Good morning, everyone. Thank you for standing by, and thank you for joining InflaRx's conference call to discuss the company's expected development plans for INF904, our orally available C5aR inhibitor with best-in-class potential. Presenting on today's call, we have Niels Riedemann, CEO and founder, and Camilla Chong, Chief Medical Officer, with Renfeng Guo, CSO and founder, and Thomas Taapken, CFO, available during the Q&A session. During today's presentation, all participants will be in a listen-only mode. Please note that today's call is being recorded. The presentation will be followed by a Q&A session where you may ask written or audio questions, and please note that you can ask questions only online. I would now like to turn the call over to Dr. Niels Riedemann, CEO and founder of InflaRx. Niels, please go ahead. Yes, thank you so much, John. We're really excited to have everyone on the call today to share with you our development plans. And I will dive right back in, into our topic. But before I do that, I think next slides will be, just a cautionary note on the forward-looking statements we're going to make today. So please take note of them. Next slide, please. So we are really about harnessing C5a and C5aR, that part of the complement pathway for controlling inflammation in the I & I space. And we have, as highlights, really uniquely targeting, mechanisms and drug candidates. And these are validated mechanisms in the meantime, and they're a critical part of the inflammation cascade. We have a first-in-class, highly potent anti-C5a monoclonal antibody known as vilobelimab, plus a second generation IFX-2 in the pipeline as a life cycle molecule. We have a best-in-class potential oral C5aR inhibitor, INF904. That inhibitor is exciting the team a lot because, first of all, we are trying to address certain limitations of the marketed comparator, and we are, at least from our phase I data, clearly differentiated, especially on the plasma PK inhibitor potential. But we also are excited because this is a pipeline and a drug potential here in this candidate, and that can address larger markets, likely, and also markets in the immunodermatology space, which we'll be talking about today, but also outside. So we have set an initial focus here on immunodermatology, and we believe that we can drive pipeline value in these markets. In immunodermatology, we have a strong IP coverage and medical use coverage, and we have both vilobelimab with a late-stage development phase III ongoing in pyoderma gangrenosum, and INF904 that will enter phase II in 2 initial indications, chronic spontaneous urticaria and hidradenitis suppurativa. Just want to make sure to mention that we feel very lucky that we are supported by world-class scientists and researchers and clinicians, key opinion leaders in this space. We have a large upside potential in additional indications, and we are open and exploring potential collaborations to unlock additional value here. We have a strong balance sheet that we just reported today, and that takes us at least into 2026 to advance our programs towards the next milestones. Our team has a proven track record in delivering clinical trials and also regulatory success with the emergency use authorization we received last year. Next slide, please. So why immunodermatology? Well, first of all, there are several attractive multibillion-dollar commercial opportunity markets to be explored. And then also, we have identified crucial unmet medical needs that we believe INF904 may address strongly. There's a sound scientific rationale, and also in the meantime, some clinical data on the role of C5a, C5aR, and this new mechanism in this space. There are established endpoints that are established for approval and, you know, there's no known safety concerns and a broad potential therapeutic index for INF904. So, this oral C5aR antagonist has a differentiated pathway. It addresses a mechanism of action that is currently not addressed by any competitor in the immunoderm space, and we are very excited about moving that in there. We have an established network of experts and also in-house trial expertise in this area, and I mentioned already the strong IP coverage. Next slide, please. So this just depicts our initial focus here in immunoderm, and we'll be talking about these two indications, chronic spontaneous urticaria and hidradenitis suppurativa today, and there are others that we may explore in the future. Now, we also list here a few selected indications in neurology and in the nephrology slash hematology space, and that is to demonstrate that we've done quite a bit of work in many other disease indications. These are some areas where we are very excited about the opportunity, either from our research or also from initial clinical data for example, the competitor drug, avacopan, that had shown initial efficacy in some of the nephrology indications here listed, of course, and of course have gotten approval in ANCA-associated vasculitis. Next slide, please. So this brings us to the pipeline here. This is basically showing our focus that I've just explained, so I don't want to reiterate that. I just want to make sure to flag this strong focus on immunodermatology and the potential outside. I do want to mention that Gohibic vilobelimab does have an emergency use authorization for certain critically ill COVID-19 patients and a potential to go into broader ARDS, and we will cover that at the end of the talk briefly. Next slide. Okay, so let's talk about the strategic positioning, and let's talk about the target. For a minute before we dive into the indications. Next slide, please. We are uniquely positioned here. We have two validated drug targets covered by two very exciting molecules. C5a, the ligand covered by vilobelimab, and the receptor covered by INF904, our new small oral inhibitor. Now, it's important to note that if you want to have control over this pathway, you need targeted inhibition. Why is that? Because upstream blockers, like at the level of C5 or higher in the complement system, they lack the ability to block the cleavage that occurs through multiple enzymes. So in other words, while they're very sufficient in blocking the complement-mediated cleavage, there's another mechanism that is not touched by them. So there's no evidence that these drugs can block C5a in humans, in disease, in a sufficient manner. So we need targeted drugs. We have two. We're excited about them. Why? Because C5a is upstream of the cytokine network. It actually boosts a lot of unknown cytokines. Some of them are listed here. It's a strong activator of neutrophils, macrophages, and other immune cells. And what does that mean? It means that it attracts neutrophils, chemotaxis, and it makes them generate oxidative radicals and granular enzymes. That is the tissue-damaging effect we'll see in many of the diseases. And there's an increasing knowledge around the role of C5a inducing NETosis. And I'm going to be speaking about that a bit later because NETosis is increasingly of interest in the immunoderm space. Now, there's over 6,000 publications in many, many different disease settings, and we are very excited, but we've chosen initial immunodermatology indications, and we will be showcasing them a bit today. Next slide. So I want to start with our running phase III in ulcerative Pyoderma Gangrenosum with vilobelimab, our first-in-class monoclonal antibody covering the ligand. Next slide. Principally, just as a very brief recapitulation here, it's a highly selective C5a blocker. It blocks it very effectively, up to 100% in human blood. It doesn't touch the MAC formation, so it leaves the defense mechanism that is known and important in the complement space intact. It's a fast