InflaRx NV Business Update Call
Good morning, everyone. Thank you for standing by.
Unknown Executive: 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 are 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.
Thank you for joining <unk> conference call to discuss the company's expected development plans for INR 904.
Orally available <unk> inhibitor with best in class potential presenting on today's call, we have Neil <unk>, CEO, and founder and Kimberly Zhang Chief Medical Officer with mainframe grow CSA went counter and Thomas Tacking CFO available during the Q&A session.
During todays presentation, all participants will be in a listen only mode. Please note that today's call is being imported.
Unknown Executive: 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 only ask questions online. I would now like to turn the call over to Dr. Niels Riedemann, CEO and founder of InflaRx. Dr. Riedemann, please go ahead.
The presentation will be followed by a Q&A session, where you you may ask written or audio questions and please note that you can ask questions only online.
Neil Freedom: I would now like to turn the call over to Dr. Neal Freedom in CEO and founder of influx Neil. Please go ahead.
Neal Freedom: Yeah. Thank you so much John we are really excited to have everyone on the call today to share with you our development plans.
Niels C. Riedemann: Yes, thank you so much, Jan. We're really excited to have everyone on the call today to share with you our development plans, and I will dive right back into our topic. But before I do that, I think the 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.
And I will dive right back in into our topic, but before I do that I think next slides would be just a cautionary note on the forward looking statements being made today.
Neal Freedom: Please take note of them next slide please.
Niels C. Riedemann: Next slide, please. So we are really about harnessing C5A and C5AR, that part of the complement pathway, for controlling inflammation in the INI space. And we have, as highlights, really unique 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 vilobilumab, plus a second generation IFX2 in the pipeline as a life cycle molecule.
Neal Freedom: So we are really about pricing <unk> and keep.
Neal Freedom: That part of the company and constantly for controlling inflammation in the ini space and we have had highlights really uniquely targeting mechanisms and dropped candidates and these are validated mechanisms and the new titles and they're a critical part of the inflammation Cascade, we havent pricing cloud highly potent anti <unk> monoclonal.
Neal Freedom: Body known as <unk>, plus a second generation <unk> two in the pipeline as a lifecycle molecule and we have a best in class potential <unk> inhibitor <unk> for us and that inhibitor is exciting the team a lot because first of all we are trying to address certain limitations of the marketing comparator and be up at least from our phase one data.
Niels C. Riedemann: And we have a potential best in class oral C5AR inhibitor, INF904. And that inhibitor is exciting the team a lot because, first of all, we are trying to address certain limitations of the market and comparator. And we are, at least from our phase one data, clearly differentiated, especially on the plasma PK and inhibitor potential. But we also are excited because this is a pipeline and drug potential here in this candidate, and that can address larger markets, likely, and also markets in the immune derm 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 for immunoderm. We have strong IP coverage and medical use coverage, and we have both vilopilimab with a late-stage development phase three ongoing in paudermaganguinosum, and ino4 that will enter phase two in two initial indications, chronic spontaneous urticaria and hydranigluciferativa We have a large upside potential in additional indications, and we are open to and exploring potential collaborations to unlock additional value. 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.
Neal Freedom: Clearly differentiated, especially on the plasma PK and anybody or potential.
Neal Freedom: But we also are excited because this is a pipeline in a drug a potential hit in this candidate and that that can address.
Neal Freedom: Larger markets up slightly and also markets that Indian derm space, which may be talking today, but also outside.
Neal Freedom: So we have set an initial focus on immuno dermatology and we believe that we can drive pipeline value in these markets and immuno germ all we have a strong IP coverage and medical use coverage and we have both of you to beat them up with a late stage development phase III ongoing in power demagoguery knows them and INO four.
Neal Freedom: Or that will enter phase two in two initial indications that chronic spontaneous urticaria and.
Neal Freedom: He'd retinitis a breakeven.
Neal Freedom: Just want to make sure I should mention that we feel very lucky that we are supported by world class scientists and researchers and clinicians Iot opinion leaders in this space.
Neal Freedom: We have a large upside potential in additional indications and we are open and are exploring a potential collaborations add to unlock additional value yet.
Neal Freedom: A strong balance sheet that we just reported today and that takes us at least into 2026th to advance our programs towards the next milestones and 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.
Niels C. Riedemann: And our team has a proven track record of delivering clinical trials and also regulatory success with the emergency use authorization we received last year. Next slide, please. So why immunoderm? Well, first of all, there are several attractive multi-billion dollar commercial opportunity markets to be explored.
Neal Freedom: So why <unk>.
Neal Freedom: Well first of all there are several attractive multibillion dollar commercial opportunity markets to be explored.
Niels C. Riedemann: And then also, we have identified crucial medical needs that we believe INF904 may address strongly. There is 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.
Neal Freedom: And then also.
Neal Freedom: We haven't identified a crucial unmet medical need that we believe INO four I have not informed me address strongly.
Neal Freedom: There's a there's a solid scientific rationale and also in the meantime subclinical.
Neal Freedom: <unk> clinical data on the role of <unk> and this new mechanism.
Neal Freedom: In this space are they're.
Their established endpoints.
That data established for approval and.
Niels C. Riedemann: And, you know, there are no known safety concerns or potential, and a broad potential therapeutic index for INF904. So this oral cVaR antagonist has a differentiated pathway that 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.
Neal Freedom: There's no known.
Neal Freedom: Safety concerns or potential broad potential therapeutic index for <unk> of 94.
Neal Freedom: So this oral <unk> antagonist has a differentiated pathway the dresses the mechanism of action that is currently not addressed by any competitor in the human the derm space.
Speaker Change: And we're very excited about moving that in there.
Niels C. Riedemann: We have an established network of experts and also in-house trial expertise in this area, and I mentioned the strong IP coverage. So this just depicts our initial focus here at Immunoderm, and we'll be talking about these two indications, chronic spontaneous uticaria and heterodonitis vertebrae 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 where we are very excited about the opportunity, either from our research or also from initial clinical data for, for example, the competitor drug Avacopan that has shown initial efficacy in some of the Next slide. So, this brings us to the pipeline. This is basically showing our focus that I've just explained. So, I don't want to reiterate that.
Speaker Change: We Havent established network of experts and also in our stride expertise into the area and the I mentioned already the strong IP coverage next slide please.
Speaker Change: So this just depicts our initial focus here in immuno derm and we'll be talking about these two indications chronic spontaneous urticaria and he'd retinitis for Teva today and there are others that we may explore in the future now. We also this year a few selected indications in neurology and in the Nephrologist SaaS hematology space and that is.
Speaker Change: Two demonstrated we've done quite a bit of work in many other disease indications deeper Assam, where we are very excited about the opportunity either from our eastern edge or also from initial clinical data for for example, the competitor dropping back a pond that had shown initial efficacy in some of the nephrology indications yet lifted of course, then end of <unk>.
Speaker Change: Might have gotten approval in <unk> associated vasculitis next slide please.
So this brings us back to the pipeline here. This is basically showing our focus that I've just explained so I don't want to reiterate that.
Speaker Change: I just wanted to make sure to flag is strong focus on immuno drum and the potential outside do want to mention that go ahead make me it'll be about does happen embed emergency use authorization plus certain critically ill COVID-19 patients and potentially do you want to broader HRD assay, we would cover that at the end of the talk briefly next site.
Niels C. Riedemann: I just want to make sure to flag this strong focus on immunoderm and the potential outside. I do want to mention that gohibic bilirubinimab does have an emergency use authorization for certain critically ill COVID-19 patients and the 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 strategic positioning, and let's talk about the target. Just for a minute before we dive into the indications. So, we are uniquely positioned here.
Speaker Change: Okay. So let's talk about the strategic positioning and let's talk about the target just give me just for a minute before we dive into the indications next slide please.
Speaker Change: So.
Speaker Change: We are uniquely positioned here, we have two validated drug targets covered by two very exciting molecule <unk> Bay, the ligand covered by VW, the mob and the receptor covered by end of <unk>, our newest small Aro <unk>.
Niels C. Riedemann: We have two validated drug targets covered by two very exciting molecules, C5A, the ligand covered by vilobilumab, 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?
Speaker Change: Inhibitors now it's important to note that if you want to have control over this past, but unique targeted inhibition why is that because upstream blockers likes at the level of <unk> five or higher in the complement system. They lack the ability to block the cleavage that occurs through multiple enzymes. So in other words.
Niels C. Riedemann: 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 effective at 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 the disease in a sufficient manner. Therefore, we need targeted drugs. We have two.
Speaker Change: While they're very sufficient and 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 C. FFA in humans in disease in a sufficient manner. So we need targeted drugs. We have to we're excited about them why because CEVA is upstream of the cytokine network.
Niels C. Riedemann: We're excited about them. Why? Because C5A is upstream of the cytokine network, and it actually boosts a lot of known cytokines. Some of them are listed here.
Speaker Change: It's actually booth a lot of unknown cytokine. Some of them are listed here, it's a strong activator of neutrophils macrophages and other immune cells and what does it mean it means that.
Niels C. Riedemann: And what does that mean? It's a strong activator of neutrophils, macrophages, and other immune cells. It means that it attracts neutrophils, and chemotaxis, and it makes them generate oxidative radicals and granular enzymes. That is a tissue-damaging effect we'll see in many diseases. And there's increasing knowledge around the role of C5A-inducing natosis, and I'm going to be speaking about that a bit later because natosis is increasingly of interest in the immunoderm. Now, there are over 6,000 publications in many, many different disease settings, and we're very excited, but we've chosen initial immunoderm indications, and we will be showcasing them a bit today. Next slide. So, I want to start with our running phase three trial in ulcerative pildermal ganglionosome with Velobelumab, 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 MEK formation, so it leaves the defense mechanism that is known and important in complement space intact.
Speaker Change: Neutrophils chemotaxis and it makes them generate oxidative radicals and granulate advanced that is a tissue damaging effect, who has seen many of the diseases and there is an increasing knowledge around the role of CMA inducing net ptosis and I'm gonna be speaking about that a bit later because that tells us is increasingly of interest in the immuno derm space.
Speaker Change: Now there's over 6000 applications in many many different disease settings, and we're very excited but we've chosen initial immuno drugs indications and we will be showcasing them a bit today next slide.
Speaker Change: So I wanted to start with our running phase three in ulcerative pyoderma gangrene ozone with millipede them up our.
Speaker Change: First in class monoclonal antibody covering the ligand next slide.
