All right. Good afternoon, everyone. Welcome to Guggenheim Healthcare Innovation Conference. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. Pleasure to welcome our next presenting company, InflaRx. We have a few executives here from the company. We have Niels Riedemann, who's the Chief Executive Officer and founder. We have Thomas Taapken, who is the Chief Financial Officer. We also have John Medina, who's the VP and head of IR here with us. And I see Renfeng also in the audience. Niels, very timely. Thank you for coming to our conference. You presented data earlier this week. Yesterday. Could you just review some of the key points from the data that you have presented? How strong is the signal or how strong is the signal of efficacy in HS and CSU? Then I have prepared a few questions that I'm going to ask you.
Absolutely. Before I forget, first of all, thanks for having us here. We are really, absolutely happy to be here again in Boston with you. Yeah. So we are very excited about the data. Obviously we have basically two data sets in two different indications. HS, Hidradenitis suppurativa, and CSU, chronic spontaneous urticaria. I want to start with HS. I want to start with what I really like about the data, and our team does as well, is small data sets in HS can be challenging because there are three different inflammatory lesions and two of them, the abscesses and nodules that make this disease, they fluctuate a lot. Obviously you get a lot of variability easily in small data sets. But we've been very granular.
I think the first thing that struck us was that there was a consistency that all the groups improved over time, particularly also on lesions that usually do not see placebo responses like the draining tunnels. That was also reflected in the typical scores. Probably most noteworthy was it was also accompanied by what the patients said, particularly on the pain score and on the life quality index. I want to speak just very, very high level about the mechanism because it is a very differentiated mechanism. Our small oral C5aR inhibitor has best in class potential. We have now over 180 patients or humans that have been on drug and have not seen signals of safety concern. It carries a pipeline and a product potential that is really great for us. In HS it is really a mechanism that caters to this disease.
Think about there is an inflammation in the skin and that drives this. What you see on the outside, these lesions, these inflammatory lesions, but it is actually an inflammatory environment in which certain immune cells play a big role like neutrophils. It's considered neutrophilic skin disease, like certain monosthetic cells, particularly also, sorry, particularly also, particularly also—apologize for that—particularly, you know, also histiocytes. If you change that inflammatory environment, if you change the cellular setup, which you will, because C5aR is an attractor, it brings the cells in the skin and activates them, then you may have a longer lasting effect on this environment and ultimately you see it in the lesions. We're excited about that. Very consistent data set and clearly active drug in our eyes.
Now CSU, very different disease, obviously mast cell driven disease, histamine release, but also has an inflammatory component in the skin. It's the first time that this mechanism has ever been put into this allergic kind of disease. Should say it's also an inflammatory disease. Here we have found one dose, the 60 milligram dose, that showed a very nice, consistent, clearly from the placebo differentiated effect on the endpoint that is used for approval, which is the Urticaria Activity Score. We also saw off drug effects, further deepening this. There's clear activity in the disease. Some subgroup analysis suggests that in the more severe patients, more inflammatory patients, there was a bit stronger response. Even so, clear interesting signals. Summing it up, we think active drug in both indications, clear promise in both indications.
As you can imagine, a safe oral is always worth a lot if it works. And HS probably like biologic-like activity and big promise.
Okay, very good. Helpful summary. Maybe just one high level question. 904 seems to be differentiated from Amgen Avacopan in what ways? I think you have shown a much faster sort of a PK and much higher exposure. Just talk about that high level. What exactly have you shown? What are the half lives, how long the drug stays in the system?
Yes. Both drugs, Avacopan you mentioned, that's a marketed comparator and our drug bind to the same binding site. It's an allosteric binding site inside the pocket of the receptor and they both do that really well. Almost identical IC50 of the two drugs. The key challenge for us was since it's an allosteric binding site, your drug needs to be relatively lipophilic to get in there. Formulation and working on how do you get a good plasma and tissue presence is key. I think that's where the huge differentiation is. We saw that possibility to close the signaling gap by having a better plasma presence and an immediate plasma presence.
