Well, good morning. Thanks for joining us at our 46th Annual Healthcare Conference, day 3. I'm Stacy Ku, part of the biotech team with my colleague Vish Shah. We are very happy to be hosting Ben Palleiko, CEO of KalVista on our fireside chat. Really impressive early launch for Ekterly, with some opening remarks. Maybe talk about how it's progressed, initially versus your expectations, and we'll drill down from there.
Sure. Thanks, Stacy. Thank you for having us today. Thank you to Colin for this conference, which is always a terrific thing to attend, so really excited to be able to talk to you about KalVista more. As most of you probably know by now, KalVista, last year in July, got approval of our first product, which is named Ekterly. It's for the on-demand treatment of hereditary angioedema attacks. It is the first and only oral therapy for treatment of this disease, which is important. Later on the year, we would follow it up with approvals in 6 other territories. The commercial launch so far has been going quite well in both locations where we launched it.
As you reflect on what we've seen so far for Ekterly, what commercial preparation and really the hard work you've done around awareness has helped with the early adoption trajectory?
Yeah, you hit it on the head. T he fact that Ekterly has done so well on the initial launch is due to the fact that for years, several years now, we've been out talking to physicians and the community at large about it. Ever since we had the phase 2 data, which was back in 2021, we, following that, we started to build out the medical team. Our Chief Medical Officer joined us, and he led this terrific effort that educated physicians on the data for many years after that, followed by the phase 3 results. We started to build a commercial team. This has really been a function of, first of all, extremely good and consistent data across the board. We ran the largest ever phase 2 trial in HAE.
We ran the largest ever Phase 3 trial in HAE. We ran the broadest, most inclusive trial ever conducted in HAE in our Phase 3 and our open-label extension, and we've been able to communicate those results to physicians and the patient community over time. The reason Ekterly has done so well is because, first of all, we've shown that it has tremendous applicability across the space. The efficacy has been terrific and consistent. The safety has been pristine throughout the program. We've shown that a lot of things that people believed about HAE just simply weren't true, right? It was believed that attacks on prophylaxis didn't occur or we've shown that to not be the case. Most recently, we showed that attacks in pediatrics, young kids occur at much higher rates than people expect.
What we have done that has also benefited us is we've just educated the community consistently in a very data-focused fashion and really shown ourselves to be what I would think really is the thought leaders in the space in a very important way.
Maybe talk about the KOL feedback you are hearing, especially 'cause you just came back from Q1. Is the drug doing what it's supposed to be doing? Maybe just help us understand that feedback.
Yeah, absolutely. F eedback across the board has been extremely positive and consistent. We had a large team at Quad I last week, including Nicole Sweeney, and met with a bunch of physicians there. The learnings were that physicians are continuing to get increased comfort with Ekterly. Right now, they've actually prescribed it to people in their practice, had good feedback from them. What we've heard is that the efficacy is all everyone would like it to be. Again, the safety profile continues to be fantastic. They're really starting to see them broaden out their willingness to prescribe this to an even larger proportion of their patient-based.
All the patient satisfaction and physician satisfaction based on some work we've done, and we'll present this at a future conference. It borders on 90%, which is tremendous for a drug that's only been on the market for roughly 7 months now.
Given that historically HAE patients have been notoriously sticky, are you surprised by the level of patient demand, and where are these patients coming from?
Yeah.
Where are they switching from?
Yeah. I don't know. Certainly the launch has outperformed our expectations because for that reason, we did think there'd probably be a little more education, a little more time required to do so. That comes back to how I started, which is we did so much of that in advance, and there was such a high level with Ekterly when it came out that w e crossed a lot of those hurdles much quicker than we thought we would. The conversions to date really mirror the market with one exception. W e're pulling people from all the on-demand therapies roughly in proportion to their market shares. The only exception being actually more so Ruconest patients than we thought we would.
It's a relatively small share of the market. They're probably repeatedly more sticky than most. To the extent there's been any surprises, it's been the extent to which they've had more interest. On the prophylaxis side, we're seeing people who are adding on-demand, who use prophylaxis, typically mirror the market, which means they're mostly TAKHZYRO and Orladeyo.
I know many of you are all familiar with Nicole Sweeney, Chief Commercial Officer, and in the crowd, rarely do we have consultants praise the patient support services hub, that is the feedback that we're getting these days, and we expect this unanimously positive experience is making access seamless. Ben, if you could, just provide some additional metrics around the QuickStart program and the ongoing peer dynamics.