Speaker Change: Principally just at a very brief recap insulation yet.
Speaker Change: How you're selective C. Five a blocker it blocks it very effectively up to 100% in human blood. It doesn't touch the Mac formation. So at least the defense mechanism that is known and important in the comparable space intact.
Niels C. Riedemann: It's a fast binder, and 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 Powdamagangrenosum 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. They are very painful.
Speaker Change: The fast binder commercially available under the EUA that I mentioned, so it is uniquely positioned to be a fast and strong binder of the ligand next slide.
Speaker Change: So power demagoguery knows them, it's a terrible disease.
Speaker Change: There is no drug approved in the U S or in Europe.
Speaker Change: It is a neutrophil <unk> skin disease that manifests with large sometimes.
Speaker Change: Very large debilitating outsource page patients suffer from these outs as dramatically as they are very painful.
Niels C. Riedemann: 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.
Occur on all Barney parts, but typically start on their lower legs.
Speaker Change: And it's a rare disease, we're estimating about 50000 patients in the U S and in Europe altogether.
But there is a significant market potential because premium pricing as possible, we have orphan drug status in the U S and in Europe, and there is nothing else approved and there is not even a consensus guideline yet in most countries how to even address this disease.
Niels C. Riedemann: We have open 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 on how to even address this disease. So 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. So, I just want to share with you some of the new research. So, there's an increasing body of evidence that neutrophils and also natosis, which I mentioned before, play a role. And I want to draw your attention first to the picture on the lower right side.
Speaker Change: Typically these patients are treated with all sorts of anti inflammatory attendance, sometimes even cop dates until either something works are they are deferred to another position.
Speaker Change: Next slide please.
Speaker Change: So I just want to share with you some of the new research that has an increasing body of evidence why neutrophils and also net told us which I mentioned before plays a role and I want to draw your attention first to the picture on the lower right side. So this was the FFA measurements here from our research group in a wound fluids and you'll see that the PD one through its show it.
Niels C. Riedemann: So, this was C5A measurements here from a research group on wound fluids. And you see that the PG wound fluid showed a higher C5A load clearly, and also you see that these wounds were containing elastase, a marker for natosis. And finally, these parameters correlated.
Speaker Change: The higher <unk>.
Speaker Change: Load clearly and also you can see that these wounds were containing Alaska the market for net TV and finally these these parameters correlated so the higher the <unk> the higher the elastase levels, that's not necessarily surprising knowing that theres a lot of recent showing that CFA induces neto as is and the same.
Niels C. Riedemann: 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 natosis. And the same paper concluded that, in the slide above, controlled neutrophils do not undergo significant natosis. But if they're 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 natosis marker. One can even say they couldn't really find another one.
Speaker Change: Paper concluded that in the slide above that controlled mature fields.
Speaker Change: Do not undergo a significant.
Speaker Change: All of this but if they are stimulated with CEVA a year in non a malls that are found in humans.
Speaker Change: You see that this is sustaining marker here for extra cellular staining and <unk> by far is the strongest inducer of this net towards this marker one can even say they couldnt really find another one maybe IL eight of the long term stimulation, you'll see that on the right side gave a bit of a cigna. So that's there's an increasing body of evidence on that on that mechanism.
Niels C. Riedemann: 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 for that, on that map. Next slide, please. So we had a very interesting phase two with a strong result on benefits for the patients. So in our high dose group, we had 86% of the patients going into clinical remission, and so these patients all ultimately closed their target ulcer. And you see, the overall results showed also an improvement of over 50%, that is, across all three dose groups. And the remarkable other thing is that all of the patients that were a valuable 17 altogether had an improvement. Not everyone in clinical remission, but over 50%, one additional patient response, and then others, seven others, a slight improvement. So, we didn't have any safety signals of larger concern. We had two reported SAEs. You can find them here below.
Speaker Change: Yes.
Speaker Change: Next slide please.
Speaker Change: So we had a very interesting phase two with a strong reside on the benefits that you have other patient so in our high dose group, we had 86% out the patients going into clinical remission. So these patients all ultimately closed their target ulcer and.
Speaker Change: And you'll see the overall results showed also eight almost 50% that is across all three dose groups and then Andy a remarkable the other thing is that all of the patients that were Evaluable 17 altogether had an improvement not everybody clinical remission, but over 50% one additional patient responds and then others seven others.
Speaker Change: A slight improvement so we didn't have any safety signals of larger concerned with two reported at the easy 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.
Niels C. Riedemann: One is a typical problem that these patients have, wound infections, and the other one was a rash likely due to the drug as a hypersensitivity. So, I mentioned the orphan drug status in the U.S., and we also have Fast-Track. We did discuss our phase 3 trial with the FDA, and that brings me to some of the results on the next slide. 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.
Speaker Change: As a hypersensitivity reaction.
Speaker Change: So we I mentioned, the orphan drug status in the Euro and the U S and we also have fast track.
Speaker Change: We did discuss our phase III trial with the FDA and that brings me to.
Speaker Change: Some of the results on the next slide piece.
Speaker Change: Why did we get so excited now when you see these patients and when you work with these spaces, you'll get excited when you can help them because they are really suffering a lot and these are just two examples.
Speaker Change: <unk> is one of my favorite examples because this is a patient that developed the PG also under the legal mop treatment under TNF Alpha and ambition and that was the patient's medications for an underlying other disease. In this case psoriasis and this said as wound with difficult to treat he was actually the fastest responder in the trial.
Niels C. Riedemann: The left side is one of my favorite examples because this is a patient that developed a PG ulcer under adalimumab treatment, under TNF ulcer inhibition. And that was the patient's medication for an underlying disease, in this case, psoriasis, and this wound was difficult to treat. He was actually the fastest responder in the trial.
Speaker Change: And he has that also very rapidly and on the right side you see a patient that had multiple treatment attempts for the bed also on the on the right the lower leg.
Niels C. Riedemann: And he had that ulcer very rapidly. And 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. And this patient was up-dosed from the medium dose to the high-dose group, which then ultimately closed the wound relatively rapidly when he was up-dosed. And this is actually a remarkable result because these wounds above the ankle are very difficult.
Speaker Change: Above the ankle and this patient was up dose from the medium dose to the high dose group, which then ultimately close the wound relatively rapidly when being up dose.
Speaker Change: And this is actually remarkable result, because these going above the ankle out very difficult to heal.
Speaker Change: Next slide please.
So this brings me to the running phase III trial in PG.
Speaker Change: This trial is currently recruiting this trial placebo controlled trial with two arms very simple the one on <unk> and the other one placebo both on a low dose of prednisone, which is tapered off during an eight week process and then the patient has reset.
Niels C. Riedemann: Next slide, please. So, this brings me to the running phase three trial in PG. This trial is currently recruiting. This trial is a placebo-controlled trial with two arms, very simple. The one arm is vilo-bilo-etmap, and the other one, placebo, both on a low dose of prednisone, which is tapered off during an eight-week process.
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 than the.
Speaker Change: Patient has transitioned out of the trial and considered a non responder for the primary endpoint.
Speaker Change: This is the way we discuss the trial with the FDA you'd 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 frosted unblinded for the IBM Z, but blinded for the team and for the trial and it.
Niels C. Riedemann: And then the patient has pre-set 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. This is how we discuss the trial with the FDA. You see, we have an interim analysis after about 30 patients, 15 in each arm. And I want to just be talking about that for 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 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 the PG arena.
Speaker Change: Can lead to stopping of utility or to an adjustment of between a final total number of patients enrolled at between 50 and 100 now. This is a this is a meaningful size in PG arena.
Speaker Change: And.
Obviously to have a P value positive readout with the patients in the range of 50 to 100 patients you need to have substantial difference between placebo.
Speaker Change: And you would drop and so for us that interim analysis, if it doesn't stop for futility is certainly a positive sign.
Speaker Change: And of course, if it were to.
Speaker Change: Just only to the minimum enrollment this installed further confidence in us. However, it is important to note that we don't stop.
Speaker Change: Enrollment during this interim read so at this stage, where we know if and how the trial at the depths.
Niels C. Riedemann: And obviously, to have a p-value positive readout with patients in the range of 50 to 100 patients, you need to have a 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 installs further confidence in us.
Speaker Change: We are we need may have reached the final enrollment at least on the low end tier and so for US. This is an interesting read and it's an important to read and this will occur as we just today guided next year in 2025.
Speaker Change: Just you mentioned the primary endpoint will be complete target ulcer closure, which we've seen with the drug in phase II.
Speaker Change: Next slide. Please so this brings me to our exciting <unk> our inhibitor of our oral drug INR 904, not be introducing the direct briefly before we go into the indications next slide.
Niels C. Riedemann: 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 may already 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 predicted, next year in 2025.
So the key feature is 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 to.
Speaker Change: The reported data from Abaco pond that we had a threefold higher C. Max 10 foot higher plasma exposure and which is probably the most significant significantly increased blocking activity, which showed above 90% blocking activity for comparable doses starting at 30 mix.
And that's that was our goal and this phase one trial really reached all of our goal as we didn't have any safety signals of concern.
Speaker Change: We were able to show this over broad dose range. We also know that the drug has less inhibitory potential on the important liver enzyme sip 384, and five when compared to the tobacco PON data and best drive position. So we'll be taking this to immuno Durham because it is an oral drug very differentiated mechanism.
Niels C. Riedemann: Just to mention, the primary endpoint will be complete target alpha closure, which we've seen with the drug. Next slide, please. So, this brings me to our exciting cPavAR inhibitor, our oral drug, INF904, and I'll be introducing the drug briefly before we go into the indications.
Speaker Change: <unk> action.
Speaker Change: And we believe that this can really bring a lot of benefit to patients that have a high unmet need next slide.
Speaker Change: So this is important and I'm not going to go into the details of the experiment, but this is a head to head experiment preclinical in our life in vivo experiments in road and CN hamsters and what that shows is on the left side that at.
Niels C. Riedemann: 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 PKBD profile when compared to the reported data from Avacopan. We had a three-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 mix. And that was our goal, and this phase one trial really reached all of our goals. We didn't have any safety signals of concern.
Speaker Change: At the exact same formulation at the exact same dose.
Speaker Change: In this model in the hamster, we doubled the inhibitory effect.
Speaker Change: With <unk> of nine four compared to a barcode Tom. So this doubling of the effect was with really very encouraging and we've seen.