Our phase one data show in comparison to the reported data from Avacopan that we have initial exposure in the first few days, we can reach area under the curve levels that they reach late in the game, already in the first week. We have a 10x area under the curve increase. We also have a differentiated half life and peak. From all what we've learned is we have an exposure right away that is a multiple, you know, differentiated from Avacopan. Coming back now to the data in HS and CSU that we just put out, that's exactly what we see. We see in week one a multiple higher exposure than for example, what was reported with Avacopan in ANCA vasculitis where the drug is approved.
Yeah, I think Avacopan takes what, 13 weeks to reach a steady state.
Yes.
You guys are.
We're still calculating that, but we see whatever they reach in 13 weeks, we have a multiple of that already in first week. First week.
Okay, so then let's just drill a little bit into the HS data. When we look at the baseline characteristics, to us it seems like the patient population might be a little bit more advanced than some of the other drugs, some of the other studies. Whether it's the draining tunnel or AN count. What is your view on the severity of these patients in the study?
I would say overall pretty balanced, but a little bit more on the severity side. A score that is usually used for severity is the IHS4 score. Here you see clearly over 30 points, up to 38 points. I would clearly say the high dose by chance was the most severe one. Normally when you think about severity, you want to see are there draining tunnels present and how high is the AN count? I would say the average reported larger trials were always in the range of 12.5 to maybe 13.5 or 14. We're here a bit higher and in the high dose group we're at 18. That is important because if you think of high score, the key component is to reduce this AN count by 50%.
It makes a difference if you come from 12 to 6 versus from 18 to 9. The higher your N count is, the more drug effect you have to have to bring it down 50% or more.
I see, I see. Okay. I think so. You were limited from the preclinical talks perspective. That's why you could only do a four week study. Now what is your view on the dose response? I mean, to us when we look at it, it seems like the 120 milligram was consistently outperforming. Whether you look at AN or draining tunnel, would you describe it as a dose response or there is more work needed to figure out the right dose?
I would definitely say from the efficacy standpoint, I would agree with you. The high dose group is just performing the best on every single level, including the patient reported outcomes. That is actually quite remarkable. Small data set. Is there a clear dose response? It is always a bit difficult in HS because of the fluctuating disease and if you have low numbers in smaller trials, it is always difficult. If you wanted to scout that, probably the draining tunnel is most suitable for that because that does not have the same variability as the other two lesions. Here indeed we have a 60, 90 and 120 milligram stack up. With that I would say clearly the high dose group is leading the game here by just performing the best on every different level.
Got it. You also presented four week off drug data on IHS4 score for these patients and the responses were improving or sustained. I think most likely they were improving. What is happening in these patients? Can you comment on the PK profile of these patients at week 8? Why are we seeing this durability and deepening effect?
Yeah, we indeed see quite an interesting and nice deepening effect after putting patients off drug. We were, of course, first thing we asked, is there still drug on board? We only have preliminary sampling. We do not have all the samples yet of all the 25 or in the end, all the 29 patients that reach this endpoint. The initial samples we had were levels of, let's say, roughly between 50 and 200 nanomolar of the drug in plasma. The IC50 is like avacopan at 25, so at least we can say there is still blocking activity in plasma at week eight. That is very preliminary. Of course, we cannot claim that we have full control over the pathway at week eight. Certainly very different from when you take the patients directly off drug.
Remember, we loaded the patients up for four weeks with bid dosing, so it is possible that terminal half life changes a bit when you are fully loaded. It's a lipophilic drug, it can go into tissue, particularly in fatty tissue, and be redistributed a bit. I would assume that several of these weeks you still have clear blocking activity and that can be explained by that. I just want to point to the mechanism. I talked a bit about changing that inflammatory environment. If you believe that the cell components have changed, particularly the immune cell components, we would also expect to have a carried forward effect of that. We did see that before when blocking the ligand with a different drug.
