopan. We are, you know, putting the studies, if you will, together, but we're also trying to weave in some of the feedback that we, you know, gathered from earlier interactions between ChemoCentryx and the agencies, particularly the FDA, as this was published in the approval document.
You see here a placebo standard of care arm with a general safer standard GC tapering approach. GC stands for glucocorticoids. A drug approach instead of placebo with the exact same underlying treatment to establish signals of efficacy. The third arm would then just go to rapid taper to say that when you rapid taper, you do not differentiate from the signals that you have detected in Arm 2. This would be a 26-week readout because we want that six-month endpoint for the renal endpoint eGFR. We may or may not go to 52 weeks to treat out to get more data, but the unblinding would take place after week 26. As far as endpoints, the first phase II here is a safety endpoint. Descriptive non-inferiority for BVAS zero .
BVAS is the score used for Birmingham Vasculitis Activity Score used to see if you get into remission, when it's at zero. We also wanna really focus our secondary efficacy on the early proteinuria. We believe there's a good reasons to believe that there's a good delta early. This was visible with treatments on C5a reduction, inhibition just as much as with avacopan. At week four, we wanna look at eGFR, a signal of renal function at week 26, and we also wanna investigate time to remission, time to BVAS zero, amongst other secondary endpoints. Next slide, please.
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. There's a scenario one where we go to a non-inferiority on BVAS paired with a superiority, which could be different in this case, for example, eGFR week 26 of 52 or time to BVAS zero. Scenario two would be to directly power for superiority if any of the endpoints allow to do 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 to through 2029 right now. We believe we will cover the readouts of that phase II study that I introduced to you in the slide before. Next slide, please. 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's 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. If the FDA, if the agency was amendable 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. Last but not least, I want to share with you a bit of the excitement around the renal 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 read out. Next slide, please. We have particularly focused on three renal indications, and we have a network that includes centers 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 through the entire slide, but why have we selected aHUS, IgAN, and C3G? All three 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, proteinuria reduction in IgAN as well as in C3G. Both will be followed by, within, an eGFR stabilization as confirmatory endpoint. 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.
In aHUS, that is actually a relatively rapid response that you could already measure early, and I will show you that too. All three indications have an interesting biomarker approval that has been, at least in IgAN and C3G, shown to be present in early studies with avacopan. In all three indications, there are complement inhibitors already approved. We may see big advantage to have a drug that you don't need vaccination with, because we don't inhibit the membrane attack complex, the arm of the complement system that if you block it, can cause serious infections, including meningococcal meningitis. We have an oral drug that may be an advantage in some of these indications. Let's look into it real quick together. Next slide, please.
aHUS, atypical hemolytic uremic syndrome, next slide, please, is an interesting indication. You know that this was one of the first indications where Alexion's drugs, SOLIRIS and now ULTOMIRIS, have seeked approval with this TMA response. You find that definition below there. That means you normalize the platelet count, you normalize the serum LDH levels, and you improve the serum creatinine by 25%. If you reach all three, you're called a TMA responder. These are small open label trials that have led to approval based on this endpoint of these complement inhibitors. Some say, okay, this is a rare disease. These are actually pretty interesting large markets, given the high price in this rare life-threatening disease. However, next slide, please. You may argue, well, isn't that a MAC-driven disease?
Which is on the 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 MAC or a C5a-driven disease, or if it's maybe even predominantly C5a-driven disease. Why are we saying that? Now, there were experiments done with avacopan on the right side here. You see that they used treated patients with aHUS and used the serum before treatment and after to excite plated endothelial cells. They saw when you excite these cells, and then you let blood flow over it, you all of 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.
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. On the right side, sorry, I should have said that the MAC formation is not affected. 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 C5aR inhibitor. We believe that C5a interaction may actually be one of the key drivers of vascular damage in this disease.
We would love to test this because we can test this 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 a rare disease but a pretty large rare disease, if you will. There are quite a few patients for being a rare disease. It's one of the larger renal diseases. This is also a disease which involves the kidney and complement activation. In this case, also an antibody-mediated injury. Without going into all details, there are complement inhibitors. One is approved, which is, you know, the factor B inhibitor. It's an oral inhibitor which has shown proteinuria reduction followed by eGFR improvement.