Speaker Change: Pretty much almost the doubling of the inhibitory potential in the phase one already so we expect that this would translate to a potential of higher <unk>.
Speaker Change: You see in human disease as well.
Speaker Change: Okay. So again I'm not going to go into the details, but just wanted to flag one thing you'd see the plasma concentration is quite different and we believe that this is really an important differentiator that we reach very different plasma levels and very rapidly with a drug so we adjust able to come into the range, where the drug can do the full trick.
Niels C. Riedemann: We were able to show this across a broad dose range. We also know that the drug has less inhibitory potential on the important liver enzymes CYP3A4 and 5 when compared to Avacopan data, and we have a strong IP position. So we'll be taking this to immunoderm because this is an oral drug with a 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.
Which may be a much more tricky task for our comparator next slide.
Speaker Change: So and this gives you a visual of this is just the single dosing and from our just reported phase one 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 Avago. Upon a superb posed into this graph and you see the comparable doses the blue line of INR 904.
Niels C. Riedemann: I'm not going to go into the details of the experiment, but this is a head-to-head experiment, preclinical, in a live in vivo experiment in rodents here and hamsters. And what that shows is, on the left side, that at the exact same formulation, at the exact same dose, in this model, in the hamster, we doubled the inhibitory effect of INF904 compared to A 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 phase one already. So we expect that this will translate to the potential for higher efficacy in human disease as well. So, again, I'm not going to go into the details, but I just want to flag one thing.
Speaker Change: He makes one shot and you see that there is a very differentiated PK profile you see that the the time to Max occur as the peak occurs later, there's a much broader area under the curve and again this confirms the Shreveport ISC Max but also the 10 foot higher plasma exposure and that was that was true for all.
Speaker Change: Comparator doses and then you can see above the dose we tested up to 240 milligrams without any safety Cigna next slide.
Speaker Change: And as a side that we are most excited about is that show up in this case in a 14 day dosing multiple ascending dose with three different doses that we have a very tight control over the C. Five a induced signaling so.
When the drug is taken out of the blocks of patients at trough.
Speaker Change: And we.
Speaker Change: We challenge that with new C. Five a it blocks that over a very broad dose range up to 90% and higher.
Speaker Change: And that really is for us something that we wanted to see and it really confirmed all the preclinical work. So next slide please.
Niels C. Riedemann: 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. So, and this gives you a visual.
Speaker Change: So we will begin a phase two of development. This year still we want to start with an initial phase iia demonstrating the pipeline in a drug potential really for this drop this will be an exploratory study, but a PK PD and safety basket study.
Speaker Change: That means a four week initial treatment into a human adult indications CSU in Hs.
And we will also look into three different doses here to assess PK and safety so the catalyst.
Niels C. Riedemann: This is just the single dose and from our just reported phase one 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 Avakopan are superimposed on this graph. And you see the comparable doses, the blue line of INF904, 30 makes one shot, and you see that there's a very differentiated PK profile. You see that the time to peak occurs, and the peak occurs later.
Wanted 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 II studies in these indications.
And they are expected to begin also in 2025 next slide please.
Speaker Change: So with that.
Speaker Change: We're going down the road now to go into the initial indications is chosen and I'm very happy to hand, this over here too our chief Medical Officer.
Speaker Change: Camilla Chong and Kimball a piece help us and speak about chronic spontaneous urticaria. Thank you.
Camilla Chong: 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 market, Maura, whom from Sherry <unk>, who many of you who have what can this space will know is a world leading expert in CSU.
Niels C. Riedemann: There's a much broader area under the curve. And again, this confirms the three-fold higher Cmax but also the ten-fold higher plus max, and that was true for all comparative doses. And then you can see above the dose we tested up to 240 milligrams without any safety. Next slide.
Camilla Chong: And it is really his conviction and deflation that will be increasing scientific evidence that has been generated recently to suggest that <unk> signaling is involved in histamine release from both mass cells and basophils.
Niels C. Riedemann: And this is the slide that we are most excited about, because in this case, in a 14-day dosing, multiple ascending dose with three different doses, that we have very tight control over the C5A-induced signaling. So, when the drug is taken out of the blood of patients at trust, 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.
Camilla Chong: In a few patients in an Iga independent manner. So this mechanism may play a role which is important for both described <unk>, which I will go into a little bit more later on.
Camilla Chong: So called type one and type TB.
Camilla Chong: So there is also believed from his group and others that despite availability of current treatment options such as anti Histamines anti Iga therapy. There is.
Niels C. Riedemann: So we will begin phase two development this year. We want to start with an initial phase 2A, 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.
Camilla Chong: Not an insubstantial number percentage of patients of Ida who had not responded to anti histamines or omalizumab therapy, who remain non responsive.
Camilla Chong: And is therefore symptomatic we believe that therefore, IMS 904 can be a convenient oral therapeutic option, particularly for the AC do not want a continuous up cut.
Niels C. Riedemann: That means a four-week initial treatment in two immunoderm indications, CSU and HF. And we will also look into three different doses here to assess PK and safety. So the catalyst, we want to start this trial end of 2024, and we want to have data in 2025 that we can share while preparing for meaningful, substantial, larger phase 2B studies, and they're expected to begin also in 2025.
Camilla Chong: Injection every month and those who may not tolerate quadrupling therapies with antihistamine or IHA, we believe that the fee a few market potential is estimated to exceed over $3 billion by 'twenty two.
Camilla Chong: Next slide, please. So 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. And Camilla, please help us and speak about chronic spontaneous uticaria. Thank you. Thanks, Niels.
Speaker Change: <unk> please.
Speaker Change: So some of you who are familiar with CSU you will recognize that as described in literature and by many experts that this is an immune mediated chronic.
Speaker Change: Inflammatory skin disease, which you know.
Speaker Change: Dis regulated inflammatory processes involve leaving patients.
Camilla Chong: 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 Marcus Mora, from Charité Berlin, who many of you who have worked in this space will know is a world-leading expert in CSU. And it is really his conviction and persuasion that with the increasing scientific evidence that has 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 way. 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
Speaker Change: Larry Predisposed to symptoms, which are both the day lets say pain and chronic in nature.
Speaker Change: Predominantly the development of EG highs and wheels that do not go away for a period of over six weeks and some moral stand associated with angioedema.
Speaker Change: 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 health care system.
Speaker Change: Okay.
Speaker Change: The estimated prevalence as has been described to be around 1% of the general population.
Speaker Change: Most countries and that up to 20% if not more of this so called population experian symptom for more than five years.
Camilla Chong: So there is also belief from his group and others that despite the availability of current treatment options such as antihistamines and anti-IgE therapy, there is not an insubstantial number, a percentage of patients who have not responded to antihistamines or homolizumab therapy who remain non-responsive and are therefore symptomatic. We believe that INF904 can therefore 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 treatments with antihistamines or IgE. We believe that the CSU market potential is estimated to exceed over $3 billion by 2032.
Speaker Change: 20 to 40 year olds are particularly affected some have described 30 to 60 year olds.
Speaker Change: And with women being impacted twice as often.
Speaker Change: Two men.
Current treatments as I've already mentioned the only approved treatments.
Speaker Change: Anti histamines anti Iga therapy.
Speaker Change: Please.
Speaker Change: Evan.
Speaker Change: Sue.
Speaker Change: As described earlier Professor Mauro and group has done a lot of work to based on their observations of treatment in CSU patients and they have described these two main endue tied for CSU.
Speaker Change: These are basically.
Speaker Change: Broken into type, one which is characterized by Iga auto antibodies directed to self antigens and therefore, the time type one or two allergens.
Camilla Chong: Next, please. For some of you who are familiar with CSU, you will recognize that, as described in the literature and by many experts, this is an immune-mediated, chronic inflammatory skin disease that has dysregulated inflammatory processes involved, leaving patients very predisposed to symptoms which are both debilitating and chronic in nature, but predominantly the development of itchy eyes and rashes 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 a high physical and economic burden not just for patients and families but also for healthcare systems. The estimated prevalence 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 experienced symptoms for more than five years. 20 to 40-year-olds are particularly affected.
Speaker Change: But they also believe that there is a tide to be auto immunity of week today's makes up something like 30% of the so coffee a few patients and this is more E G.
Speaker Change: GE mediated antibody directed specifically TVN tie I G E R.
Speaker Change: To the.
Speaker Change: F C Epsilon reset.
Speaker Change: Both Marcellus and basophils supposedly path ways is believed to involve <unk> and therefore, the <unk> signaling is important in these two cascade as shown on the diagram on the left hand side.
Speaker Change: Next slide please.
Speaker Change: Now I know that this is a slightly BV fly so if you'll indulge me too.
Speaker Change: Spend a little bit of time to walk you through it starting from the left hand side.
Speaker Change: The left hand side is basically an experiment in CSU patients, where they measure <unk> levels and as you can see here <unk> levels significantly increase compared to <unk>.
Camilla Chong: Some have described 30 to 60-year-olds, and women being impacted 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 Morrow and his group have done a lot of work 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 one, which is characterized by IgE autoantibodies directed to self-antigens, and therefore the term type one autoallergen.
Speaker Change: Control group, so <unk> levels are elevated we know in CSU patients.
Speaker Change: And then at the bottom on the left hand side, what you would see is essentially.
Speaker Change: Staining of skin biopsy in CSU patients a CDC for D, suggesting that basically there is activation of the complement system.
Speaker Change: And then now if you focus your attention to the middle graph. What's interesting here is that this is an experiment done over 20 years ago, where essentially they have been able to show from healthy donors blood.
Speaker Change: <unk> and itself can actually in juice histamine release from basophils in a very nice dose dependent manner.
Camilla Chong: But they also believe that there is a type 2b autoimmunity, which makes up something like 30% of the so-called CSU patients. And this is more 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 are believed to involve C5A, and therefore, 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, I'll spend a little bit of time walking you through it, starting from the left-hand side.
Speaker Change: And then last but not least the last part of this graph shows that actually the <unk> media histamine relief is independent of the <unk> pathway. This is an ex vivo human skin experiment, where they incubated eight with a sick inhibitor, which was at GSK.
Speaker Change: Pound that basically were predominantly via the <unk> pathway, and then added increasing levels of concentration of C. Five eight and if you can see the.
Camilla Chong: 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 groups. So, C5a levels are elevated, as we know, in CSU patients. And then, on the left-hand side, what you would see is essentially staining of a 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 on the middle graph, what's interesting here is that this was an experiment done over 20 years ago where, essentially, they were able to show from healthy donor blood, C5A in itself can actually induce histamine release from basophils in a very nice dose-dependent manner.
