Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos, a biotech analyst from Cantor. And with us, we have KalVista, a company we cover. I'm pleased to introduce Ben Palleiko, the CEO of the company. So welcome, Ben. And let's just start off with a brief intro of yourself and a description of KalVista for those who are not familiar. First of all, Pete, thank you for inviting us here today. Thank you to Cantor for this conference that they hold. And we've attended for many years. These are all great jobs [inaudible]. Can you hear me now? Here we go. Good. Thank you for inviting us today. I appreciate all the support from Cantor over the years, and thank you, as usual, for inviting us to this conference. KalVista Pharmaceuticals is a newly commercial-stage pharmaceuticals company. This is the first time I get to say this at an investor conference, actually. Our drug for acute treatment of acute attacks of hereditary angioedema, which is called EKTERLY, was approved back in early July by the FDA, and it was launched immediately afterwards, and actually, we closed our first fiscal quarter as a commercial company on July 31. In addition to that, we have been pursuing global approvals for EKTERLY, and also in July, we got approval in the U.K. MHRA approved the drug for treatment of attacks as well. And that'll be launching next year in the U.K. And also at the end of July, the CHMP and the EU recommended approval. That formal approval will come in October. And we're currently pursuing approvals in four other countries as well. So we are on the cusp of being a global commercial pharmaceutical company, but again, with the initial emphasis. And right now, with a very active launch effort ongoing in the U.S. Ben, so congratulations on the recent approval of EKTERLY. You're approved for acute HAE attacks. Just briefly, just go over the study and the data that supported the approval. Sure. EKTERLY has been the subject of actually what I think is probably the largest clinical trial program ever conducted in HAE, which is something I think we're quite proud of. We've run a number of studies that were among the largest actually ever executed in HAE to get to this point, all of which showed very robust and very consistent data. And I think led to a terrific label for us and also illustrated what is critically a pristine safety profile. In addition to the two trials of phase II and then the phase III that enabled approval, we've run an open-label extension study, which is really important because both that and the phase 3 were effectively open to essentially anybody with HAE. The studies included both adolescents as well as adults. And adolescents have a particularly high unmet need because of the lack of some of the options available to them, but we also included patients who use long-term prophylaxis. Around two-thirds of people with HAE nowadays use prophylaxis in addition to on-demand therapy, and so that group is very meaningful, and importantly, we studied all attack severities, which range from mild to very severe. We studied all attack locations, abdominal and peripheral, but also importantly, laryngeal. Laryngeal attacks are pretty infrequent in this space, but they're obviously a major concern for people living with HAE. I believe we've now treated the most laryngeal attacks ever done in a clinical trial setting, and so we've shown very robust data, and so coming out of those studies was an extremely robust set of data that, again, was very consistent. Really, it helped us as we got to the launch because we can go into physicians' offices and even talk to patients about how this drug, despite whatever their particular form of HAE is, if they lean towards some type of attack, if they have a lot of laryngeal attacks, if they use prophylaxis or not, whatever their circumstance is, we've probably developed and likely presented data that shows in a statistically significant way that EKTERLY has benefit for them. Okay. You know, the treatment guidelines for HAE say treat all attacks as early as possible. A lot of patients don't follow those guidelines, though I've heard over and over from KOLs, they try to press the patients to actually follow the guidelines. And so can you just discuss the delay in treatment, sort of the reasons behind it? And what does your phase III OLE data sort of suggest about changing patient behavior with EKTERLY? Right. On demand, until EKTERLY was approved, there were four on-demand therapies available to people living with HAE. Two of them are subcutaneous, although one of them has a black box, and the other two are actually IV delivered. Far and away, the market leader, though, is a drug called Firazyr. It went generic about five years ago. The generic form is icatibant. That is probably 70% market share overall. All of those drugs are very efficacious when taken properly, but to your point, the problem is that people don't typically take them properly. The IVs kind of speak for themselves in terms of the complexity of a self-administered IV and the challenges of just carrying it with you, but even with Firazyr, the subcutaneous versions, those are very challenging therapies for people to use. It obviously hurts because it's a needle, but also it's very acidic, and so it hurts as it disseminates. It almost 100% of the time virtually causes an injection site reaction that actually adds to the pain of the attack for people. And of course, the form factor of a subcutaneous PFS is hard to carry. You can't really store it easily, right? It's got a lot of challenges. And so what's commonly known in the space, and this is sort of where you're going to, is despite the fact that HAE treatment guidelines call for people to consider treating all attacks and to