InflaRx N.V. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Absolutely. Well, first of all, thanks Steve, for inviting us. Really thrilled to be here. Great conference so far. Yeah, we did really make a therapeutic shift into the broader renal space with the key focus first and foremost on ANCA vasculitis, followed by some other indications. As you may recall, there was always an interest in ANCA vasculitis, and that is because the research very clearly indicates the role of C5a and C5aR1 in this disease. So there's quite good research. As you also alluded to, there's an accepted path that is used as an approved drug on the C5aR1 inhibition with avacopan. So that was all in the mix. But on top of it, actually Amgen was really also reporting quite good increasing sales, showing to the investors and to the street that this is a real market, which was always a bit in debate.

As you know, we had for a while in the making a new version of a C5aR1 inhibitor with izicopan, maybe to provide some solutions to some shortcomings that we spotted in avacopan. So this was all there, and all of a sudden, this disease popped back up with the announcement that we're all aware of around potential withdrawal. So we got a lot of interest back in the ANCA vasculitis space. I should let all of you guys here know that while we had done some early studies, phase II studies with vilobelimab, our antibody, we also have the licensed vilobelimab version in China called BDB-001, which is in phase III for non-inferiority pivotal trial. So there's interest. There's clear evidence that the pathway is important. Here we go. We have a very interesting C5aR1 inhibitor that has best-in-class potential. And we have a proven market.

And we have a situation where in some major markets the current competitor is already withdrawn or on hold and an unclear situation, but also with the situation in the U.S. where the FDA has recommended that withdrawal. So we don't know how this is going to play out, but completely independent of that, with the drug properties that we may speak about, we see either way, if the drug gets pulled or not, advantages, and even if it stays on the market, we think we have a really good competitive molecule to it.

No, absolutely happy to cover that a bit. Actually it is also preclinically a very well-researched area. In ANCA vasculitis, ANCAs is an anti-neutrophil cytoplasmic antibodies. So the word ANCA implies that neutrophils are in the game. And in fact, these ANCA antibodies, they are different subtypes. They are directed against neutrophil structures that are usually inside the cell, but under certain conditions, like viral infections, that they can get on the surface of the cell. So these antibodies bind to these structures, for example, MPO, myeloperoxidase. And what happens when an antibody binds an antigen? Obviously, you activate complement. And you are doing that on the back of the very cell that has the highest density of C5a receptor 1 of all known cells. Plus, other cells have that, you monocytes, macrophages particularly.

So key cells of the immune response that actually drive damage because they have mechanisms to drive damage, like releasing granular enzymes that are very nonspecific, generating reactive oxygen species that can damage tissue, and undergoing NETosis, which is very well described in ANCA vasculitis. So that very cell gets activated by a mechanism on its back that generates more C5a. So ultimately, it is clear that everybody has almost the first go-tos, like, oh, okay, if you want to stop the damage, block the C5a1 because neutrophils get excited, they will cause damage. They will cause damage right at the vasculature site where they get activated. And in all these preclinical models, it is very clear, for example, if you take C6 knockout mice that cannot assemble the MAC, they are not protected from damage. But if you take C5AR knockout mice, complete protection.

It is very well established, the role of these innate immune cells in the damage driving mechanism. There is some new research that also suggests an impact on antibody generation from plasma cells that there is new research out just very recently in the public domain. The mechanism could be even broader disease modifying. If you think of in the ANCA vasculitis space, there is always kind of two pillars. The one is contain the life-threatening damage right there that can kill your organ. For that, currently, we use mostly high-dose corticosteroids with terrible side effects. The other pillar is drive down this ANCA antibody production, which is, for example, rituximab targeting, and maybe also to a certain extent, the old drug cyclophosphamide. Until avacopan came around, there was really no alternative to high-dose corticosteroids. The drug is really used to drive down corticosteroids.

You hear and see that from the responses. We hear that with our KOLs, with our advisors. I think the mechanism is really ideal for a drug like ours. On top of it, I want to mention that the mechanism how renal damage is established by complement activation, there is a lot of good research pointing to C5aR driving that mechanism. It is a very recent publication that shows how acute kidney injury is driven by complement, particularly C5aR, and then how C5aR plays a key role in the transition to chronic renal disease, specifically by fibrosis induction.

This is exactly the mechanism that patients suffer. They have this in ANCA, the acute kidney injury.

Yeah that over time will translate into a chronic renal impact.