Welcome everyone. My pleasure to host this fireside chat with InflaRx. Very pleased to be joined by Niels Riedemann, Chief Executive Officer, Thomas Taapken, CFO, and Jan Medina from IR. Thanks so much for joining us. Thank you. The company has gone through some significant changes since we hosted you at our conference here last year. Niels, perhaps to start, maybe you can just give us a brief overview of where we are and what your company's core focus is for 2026, before we dive into the various drivers. Yeah, happy to do that. First of all, before I forget, thanks for having us. Always a pleasure to be here in March, on behalf of the entire team. We're happy to join. Yeah, we went through a restructuring exercise, which is never easy, but on the other hand, we had a commercial angle because we got an emergency use authorization, as you'll recall, and approval in Europe with the drug for COVID-induced ARDS or, you know, lung dysfunction situation. This is thankfully for human beings almost kind of went away, right? We didn't need that commercial angle, even though we still make the drug available at this point in time. That necessitated restructuring. We have a very exciting new molecule in the same pathway, if you will, which is izicopan. It's a C5aR molecule, inhibitor. It's a chemical, so oral drug. We think it's a best-in-class potential drug. That's very exciting 'cause this complement terminal pathway is involved in a lot of immunological situations. Obviously, there is a pipeline and a product potential here. We've just completed a first trial, short-term dosing in a phase II-A trial, open label, because it wasn't. We didn't have all the tox data in which we now have, in two disease indications, hidradenitis suppurativa, where we have deep knowledge in the company in terms of this pathway, but also development, and then chronic spontaneous urticaria. We decided to put a key focus in the company now around this molecule, izicopan. We are, you know, focusing strongly with the entire team on next steps in HS development, HS being hidradenitis suppurativa, and we will follow up here shortly with an update to the capital markets, which we said we will host in spring, around the regulatory path clarity. We are in discussions with the FDA, already had one round, interesting discussions. We're having another round now around, like, what are potentials to do something a bit different, and not necessarily take binary risks in phase II, but really, like, try to focus the development more on the mechanism of action. That's exciting for us. We have a lot of folks waiting on clarity around the next steps there. We're also assessing actively some other disease indications in the I&I space, which we made public, that we are really interested in additional development. Particularly one disease that comes up, and maybe we speak about that today as well, is ANCA vasculitis because of, I would say, circumstantial evidence of this being a big market, but also a potential real opportunity for us. This is where the focus is. We can do that with a more lean team and with a more focused team. We have the entire core team intact, a team that can develop from early development, very good manufacturing work into approval. We're very proud of this team, and we kept the whole core team so we can deliver high quality next steps for izicopan. Yeah. Great. Okay. Thanks for that excellent overview. Yeah, we were impressed by the HS data. Seems like you saw a really nice onset of efficacy, very rapid, and then some deepening of response. Beyond that, is there, I guess, can you recap the data for us and highlight what's most encouraging to you? Absolutely. One year ago, when we're here sitting at the same, at the same place, we talked about our expectations of this short-term trial, four-week only dosing, and what we would see, and we guided the markets very clearly to the mechanism of action being that we should see an early, reduction already in draining tunnels in drainage. Also, in the other lesions, because we think that the mechanism particularly is interesting around that. Why? Because there's new research that shows how involved the C5a receptor is in the monocytic cells and neutrophil cells, and people tend to forget that. We're talking about a neutrophilic skin disease. This is a basket of five diseases, and HS is kind of the most prominent one, and there's no drug covering this angle really well. We knew this mechanism could work, so we focused everyone around this is what we expect to see. Why is draining tunnels interesting? Because placebo trials have really never produced a big signal on draining tunnel reduction. In average, there's a very little move, and so we said this is an indicator lesion that the drug works. Now coming to the data, what we've shown is that the drug reduced all lesions, but particularly strongly in comparison to published reported other data, the draining tunnels. That not being enough, we had probably the strongest signal that I'm aware of ever reported on pain reduction in this