treat early, what happens is they don't do either of those things. And it's commonly known that half probably of all attacks, maybe a little more, are actually treated at all by people. That's not that these attacks don't need to be treated. It's that they just choose not to in many cases. Also when people do treat, it's commonly known that they wait entirely too long. HAE attacks should be treated within the first hour, certainly the first couple of hours, right? Very early intervention matters in this space. The name EKTERLY is actually effectively a call to action to people to act early. I mean, that is the whole basis of the thing. But despite the fact that everybody knows this, people don't. If you look at the data sets, you'll see that commonly people wait three, four hours or longer, at which point the trajectory of the attack has been established. If swelling has started, none of these therapies actually make the swelling go away. They just terminate the attack. Once you have swelling, you're going to deal with all the challenges and the pain that comes from that swelling. Again, the very important idea of EKTERLY is consider treating your attack when you have it as soon as you can and treat it early. Again, against the data there I just mentioned, people waiting three or four hours to treat an attack, in our open label extension, we've shown that people are treating within less than 10 minutes after attack onset is exactly what they should do. When they do treat, we've shown that they get very rapid symptom relief. This isn't a primary endpoint, but one of the data points we gathered in the open label extension is called time to end of progression. People who treat are actually having end of progression of attacks in less than 20 minutes, which is shockingly fast. In fact, until we demonstrated this data, people thought that oral therapies couldn't be that fast. The phase 3 trial showed that at the approved dose, people had initial symptom relief in about 1.8 hours, but the open-label shows that in general, actually, it's more like 1.3 hours, which again is extraordinarily quick, and so what we've really been able to develop here, and I think this is why EKTERLY is so attractive to people, is a therapy where people are getting absolutely injectable-like efficacy. I mean, it is certainly on par with the approved therapies with a very benign safety profile with all the benefits of having a tablet that lets them treat more attacks earlier. Excuse me. So sort of staying on this theme, when you do go to your website and you go to the publications, you have 10-15 per medical conference. And you've just accumulated a ton of and have done a ton of analyses on the data that you have from the phase III, the open-label study. And again, staying in this theme, how do you think it's actually going to play out in the real world? Are you going to get patients just treating really quickly, single tablet versus two tablets, which I believe they have the ability to do, at least according to the label? And so how do you sort of see that playing out? And just remind us the current treatment rate for the injectables. Sure. To Pete's point, we've generated just vast troves of data here for EKTERLY. And it's been very high-quality data. I mean, we have always published all the details of our trial designs. Every shred of data we've generated effectively has been presented at the conference. And the trial protocols, I think we've been very open about distributing them and really making people aware of how we conducted the study, which is intended to be in accordance with how people should really treat in the real world. And I think that's a critical differentiator for us, is a lot of clinical trials that are conducted historically and even ongoing are designed to sort of create these kind of clinical outcomes, right? They're trying to get to a target number or something. We really conducted this trial to show people that this is how you should treat in the real world. And if you do, this is the results you'll get. So I think we've been very proud of our clinical trial design as well as the execution. I think the quality of the studies is just demonstrated by the fact that the phase two results were printed in The Lancet and the phase III in The New England Journal of Medicine, right? So the two top journals in the world effectively really saw enough importance to the data sets we generated to include them in the publication. So I think we're very proud of that. And then again, to your point, Pete, we have a terrific medical team and a great publications group that has gathered these data sets developed by also what I think is a terrific clinical development team and turned them into interesting, actionable insights for people. And so like I said a few minutes ago, the result of what has effectively been the largest clinical trial program in HAE has yielded these reams of data. So as we go out to physicians, we have been able to, and we have consistently talked about, here's all the data overall. Here's how the subsets look, right? Here's how people on prophylaxis perform, on specific prophylaxis. Here's how they perform. Here's how laryngeal attacks perform. Here's how adolescents do. And so as we got to the launch, being able to go out for a period of years to this community and really educate people on the disease and our treatment of it, I think has set us up really well that when we show up now with EKTERLY approved, people have great confidence. The data has been very clearly presented. The data has been very robust. We've been very open about how we share it to people. We've talked about how people should treat in accordance with the treatment guidelines, right? Treat early. We've