binder. It's commercially available under the EUA that I mentioned. So it's uniquely positioned to be a fast and strong binder of the ligand. Next slide. So pyoderma gangrenosum is a terrible disease. There's no drug approved in the U.S. or in Europe. It's a neutrophilic skin disease that manifests with large, sometimes, very large, debilitating ulcers. Patients suffer from these ulcers dramatically, as they are very painful. They can occur on all body parts, but typically start on the lower legs. And it's a rare disease. We're estimating about 50,000 patients in the U.S. and in Europe altogether. But there's a significant market potential because premium pricing is possible. We have orphan drug status in the U.S. and in Europe, and there's nothing else approved, and there's not even a consensus guideline yet in most countries, how to even address this disease. Typically, these patients are treated with all sorts of anti-inflammatory attempts, sometimes even cocktails, until either something works or they are referred to another physician. Next slide, please. I just want to share with you some of the new research. There's an increasing body of evidence why neutrophils and also netosis, which I mentioned before, plays a role. And I want to draw your attention first to the picture on the lower right side. This was C5a measurements here from a research group in wound fluids, and you see that the PG wound fluids showed a higher C5a load clearly. And also, you see that these wounds were containing elastase, a marker for netosis. And finally, these parameters correlated, so the higher the C5a, the higher the elastase levels. That's not necessarily surprising, knowing that there's a lot of research showing that C5a induces netosis, and the same paper concluded that in the slide above, that controlled neutrophils do not undergo significant netosis. But if they are stimulated with C5a here in nanomolars that are found in humans, you see that this is a staining marker here for extracellular staining, and C5a, by far, is the strongest inducer of this netosis marker. One can even say they couldn't really find another one. Maybe IL-8 after long-term stimulation, you see that on the right side, gave a bit of a signal. So that's. There's an increasing body of evidence on that mechanism. Next slide, please. So we had a very interesting phase II with a strong result on the benefit side for the patients. So in our high-dose group, we had 86% of the patients going into clinical remission. So these patients all ultimately closed their target ulcer. And you see the overall results showed also an over 50%, that is across all three dose groups. The remarkable other thing is that all of the patients that were evaluable, 17 altogether, had an improvement. Not everyone, a clinical remission, but over 50%, one additional patient, a response, and then others, seven others, a slight improvement. So we didn't have any safety signals of larger concern. We had 2 reported SAEs. You find them here below. One is a typical problem that these patients have, wound infections, and the other one was a rash, likely due to the drug, as an hypersensitivity reaction. So I mentioned the orphan drug status in the EU and the US, and we also have Fast Track. We did discuss our phase III trial with the FDA, and that brings me to some of the results on the next slide, please. Why did we get so excited? Now, when you see these patients and when you work with these patients, you get excited when you can help them because they're really suffering a lot, and these are just two examples. The left side is one of my favorite examples 'cause this is a patient that developed a PG ulcer under adalimumab treatment under TNF-alpha inhibition, and that was the patient's medication for an underlying other disease, in this case, psoriasis. And this wound was difficult to treat. He was actually the fastest responder in the trial, and healed that ulcer very rapidly. On the right side, you see a patient that had multiple treatment attempts with a bad ulcer on the right lower leg or above the ankle. This patient was up-dosed from the medium dose to the high-dose group, which then ultimately closed the wound relatively rapidly when being up-dosed. This is actually a remarkable result because these wounds above the ankle are very difficult to heal. Next slide, please. This brings me to the running phase III trial in PG. This trial is currently recruiting. This trial is a placebo-controlled trial with two arms, very simple. The one arm, vilobelimab, and the other one, placebo, both on a low dose of prednisone, which is tapered off during an eight week process. Then the patients have preset dates where we are checking for patient-level stopping criteria. And when a patient hits the stopping criteria, meaning the patient doesn't show wound improvement, then the patient is transitioned out of the trial and considered a non-responder for the primary endpoint. This is the way we discussed the trial with the FDA. You see that we have an interim analysis after about 30 patients, 15 in each arm. And I want to just be talking about that just a second here, because I think it's important to understand that this is an important interim for us. It is unblinded for the IDMC, but blinded for the team and for the trial, and it can lead to stopping of futility or to an adjustment of between a final total number of patients enrolled between 50 and 100. Now, this is a meaningful size in PG arena. And obviously, to have a p-value positive readout with the patients in the range of 50-100 patients, you need to have substantial difference between placebo and your drug. And so for us, that interim analysis, if it doesn't stop for futility, is certainly a positive sign. And of course, if it were to adjust only to the minimum enrollment, this instills further confidence in us. However, it's important to note that we don't stop enrollment during this interim read. So at the stage where we know if and how the trial adapts, we already may have reached the final enrollment, at least on the low end here. And so for us, this is an interesting read, and it's an important read, and this will occur, as we just today guided, next year in 2025. Just to mention, the primary endpoint will be complete target ulcer closure, which we've seen with the drug in phase II. Next slide, please. So this brings me to our exciting C5aR inhibitor, our oral drug, INF904, and I'll be introducing the drug briefly before we go into the indications. Next slide. So the key features, really, I'm not going to read all of this, but we are really excited because we were able to reach a very differentiated PK/PD profile when compared to the reported data from avacopan. We had a 3-fold higher Cmax, 10-fold higher plasma exposure, and which is probably most significant, a significantly increased blocking activity, which showed above 90% blocking activity for comparable doses, starting at 30 mg. And that was our goal, and this phase I trial really reached all of our goals. We didn't have any safety signals of concern. We were able to show this over a broad dose range. We also know that the drug has less inhibitory potential on the important liver enzyme CYP3A4 and 5, when compared to the Avacopan data. And we have a strong IP position. So we'll be taking this to immunodermatology because this is an oral drug, very differentiated mechanism of action, and we believe that this can really bring a lot of benefit to patients that have a high unmet need. Next slide. So this is important. I'm not going to go into the details of the experiment, but this is a head-to-head experiment, preclinical, in live in vivo experiments in rodents and hamsters. And what that shows is, on the left side, that, you