disease, which was very consistent in all three different dosing groups. This is really what excited our potential future investigators, i.e. the experts in the field, because for them, like you have to imagine these draining tunnels are deep-seated lesions in the skin, right? They. It's an inflammatory nest where there's tons of neutrophils around, NETosis going on, inflammation going on, sheath transformation of cells in the skin layer that form these draining tunnels. That is very painful, right? I mean, there are videos existing that you can drain up to a liter of pus from one draining tunnel per day. So you can imagine the dreadful impact on people's lives. If you reduce that, if you stop neutrophils from moving in and monocytic cells from getting excited and doing all this inflammatory work that leads to this pus formation, eventually you will have less tension in the skin, less pain. The combination of seeing that already after four weeks, you had about across all dose groups, every third patient free of draining tunnels, and in the high dose group, every, like 50% free of draining tunnels. At the same time, this very strong pain reduction, this combination is very convincing, and this is something we try to build on. As you may know, everybody has focused on an endpoint in the past called the HiSCR used for approval that has given us and others lots of headache, because it's so variable, particularly, on the placebo side. It's hard to predict if you don't go to very large trials. It doesn't include reduction of draining tunnels. Obviously, if you had a mechanism that works on the most progressed, most severe lesions, as this is draining tunnels and also abscesses, I should mention, then that's exciting for the people who need new drugs that help them. Yeah. You know, just wanna focus a little bit on that. We've also shown good results on this HiSCR, with all the caveats in small trials. We've shown something very interesting that when we took patients off drug at four weeks, and we only saw them one more time an additional four weeks later, where they didn't get any dosing, we saw a deepening in responses. There is this effect carrying on, and that makes a lot of sense. If you stop neutrophils from trafficking into the skin, getting excited, you will have a longer-lasting effect. We did see that already with the antibody. We see it even stronger now with our drug, but we also saw drug levels that still supported the blocking effect four weeks later. Why is it exciting for us? Because we think there's a potential in the future to explore QD once per day dosing as well. You mentioned the antibody and that you developed first for this indication. That had really strong open label data as well, but it wasn't replicated in the placebo-controlled trial. Although it was, you know. The field was much earlier in its development, and I'm sure a lot has been learned since then. Is there anything that gives you confidence besides the dynamic that you just described, that the effect is real and likely to be replicated in the next study, presumably in a randomized setting? Yeah. Absolutely. Maybe just coming back to something you just said, which is very interesting. You're right in as much as the open label data we produced with the antibody. On the HiSCR, we're not replicated to the same extent, and we had a 47% placebo response rate, and we looked foolish now that one of the big, you know, trial arms in the MoonLake data showed a 45%. We may not be that stupid anymore. The problem really is in the HiSCR. What we did replicate was reduction of the lesions, reduction of draining tunnels. We like, I think everybody who looked at the data outside this HiSCR conundrum confirmed that the drug is active and actually showed some remarkable results. Obviously, we're dealing with a problem around this created endpoint, and we have always been very active in designing and talking to the FDA about it, a new endpoint that they asked us to call modified HiSCR. Now, we're in discussions around what can be done to focus development also on this need of reduction of draining tunnels, and these discussions have not concluded at this point in time. We will address the markets as soon as we get there, which should be soon, right? Mm-hmm. We said we're gonna host a Capital Markets Day in Spring. I think if you wanna, like, just move this field forward, you need to be aware that if you do a 50-patient per arm trial and you use HiSCR, it's like flipping a coin, right? Yeah. Your drug may work, you may produce signals between 40% and 65%, but you don't know where you're ending up, and your placebo may produce signals between 25% and 45%. If you're unlucky, you get a result that we had 45% or 47% across the board, right? Right. For that particular reason, it's really more of how do you construct the trial and how do you deal with HiSCR. If you deal with HiSCR, you need to go to 180-200 patients per arm to get rid of that variability. Constant problem. Yeah. That's not very feasible for phase II, but it's something that you can