Well, with regard to patient support services, your point is well taken. That's really a key component of a successful launch. It's a, it's a, it's an absolute minimum requirement, and based upon the feedback you've heard and we've heard very consistently, we've gone well past that. We have a really experienced group. They're super high-quality folks. T hat they're getting a lot of credit to date from from both physicians and payers. With regard to QuickStart to your point, a lot of their work relates to taking these these prescriptions that come in, including with QuickStart, and then moving those folks on the pathway to commercial coverage. To date, I don't know if you're asking me to explain how QuickStart works.
That's right. Exactly.
Okay.
How does it all work when it comes to?
Yeah.
paid drug, QuickStart
Mm-hmm.
How does that maybe walk through an average patient experience?
Yeah, let's walk through it. That's great. A person goes in their physician and decides they wanna switch to Ekterly. Virtually all these are switches. There's very few people who are de novo patients in the HAE space. They will get effectively 2 prescriptions. They'll get a standard commercial prescription for Ekterly. It'll indicate some sort of initial quantity fill that's on average nowadays been right around 2 cartons, and then it's typically written as for refill as needed, and the duration of the prescription is most commonly 1 year. That's the first thing they get. The second thing they do is they fill out this QuickStart form, and they give a bunch of information, their insurance coverage.
We ask about some attributes of their disease state, and then that also comes along with the prescription to the hub, to the patient services group. At that point, the team does 2 things at the same time. They process the QuickStart form, which fundamentally means they check with their person's insurance company to make sure they're eligible for coverage, and if they are, they ship them effectively, immediately a carton of Ekterly, so they can start using it right away. At the same time, they start to work with the payer towards moving that patient onto commercial coverage. That typically takes us, for people that are getting onto coverage nowadays, that's typically happening in right around the 40-day mark. It's been in almost entirely to date through medical exception process, which is somewhat laborious.
I would say the team coming back to the services team is doing a very good job of processing those. Once their commercial coverage comes through, they will immediately receive their first commercial shipment of Ekterly. This question has come up before, Stacia, and you've done a really nice job of highlighting it. When we talk about refills, that's not a refill. That's actually the first commercial carton that gets shipped, and then after that, they'll refill as needed. QuickStart is its own independent thing. We don't count that in any dimension or really report that. We start when the commercial coverage launches.
Okay. The clinicians tell us, when they think about payer dynamics around Ekterly, they do recommend to their patient to keep a diary of treated attacks just to really understand the need and whether or not they really do need to broaden their use. Question we do get is around refills and the different dynamics there. The patient decides to use Ekterly and they need a refill. Just help us understand how that all works.
Uh, the, um-
To be just, but to be just more specific, are they have to go back to the clinician, say, "I need a refill?" Is it a little bit more seamless than that? Just help us understand the different friction points when it comes to trying to use Ekterly as needed.
Well, yeah, to the discussion earlier, once their commercial prescription is approved, that's good. That's typically valid for a year, sometimes they're a little shorter. The patient doesn't have to have any interaction with the payer at that point until the next prescription has to be written. They can really just talk to the specialty pharmacy or even our hub can help them to get their next shipment delivered as they need it. It will be completely driven by the patient. On average, what we're seeing is we thought that people would take, based upon prior experience, we thought they'd refill right around 1 carton, and we thought they'd do it right around every between 4 and 5 months on average.
To date, we've probably been, the average is act-- on refills has actually been more like 2 cartons, very consistently. Even as launch has broadened out, it's been 2 cartons, and we're seeing them refill in generally less than 2 months nowadays, so about half the time we expected, which goes to this increased use to kinda ta-- point.
Yep. We've a lot of the education for investors when we first started looking at KalVista is the range and actually the very huge range of potential scenarios for how a patient could be potentially using an on-demand agent. When we survey our clinicians, there's a huge range in the average, but around one attack per month. To your point on the refills, is that how it's trending? Just help us understand that dynamic as it relates to maybe how folks can think about Ekterly use for a year.
Because of where we are in the launch, we're still getting a higher percentage of high attack rate patients, which we describe as people who have 2 or more attacks a month. That's greater than we believe their proportion is in the overall patient population. In other words, we're sort of over-indexing on higher attack rate people. That was always what we expected to happen. We knew they'd be the first ones to come and want Ekterly because they're the ones suffering with the highest burden of disease. To your point, at the, if I was going to estimate, I would say to you at this point, we're probably doing more than that. We will trend over time. Obviously, as you get a bigger group of patients, you trend more towards population.