shown all the benefits of that, and so as we got to the launch, I think it gave us a great degree of credibility and trust with the physician community that, to your point, has led to what I think is a fairly high degree of enthusiasm among physicians across the board, and ideally, it will reflect itself as we move into being a commercial company. In terms of all these other details you ask about, the approved dosing is 600 milligrams on the label, right? So that is one of the two doses we studied in phase three. People typically are going to dose at that level. It's a very, the label in general is very straightforward and simple, which again is a great element for people to be able to sort of understand as they go forward, but I think the other benefit is, to your point, it does make it easy for people to think about how they might adjust their dosing based on attacks, right? Sometimes more severe attacks may require additional dosing. Sometimes there's adjustments you have to make for concomitant meds, so we do give people the flexibility to adjust, which we think just goes to the fact that it's part of the benefits of this therapy. So you have the open label study going. Some patients have taken multiple doses, I assume. Oh, yeah. And so I guess part of the course of an attack is you start to swell. And then when you do give some type of therapeutic, whether an injectable or EKTERLY, they stop. But it's not an immediate reduction in terms of swelling. It takes a little bit of time to resolve. Are you finding that they're actually taking it earlier and more often? So in other words, I may have an attack, so I'll just take it because I do know that it'll prevent me from getting to a certain swelling point. And so in other words, how is it going to play out in the real world? Yeah. Swelling, attacks don't progress linearly. And swelling is not typically the very first symptom of an incipient attack. It does take a little bit of time typically for that to really start to escalate, which again comes back to this whole concept of early treatment. If you treat within the first hour or so, in most cases, you're probably not going to have substantial swelling. Now, again, there are severe attacks. Abdominal attacks can be harder to feel. I'm not trying to say that's a universal statement. But as a general comment, attacks will typically escalate. And so early treatment is going to unambiguously be better for people because the symptoms will not be as severe in most cases as they will be if you treat later. Again, this is why the treatment guidelines say people should treat early. Like I said, our open label study, and we do have people who've treated 50, 60, I think maybe even more attacks at this point. We have people who've got tremendous experience with EKTERLY. And what we've seen consistently is that people do treat vastly earlier in the presence of EKTERLY. Like I said, in our open label, they're treating in something less than 10 minutes on average. I think the adolescents, I haven't looked at this data in a little while, but the last time I looked, adolescents were more like five minutes or less. I mean, really, really quickly, which is really important because adolescents today wait the longest time of anybody. Partly that's because Firazyr is not approved for usage in under 18. So their only real options are IV therapies. If you look at the data nowadays, adolescents historically wait more like eight hours to treat an attack. But again, that's a function of the fact that the therapies are really just poor. The options are poor for them right now. But adolescents treat even faster in our study. And yes, I do think that will carry through in the real world. I mean, the open label is about as real-world-ish as you're going to get. And so we'd expect that cadence to continue. And then in terms of the other sort of attributes around the trial and how real-world usage will come to pass, again, people know they're having attacks. And so you asked this question about, well, will they treat maybe what aren't attacks? That's a common concern. But again, it's a lifelong disease. It's genetically derived. People frequently, typically, often will have family members that have it. So they're very well-versed in their disease. They know their bodies. They know when they're having an attack. In our phase II, we actually, because no one had ever done this before, we actually had an interim step in our study, which turned out to be just an unnecessary delay for people, where if they thought they were having an attack, oops, sorry about that, they had to call their physician first and confirm there was an attack before they treat, and that was requested for us to insert in the protocol because it was kind of a novel thing at that point. What we found was that nobody wasn't having an attack. It was 100% actual treatment rate. So physicians never said, "No, this doesn't sound like an attack." So we actually removed it from the phase III because it's just unnecessarily delaying treatment. So I think that's a valid question: are people always going to be treating actual attacks? I think the vast evidence out there suggests that people know when they're having them and that what they are treating, they're not treating unnecessarily. I mean, why would that be a concern in terms of treating unnecessarily? If you're just going to stop a possible attack, why move forward? So you said it would be a concern. When you wrap it up into the safety profile and what's on the label, why would that be concerning to you? I can understand the payers. Why wouldn't you? Oh, it's not at all. In general, therapies should be used for the cause that they're approved for, and so we would never go out and