counteract. We did the math, by the way. It's a fun fact. We looked at 2,700 ever reported placebo arm patients in different trials, and the magic number of true HiSCR response is 32.2% that we got from these 2,700 placebo patients, but it can go as low as 16 and as high as 47, which shows the problem. Right. If you wanna contain that, go to very large trials. Again, maybe there's a potential to work with the FDA to work on new endpoints that you validate with them in a proper manner, and that also gives you a nice commercial edge because as we see these days, it's not easy to make strong commercial arguments around HiSCR placebo delta to placebo kind of. Right Right? It'll be interesting to see how it develops. We have strong confidence that we can show that the drug is active in adequately powered clinical studies, including HiSCR, but then you need to go large enough. Mm-hmm. Very interesting. Why has the field converged on HiSCR up until this point? What is it about draining tunnels that might make it less prone to placebo effect? The first question I cannot really answer in a qualified manner because I think it's not just the field. Like, the field, meaning, like, our universe of investors or stakeholders, pharmaceutical companies, biotech companies. Obviously, you deal with, you know, the first mover creates a precedent, and that was a big job that AbbVie did. Like, big congratulations on all the work they did around HS. They designed this HiSCR around the mechanism of action of their drug, right? Which was fine. They happened to not fall into the trap. If you remember, they had two phase III trials. One looked brilliant, the other one almost failed. Even there, you could already see how difficult it was with HiSCR. We had to go through a whole painful course of failing trials or overhyped phase II trials to find out that it's a difficult score. The field is ready. Like, no doctor uses HiSCR to assess patients in this practice, right? The field is ready to say, "Can we broaden mechanistically around drainage tunnel reduction, around progressive disease, and maybe also, can we find drugs or combination of drugs that get us to minimal or clear disease as in other derm indications, right? Where we started with a 50% and at the end, we basically are now in areas where we clear disease." I think that will be possible in the future. I think we hope that we can contribute to that. We're excited to be part of that. Like the field accepted what was created as a precedent as it had to. I think now that we're all aware of this problem, it is also kind of our responsibility to say, "Let's work with the regulators. Let's continue to bring this knowledge back to them and have a constructive dialogue." I know this is a tainted word since yesterday afternoon, but there are constructive dialogues, and there are destructive dialogues with regulators. Sometimes you start on the wrong foot, and it's just a long journey to come back. Mm-hmm. I think it can be done. There's great people working on both sides, and we have, you know, confidence that this can be moved also in this field. Very interesting. What should we expect at the upcoming Capital Markets Day then? Hopefully clarity around how we gonna develop next steps in HS, and we have investors waiting for us to bring that clarity to the table, and how to take a binary HiSCR risk for a phase II off the plate, which is totally understandable. Then we wanna talk about exciting new or additional developments and indications that we are working on exploring right now. Yeah, that's and maybe also hopefully guided by a good expert explaining a bit the need again and really, like, summing the medical side of things up in a more profound way than I can do that here. Super. Great. Can you talk a little bit about with so many interesting opportunities how the company is resourced and focused on allocating its capital? Yeah. Absolutely. Maybe if I take over. Sure. You know, of course, I mean, at this point, we're funded into mid-2027 with the cash we have on hand, and we are doing everything that's necessary, as Niels was describing, to work towards the start and the initiation of larger phase II-B trials. However, it's clear that you know, we need to fund these activities going forward. There is a combination of addressing the capital markets on one side, but we're also in active dialogue with several pharmaceutical companies about potential to collaborate because we believe that if you look at izicopan, which is basically a small oral molecule that can be used in theoretically other indications than HS as well, we see this big pipeline and appeal potential that is very difficult for a small company to fully exploit. We hope and we are quite confident that it might be possible to attract interest from strategics also to work with us on you know alternative indications and to broaden this as much and as quick as possible. That would be a second avenue that we're pursuing in parallel to potentially you know raising the money from the capital markets. Okay. On that