At the H.C. Wainwright 28th Annual, excuse me, Global Investment Conference. My name is Matt Keller. I am a Vice President in the Equity Research department, and it is now my pleasure to introduce our next presenting company that will actually be conducting a fireside with me. With us, we have InflaRx. Speaking for the company, we have Niels Riedemann, CEO, Thomas Taapken, CFO, and Jan Medina, VP and Head of IR. Welcome to all of you, and appreciate you for being here.
Thank you. Thanks for having us.
Of course. To get started, I guess, for our audience that might be a little newer to the story, I was wondering if you could maybe provide a more high-level, broad-stroke overview of, excuse me, the company strategy. Excuse me.
Absolutely. First of all, Matt, thanks so much for inviting us. Really a pleasure to be here. We have done a recent financing earlier this year in May to do a therapeutic shift, if you will, but not really just something completely new to us, something that we anyways had on the map, the broader renal space and particularly a space called ANCA vasculitis. It is a rare disease that is driven by anti-neutrophil cytoplasmic antibodies that can cause a vasculitis that is life-threatening. That was a bit prompted by the fact that, A, we have a very good new asset, a receptor, C5a receptor blocker that we believe has best-in-class potential.
It was also driven by the fact that, the only competitor out there, which is Amgen's TAVNEOS, was reporting, A, very good sales, and B, got a bit in an argument with some regulators around trial conduct, and also has been pulled now in Europe and in U.K., but not yet by the FDA in the U.S. So all of a sudden, there was this interesting, probably EUR 1.4+ billion market opportunity. This is data that other analysts have brought up that seemed to be creating a big opportunity. I want to remind you, we have also an antibody to the ligand C5a, so we're a complement company that really focuses on the terminal complement pathway.
This ligand has an approval in a vascular-type disease, which is COVID, in the end-stage COVID situation that creates a lung failure, ARDS, in Europe, and it has an emergency use authorization for a similar, but not the same indication in the U.S. So we know the pathway, we know the role in vasculitis, we know the role in vascular dimension. We've previously developed with our ligand antibody in ANCA vasculitis. A lot of investors were not convinced is it a real market, and if there's an oral, how much of a gain you would have. But we completed these studies, and our drug is licensed in China with a seller in there called BDB-001. They actually ran a successful phase II trial, showing that you completely throw out corticosteroids on day one, which was numerically the best treatment groups.
Now they're in phase III with a BVAS non-inferiority study that the FDA did not allow or did not agree to back then with ChemoCentryx. So we know the field very well. We have drugs that could address it, particularly izicopan. We're going to be speaking about that drug a bit.
Yep.
I want to take that up front, but this is really the space we're operating in. The drug has gotten some interesting data, early data in a skin disease called hidradenitis suppurativa and in CSU, chronic spontaneous urticaria. So the pathway seems to be very meaningful, and we're really excited to push this out further in the I and I space.
Yeah. Thank you for that overview. There's a lot to unpack there. We're going to touch on some of these topics individually as we go through this chat. Maybe let's take a step back, and again, let's orient our audience a little bit more to the mechanism to action that you spoke about. So maybe you could talk just briefly about the C5a receptor, what has been successful in the past, and maybe some challenges the space has seen as well that has led, again, you kind of mentioned this in your overview, but it's really created this opportunity that you spoke of.
Yeah. So, I was one of the research team that uncovered the signaling of the receptor, so we're really excited about having a drug that could address it. You're right, it's been a challenging field in the past, but not so much because the target wasn't known. I think it's one of the best-researched I and I space targets out there when it comes to preclinical research, and there's no like bless you. There's no kind of a signal that suggests that blocking the receptor could have a toxicity, right? In fact, it has been shown organ protective even in the liver. So, why is it a bit challenging? Because in the '90s, there were cyclic peptides. They were kind of toxic molecules, but very good blockers. With an antibody, this is a tough target because it constantly recycles.
It can be almost in every tissue of the human body upregulated during inflammation, so tough to catch it with an antibody and fully control it. But chemicals, ideal if they work, and there probably have been many efforts, but ChemoCentryx, kudos to them. They really found that allosteric binding site in the lipid layer of the receptor. So in one of the transmembranes, so to speak. But as it indicates lipid layer, so this has to be a very lipophilic molecule. In vitro, this is a perfect blocker. And our drug has pretty much the identical IC50 in various in vitro assays. But in vivo, the problem, the challenge seemed to be that the PK, so the uptake from the gut into the system in animals and then later in humans was difficult. It has, I think, a 13-week accumulation to reach steady state.