Very recently, just a couple weeks ago, Alexion's trial slash AstraZeneca's trial read out with ULTOMIRIS, with the anti-C5 antibody, and also showed a significant proteinuria reduction, which was a phase III clinical study. Next slide. Will our drug work? We believe there's a good chance. Why would we believe that? Avacopan was tested in this disease. You see here, these are just seven patients pre-selected, went into the short-term treatment of only three months. You see in the center graph that the proteinuria measured by urinary protein, creatinine ratio, greatly reduced for being such a small patient group. Certainly that looked like a signal that's kicking in after about 8 weeks of treatment. Also there were signals of less inflammatory markers in the kidney, in the urine, I should say.
Clearly early signals, but in line with the role of complement and very encouraging to test this further. Next slide, please. We come to the last indication here, C3 glomerulopathy, C3G. Next slide. Clearly another complement-driven renal disease, in this case, slightly different mechanism, predominantly involving the alternative pathway, but in the end, usually all pathways are excited through that. Again, an interesting case. This is a more rare but also very interesting disease with a very high unmet medical need. Here, you know that the former Apellis drug, pegcetacoplan, was approved for proteinuria reduction, followed by eGFR improvement. Also the role of complement well established. Next slide, please. 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. Again, you see a nice separation between the placebo and the treatment curve on UPCR, so on pro-proteinuria. Also you see the eGFR differentiation after time of treatment, which is typically 26 weeks, the first time where you see it better. There is a common thread. Next slide, please. There's a common thread in these, in these indications where complement inhibitors are improved, where the regular pathway is clearly established on signals that have been seen with C5aR inhibition.
We are very excited to test this and to put up a study in which we can prove early proof of concept to maybe then roll out into more serious development should we see 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 network. 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. Last but not least, next slide. Wanna also talk about here hidradenitis suppurativa. Next slide.
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-A readout where we showed a biological-like activity just in four weeks of treatment, a 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 moved with the agency over the years. 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 modified Hidradenitis Clinical Response Score, which could be validated in the phase II-B trial and potentially used as a new primary endpoint in pivotal trials.
Now, why would 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. 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. You can see the details. We see this as a potential, great potential for the future. We would at this point only develop this further with a collaborator. We believe that this field needs new drugs with new mechanisms, and we believe that could be an interesting path forward.
We wanted to not withhold this from you guys to make sure that we did progress there quite well. 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 would hand over now to John for the Q&A session. Thank you.
Thanks, Niels. Yes, we'll have about 15 minutes here for the Q&A session. If you wanna ask a question, you can do so by raising the using the raise hand icon below the presentation window, and we'll call on each person and ask you to unmute yourself and go from there. You can also use the Q&A button below and submit something via writing. I have a feeling we won't get to every question, so we will be available in the coming days to address those as well. We have our first question from Yatin Suneja at Guggenheim. Yatin, if you could unmute your line and ask your question.
Yes. Can you guys hear me?
Yes.
Okay, perfect. Hey, guys, thank you so much for taking the question. Very nice presentation and the overview. I have a couple, if you could sort of address them. Number one, on avacopan front, right? There are basically two debates. One is on the safety, the second one is on the efficacy. The question, and I know, Niels, 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? That's one part. The second part is also on the efficacy. I think there is some debate if we read a little bit about it, that, you know, maybe the efficacy is under question.
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 indications? Like what exactly? Because when we talk to nephrologists or rheumatologists, the reason they really like avacopan is the data on kidney protection or organ protection, which we don't see it on the label. I'd love for you to sort of put these two things in perspective, and then I have a follow-up after that. Thank you.
Thanks. Very, very good questions. Thanks, Yatin. Really appreciate that. Let me start with your liver tox question. We've done a lot of work on our molecule and tried to understand where the differences lie. I mentioned the CYP3A4 inhibition, which were not a time-dependent inhibitor. We believe this isn't 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 metabolites may get metabolized. 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 metabolites. Aside from this clear differentiation on CYP3A4, we also looked at metabolic stability.
