KalVista Pharmaceuticals, Inc. (KALV) Earnings Call Transcript & Summary

Welcome, everyone. It's my pleasure to host this fireside chat with KalVista. I'm Joe Schwartz from the Biotech Equity Research team at Leerink Partners, and it's my pleasure to be joined by Ben Palleiko, Chief Executive Officer. Thanks so much for being here to give us an update today.

Joe, thanks for inviting us. Really nice to be here. Happy to be one of the lead off hitters here for your big conference.

Fantastic. So why don't we get started by having you bring us up to speed on all the company's recent accomplishments and the value-creating catalysts that we can look forward to as you continue to advance Sebetralstat?

Sure. So as I assume everybody knows at this point, we are developing Sebetralstat for the on-demand treatment of hereditary angioedema attacks. We have filed now for marketing authorization in total of 7 territories. And so we're moving along on a fairly global plan here, as we've talked about previously. The most significant one, obviously, is the upcoming PDUFA date, which is June 17 here in the U.S. We -- as part of that, we've been building out all aspects of the commercial plan. And in fact, we -- just last month, we onboarded the field team, which is now in place and actually out and making calls to the top docs in the space already. So we're full speed ahead on getting ready to launch the drug effectively immediately after approval. And then later this year, presuming we're also able to get an approval in the EU, we'd expect to launch in Germany and then early next year in a couple of other territories.

Great. So how is the review going? Based on our math, it seems like you should have had the mid-cycle review meeting, and I heard you say that you've got the field team in place. So how much insight into the actual review process can you share?

Yes. So the review to date has been, I think, what our team would describe as broadly kind of in line with standard. You are correct. We've had the mid-cycle review meeting already. We are actually just gearing up here to move into the labeling discussions that will be going on moving into the spring. We've already got the late cycle meeting scheduled for later on this spring. And again, as I said, we're -- as far as we can tell, we're moving along smoothly here towards the PDUFA date.

Okay. Great. And then it seems like this might be a relatively more straightforward review. And I'm just wondering based on the strength of the data, I'm wondering, is an advisory meeting planned? Do you have any insight into how the FDA is thinking about that?

They've told us twice, in fact, just at the mid-cycle review, they reiterated that there will be no advisory committee.

Okay. And I know you haven't had labeling discussions yet, but how are you thinking about whether there's different scenarios, any things that you'd like to see, make it onto the label? Help us think through the puts and takes there?

Yes. Well, as you said, that the data is really very robust and quite clean. As you know, we hit all the primary and secondary endpoints in a high statistically significant manner. The safety has been pristine for the program throughout. We've had extraordinarily low levels of adverse events and never a serious or severe one. We've reinforced that with the open-label extension data that obviously goes into the safety database, FDA reviews, most recently at the last couple of scientific meetings, Western Allergy in February and then AAAAI just a week or 2 ago. We presented some of the analytics from that data cut. We did 120 days with the FDA. And again, it reinforces the fact that the efficacy is really strong. The safety, again, over 1,706 attacks just in the open label has been very clean. And we've continued to show that the drug has efficacy in effectively all HAE subgroups. We've shown all attack severities from mild to very severe. We've shown all attack locations. We've now got a very large laryngeal data set. We presented the 32 attacks from the open-label extension at AAAAI and showed really good efficacy. We've shown that it works in addition on top of prophylaxis. So my point is going back to label. We think this should be a pretty straightforward label. Things we think about, obviously, kind of the open questions, if you look at the other labels in the space, they tend to be pretty straightforward on the indication. What I assume will end up with at some point is some type of max daily dosing. I think that's probably a little bit more of a back and forth with the FDA. We don't really have any safety signals that we become limiting. But clearly, you expect to end up somewhere with some type of structure around that. But all in all, we don't really anticipate that there's a whole lot of items of concern here that we think would really restrict the label.

Okay. Great. And then you mentioned AAAAI and some other meetings. Given you've had such a major presence at all of these different allergy and immunology meetings, what has resonated the most with the KOLs?