Speaker Change: <unk> stimulation of histamine release is not affected at all via this <unk> pathway.
Speaker Change: With the sick inhibitor of GSK to seek full $6 64.
Speaker Change: Next slide please.
Speaker Change: So here what I wanted to demonstrate to you is a piece of work done by a Japanese group.
Speaker Change: Currently published in 2022.
Speaker Change: They have tried to do is they took blood from.
Speaker Change: CSU patients and measured the different levels of.
Speaker Change: Base fails.
Speaker Change: After stimulating it within anti Iga stimulus and on the left hand side. What you can see is that basophils from these patients.
Camilla Chong: And then last but not least, the last part of this graph shows that actually, the C5A-mediated histamine release, the C5A stimulation of histamine release, is not affected at all via this IgE pathway with the sick inhibitor GSK26462624. Next slide, please. So here, what I wanted to demonstrate to you is a piece of work done by a Japanese group recently published in 2022.
Speaker Change: With an anti Iga stimulus and hence they call it stimulus positive patients and with histamine release. They show a really good response and I think interestingly. These basophils also showed histamine release.
Speaker Change: In a dose dependent manner.
Speaker Change: We see <unk> stimulation.
Speaker Change: If you then focus on the graph on the right hand side.
A few patients who do not respond TD anti Iga stimulus continues to be responsive to see five eight stimulation and next please.
Camilla Chong: And 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, and on the left-hand side, what you can see is that basophils from these patients with an anti-IgE stimulus, and hence they call them IgE stimulus positive patients, with histamine release, they show a really good response. And 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 continue to be responsive to C5A stimulation. And next, please. So what they propose is that C5A-induced histamine release is important for both pathogens. IgE-dependent as well as IgE-independent, whereby if you look at the IgE-dependent pathway, C5a, via tissue factor release.
Speaker Change: So what they propose is that actually E C.
Speaker Change: <unk> and juice histamine release is imported.
Speaker Change: Those pathways.
Speaker Change: Hey dependent as well as <unk>.
Speaker Change: E independent.
Speaker Change: Whereby if you look at the E dependant pathway <unk>.
Speaker Change: Still plays a role.
Speaker Change: In addition to the other pathway, where it is non GE dependent and I think in addition to that what they have money to also.
Speaker Change: <unk>.
Speaker Change: The C. Five eight generation in CSU may be further amplified because of the activation of the coagulation pathway via tissue factor.
Speaker Change: The release in addition to this access almost like a continuous and P fake and amplification loop, which further drives disease.
Camilla Chong: In addition, this acts almost like a continuous amplification loop which further drives disease. Next slide, please. So, in conclusion, I hope you've seen that C5A signaling is involved in histamine release from both mast cells and basophils, and that certainly this has been the conviction from Professor Morrow and his group that 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. And we really believe that C5 Thank you. I'm now going to hand you over to Niels, who will take you through to our next indication. Thank you so much, Camilla.
Speaker Change: Next slide please.
Speaker Change: So in conclusion I hope you would have seen that <unk> signaling is involved at histamine release from both Marcellus and basophils and that certainly this has been the conviction from professor borrowing group that <unk> mediated histamine release.
Speaker Change: It suggests it to play a really important role in both subtypes of CSU, even though it can be shown to be relief independent of the <unk> pathway.
Speaker Change: And and we really believe that the <unk> inhibition represents a novel mechanism to address an unmet need in CSU and that.
Speaker Change: <unk> 904 has the.
Speaker Change: Oral <unk> the potential to offer an oral drug which is potent for the development in CSU.
Speaker Change: I am now going to hand back to Neil who will take you through to our next indication.
Neil Freedom: Thank you so much Camilla really appreciated.
Niels C. Riedemann: I really appreciate it. I'm excited now to speak a bit about Aedranitis Seperativa. Next slide, please. So this is another indication that we want to show the potential of the drug and show that the drug is active initially. So, when you look at this disease, it's probably well known to some of the people here on the call, there are still new mechanisms that are needed, and that's what we hear from KOLs, and we are very, very attached to that scene generally. So, especially moderate to severe patients that have active draining disease are often left with non-ideal or non-working options, even though recent progress has certainly produced drugs that are approved, like the anti-TNF-alpha class, like Umira, actually, and some anti-IL-17 agents, at least one approved, the other one on the path, and a third one coming.
Neil Freedom: Excited now to speak a bit about <unk> next slide please.
Neil Freedom: So this is another indication that we want to show.
Neil Freedom: The potential of the drug and showed that the drug is active in initially.
Neil Freedom: So when you look at this disease, it's probably well known to some of the people here on the call.
Neil Freedom: There are still new mechanisms are needed and that's what we hear from them from Kols and we're very very attached to that seen generally speaking.
Neil Freedom: So spending moderate to severe patients have active draining disease oftentimes left with non ideal or non working options.
Neil Freedom: Even though recent progress has certainly produced drugs that are approved or like the entertainer of Alpha class.
Neil Freedom: Thank you meara actually and some anti IL 17 agents of at least one approved the other one on the path and the third one coming so but the patients that respond to these drugs. They are known that for them. It's known that a significant number will have the efficacy or the effect wane over time.
Niels C. Riedemann: But these patients that respond to these drugs, they know 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 a need that is not ideally addressed by the FDA. So we know that HS patients have a preference for oral medications over injections, which has been suggested in research. And we have an oral C5AR inhibitor with a mechanism that really is addressing something, and I come back to the word neptosis 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 so.
Neil Freedom: There is a high unmet need for additional mechanisms and again there may be also a need that is not addressed by these drugs.
Neil Freedom: So we know that Hs patients have a preference for our own medications or injection that has been suggested in research and we.
Neil Freedom: We have an <unk> inhibitor with a mechanism that really addressing something and I come back to the word and they tell us this year, but also just the effect on neutrophils again Hs is a neutrophil dermatosis there.
Neil Freedom: That is not necessarily address by any of the other drugs.
Niels C. Riedemann: And there's clinical evidence, I'll be speaking about here in a second, about this pathway, that this pathway, when addressed, can reduce lesion counts in HS. And this drug has a favorable BKBD profile with a broad dose range for systemic exposure. Well, that said aside, the HS market has been described as a very attractive commercial market.
Neil Freedom: And there's clinical evidence I'll be speaking about here in a second about the pathway that this pathway when address can reduce lesion counts.
Neil Freedom: In Hs.
And this drop has a favorable PK PD profile with a broad dose range for systemic exposure well that set aside the address market has been described to be a very attractive commercial market. There are estimates that these marketed to has a multibillion peak potential for drugs.
Niels C. Riedemann: There are estimates that this market has a multi-billion peak potential for drugs by 2032. And that is an exciting side note, of course. Next slide, please.
Neil Freedom: By 2032 and that is that is an exciting side note of course next slide please.
Neil Freedom: So.
Neil Freedom: I'm not going to be speaking too much about Hs.
Niels C. Riedemann: 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 wanna 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 training tunnels because they can, 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 litter 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 more severe stage in the U.S.
Neil Freedom: Believe it's been much discussed.
Neil Freedom: Also recent research.
Neil Freedom: And just wanted to mention that this for the patients affected this is really truly living nightmare, especially those that are progressed in the disease to moderate severe stage and those that have active training tenants because they can a single channel and if you go on the Internet and research that there are there are I think there is even a video that shows that a ton of <unk>.
Neil Freedom: Reduces up to a liter of pus.
Neil Freedom: One single tunnel because the tunnel is the outside that you see but underneath it all is a deep seated lesion and these lesions are in the skin Theyre hurtful.
Neil Freedom: The Pos is.
Neil Freedom: 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.
Speaker Change: 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. There are varying reports about how large it is but it's clearly more than 12000 patients and even in the modern Cynthia stage in the U S. So on this slide I want to just basically convey one message.
Niels C. Riedemann: So on this slide, I want to basically convey one message. I don't want to walk you through the whole slide, but there's recent progress in the understanding of the pathogenesis of the disease. And this just shows that research, which is not, you know, which is not coming out of our group but out of people we know, suggests a central role for CFFA and CFFAR 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 quadri-follicular rupture, this is the current hypothesis, is set in Next slide.
Speaker Change: I 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.
Which is not coming out of our group, but out of people. We know suggest a central role vascepa vacancy where they are in the pathogenesis.
Speaker Change: In the in the mechanism that is set into place when these molecules a rupture and win in the initiation phase an immune reaction to this rupture to this quality follicular rupture. This is the current hypothesis is set in motion and so it's really a.
Speaker Change: <unk> recognized in the field that this is the central role next slide please.
Speaker Change: So we produce data a while ago that these patients have elevated <unk> levels. This is with a validated elisa.
Niels C. Riedemann: So, you know, we produced data a while ago that these patients have elevated C5A levels. This was with a validated ELISA, and this is not surprising. And actually, in the Phase 3 study that we, sorry, in the Phase 2B 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, Wilobilimab and also new data with INF904 with our oral C5AR inhibitor, have shown that they can pretty much completely abate that activation. So meaning that obviously it is C5A in that plasma from HS patients that excites fresh neutrophils and stimulates them strongly.
Speaker Change: And this is not surprising and actually in the phase III study that.
In the phase <unk> study that we ran we showed quite substantial <unk> levels. In these patients now we also have shown some interesting data that.
H F patient plasma strongly provokes neutrophil activation. So when you take the plasma from Hs patients.
Speaker Change: You subject fresh neutrophils from fresh donors.
Speaker Change: To that plasma they get activated immediately.
Speaker Change: And both drugs will beat them up and also new data was INR 904, with our <unk> inhibitors have shown that they can pretty much completely abrogate that that activation so meaning that obviously it is C 5 billion that plasma from Hs patients.
Speaker Change: <unk>.
Excites fresh neutrophils and stimulates them strong next slide please.
Niels C. Riedemann: 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 hematoxystaining 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 histocytes and giant cells.
Speaker Change: So as the receptor present.
Speaker Change: A recent study has shown that beautifully for all three stages of the disease. So you always have the common tissue hemotoxin.
Speaker Change: <unk> staining of in Red above and you'll see that the lesions a market.
Speaker Change: And then below there is sustaining fortify VR and AR neutrophils, but it's also found in other sales like his decides some giant sales and you'll see that.