know, at the exact same formulation, at the exact same dose, in this model, in the hamster, we doubled the inhibitory effect with INF904 compared to Avacopan. So this doubling of the effect was really very encouraging, and we've seen, you know, pretty much almost a doubling of the inhibitory potential in the phase I already. So we expect that this will translate to a potential of higher efficacy in human disease as well. Okay, so, again, I'm not going to go into the details, but just want to flag one thing. You see the plasma concentration is quite different, and we believe that this is really an important differentiator, that we reach very different plasma levels, very rapidly with the drug. So we are just able to come into the range where the drug can do the full trick, which may be a much more tricky task for our comparator. Next slide. And this gives you a visual. This is just the single dosing and from our just reported phase I study, and you can see in the red dotted line, this is superimposed, so this is not a head-to-head study, but the data reported from avacopan are superimposed into this graph. You see the comparable dose is the blue line of INF904, 30 mg, one shot. You see that there's a very differentiated PK profile. You see that the time to max occurs, the peak occurs later. There's a much broader area under the curve, and again, this confirms the threefold higher Cmax, but also the tenfold higher plasma exposure. That was true for all comparable doses. And then you can see above the dose, we tested up to 240 mg without any safety signal. Next slide. This is the slide that we are most excited about, that shows in this case, in a 14 day dosing, multiple ascending dose with three different doses, that we have a very tight control over the C5a-induced signaling. So when the drug is taken out of the blood of patients at trough, and we challenge that with new C5a, it blocks it over a very broad dose range, up to 90% and higher. And that really is, for us, something that we wanted to see and it really confirmed all the preclinical work. So next slide, please. So we will begin our phase II development this year still. We want to start with an initial phase IIa, demonstrating the pipeline and the drug potential really for this drug. This will be an exploratory study, but a PK, PD and safety basket study. That means a four-week initial treatment in two immunodermatology indications, CSU and HS. We will also look into three different doses here to assess PK and safety. The catalysts are, we want to start this trial end of year, 2024, and we want to have data in 2025 that we can share while preparing for a meaningful, substantial, larger phase IIb studies in this indication. They're expected to begin also in 2025. Next slide, please. With that, we're going down the road now to go into the initial indications chosen, and I'm very happy to hand this over here to our Chief Medical Officer, Camilla Chong. Camilla, please, help us and speak about chronic spontaneous urticaria. Thank you. Thanks, Niels. So next slide, please. I just wanted to start by saying that, you know, we are really thrilled to be able to, first of all, collaborate with Professor Markus Maurer, who from Charité Berlin, who many of you who have worked in this space will know, is a world-leading expert in CSU. It is really his conviction and persuasion that with the increasing scientific evidence that have been generated recently, to suggest that C5aR signaling is involved in histamine release from both mast cells and basophils, in CSU patients in an IgE-independent manner. So this mechanism may play a role, which is important for both, described endotypes, which I will go into a little bit more later on, so-called Type 1 and type IIb. So there is also belief from his group and others that despite availability of current treatment options, such as antihistamines and anti-IgE therapy, there is an not an insubstantial number or percentage of patients of either who have not responded to antihistamines or omalizumab therapy, who remain non-responsive, and is therefore symptomatic. We believe that therefore, INF904 can be a convenient oral therapeutic option, particularly for those who do not want a continuous subcut injection every month, and those who may not tolerate quadrupling therapies with antihistamines or IgE. We believe that the CSU market potential is estimated to exceed over $3 billion by 2032. Next, please. For some of you who are familiar with CSU, you will recognize that, you know, as described in literature and by many experts, that this is an immune-mediated, chronic inflammatory skin disease, which, you know, have dysregulated inflammatory processes involved, leaving patients very predisposed to symptoms which are both debilitating and are chronic in nature, predominantly the development of itchy hives and wheals that do not go away for a period of over six weeks, and some are often associated with angioedema. I think the important thing to highlight about this condition, as many of you will know, is that it has high physical and economic burden, not just for patients and families, but also for healthcare system. The estimated prevalence is, has been described to be around 1% of the general population in, most countries, and that up to 20%, if not more, of this so-called population, experience symptoms for more than five years. 20 to 40-year-olds are particularly affected. Some have described 30 to 60-year-olds, and with women being impacted, you know, twice as often, compared to men. Current treatments, as I've already mentioned, the only approved treatments are antihistamines and anti-IgE therapy. Next, please. So, as described earlier, Professor Maurer and group have done a lot of work to based on their observations of treatment in CSU patients, and they have described these two main endotypes for CSU. These are basically broken into type 1, which is characterized by IgE autoantibodies directed to self-antigens, and therefore the term type 1 autoallergens. But they also believe that there is a type IIb autoimmunity, of which this makes up something like 30% of the so-called CSU patients. And this is more IgE, IgG-mediated antibody, directed specifically to the anti-IgE or to the Fc epsilon receptor on both mast cells and basophils. So both these pathways is believed to involve C5a, and therefore, the C5a signaling is important in these two cascades, as shown on the diagram on the left-hand side. Next slide, please. Now, I know that this is a slightly busy slide, so if you'll indulge me to spend a little bit of time to walk you through it, starting from the left-hand side. So the left-hand side is basically an experiment in CSU patients where they measured C5a levels, and as you can see here, C5a levels are significantly increased compared to control group. So C5a levels are elevated, we know, in CSU patients. And then, at the bottom, on the left-hand side, what you would see is essentially, staining of skin biopsy in CSU patients of C4d, suggesting that basically there is activation of the complement system. And then, now, if you focus your attention to the middle graph, what's interesting here is that this was an experiment done over 20 years ago, where essentially, they've been able to show from healthy donors' blood, C5a in itself can actually induce histamine release from basophils in a very nice dose-dependent manner. And then last but not least, the last part of this graph shows that actually, the C5a-mediated histamine release is independent of the IgE pathway. This is an ex vivo human skin experiment where they incubated it with a Syk inhibitor, which was a GSK compound, that basically worked predominantly via the IgE pathway, and they then added increasing levels