It starts at a pretty low plasma level that may not be enough to fully cover the signal from the beginning. So there was this opportunity to create a drug that actually addresses these shortcomings. Back then, the toxicity wasn't really known much. That is more of a recent signal that became larger and larger in recent years, so one or two years or so. But that being said, the real challenge for us, the initial challenge was can we work on the findings of ChemoCentryx, really, to find a way to generate a drug that addresses this, has a better plasma presence? And as you may have seen, a couple of years ago, we put out this interesting phase I data. We had a tenfold area under the curve increase, threefold higher peak, completely different uptake, really good plasma presence.
And in the multiple ascending dose studies, a really good coverage already at 30 mgs, but we can really easily dose up to 240 mgs. So we have a very large therapeutic window. And that really excited us a lot because we knew we have something in our hands that maybe even on day one can reach plasma presence of full coverage.
And we're speaking about izicopan.
Izicopan.
Right. Yeah.
Yes, exactly. And now, the safety signals occurred. We looked into this as well. We are not inhibiting this liver detoxifying engine called CYP3A4. Avacopan is a time-dependent inhibitor of this engine. And why is this important? Because a lot of drugs, also corticosteroids, by the way, and also drug metabolites can be metabolized through CYP3A4. And if you really, after a while, when you accumulate, if you really block that, you may see toxicity from either your own metabolites, from your own drug, or from other drugs. So we don't believe we have this issue. We have a more metabolically stable drug in head-to-head comparisons, but we also don't block CYP3A4. And we have not seen, I think we have over 180 patients exposed and humans exposed to our drug so far. We have not seen liver enzyme elevations, and we have no signal in the entire preclinical package.
We may now have a drug, when we compare it to the market comparator, that seems to have a much faster onset and a better plasma coverage. Seems to have, at least from what we know today, a better safety outlook, I should say, because we haven't done long-term dosing yet. I didn't mention that we will also pack 30 mgs per one capsule, so we have a more convenience dosing, and our modeling does suggest that you can go to QD dosing. So there could be also this convenience angle to it on the-
That was something I was going to bring up. Obviously, we view it as a molecule with best-in-class potential, and one of the differentiating aspects besides safety and efficacy is its oral dosing capacity as well, right? Can you comment a little bit about that as well, and how big of a factor do you think an oral dosing strategy here has compared to maybe some other competitors, either that are approved in the space or ones that are kind of coming along as well?
Yeah, very good question. If you think of the broader renal space, we all know there's successful drugs, complement inhibitors, upstream, right? Factor B, C3, there's all these targets that have shown clear efficacy in different indications. I think there's two angles that are important. So why do you need another complement drug? We are not just another complement drug. We are at the, basically, end stage of complement activation that is believed to be the key driver of damage, which is C5a, C5aR signaling. Now, if you blocking, particularly this signaling, you have two advantages. First of all, yeah, if you're oral dosing, that's nice, but other drugs are oral, too. But the second thing, conveniently, if you're just QD dosing, so once a day.
The most important part is we don't require vaccination because upstream complement inhibitors block the membrane attack complex, so therefore they need vaccination. Despite vaccination, real-life data show that these patients have a higher infection rate, sometimes meaningfully higher, because you can only vaccinate for certain bacterial infections, for example. So really, that is a long-term benefit. You may have an oral drug, QD dosed, that doesn't require vaccination and may not have, for all we know today, that clearly driving higher infection risk.
Yeah, exactly. Let's talk about kind of the big strategic shift that you commented on in kind of the overview of the company, moving away from derm into more kidney-related diseases, initially focusing on AAV along with some other kidney indications we're going to talk about. But maybe walk through our audience about how you came to the current place you're at in kidney disease, and why you think that might be the best or greatest potential for your assets-
Sure
and C5a receptor inhibition.