Obviously, these are all preclinical assays that are meant to scout whether you fall into a certain higher or lower level of concern, so to speak. All chemical drugs can be in these categories. We've seen a very strong difference in metabolic stability, in, for example, the GSH trapping studies that we've recently done head-to-head with avacopan's molecule. There's really an initial big differentiation which stays over time and in all, like in several orders at the beginning and over the entire time in an order of magnitude, when it comes to, you know, like, in this case, you know, the active metabolite formation in this assay. We've done also other metabolic assays in liver microsomes to understand this differentiation.
We came out with the conclusion that our drug, which is very different on the three-dimensional layer, it has three chiral centers. It is an amorphous drug and not crystalline in steady state. It is quite a differentiated drug, but particularly it's pretty stable in these metabolic assays. This, including that we have over 180 patients already with very high doses tested, granted only up to four weeks, but without any signals of safety concern, with no enzyme and GOT/GPT elevations in the liver that were AEs or even serious AEs. None of this occurred. Plus the fact that we have all these differentiating mechanism, 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. 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's like a myriad of research on different C5aR blocking molecules preclinically that actually have been shown to be organ protective in certain diseases, particularly also the liver. Really, there is no reason to believe there is a class effect. We'd rather believe that this has to do with the molecules themselves when they go into a liver tox signal. I hope that covers it from all angles that we can cover it today. Your second question is the efficacy question.
Yes, there were some questions around that. I would like to start by the data that I showed you here at the end of my presentation. Very consistently, avacopan has shown that it has effects on proteinuria, on eGFR improvement, on the renal side of the game. I would argue that this was also present, by the way, in the ANCA-associated vasculitis study. Even though there's regulatory scrutiny around the molecule, and we cannot speak about, you know, the details of these ongoing scrutiny situation with the FDA. 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 debate around how BVAS was adjudicated at the end of the 52 weeks.
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. 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 at that endpoint. That's a matter of finding the right angle with the FDA how to approach this. We do believe there are various signals, valid signals of efficacy of avacopan in ANCA vasculitis, and we wanna build on them.
Got it. 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 appreciate? Thanks.
Yeah, thank you very much. That's a very good question. In the recent years, there are certain areas that have been explored by larger companies like, you know, companies like Novartis, you know, they got Alexion, and others, in the renal space, as far as I believe it's 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 know him so well is through our contacts there, but we also, we developed our BDB-001 licensed molecule that is the vilobelimab IV antibody targeting the ligand licensed to a Chinese partner. They are in phase III development.
They did a very rapid 100-patient phase II development within this network. 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 benefit from this amazing network that has ample experience, not just in ANCA-associated vasculitis, but also the three other indications we mentioned here. We really try to explore that speed factor to get faster to data. I mentioned we cannot just go to China, we'll also want to look at Caucasian patients, of course, in other regions.
Great. Thanks, Yatin. I think, just to 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 C3G in one or more of those next year. In the spirit of moving along quickly, I wanna cover a couple questions we have that were submitted to us in writing. The first one is from Sam Slutsky at LifeSci Capital asking, based on your PK/PD data, what go-forward dose do you envision using for AAV?
Yeah, thanks for this question to Sam. Great question. We have not fully concluded this, so this is being taken with a certain care. We have explored so far 60 mg, 90 mg, 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, needs a lot of drug levels to show these lesions improve. Our current data modeling 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 QD and how we best switch it. Our modeling data suggests we can do that. Not right off the bat. You know, expect us to have at least maybe during the early treatment and the remission phase to be BID, but then potentially switching to QD.
Thanks. Great. We have another question that was submitted early on, just wanting us to 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.
Yeah. I start with AAV. You know, I mentioned that there are two reports. One is actually from Yatin Suneja. 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. physicians that currently they don't have the majority of patients are not on these drugs. There's a large potential to either put them on the drugs more with maybe a differentiated label or less concerns. 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. On the other renal indications, these are all interesting indications. IgAN is a relatively competitive field, but pretty large market. These are certainly really interesting indications as well. aHUS is at a high price point, but it is also in, you know, a very large selling indication for a rare disease, life-threatening. I think C3G is not fully built out yet, so we don't fully know how large it is. All of these are believed to be up to and above $1 billion by various players. Really excited because of the profile, we'll try to capitalize on building it out in the renal space here. Thank you.
Great. Thanks . We have three questions in the live. I think if we run through them pretty quickly, we can do them all before the time's up. First one is from Timur at Cantor. If you want to go ahead and ask your question.