of concentration of C5a. As you can see, the C5a stimulation of histamine release is not affected at all via this IgE pathway with the Syk inhibitor GSK2646264. Next slide, please. Here, what I wanted to demonstrate to you is a piece of work done by a Japanese group, recently published in 2022. What they have tried to do is they took blood from CSU patients and measured the different levels of basophils after stimulating it with an anti-IgE stimulus. On the left-hand side, what you can see is that basophils from these patients, with an anti-IgE stimulus, and hence they call it, IgE stimulus-positive patients, with histamine release, they show a really good response. I think interestingly, these basophils also showed histamine release, in a dose-dependent manner with C5a stimulation. If you then focus on the graph on the right-hand side, CSU patients who do not respond to the anti-IgE stimulus continues to be responsive to C5a stimulation. Next, please. So what they propose is that actually, C5a-induced histamine release is important for both pathways, IgE dependent as well as IgE independent, whereby if you look at the IgE-dependent pathway, C5a still plays a role in addition to the other pathway where it is non-IgE dependent. And I think in addition to that, what they have managed to also show is that the C5a generation in CSU may be further amplified because of the activation of the coagulation pathways via tissue factor release. In addition, so this acts as almost like a continuous amplification loop, which further drives disease. Next slide, please. In conclusion, I hope you would have seen that, you know, C5aR signaling is involved in histamine release from both mast cells and basophils, and that certainly, this has been the conviction from Professor Maurer and group, that the C5a-mediated histamine release is suggested to play a really important role in both subtypes of CSU, even though it can be shown to be released independent of the IgE pathway. We really believe that this C5a inhibition represents a novel mechanism to address an unmet need in CSU, and that INF904 has the, you know, oral potential to offer an oral drug, which is potent for the development in CSU. Thank you. I'm now going to hand back to Niels, who will take you through to our next indication. Yes, thank you so much, Camilla. I really appreciate it. I'm excited now to speak a bit about hidradenitis suppurativa. Next slide, please. This is another indication that we want to show the potential of the drug and show that the drug is active initially. When you look at this disease, it's probably well known to some of the people here on the call. There's still new mechanisms are needed, and that's what we hear from KOLs, and we are very attached to that scene, generally speaking. Especially moderate to severe patients that have active draining disease are oftentimes left with non-ideal or non-working options. Even though recent progress has certainly produced drugs that are approved, like, the anti-TNF-α class, like Humira, actually, and some IL-17 agents, at least one approved, the other one on the path, and the third one coming. But these patients that respond to these drugs, they're known that this - for them, it's known that a significant number will have the efficacy or the effect wane over time. And so, there is a high unmet need for additional mechanisms, and again, there may be also a need that is not ideally addressed by these drugs. So we know that HS patients have a preference for oral medications over injections. That has been suggested in research. We have an oral C5aR inhibitor with a mechanism that really is addressing something, and I come back to the word netosis here, but also just the effect on neutrophils. Again, HS is a neutrophilic dermatosis that is not necessarily addressed by any of the drugs. And there's clinical evidence, I'll be speaking about here in a second, about the pathway that this pathway, when addressed, can reduce lesion counts in HS. And this drug has a favorable PK/PD profile with a broad dose range for systemic exposure. Well, that set aside, the HS market has been described to be a very attractive commercial market. There are estimates that this market has a multibillion peak potential for drugs by 2032, and that is an exciting side note, of course. Next slide, please. So, I'm not gonna be speaking too much about HS, as I believe it's been much discussed by also recent research. And just want to mention that this, for the patients affected, this is really a truly living nightmare, especially those that are progressed in the disease to moderate, severe stage, and those that have active draining tunnels. 'Cause a single tunnel, and if you go on the internet and research that, there are. I think there's even a video that shows that a tunnel produces up to a liter of pus, just one single tunnel. Because the tunnel is the outside that you see, but underneath the tunnel is a deep-seated lesion, and these lesions are in the skin. They're hurtful. The pus is really carrying a huge social burden, and you have to imagine that this disease occurs under the armpits and oftentimes in the groin area. So it really has a social, life-destroying character. Okay, so next slide, please. Or maybe the last thing I wanted to add is that this is clearly a market with a lot of patients affected. There are varying reports about how large it is, but it's clearly more than 200,000 patients, even in the moderate severe stage in the U.S. So on this slide, I want to just basically convey one message. I don't want to walk you through the whole slide, but there's recent progress on the understanding of the pathogenesis of the disease. And this just shows that research, which is not, you know, that. Which is not coming out of our group, but out of people we know, suggests a central role for C5a and C5aR in the pathogenesis, in the mechanism that is set into place when these follicles rupture. And when in the initiation phase, an immune reaction to this rupture, to this claudic follicular rupture, this is the current hypothesis, is set in motion. And so it's really recognized in the field that this is a central role. Next slide, please. So, you know, we've produced data a while ago that these patients have elevated C5a levels. This is with a validated ELISA, and this is not surprising. And actually, in the phase IIb study that we ran, we showed quite substantial C5a levels in these patients. Now, we also have shown some interesting data that, you know, HS patient plasma strongly provokes neutrophil activation. So when you take plasma from HS patients, and you subject fresh neutrophils from fresh donors to that plasma, they get activated immediately. And both drugs, vilobelimab and also new data with INF904, with our oral C5aR inhibitor, have shown that they can pretty much completely abrogate that activation. So meaning that obviously it is C5a in that plasma from HS patients that excites fresh neutrophils and stimulates them strong. Next slide, please. So is the receptor present? A recent study has shown that beautifully for all three stages of the disease. So you always have the common tissue, hematoxylin and eosin, staining, in red above, and you see that the lesions are marked. And then below, there is a staining for C5aR and, neutrophils, but it's also found in other cells, like histiocytes and giant cells. And you see that, C5aR staining is found strongly around these lesions, particularly in the middle, in the stage, early stage two, also around, when patients develop, draining tunnels, they tend to rupture, and they tend to create that large intradermal lesion. You see that, that when that happens, there's a lot of C5aR around, and then also on the right-hand side in