Yes. I think the consistency of the data has been really positive. And of course, the safety profile has been very well received. If anything, again, the data, the more we cut it, the more robust it seems to look. And so at Western Allergy, we showed that when combined with prophylaxis, sort of for breakthrough attacks that we had patients in the study seeing initial symptom relief, which, as you remember, was the primary endpoint in the Phase III and right about 1.3 hours, which is actually even better than the Phase III data set. So I think that kind of shows and close to real-world usage that, if anything, the efficacy is actually better. And then we also showed, as I mentioned a couple of minutes ago, laryngeal data at AAAAI, which was very well received. In fact, that was probably the last kind of piece of the puzzle for physicians. Laryngeal attacks are a very small percentage of attacks and the numbers move around a little bit, but maybe it's 5% or so attacks. But obviously, they're the most concerning because they're life-threatening. And what we showed is that, again, through the open-label extension data cut, we had about 32 laryngeal attacks. And what we showed is that, again, patients had initial symptom relief in about an hour and 15 minutes. So call that less than 1.3 hours actually. We showed that nobody had any trouble swallowing the drug, which I think is a major concern. Again, tablets very modest sized, and it's got a very slipper coding on it. But you always worry about whether people can swallow the tablet and retain it. And again, we had -- we've never had anybody have any trouble swallowing tablets or retaining them, which I think was very, very comforting to physicians. So I spent a lot of time at AAAAI meeting with physicians of vary types. And I will say that, that data was really well received because, again, I think that was the final piece that they hadn't seen before that really shows that this is applicable in all circumstances for everybody.

Right. That seems important in those cases, for sure. So then thinking about the commercial opportunity, how large of a sales force do you plan to have? And where are you in terms of its build-out?

Yes. So we brought them all on board the first week of February. They're here. It's -- the field team is 32 people. It's right in line with everybody else in the space in terms of size. So there's no gaps in the coverage. It's a really experienced group, a lot of folks with a lot of HAE expertise and the folks that don't generally have allergy expertise. So it's people calling on offices that they've been calling on for years in most cases. We feel like they're -- that's sufficient number. In fact, we're very comfortable that's a sufficient number to call on the docs in the space. And just to kind of talk about how the physician universe works in HAE. All in all, there's right around 2,000 physicians who effectively ever have written an HAE script. About 90% of the scripts are written by 1,000 of those docs and half of the scripts are written by 200 docs. So it's a very tight call, hence, the relatively modest sales force. Already, this team has reached out to over half of that 1,000 docs and had actually meaningful interactions with most of that. As of the end of last week, they have talked to physicians who, in total, treat around 5,000 HAE patients, which is a pretty substantial percentage of the entire population in the U.S. So I guess to say they've hit the ground running is probably to understate how fast they've gone. And the plan here is that they'll meet with those physicians, especially the top 1,000 multiple times before approval, again, to continue to foster the relationships, make people aware of the company, obviously, not the product until it's approved, but also just to kind of start to work the logistics with physicians' offices about how all this goes forward.

Okay. And there's been many new drugs introduced into the marketplace over the years, although not in a while. And your profile is very different. It's something that the market has been waiting for, for a long time. So what can be learned from existing product launches, what might apply to your upcoming launch and what might be different now as we think about the trajectory for adoption?

Yes. No, that's a great question. It's a busy space for sure. I mean -- but the important thing is almost all the activity, if you will, is really in the prophylaxis side of the universe nowadays. So right, there's 4 prophylaxis therapies approved. By my count, there's something like 6 more in development. So prophylaxis gets a lot of attention. And I think it's thrown up a little bit of a smoke screen across the space just because of all these players talk about and the market through our prophylaxis lens. I think what's interesting about where we're going into is the fact that it's effectively the quiet backwater of the space. There hasn't been a new on-demand therapy launched in right around 10 years. It's not a space where there's a lot of active detailing going on. Most of the players there are dealing with either kind of legacy products or have shifted their focus elsewhere. So we're not seeing much mind share at all, frankly, in the on-demand space. What does that mean for us? I think it does mean that, again, when we go to these physicians' offices, we're talking about something fundamentally different than they're hearing from other people, which I think is interesting to them. I think that's important because a couple of years ago, when you and I would sit down, we'd end up talking about the fact that there were these arguments that the prophylaxis market is going to sort of subsume the on-demand space, and there's no more need. And I think what's happened now as we've generated data and as people have looked at the space more broadly is they realized there's actually still and going to be for the foreseeable future, a significant need for on-demand therapy. None of the -- all of these therapies coming along broadly speaking, have roughly the same efficacy and very -- and none of them really leave people attack-free for any substantial period of time in most cases. And so -- which is why the on-demand scripts haven't really moved at all in the last 5 years for sure. And so I think people have now become more comfortable with that and they sort of understand that there is this clear unmet need that exists in the space and that we're well positioned to fill it. And that coming back to where you started that when we get out there, there should be a pretty strong reception. That brings me then to what is the comparator. Again, the most recent launch in this space was BioCryst back in 2021. They -- I think what was important about that was obviously, it was an oral therapy. But what we've always said that BioCryst did a particularly good job of was activating patients. And by making them aware of the drug post approval in a fairly robust fashion. And that's -- and that really, from their perspective, overwhelmed the fact that at approval, at least physicians didn't have a lot of enthusiasm for the drug because of the clinical data. And so they really had -- what they ended up having was a fairly passive physician base, but a really active patient base. Where we think we can actually come into the market and launch is we'd expect that we'll have a very motivated physician base because our clinical data is so much better. And we have -- and again, we've run this to my belief, that sort of the largest clinical trial program ever done in HAE and certainly the most broad. And so we've shown this works everywhere. So I think where we're going to come out is with some sort of tailwind from physicians, who I think are going to have higher enthusiasm. And we also expect that patients will be activated just as they were with BioCryst. And so all in all, I think the numbers are different on the BioCryst launch. I mean, because prophylaxis just has fundamentally different economics. But I do think we believe that we can have a pretty robust demand-based initial availability of the marketplace.