Niels C. Riedemann: And you see that C5AR staining is found strongly around these lesions, particularly in the middle, in this stage, early stage 2, also around when patients develop draining tunnels, they tend to rupture, and they tend to create that large intradermal lesion. You see that when that happens, there's a lot of C5AR around, and then also on the right-hand side in the most progressive. So, CFAVR is present, not surprising because neutrophils are present certainly in all three disease stages, and something that I won't show you on a slide, but we will go into more detail on another day, is that natosis occurs quite substantially in these patients, and that's also new research, with CFAVR being one of the key inducers of natosis.
Speaker Change: CEVA outstanding has found strongly around these lesions, particularly in the middle.
Speaker Change: In this stage early stage two also around when patients develop drain.
Speaker Change: The draining tonnages as they tend to rupture and they tend to create that large intra Germany lesion you see that when that happens. There's a lot of <unk> are round and then also on the rights and signed and the most progressive patients.
See what they are is present not surprising because neutrophils are present uncertainty in all three disease stages and something that I won't show you with this slide but we would go into more.
Speaker Change: More detail on another day is that net towards this occurs quite substantially in these patients and Thats also new research.
Speaker Change: Again, <unk> being one of the key induces avnet ptosis in neutrophils next slide please.
Niels C. Riedemann: So there's the clinical evidence I mentioned, and I just want to go into that very briefly. So with Velubenema, we did a Phase IIb study, and that clearly showed, at the high-dose level, evidence that C5A inhibition can reduce the inflammatory lesions in all of them. And there was a particularly noteworthy effect on the draining tunnels that we spoke about, and this was actually the higher and the tighter the C5A levels were controlled, the higher the draining tunnel reduction was.
Speaker Change: So that's clinical evidence I mentioned that I just want to go into that very briefly so with Philippine amount, we did a phase II B study and that clearly created.
Speaker Change: On the high dose level.
Speaker Change: Evidenced that.
Speaker Change: <unk> inhibition can reduce.
Speaker Change: The inflammatory lesions at all of them there was a particularly noteworthy effect on the draining tonnages.
Speaker Change: That we spoke about and this was actually the higher the tight <unk> control at the higher the draining kind of reduction was and the key learnings from our substantial work in the field was really that.
Niels C. Riedemann: And the key learnings from our substantial work in the field were really that Velubenema was needed to adequately control C5A-C5R signaling only when it was given at a higher dose. So, in other words, you need a very high dose. The dose we chose is probably, according to our PK-PPE and POP-PK modeling, not enough to adequately cover the signal. So that's the key learning.
Speaker Change: That <unk> bump was needed to adequately control CWC Ras signaling only when it's given at 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 thats the key learning, but the other running as it is.
Niels C. Riedemann: But the other learning is that it is an interesting path that is promising for the future to decrease these lesions. On the oral CFA-AR nebuloside, on nalvacopalm, 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 indication, for oncovascular disease, which is 30 mix twice per day, there was a p-value positive efficacy signal when they looked at the subgroup of severe HS patients, early stage three, on high Now, I do want to mention that this study was also negative on the overall study population when it comes to high scores. There was also a very high placebo response in the early stage two patients, which probably disabled them from seeing an effect.
Speaker Change: An interesting path that promise is promising for the future to to to decrease these lesion counts.
Speaker Change: On the <unk> inhibitor side in Novato PON. There's also been studies done and I want to share with you that had the standard dose which is the approved dose in another disease indication that anchor vasculitis, which is 30 makes twice per day.
Speaker Change: There was a P value a positive efficacy signal.
Speaker Change: When they look at the subgroup of severe Hs patients early stage III.
Speaker Change: On high score.
Speaker Change: With a clear separation from placebo group emerging late only mostly at week 12, now do you want to mention that this study was also negative on the overall study population when it comes to high school.
Speaker Change: There was also.
Speaker Change: A very high placebo response in the early stage, two patients, which probably disabled to see an effect but.
Niels C. Riedemann: But the interesting part is really that in the stage three patients, these were not able to see an effect; groups and the lesion count really separated at week 12. And so when we looked into switching to ankle vasculitis, which is the area where Avagopan 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 of the accumulation phase. So that's fitted quite well with this observation. I'm going to show you a picture in just a second.
Speaker Change: The interesting part is really that in this stage III patients fees.
Speaker Change: Growth in the lesion count separated really at week 12, and so when we looked into the switching to anchor vasculitis, which is the area. We have a coupon is approved the filing data showed that the drug has a very strong accumulations pattern Forex and it takes approximately three months.
Speaker Change: Until it reaches the plateauing of.
Speaker Change: The accumulation phase so that's fit it quite well with this observation and when I show you a picture you just a second so how we interpret that is that a fairly mixed twice per day dosing regimen of that drug because of its PK features.
Niels C. Riedemann: So how we interpret that is that the 30 mix twice per day dosing regimen of that drug, because of its PK features, was probably not adequate, not high enough to show efficacy early and the separation early. And of course, we conclude from that that that is a problem that could be handled with the right PK and the right drug. Next slide, please.
Speaker Change: It was probably not adequate not high enough to.
Speaker Change: To show an efficacy early on the separation early.
And of course, we conclude from that that that is.
Speaker Change: As a problem that could be tendered with the right PK and the right truck next slide please.
Speaker Change: So these are the data from the chemo Centrex reports back then from the Aurora study and again I mentioned that the overall trial results were not P value partners, but the early stage III patients showed the separation.
Niels C. Riedemann: So these are the data from the chemocentric 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 three patients showed separation. You see, the gray curves are placebo, the orange curves were Avakopan at the dose that I explained, and you see the end 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 8 and week 12, there was the separation occurring. And you see the high-square splitting also relatively late here on the right side.
Speaker Change: See the great curves are placebo with the Orange crops were a buckle upon at the dose that I explained in UCD and count on the left side you see the nodule column in the middle and you see the draining tunnel column and you see that really the separation starts only to be visitor Blake strongly visual at week 12, so somewhere between the last visit.
Speaker Change: At week eight.
Speaker Change: The second last visit at week, eight and week 12, there was the separation of occurring and you see the highest scores plaguing also led to delayed here on the right side now again I explained already that from another disease from the anchor disease, we learned about the late accumulation.
Niels C. Riedemann: Now, again, I explained already that from another disease, from the antidisease, we learned about late accumulation. And again, our conclusion is that this may not be the right dose and the right PK profile, but there is efficacy. Next slide.
Speaker Change: And again, our conclusion is that this may not be the right dosing and the right PK profile.
Speaker Change: But there is efficacy next slide.
Niels C. Riedemann: And this is what we graphically worked this up. This is the publicly filed NDA filing for the Ankylosophia 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.
Speaker Change: And this is the.
That we re graphically work this up this is the.
Speaker Change: Publicly filed NDA filing for the anchor socio vasculitis PK accumulation again, it's a different disease, but it's interesting because I chose this roughly fourfold accumulation and you see the steep curve has kind of started flattening out around <unk> 12. In fact, it was week 13, where the steady state was reached.
Niels C. Riedemann: In fact, it was week 13 where the steady state was reached, and the plasma exposure is given here on the right. So, on the next slide, I've come to a conclusion here. And the conclusion is, overall, speaking with the available evidence and knowledge, that there's a strong scientific rationale for the role of C5AR in HS. Now both C5AR signaling or blockade of that signaling has resulted in signals of efficacy in HS patients. We believe that tight control over the signaling of C5AR signaling is required to achieve optimal efficacy.
And the plasma exposure given you're on the right side.
Speaker Change: So next slide I have come to a conclusion here and the conclusion is overall speaking with the available evidence and knowledge.
Speaker Change: Is that there's a strong scientific rationale for the role of CFO. They are in Hs now.
Speaker Change: Now both <unk> and see where we are signaling a blockade of that signaling has resulted in signals of efficacy in Hs patients. We believe that a tight control over the signaling of Seabury are signaling is required to achieve an optimal efficacy.
Niels C. Riedemann: 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 CPAPR inhibitor with an 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.
Speaker Change: So we all know dosing is important NHS, which is basically true for all drugs tested if you consider that some of the approved trucks were only showing efficacy when they're approved dose from other indications was doublet.
Speaker Change: Take for example, Humira.
Speaker Change: No.
Speaker Change: That brings us to our conclusion that INR 904 is ideally positioned as an oral <unk> inhibitor with optimized PK PD profile.
Speaker Change: Addressed an existing high unmet medical need in these patients and we're really excited to move this drug into this new direction.
Next slide please.
Speaker Change: So at the end of our presentation I want to speak about <unk> briefly now and this is for <unk>.
Niels C. Riedemann: So, at the end of our presentation, I want to speak about GO-HEBIG briefly. Now, this is for Bilobelima, 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.
Speaker Change: <unk>, where we got the emergency use authorization and I want to first mention that our team feels privilege honored and very excited about the fact that we were able to get to an emergency use authorization.
Speaker Change: This was the only emergency use authorization granted in 2023 is the only one for a small biotech company and it's also the only one with a first in class mechanism.
Niels C. Riedemann: It'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 continuing making the drug available to patients in need. We have recently released our commitment program that helps address some of the issues that the acute care slash hospital healthcare system has. And we're in active discussions, and we get a lot of good feedback about this commitment program. And so the next slide, please.
That addresses an unmet need in the immuno mod inventory space. So we're excited we are definitely committed to continue making the drug available to patients at need.
Speaker Change: We have recently press released our commitment program that helps addressing some of the issues that the acute TR Slash hospital healthcare system has.
Speaker Change: And we are in active discussions and we get a lot of good feedback about this.
Speaker Change: This commitment program and so next slide piece of this just summarizes the legal hit big emergency use authorization and our commitment to keep the drug <unk>.
Niels C. Riedemann: So this just summarizes the GoHIBG 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 never anticipated and cannot anticipate how this market may look, which comes along with the situation switching from a pandemic into maybe an endemic state. So we're very frugal.
Speaker Change: Available for patients.
Speaker Change: And also we did talked about the fact that we may get a full BLA with one additional study in the Rds Trust now we are very frugal with our spend in this area because we never anticipated and cannot anticipate how this market may look like.
Speaker Change: Which comes along with these situations switching from a pandemic into maybe an endemic state.
Speaker Change: Were very frugal and we also mentioned that we would only look into such development. If we got public funding or the help or other non diluted funding in the company. So with that statement I want to close out.