the most progressed patients. So C5aR is present, not surprising, because neutrophils are present, certainly in all three disease stages. Something that I won't show you with a slide, but we will go into more detail on another day, is that netosis occurs quite substantially in these patients, and that's also new research. Again, C5a being one of the key inducers of netosis in neutrophils. Next slide, please. So there's clinical evidence I mentioned, and I just want to go into that very briefly. So with vilobelimab, we did a phase IIb study, and that clearly created, on the high dose level, evidence that C5a inhibition can reduce the inflammatory lesions and all of them. There was a particularly noteworthy effect on the draining tunnels that we spoke about, and this was actually the tighter the C5a levels were controlled, the higher the draining tunnel reduction was. And the key learnings from our, like, substantial work in the field was really that vilobelimab was needed to adequately control C5a/C5aR signaling only when it's given in a higher dose. So in other words, you need a very high dose. The dose we've chosen is probably was, according to our PK, PD and pop PK modeling, not enough to adequately cover the signal. So that's the key learning. But the other learning is, it is an interesting path that is promising for the future to decrease these lesion counts. On the oral C5aR inhibitor side, on avacopan, there's also been studies done, and I want to share with you that at a standard dose, which is the approved dose in another disease indication, at ANCA vasculitis, which is 30 mg twice per day, there was a p-value positive efficacy signal, when they looked at the subgroup of severe HS patients, early stage 3, on HiSCR, with a clear separation from placebo group emerging late, only mostly on at week 12. Now, I do want to mention that this study was also negative on the overall study population when it comes to HiSCR. There was also a very high placebo response in the early stage 2 patients, which probably disabled to see an effect. But the interesting part is really that in the stage 3 patients, these groups and the lesion counts separated really at week 12. And so when we looked into the switching to ANCA vasculitis, which is the area where avacopan is approved, the filing data showed that the drug has a very strong accumulation pattern, 4x, and it takes approximately three months until it reaches the plateau, like, of the accumulation phase. So that's fitted quite well with this observation. I'm gonna show you a picture here in just a second. So how we interpret that is that the 30 mg twice per day dosing regimen of that drug, because of its PK features, was probably not adequate, not high enough to show an efficacy early and the separation early. And of course, we conclude from that, that is a problem that could be handled with the right PK and the right drug. Next slide, please. So these are the data from the ChemoCentryx reports back then, from the AURORA study. And again, I mentioned that the overall trial results were not p-value positive, but the early stage 3 patients showed the separation. You see the gray curves are placebo, the orange curves were avacopan at the dose that I explained, and you see the ANCA count on the left side, you see the nodule count in the middle, and you see the draining tunnel count. And you see that really the separation starts only to be visible, like, strongly visible, at week 12. So somewhere between the last visit at week 8 and the second last visit at week eight and week 12, there was the separation occurring, and you see the HiSCR splitting also relatively late here on the right side. Now, again, I explained already that from another disease, from the ANCA disease, we learned about the late accumulation. And again, our conclusion is that this may not be the right dosing and the right PK profile, but there is efficacy. Next slide. And this is the that we graphically work this up. This is the publicly filed NDA filing for the ANCA-associated vasculitis PK accumulation. Again, it's a different disease, but it's interesting because it shows this roughly fourfold accumulation, and you see the steep curve is kind of starting, flattening out around week 12. In fact, it was week 13 where the steady state was reached, and this plasma exposure is given here on the right side. So next slide. I come to a conclusion here, and the conclusion is, overall speaking with the available evidence and knowledge, is that there's a strong scientific rationale for the role of C5aR in HS. Now, both C5a and C5aR signaling or blockade of that signaling has resulted in signals of efficacy in HS patients. We believe that a tight control over the signaling, as C5aR signaling, is required to achieve an optimal efficacy. So we all know dosing is important in HS, which is basically true for all drugs tested, if you consider that some of the approved drugs were only showing efficacy when their approved dose from other indications was doubled. Take, for example, Humira. So, that brings us to our conclusion, that INF904 is ideally positioned as an oral C5aR inhibitor with optimized PK/PD profile to address an existing high unmet medical need in these patients, and we are really excited to move this drug into this new direction. Next slide, please. So at the end of our presentation, I want to speak about Gohibic briefly. Now, this is for the vilobelimab, where we got the emergency use authorization. And I want to first mention that our team feels privileged, honored, and is very excited about the fact that we were able to get an emergency use authorization. This was the only emergency use authorization granted in 2023. I s the only one for a small biotech company, and it's also the only one with a first-in-class mechanism, that addresses, an unmet need, in the immunomodulatory, space. So we're excited. We are definitely committed to continue making the drug available to patients at need. We have recently, press released our commitment program that, helps addressing some of the issues that the acute care/hospital healthcare system has. And we're in active discussions, and we get a lot of good feedback about this commitment program. And so next slide, please. So this just summarizes the Gohibic Emergency Use Authorization and our commitment to keep the drug, available for patients. And also, we did talk about the fact that we may get a full BLA with one additional study in the ARDS trial. Now, we are very frugal with our spend in this area because we had never anticipated and cannot anticipate how this market may look like, which comes along with the situation switching from a pandemic into maybe an endemic state. So we're very frugal, and we also mentioned that we would only look into such development if we get public funding or the help or other non-dilutive funding in the company. So with that statement, I want to close out our today's presentation and open for Q&A. Again, I want to summarize the excitement of the entire team to focus now on immunodermatology with our upfront running phase III program, but also with the new additions with our oral INF-904. So with that, I hand back to you, John, and yes, thank you for your attention, and the team is happy to answer any questions you might have. Thank you. Thanks, Niels. So, audience, this concludes the formal presentation, so we'll open the call to questions now, and there are two ways you can do so. First, you can submit a question in writing via the Q&A button below the presentation window. I'll then read that question aloud during the Q&A session. Or you can ask a question live by raising your hand icon under the presentation window, and then we'll announce the call for each person at that