Even then, I would say to you, our baseline expectation based upon this early experience will be people will use more Ekterly on a routine basis going forward than they have their historic therapies. Just based on some of the data we've seen from our open-label study and some other data we've gathered about patient usage, which seems to go meaningfully higher in the presence of Ekterly.
Okay. You all have spent a lot of time telling us that the demand will normalize-
Mm-hmm.
That it really, the linear patient growth should reflect a more normal HAE patient and we hear you.
Yeah.
We do get a lot of questions around the high burden patients, which we view as maybe a potential patient foundation for you all. Just help us understand what percentage of HAE patients are high burden, and maybe where you are in the penetration of that specific subgroup of patients?
Absolutely. high burden as we define it, that 2 attacks or more a month, is probably in the vicinity of 20% of the patient population. They probably, however, use something more like twice that amount of on-demand therapy. In other words, they may be 35% to 40% of total on-demand usage because they have such high attack burden. We estimated that at the end of last year, we had about a quarter of those people who were transitioning to Ekterly. That group continues to transition Ekterly this year at a higher than average rate. We still think it'll be...
We have a long way to go is the point, is there's a lot of growth left in that population, even though we're certainly bringing them on at faster rates than you might expect based upon their proportion of the total population.
How are they doing, on Ekterly, these high burden patients? Are they finding the satisfaction that's needed to stay on drug?
As a general comment, like I said, this patient satisfaction's been really high. To the extent we've had any feedback on efficacy, or anything really, anything that might lead to like a discontinuation, it's really been sort of a handful, onesies and twosies. There's really been no broad indicators of any challenges of any sort.
Okay. Maybe some of the other questions we get when it comes to the high burden patients is the payer willingness to treat these patients. Sounds like they're well known with a lot of documented attacks. And on an extreme, we do get questions on the quantity limits . Just help us understand how all that works as it relates to payer willingness to support Ekterly access.
For sure. Since we're early in the launch, payers are still getting experience with how their population is going to use Ekterly. We don't see a lot of control by payers as yet on Ekterly usage or access to Ekterly. We do. In this space, however, more broadly, you do definitely see payers, typically to the extent they manage HAE or on-demand HAE, they tend to do it through quantity limits. I will say those policies can vary broadly. We've seen some policies that are pretty tight. We've seen policies that factor by I'm sorry, vary by a factor of maybe 4. L ke, you can see really big swings depending on how that policy is calculated.
Over time, we do expect that payers will move in that direction to try to manage Ekterly in that fashion. That said, to your point, these folks that have high burden disease are well known to the payers because they have a long history of using a lot of medication. We've absolutely seen, even among the payers that are, that seem to be more focused on management of access, that they understand that those patients require more therapy, and they're willing to provide that therapy as needed. We don't think that they're going to dramatically limit anyone's access.
Yeah. As a point of clarification, because we do get this question a lot, one carton would equal about 2 doses.
One carton is 2 doses, yes.
Okay. let's move to the performance we've seen so far. The H2 was impressive, around $35 million in Q4 and $49 million since launch. In the last pre-announcement, talked about the refill revenue being greater than sales, from new patient starts in Q4. Just first clarify that piece, and then maybe we're gonna look forward from there.
Sure. Again, long term, this is an attack-driven usage, not a patient individual-driven usage, right? Not all patients are equal. Sometimes where people have questions is if they think about this market like they think about the prophy market, which is effectively all patients are equal, more patients is better, right? In this case, you do have this meaningful distribution of patients. What really happens is it's really more driven by obviously the number of doses that are used in a quarter, which can vary widely. Which is a long-winded way of saying refills dominate your revenue base fairly quickly. In the Q4 already, as you said, refills were a majority of revenues. That will continue to become even more the case in this quarter and future quarters.
Which is why, and we've said this before, patient adds are a metric we've talked about a lot 'cause they're really useful in the early. When it is all about just sheer numbers. Over time, patient start forms will become a much less useful indicator of for future growth because so much of it is based upon the people you already have who are presumably treating at a higher attack rate. It's the refills that really drive you from a revenue basis.