encourage people to just sort of take this randomly every time they feel it. But again, I think there's a bunch of things that happen whenever you launch a new drug that are theoretically concerning, but practically are utterly unconcerning, and this is probably one of them, right? The rate of whatever you want to call it, false treatment, I suspect is extraordinarily low, and I wouldn't expect it to go up a lot. I think what's really happening is the converse nowadays, where people have these attacks. They don't treat them on purpose. They don't treat them on purpose because the therapeutic options are poor or because they don't have it with them because they're traveling or they're at work or whatever and they can't treat. It's much more like the real problem in the space today is involuntary, if you will, lack of treatment, not excess treatment. I would not expect this to shift to the whatever, to the unnecessary treatment side. I think what's really going to happen is people should just absolutely treat more attacks. They will now. They'll do better. That's a great outcome. Okay. All right. Just sort of we can talk briefly about the label and what differentiates it, like maybe one minute relative to approved agents. Yeah. I I think the key thing of the label is it's extraordinarily clean. Our CMO said he's never seen a safety profile like this, and he doesn't expect to again. There's one item listed that's greater than placebo. I mean, it's just shockingly simple. The approved dosing is 600 milligrams per attack, which is exactly what we thought it should be. It gives a really high level of plasma kallikrein suppression for a long time. I think it's just unquestionably a terrific dose for people to take. And then there's minor adjustments for DDIs, right? Certain sort of things. But that's really all there is to it. I mean, it's a very, very simple label, very patient-favorable, very understandable for everyone. And so we couldn't be happier with how that worked out. Okay. And I guess let's move forward to the market size. In terms of the U.S. and Europe, where do you peg HAE prevalence? It seems to be, based upon all the data that's been generated, that HAE rates are roughly similar around the world. You find it between, and again, because it's a small number, these estimates kind of vary a little bit, but between one in 30 to one in 50,000 people seems to be kind of the way the math works. We're not aware of any racial or ethnic or any other kind of differentials anywhere else. It seems to be very, very consistent. Okay. And then in terms of being segmented into two markets, acute on-demand and prophylactic treatment, physicians and KOLs that we've spoken to, it's pretty clear-cut. All new patients will likely go on EKTERLY, and the majority on injectables, meaning for acute treatment, will switch eventually. So how does that actually fit into the landscape for patients already on long-term prophylaxis? Sure. This is only U.S. Ex-U.S., the world is almost entirely on-demand only, and it's probably going to stay that way. There's very low rates of prophylaxis. So I'm just going to focus on the U.S. part. In the U.S., people treat two ways. About a third treat with on-demand only, and about two-thirds treat with prophylaxis plus on-demand. It is important to note that despite the fact that there's very good prophylaxis, and there has been for 10 years, people still have breakthrough attacks. And so virtually everybody with HAE has a prescription for an on-demand. It's probably 90%+. What we have found over time is that the rates of attacks for people—we did a survey recently—and what we found is that people who only treat with on-demand are probably having something in the order of 14 attacks a year, kind of what's that? A little more than one attack a month. Counterintuitively, perhaps, we actually found that people using prophylaxis have higher rates of attacks. Now, that's probably driven by the fact that you've got some number of people with very severe disease who have very high attack rates. Just one anecdote, we did a survey, whatever, six months ago, and we actually found the person we found who had the highest number of attacks was actually a woman who uses Takhzyro, who, despite being on Takhzyro, was having 10 breakthrough attacks a month, 120 attacks a year. So an astonishing number. That clearly pulls the average up. But the average, actually, in the prophylaxis space from our survey, was more like 20 attacks a year. So again, somewhat counterintuitively, it's the higher rate. But it's probably driven by the fact that people with more severe disease go on prophylaxis. People talk a lot about attack-free rates, and there's certainly a population that has very infrequent attacks, right? Half attack or less per month. It does seem to be less than a majority of folks. Again, part of the challenges of HAE is that it can be somewhat episodic, right? Attack rates can flare or decrease over time. I know one person, not to tell too many stories, but who has HAE, and his baseline attack rate is right around two attacks a month. So he's an on-demand primary user. He was talking to me one time, and he said how he'd been going through a very stressful period. Triggers for HAE are varied. He was going through a very stressful period, and all of a sudden, he said he was having seven attacks a month. So the point is, even baseline attack rates are useful, but HAE does kind of wax and wane over a person's life. And so you can be attack-free for a long time, but then something happens, and all of a sudden, you're having more attacks. The point here is, though, that the rate of attacks is pretty consistent across the population. That means that the usage of on-demand