Yeah. While it was a clear shift of key focus, it was in our slide decks that the renal space was of key interest for us for a while. Again, because other complement drugs have successfully been developed, there's also a mechanistic idea of why C5aR blockade in the kidney has a particular effect. That is for acute kidney injury, but particularly interesting new data suggests also for the shift from acute injury to chronic to the fibrosis angle. C5a receptor seems to be a key driver of this. There's just very new research suggesting that. That is of interest. So there's precedence. There's these advantages we just talked about. And there is also a real big market opportunity as we see it now in ANCA vasculitis. So we have everything that it takes to focus on that particular angle. Yes, we had previously developed an HS.
I think we have very good data on our hands. We could further develop. That's not our current focus. Our current financing and money goes where we just discussed. But it is an opportunity for the future. So we haven't dropped it as of, oh, the data were not good enough. We think they're really good data, so they can be developed in the future.
This kind of brings me to another, I think, differentiating aspect of this asset. We like to use kind of a cliché term, a pipeline in a pill, right? There's many applications for this mechanism of action, with the priority being AAV, but you've also selected some other renal indications as well as potential avenues of development as well, including aHUS, IgAN, and C3G. I wondered if maybe you can comment on those indications as well. I know you said we're prioritizing AAV, but what's the plan here? One of those will get a priority. What are your thoughts as well as applying this expand in other indications as well?
Yeah, great question. I want to take this into two parts. One is the other renal indication part, where we are planning a basket study, which would probably more focus on subtypes that are usually not enrolled in trials that have a lot of serious kidney injury, where we believe our mechanism may play a better role than others. We want to get early signals to say, this is something you could build on. IgAN, is a very busy space with great successes recently, so we may not look into a de novo many years long development, but we think there are patients underserved that could be in a basket study, so create interest and open label data while we have to wait for the large ANCA studies to read out.
aHUS is a separate study that I carve out here a bit because aHUS, yes, it somewhat falls in the renal space, but aHUS is a paradigm shift for us because people believe it's MAC driven and we are not so sure if the damage is MAC driven. We think C5a, C5aR could drive a big part of that damage, if not the main. That has to be proven clinically. For us, it's more like we want to make sure we're looking really at complement mediated aHUS. There's also non-complement mediated kind of subtypes in that basket. Then say, can we really find a signal that safely gets the patients on this very nicely established surrogate endpoint where a few patients open label will tell you if the drug is active or not.
Right.
If it is, that all of a sudden means in that indication, you may have an oral with all the advantages we discussed, particularly without blocking MAC. It's a bit of an experiment, if you will. I've carved this out, but it's interesting because some people may have not grasped the idea yet that we've seen such a great success in C5 blockers, right?
Right.
Kudos to Alexion that created all of this. Some of these indications clearly are MAC driven. If you think of PNH, our drug would not work there. But some others, the damage may actually come from C5a, C5aR, and if that's the case, we may have a better drug for some of these. That's why we're looking into this paradigm shift. I carved this out as a little bit of a separate study, which we're already in the planning stage on setting that up.
We're carving out some of the studies for the other renal indications, but maybe you could give us a preview of what you're thinking for the AAV program, timeline, study design. What are we thinking for that program, as you already touched on some of the other renal indications you're thinking about?
We're currently working on the base case study design. We will have an update in our capital markets data around that. The base case covers what we've gathered from their interactions with ChemoCentryx back then, as far as they are public. If the FDA hasn't moved the way they think about the space, this is a concession to say we get the data the FDA requires us to get in the phase II. That's in the making. We will start initiating trial sites early next year. We are working towards that. Now, that's kind of a phase II with a certain renal angle with getting the data we believe FDA needs to see. We call that the base case. That's what we got the financing for to complete. It will be a meaningful phase II-B study in this space.
We're having the renal angle, looking at renal function as well, particularly early, UPCR or UACR signals that show us that the drug's clearly active next to the BVAS, which is always the endpoint you have to at least be equivalent. Next to the base case, we're now entering into a series of interesting interactions with the FDA coming up soon, actually at two different interactions, where we are trying to display our thought of how this can be developed and trying to find a path to an agreed on endpoint that doesn't necessarily say you have to be superior on BVAS at week 52, which they demanded not necessary. They just said we need a superiority signal. They didn't say that has to be that.
If we can find an agreement on the endpoint, we want to discuss a seamless phase II/III, maybe straight to phase III for izicopan. That's a bit dreaming, but there is evidence that happened. I want to caveat two things. Endpoint is one of the key gating items. You can't start a phase III without having agreement on the endpoint. The other one is some technicals. You need sometimes to have delivered certain data before they technically allow you to say this is a phase III. Manufacturing has to be at market kind of size. There are some technicals behind that we're working on already, and then this agreement level. That would excite us a lot because it would accelerate the speed towards getting the drug out there for patients.
