Hi, everyone. I'm Andrew Fein, one of the biotech analysts at H.C. Wainwright. Thank you very much for joining us on our HAE Day event. Next group presenting will be KalVista. From KalVista, we have Andy, Chris, and Ben, senior management team. We can just dive right into it. It's been an interesting day from a physician perspective, I'd say. You know, we've heard one major academician who was quite willing to switch patients from prophylactic treatment to acute treatment, and didn't seem to have necessarily a lot of stickiness to any particular treatment. Another physician who was, you know, a bit stickier, I'd say, in terms of, you know, lack of a willingness to perhaps, you know, shift patients if they're doing perfectly fine.
I guess, Andy, you know, or any of you guys, you know, how does that jive with what you guys, you know, have diligence from a market research perspective? Do you think it all comes down to a threshold? You know, if there's a sufficient threshold, then the answer is shift. Or do you think it's simply a matter of, you know, each physician is different and each patient is different and each patient has different level of anxiety associated with new therapies? I guess, how should we think about things broadly?
Yeah, I mean, I'm sure a lot of those things, right? I'm sure some combination of those things are always the truth. You'll find the truth, right? I think one thing that's really important to remember in HAE is that the patient is a really important driver in the decision-making and often leading their physicians to their medicine of choice, right? Obviously, with academicians, you may have, you know, kind of a different hierarchy there than your kind of standard, you know, treatment paradigm. We have certainly found in our research that the patients are a major driver in the decision-making, and their preferences do ultimately make a big difference. You know, I
You know, we certainly believe that, you know, in the situation where you have a product that, you know, is, you know, potentially less efficacious than kind of your gold standard therapy, but maybe more convenient, then you're probably gonna see some variability in people's responses, right? You're gonna see some people, you know, choose one or the other for a different set of reasons. I think you'll see that among patients. You'll see it among physicians as well. I think, you know, I think one interesting, you know, look into the marketplace is when you find a situation like, let's take, for example, the on-demand injectable on-demand marketplace, right? We're clear in a way the market leader is FIRAZYR or KALBITOR, right? Why is that? It's not because the program is more or less efficacious. It's actually very much the same.
It's because it's subcutaneous, and that drove the market share, right? I think, you know, if we kind of forecast a little bit into the future, if companies like us are able to deliver on oral medicines that don't ask people to make those sacrifices in efficacy or safety, then I think you'll have a substantial shift in the decision-making there.
That's very helpful, I guess, context. I guess maybe in the backdrop as well, kind of setting the stage for 2023, right? When you've got data from both programs. As you set expectations among investors, is the threshold? I guess, what's the right way to think about that? I mean, obviously, you know, there are investor expectations. As BioCryst has shown, you know, sometimes you can disappoint investors and still satiate the market. I guess, you know, what's the right context with which to evaluate, you know, your 2023 data for both programs?
Yeah. I mean, I think first, just to your last comment there, I mean, I think we have to be careful. We're still in the early days of this launch with ORLADEYO, right? You know, without question, I think they've exceeded expectation. We'll have to see as that moves into the future, if they're able to continue to kinda over-deliver or whether, you know, whether some of the fundamentals will start to kick in more. We'll see. I don't have any way of predicting that. From our perspective, as we think about our programs, is I think we've been very clear from the beginning, both with sebetralstat and with KVD-824, our objective here is to provide patients with HAE oral therapies that are every bit as efficacious and safe as what we see with injectable therapies.
That's our goal. With sebetralstat and the phase II data, I think we delivered on that, across you know all the primary secondary endpoints. You know, every bit of the data from that trial would suggest that sebetralstat is every bit as efficacious as the injectable therapies we've seen, if not better, because we know that patients will use that therapy sooner, and if they intervene earlier, they'll have better outcomes. We feel really good about that. Similarly, with KVD-824, we expect to deliver on injectable-like efficacy, and we haven't been shy in saying that yes, it's a high bar, but we believe the PK/PD that we have on that program would convey that high bar of expectation. In the marketplace, as we've been discussing, that's really important if you're gonna be competitive.
Can you speak a little bit to the speed, you know, the onset of action, you know, how important that seems to be, as you speak with physicians and patients, as they think about, you know, potentially trying a different on-demand treatment?