point. So, we do have a question from Steve Seedhouse. If you can accept your unmute request, and we'll get your question started. Yeah. Hi, everyone. Can you hear me okay, John? Yes. Okay, great. Thanks so much for hosting this call and for the overview and all of the detail and context. A couple questions here, just starting with HS maybe. Obviously, interesting opportunity you have experience here to maybe offer an orthogonal mechanism to IL-17s or TNFs and also the oral, you know, presentation is a differentiator. But widening the lens also just seems like an opportunity to establish, really in patients, the PK/PD advantages of INF904, if that translates from what you've seen so far, versus avacopan or IFX-1, of course. So, just curious in that regard, if you will be sort of closely analyzing PK/PD data in these patients? Will you be able to compare to maybe some of the avacopan data that's publicly available, you shared some in ANCA-associated vasculitis or your own IFX-1 data, and really determine if you're getting a better coverage of C5aR inhibition, essentially, in patients in this phase IIa? Yes. Thank you, Steve. I'm happy to take that question, if I may. First of all, it's a great question. Thanks for asking that. The answer is yes, we will closely monitor PK. This is like a PK-focused study, and on the PD angle, we're looking, of course, at various efficacy signals. Now, you may see that it's a four-week initial exposure. We, of course, have done a lot of work into thinking what can we show at four weeks. And we're quite convinced that with the high doses that we can administer our drug, INF904, and we will end, and being a small molecule and anticipate a high tissue penetration levels, that we can see a differentiation or that we can see also efficacy signals at week 4. Now, there are comparatives. We have the week 4 data with our slightly underdosed vilobelimab trial. We have the week 4 data, at least in the early stages, we reported by avacopan, and we have a lot of in house data. So I think the goal is really to say, on the PD level, that may translate into, I would say, a signal that when you compare it, especially to known placebo responses at week four, that will at least give us a good confidence that we're seeing, efficacy of the drug here. So we've done a lot of - a nd we will go into this into more detail. The press release today will - has also announced that we're planning an R&D day in due course. So one of our goals for that R&D day is to have some of the experts we're working with, speaking about what we're doing and about, what they get, what excites them, but also a bit more into exactly such details that you just mentioned about the trial. Now, what is difficult to do is the PD, as we've done it in a phase I, where you have these flow cytometric data on the, on the neutrophil ex vivo excitation, which requires really a very full on-site training of a team that on-site does the measurement with the fresh drawn blood. So that can be done in trained phase I units, but you have to almost train the entire team. And we're looking into whether we can get some of that data, maybe at few sites, but that is something we cannot fully promise at this point in time. That would be, of course, nice because you can directly compare that to the phase I data then. Okay, thanks, Niels. Just you, I mean, you guys have more experience than maybe anyone with regulators discussing HS and the endpoints and the evolving landscape. Where, I guess, where are we at today from your perspective, with draining tunnels and endpoints and how to develop something to the finish line in HS? Yeah. Anything? Yeah, great question. So first of all, I want to make sure that it's clear that we're not, like, basing the entire development on draining tunnels or on whether or not we can, you know, maybe develop better tools to show something. We believe that this drug can also be successful on the HiSCR. It's an oral drug. There's an improved endpoint, which is the HiSCR. The orals have, in the past, shown consistently, lower placebo response rates when you compare that to, IV infusions, for example. And that has to do with placebo response of patients. But that set aside, we know that there's a very special additional mechanism of action, as you pointed out, on the most severe lesions. And of course, that can be worked out nicely, either on secondary endpoints. Yeah, we've come back then very close. I think we have, with a minimum ambiguity, had an agreement on running into a phase IIIa trial with a new endpoint. You know, we are consulted by former office directors of the FDA. On that end, there's certainly something we can work out, but I do want to flag that we're not, like, basically basing our whole development on whether or not we can come to terms for exciting research. We think that we can win the game and win the market approval also on the HiSCR. we've come back then very close. I think we have, with a minimum ambiguity, had an agreement on running into a phase IIIa trial with a new endpoint. You know, we are consulted by former office directors of the FDA. On that end, there's certainly something we can work out, but I do want to flag that we're not, like, basically basing our whole development on whether or not we can come to terms for exciting research. We think that we can win the game and win the market approval also on the HiSCR. we've come back then very close. I think we have, with a minimum ambiguity, had an agreement on running into a phase IIIa trial with a new endpoint. You know, we are consulted by former office directors of the FDA. On that end, there's certainly something we can work out, but I do want to flag that we're not, like, basically basing our whole development on whether or not we can come to terms for exciting research. We think that we can win the game and win the market approval also on the HiSCR. we've come back then very close. I think we have, with a minimum ambiguity, had an agreement on running into a phase IIIa trial with a new endpoint. You know, we are consulted by former office directors of the FDA. On that end, there's certainly something we can work out, but I do want to flag that we're not, like, basically basing our whole development on whether or not we can come to terms for exciting research. We think that we can win the game and win the market approval also on the HiSCR. we've come back then very close. I think we have, with a minimum ambiguity, had an agreement on running into a phase IIIa trial with a new endpoint. You know, we are consulted by former office directors of the FDA. On that end, there's certainly something we can work out, but I do want to flag that we're not, like, basically basing our whole development on whether or not we can come to terms for exciting research. We think that we can win the game and win the market approval also on the HiSCR. Great. And then just to wrap, the parallel track here in CSU is interesting. So, two-part question on that. First, I mean, do you view this as really just the sort of lowest hanging fruit proof of concept for mast cell biology in general, that would open up, you know, myriad development opportunities across the spectrum of mast cell biology? Or is there something specific about CSU that drew your attention? And then also, do you think... You mentioned the two endotypes and the contribution of C5aR to both. Is that something that you think you can parse out, the relative activity in this phase IIa, or would that be too challenging to do? Yeah, I'm happy to pass this over to Camilla, and maybe I chime in with an additional thought, but Camilla, please. Sure. Yeah. I'd be happy to perhaps answer the last part of your question. So we believe that in our phase IIa