Okay, so you presented data on pain DLQI. I think on those endpoint we can just all assume that if the drug is working, you will see very fast effect. And that's what you saw both on pain and DLQI. But this draining tunnel generally takes a little bit longer. So what is driving such a rapid improvement in draining tunnel with this mechanism?
Most people, when they hear draining tunnels and when they see photos, you see this opening that can be actually quite unimpressive until you see a video where someone drains 1 liter of pus out of one of those tunnels. What I'm trying to say is what you see on the outside may be that little opening, but to have that pus formation, there is a deep-seated large inflammatory lesion and that is driven, surrounded by neutrophils, driven by netosis, which is a phenomenon in neutrophils and with also certain cells like monocytic cells. You have an effect on neutrophils within days. You are capable of reducing this pus production and this large inflammation in the skin after a few weeks. We are not surprised. We did see initial drops in draining tunnels already with our antibody back then also in the first four weeks.
Not as steep, not as dramatic as we see it here with the good tissue-penetrating INF904, but still the mechanism. That's why we guided you guys a bit to like let's, let's look at that when the data come out.
Okay. Now what is the plan going forward? Have you completed the preclinical talks? Twelve weeks and six months. What type of a study? Just focusing on HS, you would be thinking what type of a dose?
Yeah, yeah. First question, we have absolutely completed that required tox up to nine months, non-human primate tox. We have also reported that we have not seen any signal of safety concern and no dose-limiting toxicity in these studies. So we are prepared for indefinite dosing. We have to still have that interaction with the FDA of course, to get this on the road. Second part of the question, like how does the trial, how will the trial look like? We are still finishing up some work. We're still doing simulation work on PK as the samples come in. At the moment we're thinking of a typical larger phase 2b study like peers have done in the past and then to look into maybe two or three doses versus placebo.
We haven't yet figured out exact dosing. I would say it's likely that the 120 mg are in the mix because just clinically it was so fantastic in that dose.
Do you need to go even higher than. Because I think for some reason and we, I don't know if we understand, most of these drugs metabolize faster in HS patient than other indications.
Yeah. The way we approach dosing is we knew that 30 mg, which is Avacopan's approved dose, already gave us with our drug full control, 90%-100%, closing that control on neutrophils in plasma in phase one. 60 mg, if you will, was already a dose where we felt that gives us good control and we wanted to explore efficacy upwards. 120 for our drug is already quite high. We currently do not plan to go higher than that. We were already discussing is this too high? The clinic safety looks good. Safety looks good too.
Okay, I think I want you to sort of discuss the Avacopan data because I do believe that this is the second independent study with this same mechanism that is showing effect in HS. So relative to what Avacopan has shown, how does your status stack up considering it's only four weeks versus a longer treatment that Avacopan had in HS?
Yeah, great question. I mean we've discussed this in the past way before the readout and I've always said there is evidence of efficacy of Avacopan in HS. They did a pretty sizable phase 2b study back then. And what's reported on ClinicalTrials.gov shows that they reduced the AN count even in a dose-dependent manner. They didn't show separation on draining tunnels. The more granular data released was only on early stage 3 patients where they saw a pretty good response on IHS4 score, which has its limitations. The interesting part of the Avacopan data was when we first saw them, they seemed to separate from placebo and they had a pill placebo right arm. That only between the last, like between week eight and 12, the last treatment time point.
We felt that does not make any sense, it should work faster until we have seen for the first time when they put out the approval data package, the PK in the disease, it took 13 weeks and the steep part of the accumulation was basically stopping between 8 and 10 weeks. It fitted exactly that PK data set that was put out from a different disease. We concluded at that time point they start reaching minimal effective dose. What they see, remember we had the discussion, if I am right about it, we should see something like this already at week four or more, which is exactly what happened.
Okay, okay. Maybe just one more question on HS. So the next study that you'll do will. I mean, it's likely going to have either 12 weeks, 16 weeks, but will there be an open label extension in that?