Yeah, it's critical, right? I mean, I think it's something that we've been asked a lot about, even since the early days when we were developing sebetralstat, just given that it's oral therapy and the expectation is intuitively that oral therapy will take longer to work than the injectable therapies. In some ways, the data has had to help us overcome that inertia, but it certainly, you know, has delivered on that. Every bit of data that we have, PK/PD and now the efficacy data suggests that's true. That is really important for patients because especially as you're treating on-demand as an attack begins, the whole idea here is to help patients remove the obstacles that they currently have that are either preventing them or compromising their ability to intervene early, right?
All patients know that if you intervene early with their on-demand medications, they're gonna have better outcomes. Despite that, we know that the data, the real-world data tells us that patients don't do that for a variety of reasons. Most of those reasons are attributable to injectable medicine, whether it be because of pain, whether it be because of their inability to access the medication at the right time, difficulty of administering it. What we wanna do is remove all those barriers. If your medicine still has to work quickly. If you remove all those barriers and your medicine, your oral medicine works quickly, we think that provides for a really substantial opportunity and makes it simple for patients when they have decisions to make about which medication to use.
Yeah. At least, you know, we heard interesting, kind of, slightly differentiating, differing commentary from the two docs about, you know, how a new on-demand therapy might impact prophylactic usage. You know, the docs this morning said pretty clearly that if there was a new, highly efficacious oral on-demand therapy, you know, in his opinion, you would see patients use less prophylactic treatment. You know, does that, seemingly, that's very positive for you guys, but does that, is that what your research has shown as well? I mean, I think more people have thought about the other, you know, sort of things from the other direction, right? You know, how prophylactic treatment would negatively impact on-demand usage and, you know, we haven't really seen that. What are your thoughts there?
Yeah. Ben, you wanna take that one?
Sure. First off, Andy, we agree. I mean, if you look at the prophylaxis usage to date, even in the presence of ORLADEYO, you don't really see a decline at all in prescriptions on the on-demand side. We have IQVIA data that's probably the same as everyone else does. More or less, acute scripts have been essentially flat for the past three years. The dollar volumes come way down because icatibant went generic three years ago, and so the dollar size of the market is much smaller. From a script side, it's basically flat. That reflects an important element of the marketplace, which is that a large substantive proportion of patients prefer to treat their attacks in an on-demand manner, even in the presence of very efficacious prophylaxis.
As Andy's you sort of touched on, and Andy kind of spoke to a few minutes ago, that's for a variety of reasons. There are when we talk to patients, what we hear in, is a somewhat consistent theme of a lot of patients like to treat on demand because it makes them feel like they're in control of their disease. It isn't like they have something that chronic that is really severe. It's just they're comfortable with the disease as it is, and they do that even in the presence of the fact they have to give themselves maybe perhaps a couple injections a month.
It's also important to note that that's not an irrational viewpoint, even in the context of current therapies, because the average HAE patient has about two attacks a month. If you look at it just on sort of almost an injection basis, if you have two attacks a month and you're taking two icatibant injections versus you have two attacks a month and you take Takhzyro, which obviously drives that to less than two attacks a month, but you're still getting two injections a month, you're more or less neutral. You don't get the big lifestyle pickup that some people perceive you get from prophylaxis. Of course, TAKHZYRO's got the most favorable dosing schedule of anybody right now. I mean, HAEGARDA's a couple times a week.
Even the therapies that are coming along that may or may not have better dosing schedules, less frequent injections, still offer patients a fair number of injections, which is more than they want. To these patients, there isn't really a benefit necessarily of going to prophylaxis, except for other reasons. They have very severe disease. They have a lot of, sometimes patients will have sort of psychological challenges associated with disease because the burden of the illness kind of weighs upon them so much. Those kind of patients you might see move to prophylaxis for different reasons. It's not necessarily just because of the fact that it offers some kind of more favorable dosing schedule.
This goes to your question about what's gonna happen with patients on the on-demand space in the presence of sebetralstat. Like I said, we think the on-demand market is quite stable, and we think obviously sebetralstat should be well-positioned to capture a very substantial share of those patients so fairly quickly actually. Beyond that, this question of where patients go, we think becomes interesting because prophylaxis has in all likelihood probably captured some fair number of patients who don't have the kind of severe disease that might really require a prophylaxis. Again, if the average patient has two attacks a month, there's and you have more than majority of the market is on prophylaxis. Substantial number of patients who maybe don't actually require a prophylaxis therapy, but they want it for other reasons.
We think there's going to be opportunity if sebetralstat performs like we think it should to bring some of those patients back to on-demand. Because fundamentally they'll be no worse off in terms of their ability to treat the disease and they'd be well-qualified for the disease just by virtue of the fact that their burden isn't all that high to begin with. We're firmly on the side of, if anything, pro-sebetralstat trials that's gonna pull patients back from prophylaxis. I don't think we're gonna continue to lose them there.