study that we're looking at, that we should be able to address both endotypes, right? That we're not just restricting it to the very refractory type of CSU patients. So there is no reason why it should not work in either endotypes, firstly. And I think, you know, CSU is one of those conditions where you can show relatively quick clinical effect within two weeks, if not up to four weeks. Now, obviously, you know, that's different from showing maintenance, but I think this could be a very quick indication for us to be able to really dwell into, to really be able to explore the biology of this drug. The endpoints are fairly straightforward. They're fairly, you know, well accepted by regulators. So we feel that, you know, this would be a relatively not easy, but it would be a less complicated one to be able to do. Plus, the fact that, you know, it's not a rare indication, so we will get the patients that we would need to be able to study this in a relatively efficient manner. Yeah, maybe. And just to add to that, Camilla, I think we are very close here with a team of Dr. Maurer at Charité in Berlin. They have worked out the concept. They initially suggested to us that we should do this development some while ago with Vilo, and when they heard we have the oral, we came back into really strong discussions. So yes, the idea would be, and they, there's a strong support, so they are willing to support us also by recruiting patients and by recruiting both subtypes, as Camilla just said. Now, you asked for the more broad, general, like, mast cell biology. I would say at this point in time, we are focusing on this attractive market, and we know, and that was part of the central discussions with the Maurer team, is we know that there's like really a decent number of patients that are underserved, even with the treatments. And that one of the thoughts is they may be underserved because that second angle, which is independent of IG, is not addressed. And that's exactly... If that's true, we may address a very broad patient population. We may address all of the population, and that's something we need to work out. So that's too early to make that statement, but we are excited about this indication and all the work that the Maurer Group and others have done so far. Whether we take it to a more broader mast cell, I think we would definitely not make these conclusions before we don't have the data to speak about it. Thanks for the questions. Great, so we have a few here from that have been submitted in writing. So I'll go to the first by Joe Schwartz at Leerink Partners. So the first part is, they're asking us about the goals of the phase IIa study in terms of what kind of early efficacy endpoints we'll be including, how informative we think the endpoints will be at four weeks, and anything we'll be looking for as we consider a go/no-go in either of the indications. Yeah, I'm happy to tackle that. So that's very straightforward. On the efficacy side, this is exploratory, but Camilla already mentioned in CSU, there is this seven-day score established that is, like, that is the primary endpoint in trials and very broadly used and accepted. And that gives you a very good look and should give you a read whether the patients respond to the drug in four weeks or not. So that is something you can definitely scout at four weeks, and that endpoint is clear. So the UAS7 is something that is broadly used. Then in the hidradenitis suppurativa population, we will look at reductions of all three lesions and compare that to the four-week reductions, either reported from other drugs or seen with our own drug, to scout. You know, we just shown you some of the data that were published from the avacopan trial, and we've shown you that there's a very late onset of efficacy. For example, if you know that the draining tunnels did not even move before week 12. And we will definitely see and compare that and hope that we see already these signals moving at week 4 quite a bit. And of course, with the three lesion counts established, we can then, of course, derive all the typical endpoints that you look at. Obviously, with a lower number and a PK focused study, things like HiSCR are not extremely informative. For us, the key is, at that stage of the development, to show you how much the three lesions moved at week four. I hope that helps for... And again, we will probably provide then more color in our R&D event following. Great. Then we have a follow-up there in terms of the preclinical tox work. Could you remind us where we are in the progress, and if this will be a gating factor for the phase II, or will the timing line up where you can start, you know, go seamlessly into the phase IIb next year? Yeah, maybe I can take that. So yeah, for tox, we already start with the chronic tox, as we mentioned earlier, that we plan to do six months rat and the nine months monkey. Those already start early this month. So yeah, we are planning seamlessly with all the clinical development, including phase IIa, phase IIb. So data expected for six months rat will be end of this year and early next year for nine months monkey. So to answer your question, we are planning this, you know, together with all the clinical development. We have a couple questions from Evan today. I would add Guggenheim again on the preclinical. What kind of preclinical work have you done with INF904 in CSU? Can INF904 decrease the number of mast cells? And given its unique MOA, how are you thinking about positioning in CSU? Yeah, maybe for the second one, we don't know if the INF904 gonna decrease the number of mast cell. In theory, they should it, and there's no reason to believe that INF904 does not to delete the mast cell based on mode of actions. For the first one, in the literature, there's tons of study that's already been worked out for the role of C5aR in the CSU, with the CSU patient samples, especially with the serum and plasma samples, with a blockade of C5aR and with antibody or peptide, it all show, like, pretty good blockade to the histamine release from either mast cell or from basophil. So we are currently working with a pretty well-known laboratory for CRO laboratory to work out more details with the INF904. So, yeah, I think the second question Niels and Camilla already addressed the position in the CSU. We're not thinking that it's gonna be just to treat a few areas, but you know, basically, we are, yeah, able to, should be able to treat both type of CSU. Got it. And then a follow-up, what would you expect the C5aR coverage required for clinical benefit in CSU and HS? Would they be different in one versus the other and in the other indications? Yeah. You know, for CSU and HS, they're both a skin disease, and we generally believe that you do need a higher dose because you need a good coverage on the skin for the drug. So, yeah, so maybe... But I don't. There's no reason to believe that it's gonna be a different dose for two diseases at this point, but we have to wait to see the data because, you know, our phase III, we do plan a pretty broad dose coverage of those two, and to be able to work out the dose. Regarding the other disease, I think it's too early to say for that. So that I... You know, in theory, for onco, probably you don't need a lot of coverage because it's the focus on the vasculature, and that's pretty general answer, for this one. Great. Then we've got a couple questions regarding the partnering strategy that we mentioned. So I'm wondering if you can provide just some high-level, you know, thinking and strategy on how we would approach or could approach partnering. Yeah, Tom, do you want to take that? Yeah, happy to do that. Well, I mean, obviously, our focus on immunodermatology will lead us to put our efforts