Niels C. Riedemann: And we also mentioned that we would only look into such a 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 the floor to Q&A. Again, I want to summarize the excitement of the entire team to focus now on immunoderm with our upfront running phase three program, but also with the new additions with our oral INF904. So with that, I hand over to you, John.
Our today's presentation and open for Q&A.
Speaker Change: <unk>.
Speaker Change: Summarize the excitement of the entire team.
Speaker Change: To focus now on immunotherapy with our upfront running phase III program, but also with the new additions with our own line of INR 904, So with that I hand back to you John and thank you all for your attention and we are the team is happy to answer any questions you might have thank you.
Unknown Executive: And yes, thank you for your attention. And the team is happy to answer any questions you might have. Thanks, Niels.
John: Thanks Niels.
Unknown Executive: 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 request, and we'll get your question started. Yeah, hi everyone. Can you hear me okay, John?
Speaker Change: <unk> audience. This concludes our 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 will then read that western allowed during the Q&A session or you can ask a question lie by raising your hand icon under the presentation window and then we will announce.
Speaker Change: On the call for each person at that point.
Speaker Change: So we.
Speaker Change: We do have a question from Steve seat House.
Speaker Change: If you can.
Speaker Change: Except.
Speaker Change: Request and we'll get you get your question started.
Steven James Seedhouse: Yes. Okay, great. Thanks so much for hosting this call and for the overview and all the detail and context. A couple questions here, just starting with HS, maybe.
Yeah, Hi, everyone can you hear me okay.
Speaker Change: Yes.
Speaker Change: Great. Thanks, so much for hosting this call for the overview.
Speaker Change: All of the detail and context.
Speaker Change: Questions here, just starting with Hs, maybe obviously interesting opportunity of experience here.
Niels C. Riedemann: Obviously, interesting opportunity you have experience here to maybe offer an orthogonal mechanism to IL-17s or TNS and also the oral presentation is a differentiator. But widening the lens also seems like an opportunity to establish in patients the PK and PD advantages of if that translates from what you've seen so far versus Avocapan or IFX-1, of course. So just curious in that regard, will you be sort of closely analyzing PK and PD data in these patients? Will you be able to compare it to maybe some of the Avocapan data that's publicly available? You shared some in ankylobasculitis or your own IFX-1 data and really determined if you're getting better coverage of C5AR inhibition essentially in patients in this phase 2a. Yes, thank you, Steve.
Speaker Change: So maybe offer an orthogonal mechanisms to the IL seventeens or DNS and also the oral.
Speaker Change: The presentation is.
Speaker Change: As a differentiator, but widening the lens also just seems like an opportunity to establish really in patients. The PK PD advantages of Dino for if that translates from from what you've seen so far versus of occupy or effects. One of course so.
Speaker Change: I'm just curious in that regard.
Speaker Change: Will you be sort of closely analyzing PK PD data in these patients will you be able to compare.
Speaker Change: To maybe some of the <unk> data that's publicly available you shared some of the antibody escalators or your own FX, one data and really determine if youre getting.
Speaker Change: Better coverage of <unk> inhibition essentially in patients in this phase Iia.
Speaker Change: Yes, Thank you, Steve and happy to take that.
Niels C. Riedemann: I'm happy to take that question, if I may. So, first of all, it's a great, great question. Thanks for asking that. And 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.
Speaker Change: Question.
Speaker Change: If I may so first of all it's great. Great question, Thanks for asking that and the answer is yes.
Speaker Change: We will closely monitor PK this as they get PK focused study and on the PD angle. We're looking of course at various efficacy signals now you may see.
Speaker Change: A four week initial exposure.
Niels C. Riedemann: And we, of course, have done a lot of work thinking about what we can show at four weeks. And we're quite convinced that with the high doses that we can administer our drug, INF904, and being a small molecule, and anticipated high tissue penetration levels, that we can see differentiation, or that we can see also efficacy signals at week four. Now, there are some comparisons.
Speaker Change: And we of course have done a lot of work into thinking what can we show at four weeks.
Speaker Change: And we are quite convinced that with the with the high doses that we can administer our drug INR 904 in vivo and being a small molecule and anticipated high tissue.
Speaker Change: Penetration levels.
Speaker Change: We can see a differentiation are then we can see also efficacy signals Ed at week four now there are comparative.
Speaker Change: We have them for a week for data with our slightly under dose <unk> trial, we have to wait for data at least in the early stage III reported by of a coupon and we have a lot of in house data. So I think the goal is really to say on the PD level that that may translate into I would say.
Niels C. Riedemann: We have week four data with our slightly underdosed vilobilumab trial. We have week four data, at least in early stage three, reported by Avakopan. And we have a lot of in-house data.
Niels C. Riedemann: So, I think the goal is really to say, at the PD level, that 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 good confidence that we're seeing efficacy of the drug here. So, we've done a lot of, and we will go into this in more detail. The press release today also announced that we're planning an R&D day in due course.
Speaker Change: A signal that when you compare it especially to known placebo responses at week four that will at least give us good confidence that we're seeing efficacy of the drug here. So we've done a lot of and we will go into this into more detailed press release today, which has also announced that we're planning an R&D day in due course.
Niels C. Riedemann: So one of our goals for that R&D day is to have some of the experts we're working with speak about what we're doing and about what they get, what excites them, but also a bit more into the exact details that you just mentioned about the trial. Now, what is difficult to do is the PD, as we've done it in phase one, where you have these flow cytometry data on the neutrophil ex vivo excitation, which requires really very full on-site training of a team that does the measurement with fresh drawn blood. So that can be done in trained phase one units, but you have to almost train the entire team.
Speaker Change: One of our goals for the R&D day is to have some of the experts who are working with speaking about what we're doing in about what they get.
Speaker Change: Excites them, but also a bit more into exactly such details that you just mentioned about the trial now.
Now what is difficult to do is the PD as we've done it in a phase one where you have these flow cytometry data on the <unk>.
Speaker Change: On the neutrophil ex vivo expectation.
Speaker Change: Which requires really a very full onside training of the team that onsite data measurement with a fresh strong blood.
Speaker Change: So that can be done in trained phase one unit, but you have to almost train the entire team and we're looking into whether we can get some of that data may be a few sites, but that is something we cannot fully promise at this point in time that would be of course nice because you can trend that you can directly compare it to the phase one data that.
Niels C. Riedemann: And we're looking into whether we can get some of the data maybe at a 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 one data. Okay, thanks, Niels. And 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 we are today from your perspective with draining tunnels and endpoints and how to develop something to the finish line in HS. Yeah, yeah, a great question.
Speaker Change: Okay. Thanks, guys.
Speaker Change: I mean, you guys have more experience in.
Speaker Change: Maybe anyone with regulators discussing Hs and the endpoints in the evolving landscape, where I guess where are we at today from your perspective with trading tunnels and endpoints.
Speaker Change: How to develop something to the finish line in Hs.
Speaker Change: Yes.
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 kind of throw in whether or not we can.
Niels C. Riedemann: So first of all, I want to make sure that it's clear that we're not basing the entire development on drainage 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 a high score. It's an oral drug.
Speaker Change: Maybe develop better towards to show something we believe that this drug can also be successful on the ice for it's an oral dropped as an improved end point, which is the high score.
Niels C. Riedemann: There's an improved endpoint, which is the high score. Oral antipsychotics 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. But that set aside, we know that there is 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 minimal ambiguity, an agreement on running into a phase three trial with a new endpoint. You know, we are consulted by former FDA office directors. On that end, there's certainly something we can work out. But I do want to point out that we're not basically basing our whole development on whether or not we can come to terms on exciting research. We think that we can win the game and win market approval also on a high. Great. And then just to wrap up, the parallel track here in CSU is interesting.
Speaker Change: <unk> has in the past shown consistently.
Speaker Change: Lower placebo response rates when you compare that to <unk>.
Speaker Change: Infusions for example, and that has to deal with with placebo response.
Speaker Change: But.
Speaker Change: But that set aside.
Speaker Change: Note that there is a very special edition of the 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. Yes. We've come back then very close I think we have with a minimum ambiguity had had an agreement on a running.
Speaker Change: We're running into a phase III trial with a new endpoint.
Speaker Change:
Speaker Change: We have consulted by a former office directors of the FDA.
Speaker Change: And there is certainly something we can work out, but I do want to flag that we're not like.
Speaker Change: 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 high school.
Speaker Change: Great.
Speaker Change: And then just to wrap the parallel track here in CSU is interesting so.
Niels C. Riedemann: So, two part question on that. First, do you view this as really just the sort of lowest hanging 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?
Speaker Change: Two two part question on that.
Speaker Change: First I mean do you view this as really just the sort of lowest hanging fruit proof of concept for mass cell biology in general that would open up.
Speaker Change: Myriad development opportunities across the spectrum of mast cell biology or is there something specific about CSU that drew your attention and then also.
Camilla Chong: And then also, 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 2a, or would that be too challenging to do? Yeah, I'm happy to pass this over to Camilla, and maybe I can chime in with an additional thought, but Camilla, please.
You mentioned, the two enterprises and the contribution of <unk> they are.
Speaker Change: Both is that something that you think you can parse out the relative activity in.
Speaker Change: In this phase iia or would that be too.
I'd like to do.
Speaker Change: Yes, I'm happy to pass this over to Camilla, maybe on timing with an additional thought but Camilla. Please sure yeah I'll be happy to perhaps answer the last part of your question.
Camilla Chong: Sure. Yeah, I'd be happy to perhaps answer the last part of your question. So we believe that in the 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 endotype, firstly.
Camilla Chong: So we believe that in our phase Iia study that we're looking at that we should be able to address both enter types right. We're not just restricting it to the very refractory Tycho to see a few patients. So there is no reason why it should not work in either and the types.
Camilla Chong: Firstly and I think.
Camilla Chong: And I think, you know, CSU is one of those conditions where you can show relatively quick clinical effects within two weeks, if not up to four weeks. Now, obviously, that's different from showing maintenance, but I think this could be a very quick indication for us to be able to really dwell in, to really be able to explore the biology of this drug. And the endpoints are fairly straightforward; they're fairly, you know, well accepted by regulators.
Camilla Chong: <unk> is one of those conditions, where you can show relatively quick clinical effect within two weeks, if not up to four weeks now obviously, that's different from showing maintenance, but I think this could be a very quick indication for us to be able to to really dwell into to really be able to explore the <unk>.