That's currently in the planning. So very likely, yes. We are of course interested in seeing if we can replicate on the mechanism that over time we see more and more improvement. Like you remember, we had our KOL yesterday in the call, Professor John Ingram, and he said, like, look, we need to see mechanisms that get patients to minimal disease or disease resolution. That's still missing. And that's one hope that, you know, lies in the future of development.
Got it. For CSU, I think there was an interesting analysis where you showed that if you had a higher level of disease at baseline, there was a benefit. What are your plans in CSU? Is that something you pursue further or.
We think that the signal in CSU is real, particularly the 60 milligram group. I mean, we are at eight weeks down to a 16.3 reduction. Right. Which is. Right. We are successful. Drugs are particularly didn't seem to level out. We discussed this with our expert at Charité Berlin, Professor Martin Metz. He said, look, it's very hard in small data sets to get this type of good curve into the right direction. We cannot automatically assume that all the drugs work the same. If you deplete mast cells, clearly you will have the histamine problem solved over time. You see that fast. The disease is not just mast cells. There is also an inflammatory component. It is possible that the mechanism just takes a bit longer. Consider Dupixent. They go out to 24 weeks. It's a great selling drug because it's very safe.
We do see that opportunity if you could deliver a safe oral at a good dosing that shows over time deepening in the more severe patients. I think that's a great win still.
How is the, so for in HS? 120. Right. Seems good. In here it's 60. How is the, the PK for 60 milligram in CSU patient versus the HS? Similar sort of level.
It's high level. Similar. Overall, the CSU show a higher exposure, which again speaks for HS. You also have higher body mass index patients in HS, so the volume distribution, volume is a bit different. Long story short, the preliminary data show that we have good exposure at 16 CSU.
Okay, very good on these two sides. When will you inform us about the next plans? Are you going. Also, the divisions are different, right? One is the. Are you going to have separate meetings with these divisions and then inform us?
Yes, we are already working on the phase to be set up. Again, I mentioned PK modeling and other things that still go in it. We will address this with the FDA. We are already in discussions with the FDA, not on the concrete trial design, but on other aspects. You mentioned it's two different divisions, that is now the Derm division and CSU is in the allergy division. Clearly separated. The priority will now, first interaction will now lie on the HS part and then the CSU part comes later.
Okay, Thomas, maybe a question for you. How are the financials looking for the company?
We're of course always very optimistic about the financing. We have currently EUR 44.4 million at the end of Q3. That's a bit north of $50 million and that carries us into 2027. It includes all the preparatory work that Niels is alluding to. So basically we are in a comfortable situation now to, you know, prepare ourselves for the next steps. We're evaluating options, of course, as you can imagine, including both on the BD side as well as on the financing side.
Got it?
Yeah.
Yeah. I think on the BD side also recently there was a similar asset that was acquired by Biogen.
Yes, very interesting to see that, you know, the industry is picking up interest in this mechanism. You know, we do not know very much about the other asset, but it is very clear that it is an early stage product at this point and we see clear amount of differentiation for our product and we are very optimistic that it will be possible to attract interest going forward because it is indeed a very exciting data set we generated and there is sufficient unmet medical needs and industry interests for us to warrant further discussions.
Got it. Maybe one more question. Do we know where Amgen is taking Avacopan next? It doesn't seem like we are seeing much from them.
We've been following, of course, very closely what's happening there. And what we can see and tell so far is that, you know, they have been focusing quite successfully, one has to say, on ANCA-associated vasculitis. So the sales are growing nicely quarter to quarter. They're at $400 million run rate right now. So that's quite encouraging to see that here. Again, the mechanism seems to be, you know, very successfully applied in this indication. However, we do not see a lot of activity in other diseases, and that might be due to the restrictions that the drug has in terms of PK and other issues. So we hope that this will open up an avenue for us to validate the mechanism with our drug and other indications as well.
Very good, gentlemen. Thank you so much for your time. We appreciate it.
Thanks for having us.
Thank you.
Thank you.