Okay. Consensus at is now at $185. We're at $180, and that's based on what we view as a relatively conservative view on a patient start form build. Just talked about the really great feedback from the QuickStart program. The feedback we also hear is sounds like you do not need significant patient adds, although you all are commenting on the fact that you expect the cadence of patient additions to remain linear in the near term. Just maybe provide some context when it comes to your views for the year. Obviously, we're not asking you to guide. And if you're willing to, do you wanna make any comments on Q1? A lot of questions.
Yeah, right. There's a lot of questions. The consistent linear trend we said existed last year is continuing this year, and we don't see anything that really changes that trajectory. Now, again, coming back to it, as you move further into the year, your just your gross number of patient adds becomes less useful as a predictor coming back to the refill commentary from before. We focus on the fundamentals here, which is that people really like the drug. They're clearly using it and getting benefit out of it. We're comfortable based upon refill patterns that they're using a higher quantity of it than they might have used their previous therapies in the past.
We see those trends continuing, which we think will turn Ekterly into a very successful drug over time.
Okay. maybe remind us then on gross-to-net as we think about how to calculate an annual net pricing.
Sure. What we have said so far is that gross-to-nets in the space average high teens, low 20s, and we'll be right in line there. Q1 does tend to be a little bit higher because patient co-pays reset, and so that has a little bit of an impact. We'll be within the relevant range for all the other players in the space.
Okay. As payer reimbursement comes online, maybe, in the latter half this year, potentially, what expectations would you have on the impact gross nets?
Yeah. H istorically, contracting hasn't really been a feature of the HAE space. That said, it has become certainly one much more in the past couple years as so many new therapies have come. Particularly, it's become an issue in the prophylaxis space, where I there's more aggressive activity there. That is certainly carrying itself over into the on-demand space . There'll be some expectation of that. That said, this is not a high discounting contracting space. The numbers that we've seen range , mid-teens-ish, maybe 20. Like it's. We're not giving guidance there. We haven't even started these conversations yet with payers.
To your point, we haven't felt a pressure to do so because the medical exception process has been working quite well for us. As we move forward that's sort of a range that most people seem to end up in.
Okay. We understand it's a bit of an outdated update when you said about 4,000 patients, and caregivers had signed up for Ekterly updates. It, it is very helpful for us to think about it, in perspective with the patient start form adds that you all have provided to us so far, which is above 1,300. Just help us understand that dynamic when it comes to those that have been, early awareness, signed up, maybe using the drug, and those that you all are also collecting on the side. Is the majority from this database or, or are they coming from somewhere else?
Yeah. The database that you're referencing was a project we'd put together starting, I don't know, probably almost 2 years ago now, to make people aware of early updates on what was then several trials that progressed through to approval, and once it got approved, to help people work through a process of learning about Ekterly to go to have the conversation with their physician. That database, to your point, got to over 4,000 names, and i t's even higher now. That was really important to us in the early phase of the launch because it did help educate the highest activity level patients who would presumably come early to switch to Ekterly.
In the early days, a lot of those people that came in to get a prescription for Ekterly were people that seemed to have been making use of the, their, that email chain that we provide to them if they'd signed up for it. As the launch has expanded, though, the proportion of those people that are coming in off the database has absolutely declined. That's probably because what happens, remembering again that HAE is a familial disease, it's a very small community that's very tight-knit. What we find increasingly is that these patient additions are driven more by references from other people, and it could be family members, it could be friends, people they know through the advocacy organization.
We've evolved into this point where it's more of a referential phase is how I would describe it. People having early success with Ekterly, telling people about it, and that leads to those people now wanting to go in and talk to their physician about Ekterly.
Do you wanna talk about those next patient initiatives?
Yeah. Yeah. 2026 is really all about starting to help people who may not be in the early adopter group get more comfortable with understanding whether Ekterly may be for them. There's a lot of avenues for that. There's certainly the advocacy organizations continue to put people together. A gain, a lot of it just happens through Facebook groups or, like I said, just family connectivity. One of the things we've really definitely put in place in a substantial way is this patient ambassador program, where we've gathered a group of people who are representative of the HAE population generally, many of whom have different disease attributes, severities.
We're getting, making them available to actually talk to patients about their experience, and some of those will be live, some of those will be webinars. It's really helping people living with HAE to hear from someone who they can think, "Oh, yeah that person is, that person's dealing with what I'm dealing with." It helps them to understand how it's worked for that person and help them further consider whether Ekterly may be appropriate for them.