I should mention, when you talk to physicians, which we do frequently, and we have in the past because we have a network because of our past experience in the U.K., in Europe, in the U.S., they actually all like avacopan. The mechanism is well established. They think this is the only drug that helps to reduce corticosteroid load and makes the life clearly better of patients in this disease. There's a huge need now created already in Europe and U.K. because of the withdrawal. We also think that if the drug gets withdrawn or not in the U.S., we see upside either way because we have so many angles that our drug could be preferable that we're not threatened by if the drug stays on the market or not. For us, this is not a gating item at all.
But the interesting learning is the mechanism is well-liked, and if you brought an even safer drug or had less safety issues or showed even a better signal with a faster onset, all that could be upside.
Right, and this is jumping to actually what my next question was going to be.
No, please. It's okay. But yes, maybe just reiterate for our audience just so it's clear. There was a competitor who has had a negative recommendation from European regulators.
Right.
Avacopan. I'm kind of wondering how the investor audience should think about that news, how it relates to your own pipeline, and you've already touched upon it here, but again, maybe just reiterate how that will influence your development moving forward, if really at all. Obviously, you said there's a lot of potential upside actually with this, but maybe you can comment on that recent news as well.
Yeah. Obviously, it's always tough to comment on other drugs news. Our understanding is that the regulators in Europe said, "Well, we don't regard what the other company had delivered as a GCP compliant trial, so we can't use it as a basis of evaluating efficacy." Easy enough, end of story for them.
Right.
In the U.S., this is playing out so far a bit differently. I think there's a lot of considerations what the patients' needs are, but we will see. The FDA has to be now either scheduling a hearing or staying of the same opinion and pulling the drug. There are different possibilities, which I don't want to speculate about too much. All I could say, in Europe, this created really a void of a drug, of the mechanism that really helps this main need to reduce corticosteroids. If you will create an alternative to the constant use of corticosteroids. In the U.S., I think the need is the same. The question is, will the other drug be pulled or not?
Right.
Even if not, we see a real big market opportunity. For us, this seems to be all upside at this point in time. We're very excited because we've been saying that to our investors communities, "This is a big market." Even I think you can go back in our slide deck like some three, four, five years ago where we said there could be a billion-plus market opportunity, and now it's almost proven out by the numbers that Amgen produced.
Yeah. You have the data to back that up, right?
Yeah.
For the second time, I would like to just ask one more question. One that I think is kind of important because we spoke and we touched about how you have a pipeline and a pill aspect here, and there's a lot of opportunity, and currently a lot of that is being driven in-house. I was wondering if you could talk about, number one, what your thoughts are on BD and partnering some of these so that you can maybe develop quicker or branch into additional indications, and also how you're thinking about your current cash and capital resources, and how you're using that to kind of get this across the finish line with certain indications, certain diseases.
Yeah. I would love to pass this over to Tom here because first of all-
Sure
he handles a lot of the BD and of course the cash.
Happy to talk to that, of course. The shift that we did away from immunodermatology into the more renal-driven diseases does not mean that we do not believe in the value of the drug in those indications. We have had a lot of very interesting and encouraging discussions with a lot of the large pharmaceutical companies, and we will continue that dialogue because we believe some of these indications can still be developed in partnerships and good value can be delivered to our shareholders through that. In terms of the second question, the cash reach, we have raised this $150 million in May that would allow us to cover the cost of our base case scenario, which is the phase II trial in AAV plus all the ancillary studies that we were talking about in the renal space.
With that, anything that goes beyond that will have to be reevaluated if we are there, if the FDA grants us a quicker path to approval, potentially by combining the phase II-III or something like that might actually have to let us reconsider what the actual cash needs for such a scenario would be. But at this point, we are funded through 2029, and we are very happy with that.
Which is a great place to be, right?
Exactly.
With that note, with time, we're going to have to wrap it up. I want to say thank you to each of you for being here and speaking with me today. Thank you for everyone presenting at the H.C. Wainwright Conference this year. We appreciate the time, the effort, and the attendance. Thank you very much.
Thank you.
Thanks so much.
Thank you, guys. Thank you.