in this area, but we see the broader potential both of INF904 and of vilobelimab in other indications. So we have initiated discussions with a variety of pharmaceutical companies that might have an interest in also helping us develop it in other indications. It's, at this point, maybe too early to really say what it would look like and how these relationships could ultimately shape up being. But I think that to explore the full potential of both drugs, it would be very advantageous to have somebody who would have an interest to focus on some of the areas that, for resource reasons, we have to leave on the side for the time being. Yeah, so it's really, like, our wish to find pathways to faster unlock more value for the drug, right? We, as Tom just said, we are really convinced that there's a broad applicability to this pathway. So our idea is, like, what can we do to speed up and unlock as much value as possible? Great. So we've kind of covered this already, but I'll just bring it up since it was put in through the written dashboard. Again, from Joe at Leerink Partners, saying, "The prior oral C5aR inhibitor showed better efficacy in HS patients who were more severe or early stage III. Will you be targeting any particular kinds of HS patients in the studies? And can you give us your thoughts on how trial endpoints and studies may have evolved since your initial vilobelimab studies, and what learnings can you apply to the development of INF904 with that?" So covered a fair bit of that, maybe just kind of covering again. Yeah, I think it's from the general understanding of the disease, we all have learned that there are three lesions, and they need to be reduced if patients want to like experience an improvement. We know that the most difficult to treat are the draining tunnels. They are not captured by the currently used score, the high score. This score is established. It's been used now many times. It's been used in phase III studies. People have used the old HiSCR50, now there's even HiSCR75 being explored. But we've also learned that high score is not used by physicians. I don't know any physician that would say, "I'm assessing my patients with a HiSCR." It's a score that's only applied in clinical studies, and we've also learned that oftentimes, when you think about the IL-17 studies in phase III, they came in a bit underwhelming. So the score may not necessarily reflect a good path to differentiate from existing mechanisms, right? I think IL-17s are thought to be probably better drugs than anti-TNF in this disease, but yet on the HiSCR, this could not be shown. So in other words, the field has the understanding about the limitations have evolved, but it's been used, and so it's the path to win the game. But I think as far as we know from our discussions, there's still a pretty high unmet need in patients with active draining tunnels. There's a belief that draining disease is still not adequately addressed, even though there is a signal in IL-17 inhibitors that may not be strong enough to cover a lot of the patients. And so there are areas of unmet needs that relate to active draining disease, which is, you know, one area that we're definitely interested in looking in, whether we can bring more benefit to these patients. But at the same time, as I've shown you with the C5aR staining, there's no reason to believe why the drug shouldn't work in the overall patient population. Second thing is also on maybe the other endpoints you asked for. I think, you know, the established endpoint is the HiSCR. I mentioned that already. And then there's the lesions itself, and then there's lesion-derived scores that don't vary as much. Most of them emphasize the draining tunnels as the most severe. So I would say there's another need I want to flag, which is, I mentioned in the talk that a lot of the patients on these active drugs that are approved may have an efficacy loss over time, where the efficacy wanes. And I think one need is also to demonstrate, at least in the phase III studies, that can certainly not be demonstrated early, that a long-term exposure leads to a significant improvement, long-term improvement in more patients. That is a big need. So if the average patient doesn't think that, oh, with a 50%, my efficacy wanes in the next six or nine months, but I have a good chance, if I'm a responder, to stay a responder, that would be a big win. So I would say we understand the need that has evolved. There is need for new mechanisms, especially sustained improvement and work on the active draining disease. It's too early for us to tell you exactly which one we will focus finally, but I would say, generally speaking, it is our belief that the drug works in all disease stages, and that's our starting point. Okay. Great. We have one more before we wrap up. It's again a written question asking us: in terms of efficacy and safety, how does INF904 compare to avacopan, and are there any significant advantages or improvements for INF904 as a better choice for patients and for, you know, treating physicians? So just maybe perhaps summarize what we've discussed on that. Yeah. I want to, handle this very briefly, and Renfeng, please chime in if I forget anything. So I would start with the safety first. The one thing that is known about avacopan, I think in all fairness, it's been a very safe drug. I don't... There was one liver tox in the ANCA approval that was, you know, heavily discussed, and that may have to do with the drug being like many oral chemical inhibitors a CYP3A4 liver enzyme blocker. Meaning it can lead to plasma accumulation of other drugs, like corticosteroids or, you know, other drugs. And that can lead to other drugs getting higher and maybe causing liver tox. Now, we have in pre-clinical studies shown that we have an over 30-fold less inhibitory potential to CYP3A4. So we have really very low, if minimal engagement with CYP3A4, which is, of course, comforting as we move forward. But again, flagging that generally speaking, avacopan was a relatively safe drug, as far as we know from the filings. I hope that that covers the safety question. Now, the other question is the efficacy question. Yes, we actually do believe that we can show a different efficacy, and that is based on the fact that I showed you how long the drug takes, avacopan takes to accumulate and what they're finally reaching, which was a bit over around 3,300, the area under the curve. And we can reach that with a higher dose on the first day of exposure, and on the equivalent dose, certainly within the first 14 days. So we have a very different bandwidth of reaching such an exposure level that they have at their maximum exposure accumulation, and we can exceed this by multiples. At least that's what our phase I data indicate. Now, of course, we have to still prove that that translates into a better efficacy in humans, and there may be diseases where you can show that well, and diseases where you cannot show it so well. We believe AGS is a disease where you may be able to show that, especially with a more early onset and a more sustained reduction of these lesions. I hope that covers that. Great. So, we are finished with the Q&A session. If anyone in the audience, if we didn't get to your question or didn't address it suitably, please feel free to reach out to ir@inflarx.de, and we can address it at that point. So right now, I'll turn the call back over to Niels, for closing remarks. Niels? Yeah, make it short. Thanks so much for joining. We are very excited to have you and to share more with you to come in an R&D day that we're planning. And happy to take calls and happy to take questions through the IR route, as usual, in due course. So thank you, everyone. Have a great day. Bye. Bye.