Yeah. Thank you very much, guys. This is Timur on for Steve. 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. Why do you think the FDA would think differently now and, when do you expect to discuss this design with the FDA? Thank you.
Thank you, Timur. 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. 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 zero, time to remission, and others. I don't think they were insisting on it. This is what, in my understanding back then, ChemoCentryx came back with to say, "This is a non-inferiority study, but we will test for superiority at week 62." At least, this is the order of events that I recall from reading through this very carefully. There was space to discuss different endpoints with the FDA.
Great. Let's go quickly to Ryan Deschner. Ryan.
Thank you very much. Two questions from me. One, how big of a factor at this point is the potential for avacopan to be forced from market by regulators? Is it more nice to have or critical? You know, 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. Yeah, it's hard for me to speak. I don't want to speak on behalf of another company. They made a huge effort to bring this mechanism to ANCA-associated 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, for all we understand is that, according to what was filed by the FDA, there was no raw data manipulation, but a change on how the BVAS zero was assessed. From my understanding, if that had occurred before unblinding, that would have probably been okay, but it didn't. That's probably where the FDA is hung up. Again, that's purely my interpretation. I don't wanna speak on behalf of any other company. I can't say how high the likelihood is. We just noticed that the language is very harsh.
Is your program that you're launching 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, we looked at market research, 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. We're not contingent on that decision.
Got it. 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, you know, sort of uptake and response from physicians on avacopan? Thanks.
I think really good question. I think really both, but I wanna reiterate that the signal that was there, particularly on proteinuria, in the early time points, so reversal of the kidney injury that occurs in the major flare, was present also in the phase II study and in the phase III. Whenever the drug was in there, it's a very consistent signal. I've shown you that is a signal present in other diseases as well. 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. 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 better, potentially better profile drug.
We are encouraged by this. Secondly, when we speak to experts and also the researcher I mentioned, there's really excitement around the mechanism. It's well established. Yes, of course, no one wants to see any tox signals. Like, 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. The trial showed that they reduced the intake at least. 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. This really prompted us to switch and to really focus on this development here with this opportunity.
Okay. Thank you, Niels.
Great. Thanks. Niels, I think we have time for one more question from Mazi at Oppenheimer. Mazi?
Thanks, John. Thanks, Niels, for the comprehensive presentation. That was great. I guess just to, the first one was really kind of around the opportunity. Kind of given the, like, the agency's 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? Also, I guess secondly, like, in terms of the FDA interactions and the expedited timeline, could you kind of just help us understand when we could expect an update on that conversation? Second is kind of thinking about trial enrollment.
Given this is, you know, regardless of whether avacopan works for it or not, but just given the uncertainty created, do you think that, or I guess maybe rephrase, 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? I guess lastly, do you anticipate the current competitive vacuum, I guess, accelerating your enrollment timeline or could potentially accelerate your enrollment timeline?
Yeah, great question. I'll start with the second first, Mazi. We think that because the mechanism is so well accepted and not every patient is eligible, you know, this is also an expensive drug, obviously you need coverage, et cetera. 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, we're not there. Of course, if the other drug 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.
I think it helps us that it is an accepted mechanism in the very first place and obviously, there may be an additively effect in certain areas of the world. Your other question, when can we expect FDA interaction? 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, you know, maybe ignite a discussion on an expedited path. Usually it takes three 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.
I don't want to give a concrete month guidance, but it will be a second half of the year endeavor where we are, you know, talking to the FDA, as early as four, maybe as long as six, seven months from now is kind of where the current estimate lands. You know, we want to prepare that well. Last but 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 have the data, for example, from a phase II trial, that is a route we could explore. Hope that helps.
Yeah, helps a lot. Thanks for the update, going.
Great. Thanks, Mazi. We are at our time unfortunately, this, you know, think we will be available over the coming days, if anyone has any follow-up. Our 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, here together with John, me, will be here available for you guys in the coming days. If you have follow-up questions, we are certainly excited. I hope you see the excitement from us. Yeah, we will be in touch. Thank you so much for listening and appreciate it. Thank you.
Great. We are now done. Conference call is over. Everyone have a good weekend and Happy Mother's Day for those who are celebrating.
Thanks.