Clearly the team is very much focused on working on the first mover advantage, something that the KOLs highlight to us as when we ask about maybe the potential competitive dynamics between you and Pharvaris. Sounds like your view is that the data looks more similar than not when it comes to Pharvaris. Really help us understand ahead of their potential launch in the H1 of next year, what are you all doing to make sure you really cement your position?
Sure. T he plan is to a large degree, keep on doing what we're doing. E ducate people that Ekterly, it's not a challenging proposition to explain to people, talk about the data, right? All the things that make this what we think is a really good drug, just continue to relay that to people. Importantly though, we do continue to look for ways to grow the benefit to patients of Ekterly. We have a pediatrics filing we've said we plan to make in the Q3 so that should get approval next year, whether early in the year or mid-year, we'll see.
Pediatrics, which will be 2-11 'cause we're already approved for 12 and up, really once you get that approval, Ekterly becomes a full family solution. For everybody, it can work for them. What's important about pediatrics is they're not a huge proportion of the population, but what we discovered actually through our clinical trial is there's an enormous level of unmet need that was previously unrecognized there. The only thing that's approved right now for kids nowadays in the on-demand space is an IV-delivered therapy, which it turns out has led to massive undertreatment, in our belief, of attacks in these young children. Ekterly fundamentally changes that equation.
The other thing we're working on from a lifecycle management standpoint is we are going to be developing data to support use in short-term prophylaxis. That's another area where there's a lot of need for patients nowadays. They go in for procedures, whatever that may be, dental other things, commonly those can serve as triggers for attacks. And what we plan to do is show data that helps physicians understand that Ekterly in the STP setting may offer value. Our plan is next year, by next year, we have a very high proportion of people in the space using Ekterly. The satisfaction rates are extremely high. Physicians are very comfortable with it. The patient support services team is continuing to offer really high quality support to these folks along the way.
We've generated lots of real-world evidence to show patient satisfaction and all the benefits. Then we've got these other areas where we're continuing to show expansion. Ekterly's in a fundamentally different place next year than another drug that's coming to market with little data and a lot of a label conversation.
Okay. In the last few moments. Okay. Keep it here available if you need it. In the last few moments, maybe talk about the HAE on-demand market. This is something that has required a lot of education, given a largely genericized dynamic ahead of your launch. Just what are your key learnings? Maybe talk about your conviction in the $1.5 billion total addressable market that you've talked about in the past?
Yeah, sure. The market nowadays is from a dollar size is pretty small. If you just added up the dollars of the, of all the therapy sold, it's something in below less than probably $700 million nowadays, which doesn't look terribly compelling to for multiple candidates. What that doesn't capture is, to your point, the market's been heavily genericized through with Firazyr going generic and generic icatibant. Generic icatibant tends the majority of market share nowadays. What we have been doing, however, is converting in patients across the board, including those on generic icatibant, to Ekterly. Every person who's on a generic that switches to Ekterly obviously increases the total market size right there.
The reason, the way we get to this $1.5 billion TAM was really not in any way sort of an aggressive accounting. We basically took an average, which is right around 84,000 doses per year sold in the space. T his, that number's been very consistent for at least the last 5 or 5 or s 6 years. If you, if you have those doses and you put an Ekterly price on them, and Ekterly's priced, I should be clear, in line with all the other branded therapies. Like we Ekterly's not a premium priced product, even though we could have. That gets you to this low billion-dollar mark, if you assume people will use a small amount more of Ekterly, that's how the market grows.
There's no tremendous sleight of hand here to get to the numbers and frankly, we probably could have been a whole lot more aggressive because just the key point here is that 84,000 doses represents a fraction of all the total number of attacks because it's commonly believed that only 50% or 60% of attacks are treated at all. If you assume that treatment rates generally go up that you could easily get to a much higher number of attacks at a much higher size. W e've tried to show people that the numbers today aren't really representative, and we have tried to, in a relatively reasonable way, show them what the market size could be.
I don't think we've tried at all to take this to the extreme level.
Okay. Wonderful. Well, a relatively full room on a, on a Wednesday. Clearly everyone is really keen to see your progress and is interested to hear about Ekterly. With that, looking forward to seeing your progress this year, and thanks so much for the time.
Thanks again for having us here today.
Thanks everyone for listening in.