therapy, despite the fact that there's very good prophylaxis over the past few years, hasn't really declined at all. If you look at the number of doses of on-demand issued every year, it's been pretty steady in the low 80,000 number, going back at least to 2019, which is the earliest year we have data for. I guess all of which leads to the fact that certainly in the U.S., even despite the fact you have a lot of people on prophylaxis, you still have a significant need for on-demand. That need seems to not have been reduced at all by the fact that the prophylaxis exists, and that's why I think we're very comfortable that even looking forward, there's going to be a continued need for this and maybe even greater use of on-demand going forward for people given the benefits of the oral therapy. Okay. We have about five minutes left. Let's move to the launch. How are you approaching it in terms of targeting physicians? Are you focusing on centers of excellence? Yeah. Yeah. So we were working on launch almost two years ago, and we've been, again, coming back to all that medical education, right? Right after we had the phase III data, we started to build a medical team. That was in 2021. So ever since then, we've been out talking to people by phone and educating them on the dataset. As we got closer to the launch, we started to build the commercial team about 18 months prior to approval. We had the field team out starting to meet with physicians earlier this year, Q1 of this year, so fully four or five months in advance of approval. The physician community is right around 2,000 docs in total, about 200 of them, so 10%, right about half the scripts. Another 800, right about 40% of the scripts. So it's really concentrated. 90% of scripts are written by about 1,000 physicians. By the time we got to the approval, we had actually called on effectively all of those, virtually all of the tier one and tier twos, and maybe 95%-96% of the tier three. So we really got out far and wide to meet this community. Again, we were armed with a truly outstanding dataset. And as a result, I think that positioned us really well to go into the launch with a very high degree of physician enthusiasm, and I think is going to start to show here as the prescriptions start to occur. Importantly, even though you can't obviously promote a drug to people living with HAE prior to approval, we also, however, did have a terrific and do have a terrific patient marketing team. Actually, in advance of approval, we'd already built a database that was over 3,000 people. Now I checked last week, and it was over 4,000 people now. That's almost half the entire HAE population. I think we've done an extraordinary effort in terms of certainly making physician awareness high and giving them great levels of comfort in advance of the approval. Since approval, I think we're doing a really terrific job of patient outreach and sort of continuing to build that awareness. It helped us that 10 days after our approval, the bi-annual HAE patient summit actually was held. We were able to go down to that summit with a brand new approval and meet 1,400 people for a couple of days. So we're the beneficiaries of, obviously, what we believe is a terrific drug, of a great clinical development program, of a lot of work for two years prior to approval to get ready to launch, and then of some lucky strikes like having that patient meeting happen 10 days later. Nice. So part of the patient access is a Quick Start program. Can you just give us a sense of how many patients have actually accessed the program? We will be reporting that that was a good year. I'm going to take full credit. We had a fiscal year that was off calendar, and so we closed our fiscal quarter on July 31st, so in the next week or so, we'll be presenting our first-ever commercial results, which will include some number of data, probably just start forms, frankly, through July 31st. We'll have some other metrics as well, but then after that, we're going to switch to calendar quarters, so we'll also be giving an update in November on the data through September 30th. Okay. And then in terms of the OLE patients, have any of them switched to commercial scripts or? Yes. So we have the OLE is still ongoing, so people have to come off that to go on to finish up that to move on. We do have an EAP, but I don't want to overestimate the size of those. I mean, HAE is a small indication. The open label's less than 150 people total. So you're talking about, and many of whom are ex-US. So you're talking about dozens of people, not hundreds of people here. My hope would be that rather than I get asked all the time about this kind of bolus, and I'd be perfectly content with a relatively high level of demand that grows consistently. Nothing makes me happier than to see those patients be subsumed into a larger number as opposed to reflecting some immediate jump that stops. All right. We're at the end of our time here. But if we're sitting here 12 months from now, what do you want to say that you accomplished to create value for the company? Our goal, and we've been saying this for several years, is to have the largest and fastest launch of an HAE drug ever. I think we're well on our pathway to that. Again, with three approvals issued or pending and another four to come in the next six months, we can reasonably be a commercial company in nine countries within nine months of launch. And so I think that's a great objective for a company like ours, and I'm very pleased to say I think we're well on our way to doing that. Okay. Well, thank you very much for attending our healthcare conference and doing the Fireside Chat. Always nice to see you. Yeah. Congratulations on the progress. Thanks again for having me.