That's very interesting. Dave, original research, I thought it was interesting from the last KOL as well, that he said, you know, he's not, his center at least is not getting a lot of new patients.
Yeah.
Does that jive with what you guys are hearing? I guess, is that an anomaly? How, what's the right way to think about that?
The U.S. has a fairly distributed care network for HAE patients. You do tend to see a lot more docs treated here in practices that tend to be a lot smaller. A doc with 10 patients in the U.S. would be a fairly substantive HAE prescriber. If you think about what that really means, he had one person who then brought the rest of their family because they came along, and then another family they knew heard about him and went to them, right? You can almost see how this would happen organically, where a doc is gonna have a couple, three families in the United States. In Europe, it tends to be different.
Their patients are treated in these fairly large catchment centers, so a good-sized European center might have 200 patients. I don't know that I think we'd consider it all that remarkable that this particular doc isn't getting more patients 'cause it just seems to be the way the disease works. There are certainly centers that are bigger than others. There's a number of locations that have fairly large patient treatment populations. No, I don't think that inherently we're shocked by him saying he's not seeing a whole bunch of new folks.
Since you brought up Europe, I guess, you know, how are you thinking about, you know, the ex-U.S opportunity at this point? You know, clearly it's an important one. You know, when's the right time to kind of lay the groundwork there? Or if the data are simply strong, as strong as you expect them to be, you know, that'll be an issue for a larger company to figure out.
Oh, we already are. I mean, our we believe that sebetralstat should be a global product. It has many advantages, obviously, over the current therapies that we've talked about already in terms of the oral dosing and the efficacy. Also important that people forget about is a number of these modern therapies aren't really seen in much of the rest of the world for a variety of reasons. One of them is cost, obviously, but also just the logistics of the thing. I mean, proteins, antibodies, they all start to have cold chain challenges once you get above maybe 80 degrees on a consistent basis. That has also been a burden in terms of getting these therapies introduced around the world.
Sebetralstat, by comparison, very stable tablet. We think this actually has the potential to go globally as a product. We're actually absolutely setting the stage to be able to do that. We've always said we're gonna commercialize this ourselves in the U.S. and the major E.U. We're already setting the groundwork to do that. Beyond that, we obviously will consider collaborations of some sort, whether it's a rest of world type thing or it's smaller geographies. We intend to make this as big and broad a launch as has ever been seen in HAE.
I guess as we get into next year and the data release, you know, is the pushback that you get from folks, you know, simply them not being aware of you? Do you get pushback on the market? And the data thus far has been very strong, so it's not pushback on the data I suspect. You know, what do you think you need to overcome in order to, you know, get people fully engaged?
You know, I think some of the dynamics we've been talking about the market, you know, certainly are something that we need to continue to help investors fully appreciate, right? The dynamic. I think, you know, in our previous discussion, Andrew, in the last call with the last physician, you know, his comment that in the U.S., the market's kinda 50/50, and that's what he sees in his practice. I think most investors have this thought that perhaps the on-demand market has gone to zero, right? I mean, that there's just this. There's a number of things that play into that.
I think that the dollar volume because of generics has eroded significantly, but they're not appreciating that those are kind of, if you will, two kind of independent variables, the demand side versus the dollar side when we're talking. I think, you know, helping people underappreciate the opportunities for us in the market, I think is really important. You know, I think that as you said, the data's been very good. I think that our ability to predict data has also been pretty good based upon our PK/PD work that we've done. I think we've always been pretty open about our thoughts about, you know, where we should be looking and how aggressively we should be thinking about our efficacy given what we see in PK/PD.
I think we've tried to set pretty good expectations here and we have a really significant opportunity. I think, you know, beyond that, I think also what we'll start to work in our favor is people's appreciation of our Factor XIIa asset, right? Obviously it's preclinical, and so that doesn't get as much attention, but we have a really, I think, you know, important program there that will complement what we're doing in HAE and then also help the company start to move beyond HAE as we think about, you know, other opportunities for Factor XIIa. I think, you know, a combination of those things will start to work in our favor.
You guys are in a very interesting spot as we get into next time. Stay tuned. I think we've ran out of time, but very helpful update. You know, hopefully it was the dialogue earlier in the day with the KOLs were helpful too for providing some context. Thank you very much for participating. Appreciate it. I look forward to staying in touch.
Thanks Andrew.
Great. Take care.
Thank you guys very much.