front, we recently saw the FDA request that avacopan be removed from the market. Do you have insight into what's behind that? Is there an opportunity for you in AAV now? Yeah, very, very good question. Let's start with AAV. We've taken a deep look into ANCA vasculitis with our antibody where we did two studies. It's an IV antibody, and I just wanna say that in the European trial, we exchanged corticosteroids to a point where the GTIs or the Glucocorticoid Toxicity Index was zero in mean, 0.8 to be precise. That's never been shown in any trial. We really got rid of that problem. Think about this disease as you're life-threatening endangered. You will die without treatment, right? It's an acute onset of vasculitis that will kill you. By the way, some analogies to COVID when it comes to what happens in the vasculature in this vasculitis situation. Anti-neutrophil cytoplasmic antibodies so that excite the neutrophil right on the surface of the neutrophil where C5a is generated working through the C5a receptor. Clearly C5aR is involved. Now we have a situation where these patients will die, but most of them survive if they get high-dose corticosteroids together with either cyclophosphamide, which is also can be a very toxic drug, or rituximab, which is less toxic but has other issues. This combination gets you out of danger in 80%-90% of the cases, but then you are suffering from these high-dose corticosteroids to a large extent. Diabetes onset, high blood pressure, depression, including suicidal tendencies, super high infection rates, including life-threatening infections. The price you pay for getting out of danger is so high that when you talk to these KOLs in the field that we know well, they will tell you there's three key medical needs. First, get rid of corticosteroids, like reduce the corticosteroid load. Second, get as fast as possible in remission. The third is sustained remission. Avacopan was created to cater to that, but they didn't get the label for corticosteroid sparing. Now as far as I understand, if it's for safety reasons, the FDA can always pull a drug. That despite there being safety signals that may be related to liver tox issues of the drug, that hasn't happened. They have asked Amgen, "Why don't you voluntarily withdraw the drug that globally probably drives sales a bit north of $700 million right now?" Obviously, big market. Things have changed. People look at it now as, oh, this is a big market. There seems to be a real medical need for a product that people use to reduce corticosteroids even though it's not labeled for it. Now, the FDA didn't give the label because the drug blocks this CYP3A4 enzyme in the liver that also breaks down corticosteroids. They said, "You've just shown you have lower intake, but you haven't proven that you have lower blood levels," right? They didn't get the label, and now they had these liver tox signals, and they became a bit more prominent lately, all related to this inhibition of this enzyme, which our drug does not block. That could be a huge opportunity. Right. Second thing is FDA talked about apparently, actually not FDA, Amgen in their release talked about some nine patients, if I recall correctly, that need to be re-adjudicated to this BVAS score, which is the primary endpoint. Like BVAS zero means you're in remission, right? That was the endpoint. Now, what we believe, and we don't know that for sure, is like they may look at that in a way of risk-benefit, and if the nine patients kind of tip the balance that they couldn't prove non-inferiority, then we have an interesting situation, right? There's a little bit of a safety signal, but at the same time, non-inferiority has not fully been proven. This is now guessing, right? This is I don't know that. So maybe that's what prompted them to ask Amgen to withdraw it, and will be interesting to see what happens in the future. Let's park this for a second 'cause we're not assessing AAV only if the drug is pulled or not. I think we have a clearly differentiated drug. I already mentioned we don't block this enzyme apparatus, so we don't expect this liver tox issue, which we still have to prove, but we don't expect it. We believe we can show corticosteroid sparing, and we pack 30 mg in one capsule and can go to much better, faster onset of drug action already on day one. We multiply what the drug avacopan accumulates to after 13 weeks. All this together makes for potential more convenient dosing, potential less side effect safety, and a corticosteroid label. If all works out, maybe even some secondary signals on efficacy that may be more prominent. Like if you think of what truly matters is renal function, right? You wanna preserve as much functional tissue as you can. If you have a fast onset, you block the pathway right away, there is the hope that you see a better long-term function. Nils, as you said, a potential for once daily dosing as well. Yeah, convenient dosing. Yeah, QD, for example. Yeah That's also still. All this together makes, and then a $1 billion+ peak sales market makes it much