Yes. Can we double-click on that a little bit more? It seems like the BioCryst launch was very robust because people were waiting for that for a long time, and people have been waiting for this new treatment option for a long time to have a pill in the pocket that could aggregate an attack. So I heard you say that the prophy options, we've gotten more of them and yet they still leave some attacks. How many attacks are actually treated? And is there room for that number to go up? I know -- and then how does that play against new prophy options and how they might be adopted? And it seems like there's a couple of moving pieces here. Which of these will offset the other? And what will happen to the overall size of the on-demand market opportunity?

Yes, it's a great question. Yes, and that really is a crux of the issue, right? The -- yes, so -- and it's kind of multipart. So again, prophylaxis is -- if you look at the data from all the prophylaxis players that are out there, whether it's Phase II or Phase III, they tend to show very high attack rate reductions. And so you're probably talking somewhere in that 85% to 90% in the clinical trial setting. But honestly, 10 years ago, CINRYZE was a pretty good drug. It was probably -- it was in the 70s, I think, in the clinical trial and in real world, it kind of did better. And then Takhzyro has been on the market since 2019, and that's a very good drug, and that's probably 85% or 90% attack rate reduction. So my point is in the clinical trial setting, they all highlight these efficacy rates. And they're very respectable. I'm not being critical at all of them. But I think what it misses the fact is that having attack rate reductions and being attack-free are actually 2 different things. And when we look at the space, what we find is that -- and we've done some studies on this is that only half roughly of people are attack-free for what I would describe as any substantive period of right, maybe 6 months or something. And the rest vary between reasonably well controlled and actually quite poorly controlled in some cases. We put out some data last year that was an analysis of patients in the HAE space generally. And what we found was that the market kind of breaks into 3 pieces. There's people who treat on-demand only. And what we found was that they're having about 14 attacks a year -- treated attacks a year. And then we found that the prophylaxis world that kind of broke into 2 pieces. There's a portion of the prophylaxis world that's quite well controlled and maybe they're having 0 to 6 attacks a year, kind of a half attack a month, very well controlled. But then there's this other part of the prophylaxis market that despite being on prophylaxis, these people are actually still having challenges and can be quite poorly controlled. The average rate of attacks in that population we looked at was 22%, I think it was. It was actually 50% higher than in the on-demand-only population. Now they have fairly severe disease clearly. And so their challenges remain. In fact, they're the highest frequency users of on-demand of anybody. If the highest number of attacks we found at all was some person, who was on Takhzyro and still having 10 breakthrough attacks a month, 120 attacks a year. So the point is you're right. I mean a lot of these prophylaxis therapies are coming and they're -- the efficacy is unquestionable, but it's not -- it doesn't necessarily lead to the inference that people all draw from it, which is that these folks are going along and really not having attacks. That's actually fairly uncommon. And we don't really have time to dive into why. But it's kind of a multifactorial reason why these folks are having breakthroughs. And some of it's disease state and some of it's adherence and some of it's some other things probably. So that comes back to the question -- part of your question, which was what's going to happen to me on-demand space. And again, our broad viewpoint is none of these attacks really -- none of these prophylaxis therapies in development are going to meaningfully change that attack-free rate for people. We just don't -- we don't see the kind of efficacy -- we think there's probably some upper limit of efficacy for whatever reason, and that's why. So it has -- again, I'm not being all critically this prophylaxis therapy. Some of them are really good. It's just the fact that you bump into some upper limit for whatever reason. And so it seems like you're almost always going to need on demand. And again, we've just shown multiple data sets. We actually put out some data also Western Allergy that showed people on prophylaxis. We looked at both Takhzyro and Orladeyo. And they were having right around 1.8 attacks a month in our study on average. So -- so again, so that's almost 24 attacks a year for people that we've seen. So I guess my point is we continue to have high levels of confidence about the attacks. Now sorry, I know this is a long answer, but going to your last part of your question, which is what's going to happen to people in the world and what do they treat now. You hit on the head one of the key points, which is right now, it's commonly accepted about 2/3 of all attacks are treated. Now that's -- some of that's because maybe not all attacks need to be treated, but a large amount is because the burden of treatment in many cases, is assessed by the person living with HAE to be greater than the benefit of the treatment. Firazyr is an efficacious drug, if taken early, but everybody knows they don't take it early enough. And on average, it's been shown in multiple studies that they wait 3 hours or more to treat, which is entirely too long. Why do they do that? Firazyr hurts -- it's not -- obviously, the needle hurts, but it's -- as it disseminates it burns, it's very acidic. It causes almost uniformly an injection site reaction for people that can be quite painful and last for several hours. And so it has a lot of challenges. And that doesn't even set aside the fact that it's just hard to carry. I mean it's a prefilled syringe, either you assemble it and it's long or you don't assemble it and it's in a box, it's hard to carry. You can't leave your glove compartment, right? You can't kind of have it in your office draw. And so the problem is for all these reasons, not enough attacks are treated. What -- and again, and maybe that's 2/3, there's actually a really high-quality Italian study that showed that only about half attacks are treated. So the 2/3 may actually even be aspirational. In contrast, in our open-label extension, right now, we have people treating right around 85% of their attacks. -- again, maybe that's -- there's probably friction in the real world that you don't have an open-label study. So maybe they wouldn't treat 85% in the real world. But my point is they should definitely treat more than 2/3. And so somewhere in there is the natural rate of treatment, which kind of to wrap it up for you is going -- we think it's going to accrue to us. And if people go from 2/3 to 80%, they'll be better and that obviously has implications going forward for us from that commercial standpoint.