Camilla Chong: <unk> of this drug and and the end points are fairly straightforward that fared fairly well accepted by regulators. So we feel that.
Camilla Chong: So we feel that, you know, this would be 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.
Camilla Chong: This would be a relatively.
Camilla Chong: Not easy, but it would be a less complicated wanted to be able to do plus the fact that you know it is 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.
Niels C. Riedemann: And just to add to that, Camilla, I think we are very close here with the 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 time ago with Velo. And when they heard we had the oral, we went back into really strong discussion.
Yes, maybe just to add to that Camilla I think we are very close here with a team of Dr. Tomorrow at the surety in Berlin, Therefore worked out the concept.
Camilla Chong: Initially suggested to us that we should do this development some while ago with below.
Speaker Change: And when they heard we have the ROE we came back into really strong discussion. So so yes. The idea would be and there is a strong support. So they are willing to support is also by recruiting patients and by recruiting both subtypes Escamilla just said.
Niels C. Riedemann: So yes, the idea would be, and there's 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 more broad general terms like mast cell biology.
Speaker Change: Now you asked for the more broad general like mast cell biology.
Niels C. Riedemann: 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 it with the Maurer team, that there are really, really a decent number of patients that are underserved, even with the treatments. And that and and and one of the thoughts is that they may be underserved because that second angle, which is independent of IgE, is not addressed.
Speaker Change: I would say at this point in time, we are focusing on this attractive market and we know that was part of the central discussions with Mora team is we know that there is.
Speaker Change: Really a decent number of patients that are underserved, even with the treatments and that and one of the one of the thoughts is there may be underserved.
Speaker Change: Because that's the second angle, which is independent of Iga is not addressed and Thats exactly if that's true we may address a very broad patient population.
Niels C. Riedemann: And that's exactly why, 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 it'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 level, I think we will definitely not make these conclusions before we don't have the data to speak about it. Thanks for the question. Great. So, we have a few here that have been submitted in writing. So, I'll go to the first one by Joe Schwartz at Lyric Partners.
Speaker Change: The 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 Mira group and others have done so far.
Speaker Change: Whether we take it to a more broader mass cell I think we would definitely not make these conclusions before we don't have the data to assess.
Speaker Change: Speaking about it.
Speaker Change: Yes, thanks for the question.
Speaker Change: Great. So we have a few here from may be submitted in writing. So I'll go the first by Joe Schwartz at Leerink partners. So the first part is the asking us about the goals of the phase Iia study in terms of what kind of early efficacy endpoints will be including.
Unknown Executive: So, the first part is to ask us about the goals of the Phase 2a 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.
Speaker Change: How informative we think the endpoints will be at four weeks and anything we'll be looking for.
Speaker Change: As we consider a go no go in either of the indications.
Speaker Change: Yes, Im happy to tackle that so that's very straightforward.
On the efficacy side. This is exploratory but camelot already mentioned in CSU. There is the seven day score established that as 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 patients respond to the drug in four weeks or not.
Niels C. Riedemann: On the efficacy side, this is exploratory, but as Camilla already mentioned in CSU, there is the seven-day score established 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 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 EOA7 is something that is broadly used.
Speaker Change: So that is something you can definitely scout at four weeks and that endpoint is clear.
Speaker Change: So the <unk> seven is something that is broadly used than in the <unk>.
Niels C. Riedemann: Then, in the, in the hetero-nitroseparativa population, we will look at reductions in all three lesions and compare that to the four-week reductions, either reported from other drugs or seen with our own drug to scout. And, you know, we just showed you some of the data that was public from the Abacopan trial, and we've shown you that there's a very late onset of effic For example, if you know that the draining tunnels did not even move before week 12.
Speaker Change: In the Hidradenitis Suppurativa population, we will look at reductions of all three lesions and compare that to the full week reductions either reported from other drugs or seen with our own drugs to to scout.
Speaker Change: And you know we just shown you some of the data that were published from the <unk> trial and we've shown you that theres a very late onset of efficacy. For example, if you noted the draining tonnage did not even more before we before week 12.
Niels C. Riedemann: And we will definitely see and compare that and hope that we see signals already moving at week four 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 a high score 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. And again, we will probably provide them with more color in our R&D event following. Great
Speaker Change: And we will we will definitely see and compare that and hope that we see already these signals moving at week four quite a bit and of course, we will.
Speaker Change: Three lesion counts established we can then of course derive all the typical endpoints that you look at obviously with a lower number than a PK focused study things like high school or not.
Speaker Change: Treatment informative.
Speaker Change: For us the key is at that stage of the development to show you how much.
Speaker Change: The three lesions moved equity before.
Speaker Change: I hope that helps for and again, we will probably provide some more color in our R&D event following.
Renfeng Guo: And we have a follow-up there in terms of the preclinical talks work. Could you remind us where we are in the progress? And if this will be a gating factor for phase two, or will the timing line up so that you can start, you know, go seamlessly into phase two B next year? Yeah, maybe I can take that on.
Speaker Change: Great and then we have a follow up there in terms of the preclinical tox work on could you remind us.
Speaker Change: Where we are in the progress.
Speaker Change: And if this will be a gating factor for the phase II or will the timing lineup, where you can.
Speaker Change: Start.
Seamlessly into the phase to be next year.
Speaker Change: Yes, maybe I can take that.
Renfeng Guo: So yeah, for talks, we already started with the chronic talks, as we mentioned earlier that we plan to do a six-month study on rats and the nine-month monkey. Those already start early this month. So yeah, we are planning simply with all the clinical development, including phase 2a, phase 2b, so data expected for six months on rats will be end of this year and early next year for the nine-month monkey. So, to answer your question, we are together with all the clinical departments, and so we have a couple of questions from Evan Taddeo at Guggenheim, again on preclinical. What kind of preclinical work have we done with 904 in CSU? Can 904 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 NIL4 is going to decrease the number of mast cells. In theory, they shouldn't do that.
Speaker Change: So yes, botox, we already start with the chronic talks as Larry mentioned earlier that every year frankly.
Speaker Change: Six months.
Speaker Change: Rather than the nine months monkeys dose already start early this month.
Speaker Change: So yes.
Speaker Change: We are planning seamlessly with all of the clinical development you put in place to place to be.
Speaker Change: Data expected about six months ramp will be end of this year and early next year, probably nine months margin. So.
Speaker Change: So to answer your question we are.
Speaker Change: Yes.
Speaker Change: Together with all of the clinical development.
Speaker Change: And so we have a couple of questions from <unk>.
Guggenheim again on the preclinical what kind of preclinical work that we have you done with 904 and CSU.
Speaker Change: 904 decrease the number of mast cells and given its unique MLA how are you thinking about positioning in CSU.
Speaker Change: Yes, maybe for the second one we don't know.
Speaker Change: Nope I'll kind of decrease the number of master in theory, they should it.
Renfeng Guo: There's no reason to believe that NIL4 would be a mast cell based on the model action. For the first one, in the literature, there are a ton of studies that have 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, they all showed pretty good blockade to the histamine release from either muscle cell or from basal cell. So we are currently working with a pretty well-known laboratory for CSU to work out more details with NIL. So, um, yeah, I think the second question is already addressed by Nielsen-Kamena.
Speaker Change: And Theres no reason to believe that narrow.
Speaker Change: With CBD in Moscow based on the mode of actions.
Speaker Change: For the first month.
Speaker Change: In the literature, there's tons of study Thats already.
Speaker Change: Work out, but a little obviously by our in CSU.
Speaker Change: Patient samples.
Speaker Change: Parcenary serum and plasma samples with the blockade of <unk> by our end with antibody or appetite our show like pretty good blockage.
Speaker Change: Dmitry lease, while you can master cell or <unk>.
Speaker Change: Battlefield.
Speaker Change: So we are currently working with a pretty well known laboratory cost.
Speaker Change: Yes, absolutely.
Speaker Change: Account more details with Nio.
Speaker Change: So.
Speaker Change: Yes, I think the second question.
Speaker Change: Nielsen come into already addressed.
Renfeng Guo: The patient, we're not thinking that it's going to be just to treat for a few years, but, you know, basically, we are. Yeah, able to, should be able to treat both types of CS. Got it.
Speaker Change: No titration.
Speaker Change: They are not thinking that it's going to be just to treat the theaters.
Speaker Change: Basically what we are.
Speaker Change: Yes, able to should be able to treat both type of CSC.
Speaker Change: Got it and then a follow up.
Renfeng Guo: And then to 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, for CSU and HS, they're both skin diseases, and we generally believe that you do need a higher dose because you do need good coverage on the skin for the drug. So, yeah, so maybe, but I don't, there's no reason to believe that if they're going to be a different dose for two diseases at this point, but we have to remain to see the data. In the RO32A, we do plan to have pretty broad dose coverage of RO32A and to be able to work out a dose. With regard to the other disease, I think it's too early to say for that. So that way, you know, in theory, for UNCOV, you probably don't need a lot of coverage because it's the focus on the vasculature and that's. A pretty general answer.
Speaker Change: What would you expect to see five coverage required for clinical benefit in CSU in Hs, which may be different in one versus the other and in the other indications.
Speaker Change: Yes.
Speaker Change: For CSU.
Speaker Change: <unk> skin disease, and we generate the better you do need a higher dose.
Speaker Change: You need a good coverage on the steam.
Speaker Change: While the drug.
Speaker Change: So yes, so maybe.
Speaker Change: There is no reason to believe that if theyre going to be a different dose would.
Speaker Change: The disease at this point and by the way have to remain to see the data.
Speaker Change: Our first way, we do plan how pretty proud.
Speaker Change: Those coverage.
Speaker Change: And to able to work out the dose right.
Speaker Change: With regarding to the other disease right.
Speaker Change: I think it's too early to say on that.
Speaker Change: So is that right.
Speaker Change: Theory of Hong Kong, probably are the lead.
A lot of coverage.
Speaker Change: On the Nebraska Richard.
Speaker Change: And that's pretty general answer.
Thomas Taapken: Great. And then we've got a couple questions regarding the partnering strategy that we mentioned. So I'm wondering if you can provide us with some high-level thinking and strategy on how we would approach or could approach partnering. Yeah, Tom, do you want to take that?
Speaker Change: Morning.
Speaker Change: Great and then you've got a couple questions regarding the partnering strategy that we mentioned so I'm wondering if you can.
Speaker Change: Can you provide us some high level, taking a strategy on how we would approach it could approach partnering.
Speaker Change: Tom do you want to take that yeah happy to do that.