more attractive to look at it with our new drug. It's commercially validated. Yeah. Absolutely. Very interesting. How do you think about development in this indication where there's clearly good biologic rationale as there was in CSU, but izicopan, you know, showed some signals, but I don't think it was quite up to, you know, your full hopes. I mean, you have to understand that, again, you cannot show superiority on top of this high-dose treatment the patients get. Like you need to get them in remission safely, right? That's the key. As I said, it comes with this toll, and you can reduce this toll, and you maybe even in the long run have a better function, tissue function and maybe sustained remission is another thing you will look at. I think there is this clear rationale. I think the development path is that you have to prove this with this drug, that you can also replace corticosteroids. Maybe as a fun fact for you, the antibody that we out-licensed to our partner in China has reproduced the same great phase II data. They showed it to the Chinese FDA, who gave them the permission to start, and they're already enrolling a phase III trial. Joe, I think where you ask about CSU, is that. Well, I was asking. Oh, I'm sorry. Did I miss? No, it's fine. Yeah. I didn't word it great. CSU showed us some interesting signals, but, you know, the efficacy wasn't quite as CSU. I'm sorry, I missed. I'm just wondering for izicopan, which has biologic rationale in CSU, but yet, you know, we didn't see it translate perfectly, you know, whether there's, you know, read through, like why did that happen essentially, and, are there any learnings heading into, you know, potential development in AAV. Yeah, yeah. with izicopan? First of all, I and the team clearly believes that we have a signal in CSU that's very interesting. I mean, we just learned again about new Dupixent data, which is a great selling drug, 'cause it's safe in CSU. That after many weeks of treatment, they reach reductions in the primary endpoint that we've seen with the lower dose group already, just to slot this in at four weeks. What we didn't show is that the higher dose group produced a better signal. There was a bit of a kink, which can be explained by a few patients, one having a major flare. Maybe, you know, also there's imprecision of diagnosis, so this is not uncommon. Our experts from the Berlin Charité on CSU, they clearly think this drug has legs in CSU and should be further developed as a safe oral option. Here comes why. Everybody talks about mast cells, and we do too, because they drive histamine release. However, the interesting part here is that, there's a neutrophilic angle to the disease which is underappreciated. There's more and more evidence, you can read some review articles about the role of neutrophils clustering around, the mast cells and how this creates an inflammatory environment, particularly in the more severe cases. When you look at the more severe cases in our study, we saw the best signal there. Particularly those cases with angioedema had a very fast reduction of angioedema to a point where it vanished. A very steep drop in this Urticaria Activity Score. I would really say this drug is active. We have to prioritize, right? We can't do it all at once. We're further assessing this opportunity. When you compare it to other drugs, we've shown what it can do already. If you think about that mechanistically again, we may add a second angle. You know, our experts clearly would like to see this drug being further explored in a randomized controlled study. As I said, we can't do it all at once, but we would be open to that as soon as funding permits. Mm-hmm. This is where potential collaborations come back into play. If we talk to companies, we see that there is interest beyond CSU and HS, in fact. Some companies that understand the mechanism look at this and say, "Well, can we not consider even alternative and other indications to do exploratory work?" In order to facilitate that, we have initiated now some PK bridging studies in China because we believe in China we can get some of this exploratory data generated much faster and more cost efficiently, and that's something we want to do in short term in order to be able to, you know, broaden the potential applications of the drug in different diseases. Interesting. What are you aiming to learn from the PK bridging studies? Why is that a important step? I don't think the learnings will be overly high. It's a regulatory requirement for us to be able to run phase II-A studies in China in patients. This is really more to bridge the PK data we have generated here in the United States or in Europe, I have to say, to the Chinese population and enable us to go out and do studies in different indications. Okay. That makes sense. Well, thank you so much for a very comprehensive update, and we will absolutely keep focused on all of the progress and look forward to the Capital Markets Day. Thank you. Great to have you. Thanks for having us again. Yeah. Thank you. Thanks, Joe. Thank you.