Super helpful perspective. So can you maybe help us shift gears and talk about the other side of the revenue equation, which is the cost to treat these attacks. Obviously, they can be quite disruptive in the real world and the treatments that are currently commercially available aren't cheap. So how should we think about -- or how are you thinking about obtaining value for the value that Sebetralstat brings?

Great question. The -- so let's see. So the landscape today in HAE is therapies range from Firazyr, branded Firazyr is sold at something over $11,000 a dose nowadays, by which I mean one syringe. And then the other therapies that are out there, Ruconest, Berinert, Kalbitor, on a per vial or per syringe basis are lower priced, but you tend to need multiple vials to treat attack. And so actually, if you look at them on an equivalency basis, equivalency of to one syringe of Firazyr, they're actually much more expensive. They're all kind of mid-teens, $15,000, $16,000 range. We expect that we can price Sebetralstat somewhere in that range. We are comfortable it can be at a premium product because of the value it provides. And we think we don't have to be heroic in terms of pricing expectations, and we'd obviously like to maximize access. So somewhere in that range is probably where the reasonable level sits. Even at those kind of prices, though, the pharmacoeconomics are fairly compelling. On-demand, people using on-demand nowadays use on-demand because they like it, and they're going to like it even more in the presence of Sebetralstat. But even if you're using 2 doses a month of Sebetralstat, you're still paying a whole lot less for that than you are for prophylaxis. And so certainly, there -- when you think about this in comparison to the other therapies out there and the pricing they use and the fact that, again, coming back to the conversation a couple of minutes ago, most people are still using on-demand on top of that. It's not hard to see where the value can come from this therapy from the payer perspective. So but I want to point out that's not really the central point of the argument. We've had a lot of payer meetings. What I can say is based upon those price ranges and based upon the data we've generated and the value-based arguments we can provide, we're very comfortable that they're not going to be challenging us at all in that range. We expect our formulary access to be comparable to everything else out there. And so we really don't believe that pricing in that vicinity is going to put any unnecessary roadblocks in the way in terms of access for patients.

Okay. Very good. So how should we think about how the product itself will actually be presented and adopted, right? This is -- I keep coming back to this notion that this is something the community has been waiting a long time for. These aren't infusions that they need to stop what they're doing, leave whomever they're with, go find a place and infuse. These are pills that they can put in various places. And I'm just wondering like 2 things. What does that look like? And then what does that -- how does that influence the shape of the launch curve? Will there be like big upfront purchases by patients to stock these pills -- can we talk about that a little bit?