Tom: Well I mean, obviously our focus in immuno dermatology.
Thomas Taapken: Yeah, happy to do that. Well, 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 opilobelimab 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.
Tom: Will lead us to put our efforts in this area, but we see the broader potential both of INR 904, and <unk> in other indications. So we have initiated discussions with a variety of pharmaceutical companies that might have an interest and also helping us develop it in other indications. It's at this point, maybe too early to really say.
Tom: What it would look like and how these relationships could ultimately shape up being but I think that to exploit 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 it on the side for the time being.
Niels C. Riedemann: But I think that to exploit 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 now. Yeah, so it's really like our wish to find, and I'm going to talk a little bit about how we use these pathways to faster unlock more value for the drug. As Tom just said, we are really convinced that there is broad applicability to this pathway. So our idea is, like, what can we do to speed things up and unlock as much value as possible?
Speaker Change: Yes, so it's really like our wish to find.
Speaker Change: Ways to faster unlock more value for the drop that we as Tom said, we are really convinced that there is a broad applicability to this pathway. So.
Speaker Change: Our ideas like what can we do to <unk>.
Speaker Change: Speed up and unlocked as much value as possible.
Unknown Executive: Great. So we've kind of covered this already, but I'll just bring it up to it was put in through the written dashboard. Again, from Joe at Lyric Partners, saying that prior oral C5AR inhibitors showed better efficacy in HS patients who were more severe or early stage three. 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 VLO studies? And what learnings can you apply to the development of 904 from that?
Speaker Change: So we've kind of covered this already but I'll just bring it up as soon as it was put in through the written.
Speaker Change: <unk> against <unk> at Leerink partners.
Speaker Change: Our oral <unk> 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 our studies and can you give us your thoughts on how trial endpoints and studies may have evolved since your initial.
Speaker Change: Zillow studies and what learnings can you apply to the development of 901 with that so it covered a fair bit of that maybe just cover it again.
Niels C. Riedemann: So covered a fair bit of that, maybe just kind of covering it again. Yeah, I think it's, I think, 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 just have the experience and improve. We know that the most difficult to treat are the draining tunnels.
Speaker Change: Yes, I think it's.
Speaker Change: I think from from from the general understanding of the disease.
Speaker Change: We all have learned that.
Speaker Change: There are three lesions and they need to be reduced if patients wanted to dislike experienced an improvement we know that the most difficult to treat other draining tunnels theyre not captured by the currently used score the highest score the score has established its being used now many times, it's been used in the phase III studies.
Niels C. Riedemann: They are not captured by the currently used score, the high score. This score is established. It's been used many times before.
Niels C. Riedemann: It's been used in phase three studies. People have used the old high score of 50. Now there's even a high score of 75 being explored. But we've also learned that the high score is not used by physicians. I don't know any physician that would say, I'm assessing my patients with a high score. It's a score that's only applied in clinical studies.
Speaker Change: Use the old High School 50, now Theres, even high school 75 being explored but we've also learned that high score is not used by physicians.
Speaker Change: I don't know any physician that would say I'm assessing my patients with the highest score. 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.
Niels C. Riedemann: And we've also learned that oftentimes when you think about the IL-17 studies in phase three, 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 high score, this could not be shown. So in other words, the field has the understanding about the limitations involved, but it's been used. And so it's the path to win the game.
Speaker Change: The score may not necessarily reflect a good path to differentiate from existing mechanisms right. I think IL seventeens are thought to be probably better drugs. The anti TNF in this disease, but yet on the highest score this could not be shown so in other words. The field has the understanding about the limitations have been.
Speaker Change: But it's being used and so it's the path to win the game.
Niels C. Riedemann: But I think, as far as we know from our discussion, there's still a pretty high unmet need in patients with active draining tunnels. There is 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 patients. And so there are areas of unmet needs that relate to active training disease, which is one area that we're definitely interested in looking at whether we can bring more benefit to these patients. But at the same time, as I've shown you with the CFAR staining, there's no reason to believe why the drug shouldn't work in the overall patient. Second thing is also on maybe the other endpoints you asked for.
Speaker Change: But I think as far as we know from our discussions there is still a pretty high unmet need in patients with active training tunnels. There's a belief that training training disease is still not adequately addressed even though there is a signal an IL 17 inhibitors.
Speaker Change: That may not be strong enough to cover a lot of the patients.
Speaker Change: And so there are.
Speaker Change: The areas of unmet needs that relate to active trading disease, which is.
Speaker Change: No one area that we are definitely interested in looking at whether we can bring more benefit to these patients.
Speaker Change: But at the same time as I've shown you with the theater. They are standing there is no reason to believe why the druck shouldn't work in the overall patient population.
Speaker Change: Thing is also on maybe the you asked for the other endpoints I think.
Niels C. Riedemann: I think, you know, the established endpoint is the high score. I mentioned that already. And then there's the lesions themselves, and then there's lesion-derived scores that don't vary as much. Most of them emphasize the draining tunnels as the most severe.
Speaker Change: The established endpoint as the ice bar I mentioned that already and then there's the lesions itself and then theres lesion derived scores that don't vary as much most of them emphasize the draining tunnels at the most severe so I would say theres another need I want to flag.
Niels C. Riedemann: So I would say there's another need I want to flag, which is that 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 their efficacy wanes. And I think one need is also to demonstrate, at least in the phase three study, that can certainly not be demonstrated early, that long-term exposure leads to a significant improvement, long-term improvement in more patients. That is a big need.
Speaker Change: 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 wane.
Speaker Change: And I think one need is also to demonstrate.
Speaker Change: At least in the phase III studies that can certainly not be demonstrated early that long term exposure leads to a significant improvement long term improvement in more patients that has a big need. So if the average patient doesn't think that all with a 50% my efficacy wanes in the next six or nine months.
Niels C. Riedemann: So if the average patient doesn't think that, oh, with a 50% chance, 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. We understand the need that has evolved. There is a need for new mechanisms, especially sustained improvement and work on active training. It's too early for us to tell you exactly which one we will focus on, but, generally speaking, it is our belief that the drug works in all disease stages. And that's our starting point.
Speaker Change: But I have a good chance if I'm a responder to stay responder that would be a big win so I would say.
Speaker Change: We understand the need that has evolved there is need for new mechanisms, especially sustained improvement.
Speaker Change: And our work on the active training disease.
Speaker Change: It's too early for us to tell US 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.
Speaker Change: And that's our that's our starting point.
Niels C. Riedemann: Okay. Great. And so we have one more before we wrap up. It's again, a written question asking us, in terms of efficacy and safety, how does 904 compare to Evacapan, and are there any significant advantages or improvements for 904 as a better choice for patients and for treating physicians?
Speaker Change: Okay.
Speaker Change: Great and so we have one more before I wrap ups again, a written question asking us in terms of efficacy and safety. How does 904 compare to Omega Pan and are there any significant advantages or improvements for <unk> four is a better choice for patients and for treaty.
Speaker Change: Treating physicians so they get to say, perhaps summarize that we've discussed on that.
Renfeng Guo: So I think I've just made the wrap, summarized what we've discussed on that. Yeah, I want to, I want to handle this very briefly. And Renfeng, please chime in if I forget anything.
Speaker Change: Yes, I want to handle this very brief and Brent thing please chime in if I.
Speaker Change: Got anything so I will start with safety first we.
Niels C. Riedemann: So I will start with safety first. The one thing that is known about Avacopan, I think, by all standards, it's been a very, very safe drug. I don't, there was one liver toxin 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 the plasma accumulation of other drugs like corticosteroids or, you know, other drugs.
Speaker Change: The one thing that is known about <unk> I think in all standards, it's been a very very safe drug.
Speaker Change: There was one liver tox in the anchor approval that was.
Speaker Change: Heavily discussed.
Brent: And that may have to do with the drop being like many aro chemical inhibitors, CEP III for liver enzyme blocker, meaning.
Brent: Meaning it can lead to plasma accumulation of other drugs like corticosteroids are.
Brent: Other drugs.
Brent: And that can lead to other drugs getting higher and maybe causing liver tox now we have in preclinical data has shown that we have been over 30 forward less inhibitory potential to ship 384. So we have really very low if minimal engagement with Sip three explore which is of course comforting as well.
Niels C. Riedemann: And that can lead to other drugs getting higher and causing liver tox. Now we have in preclinics shown that we have an over 30 fold less inhibitory potential for 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 files. So 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 Avocapone 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 for reaching such an exposure level that they have their maximum accumulation, and we can exceed this by multiples.
Brent: Move forward, but again flagging that generally speaking of our coupon was a relatively safe drug as far as we know from the filings.
Speaker Change: So I hope that covers the the safety question now the other question is the efficacy question, Yes, we actually do believe that we can show a different efficacy and then based on the fact that I showed you how long the drug takes avago pantex to accumulate and what they are finally, reaching which was a bit over.
Speaker Change: Around 3300.
Speaker Change: The area under the curve.
Speaker Change: And we can reach that with a higher dose on the first day.
Speaker Change: Of exposure.
Speaker Change: 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 makes the accumulation and we can exceed this by multiple multiples at least that's what our phase one data indicate.
Niels C. Riedemann: At least that's what our phase one data indicates. Now, of course, we have to prove that that translates into 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 HHS is a disease where you may be able to show that, especially with a more early onset and a more sustained reduction in, I hope that covers that.
Speaker Change: 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 and so while we believe <unk> is a disease, where you may be able to show that especially with a more early onset in a more sustained reduction of these lesions I hope that covers that.
Niels C. Riedemann: Great. So, we are finished with the Q&A session. If anyone in the audience, if we didn't get your question or didn't address it suitably, please feel free to reach out to ir at 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.
Speaker Change: Right. So when we are finished with the Q&A session. If anyone in the audience. If we didn't get to your question I Didnt address it suitably please feel free to reach out to IR at <unk> Dot D E and we can address it at that point, so right now I'll turn the call back over to Neil for closing remarks, Niels <unk>.
Niels C. Riedemann: Yeah, make it short. Thanks so much for joining us and to share more with you to come on 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. Thank you, bye-bye. Goodbye.
Niels: Sure. Thanks, so much for joining we are very excited to have you and to share more with you to come in at R&D day that we're planning.
Niels: Happy to take calls and happy to take questions through the IRR as usual and in due course. So thank you everyone have a great day bye.
Niels: Okay.
Niels: Alright.
Goodbye.