Yes, sure. Yes. This is a fun part, the box. So how far we've come from Phase II data. So the drug will be sold in a multipack, Firazyr, just by comparison, Firazyr sold in 3 packs typically. So each refill gets 3 syringes of Firazyr delivered at once. And we're not really talking about how many doses we'll have in the box. But it will be a box of reasonable size. And the box will contain a series of the tablets, which will be blistered obviously, because they have to be. And then they're contained in a sort of a protective wallet, if you will, maybe most of the size of a credit card, not 2/3, maybe 3/4 the size of a credit card. The idea being here that -- let's come back to what I said you can't do with your Firazyr. You can't leave any guff carbon, you can't bring your backpack, whatever. The idea here is that this becomes something that from a form factor perspective, allows you to have it handy, when you need it, right? A lot of the time, attacks aren't treated nowadays because you're at work or you're sitting up here and you have an attack come on and your Firazyr is generally a home and refrigerator. And so you have to go -- and most people like to treat at home because -- and that's, again, coming back to all the drawbacks of Firazyr. We envision a future where that's not the case anymore, right? You're sitting in your office and you feel an attack coming on and you do know when there's attack coming on, and you reach in your pocket and you pull it out or you pull it out of your desk draw or you get it out of your console in your car. You can put this in the nooks and crannies of your life where attacks may occur and where nowadays you have no means to treat them. And so the idea is again, it's protected, so you can leave it there for a while, right? You can sit in your glove compartment safely and not be damaged. You take it out, you open up the wallet, you pop it through the foil. Again, you don't even need water to take it. It's very, very slippery and you go about your day. And so it really -- it starts to feel a lot more like when you have a headache or something coming on and you take a Firazyr. I mean it really transitioned this into a much simpler, straightforward, more discrete, if you will, way to treat, which again, in and of itself will improve treatment rates.

Okay. Interesting. Anything else that we should think about as we model the launch and try to envision the trajectory besides that aspect of stocking?

Yes. Well, certainly, we will have a quick start program. So a lot of the initial volume will be going through that, and so will not be sort of publicly available information. But again, we have a whole team that's dedicated to putting people on getting people on to commercial supply as soon as possible. So I think the early parts of launch, I think the 2 things people should be aware of is there won't be a lot of data available at all. IQVIA doesn't really track the space all that well, plus Quick Start kind of avoids the whole IQVIA pathway anyway or IQVIA reported pathway anyway. The -- in terms of uptake curves from a volume perspective, we think Firazyr, ORLADEYO, the kind of standard launch curves look reasonable. The key difference being, of course, once you're on ORLADEYO and assuming you get on paid drug, your -- the revenues become kind of a steady state, like a constant number. Certainly, when we're dealing with small ends in the early part of the launch, you're going to probably see a little more of a jagged curve just because people have to refill. It is essentially right. And so at some point, the number of patients overwhelms all that and you get to more of a flat line, but it could be a little jagged early on. In the commercial day that we announced this morning that we'll be holding in 2 weeks, we are going to talk about, again, some of these metrics that we'll report to people to help them understand the launch. We know that the burden is on us to help people understand how this is going and to make sure they have sufficient information to be able to analyze this compared to expectations. So one of the things we'll talk about in Commercial Day is how do we expect the launch dynamics to go, what would be useful parameters that we'll report to people in the early stages of the launch versus a few months into it versus next year. And so we'll -- we'll try to lay out for people how we think that information should evolve to give them what they need to be able to recognize where they think this stands.

Super. Anything we didn't touch on that we should note before we break?

Just the last mention that we've got a whole bunch of other regulatory filings underway that we're moving forward at the same time. So PDUFA is obviously the first and certainly the most important. But again, we're filed in the EMA. We expect to be launching there before the end of the year in at least one country. And then we also expect to be launching in multiple countries next year. We've got filings in the U.K. We've got a filing in Japan. We've got filings in a number of other territories. So this will be a commercial story that I think fairly quickly broadens globally just in the way we've always said it would. And so I mean, Sebetralstat is a kind of drug we think that really deserves to be a global product. I mean it's everything about it, I think, can address patient needs around the world in a way that other therapies really can't nowadays. And so we're committed to taking this far and wide and ideally bring a benefit to people living with HAE everywhere.

Fantastic. Thank you for the update, Ben.

Always good to see you, Joe. Thanks...

Likewise.