KalVista Pharmaceuticals, Inc. Aktie

Good morning, and welcome to KalVista Pharmaceuticals 8-month Fiscal Year 2025 Financial Results and Corporate Update Conference Call. [Operator Instructions] I would now like to turn the call over to Ryan Baker, Head of Investor Relations for introductory comments.

Thank you, operator, and good morning. As previously announced, the company changed its fiscal year from ending April 30 of each year to ending December 31 of each year. There was an 8-month transition period from May 1, 2025, to December 31, 2025. With that in mind, earlier today, KalVista issued a press release reporting financial results for the 8 months ended December 31, 2025, and provided a corporate update. A copy of the release is available on the Investors section of our website. Before we begin, I'd like to remind listeners that today's discussion will include forward-looking statements.

These statements are subject to risks and uncertainties that may cause actual results to differ materially. Please refer to our SEC filings for a discussion of these risks. KalVista undertakes no obligation to update forward-looking statements, except as required by law. I will now turn the call over to our Chief Executive Officer, Ben Palleiko.

Good morning, and thank you for joining us. 2025 was a pivotal year for KalVista highlighted by the successful multinational launch of Eckerle, the first and only oral on-demand treatment for hereditary angioedema. Since launching in the U.S. last July, we've seen higher rates of early adoption increasing physician engagement and positive patient feedback. Together, these signals reinforce our belief that Early has the potential to transform the treatment of HAE. As we build on this foundation, we remain focused on launch execution in the U.S. and Germany, expanding access globally and continuing to generate clinical and real-world evidence to support long-term growth of Vector.

The momentum we are seeing in the launch translated into $35 million in global net product revenue in the fourth quarter bringing revenue from launch through December 31, 2025, to $49 million and reflecting steady and consistent growth during the first 6 months of launch. Turning to the U.S. launch. As of February 28, we've received 1,702 patient start forms and activated 724 unique prescribers across the United States since the launch last July. These metrics reflect broad engagement across the HAE community and strong awareness on both physicians and people living with HAE. One of the most encouraging signals we are seeing reflects what we believe to be favorable utilization trends.

Refills now represent the majority of prescriptions and revenue, indicating that individuals who have tried entry are continuing to use it to treat attacks. This pattern suggests sustained usage and growing confidence as people living with HAE incorporate after into their ongoing management of attacks. We are also expanding the global footprint of actually. In Germany, the launch is off to a strong start with early adoption trends tracking similarly to those we see in the United States.

In Japan, our partner, Kaken Pharmaceutical, has initiated launch activities following Eckerle being listed on the national health insurance reimbursement schedule. And in Latin America, we recently announced a partnership with MultiCare pharma to commercialize across several key markets. Collectively, these efforts are expanding access to and strengthening our global commercial presence. Looking ahead, our focus this year is on advancing the pediatric opportunity for Actually, extending its availability to this high unmet need population. We plan to submit an NDA in the third quarter of 2026 and seeking approval for its use in children ages 2 to 11, which could support a potential U.S. launch in 2027.

Alongside commercial progress, we continue to strengthen the clinical evidence supporting Eckerle. At the recent Quade and Western allergy meetings, we presented new analyses highlighting the potential for sevetrelstat to help people treat more attacks earlier with sustained efficacy and high satisfaction. By reducing barriers to treatment, sevetrelstat supports early intervention, which is associated with an improved treatment response. We are particularly proud that Ekerle was recently recommended as a first-line treatment for adolescents ages 12 and older in the international guideline on the diagnosis and management of pediatric patients with HAE -- the first-line recommendation for Ekerle so soon after becoming commercially available, underscores the strength of our clinical data and reinforces the importance of ensuring individuals have immediate access to on-demand therapy.

Overall, our objective remains consistent. To establish Ekerle as a foundational treatment for HAE worldwide. Based on feedback from physicians and patients, it is becoming increasingly clear that the ability for people to treat all attacks quickly and conveniently with an oral therapy represents a meaningful advancement in HAE management. While we are still early in the launch, we believe we have built a strong base across commercial execution, clinical evidence, and regulatory progress to drive long-term growth and deliver lasting benefit for the entire HAE community.

With that, I'll turn the call over to Paul to discuss the new clinical data presented at Quad AI and the Western meetings in more detail.

Thank you, Ben. The recent Western and Katie scientific meetings, we presented several new analyses from the Sevitrolsad clinical trial program, including updated findings from the Confidence open-label extension study. These data further expand our understanding of the clinical performance of EKTERLY and the evolution of treatment patterns with an oral on-demand therapy. First, looking at the longitudinal data presented at Western, we observed that sevetrolostat performed consistently and effectively in nearly 2,500 attacks treated through September of 2025. What was particularly encouraging was that the use of a second dose occurred in only 19.3% of attacks and actually showed a decreasing trend of repeated attacks to about 12%.

The use of conventional injectable treatments occurred in only 5.1% of attacks, which also trended downwards toward 2%. The -- while there have been no head-to-head trial, these data are favorable in the context of what has been published in the literature for other on-demand treatments. These findings are also evidence of growing confidence with sevetrilstat as patients gained experience. This sustained clinical performance was mirrored by high and durable patient satisfaction with 91.1% of attacks rated as neutral to extremely satisfied and a median overall score of very satisfied.

This leads to Quad AI, where we reported a clear preference for sevetrolstat over conventional injectable treatments in the confidence study. A unique part of the open-label real-world study design was that patients were allowed to choose either sevitrolfat or their historic injectable treatment for each attack depending on their preference. Under these conditions, participants chose to treat over 84% of their attacks with. Further, as the study progressed, the preference for sevetrolstat grew as patients treated more attacks.

Collectively, these findings from confidence reinforce a powerful narrative actually is a preferred on-demand therapy, enabling patients to treat the vast majority of attacks treat them early and achieve high levels of sustained satisfaction after switching from injectables. Importantly, these results also reflect the trends we are seeing commercially, including growing physician confidence and increasing adoption by people living with HAE. Finally, I am pleased to highlight that these clinical insights are already translated into global standard of care recommendations. The newly released international Pediatric HAE guideline recommends actually as a first-line therapy for adolescents aged 12 and older.

The guideline committee issued a strong recommendation based on our robust clinical data published in high-tier peer-reviewed journals. Importantly, the guidelines emphasize that early intervention and ready access to on-demand treatment are the keys to better outcomes. This directly supports our findings that oral therapy has the potential to remove the barriers that have historically caused adolescents to wait nearly 8 hours before treating an attack with injectable therapy.

With that, I'll turn the call over to Nicole to provide an update on the commercial launch.

Thank you, Paul. We launched actually in the U.S. on July 7, 2025, and now approximately 9 months into the launch, we continue to see steady growth, driven by increasing prescriber engagement and positive patient experience. As Paul outlined earlier, data presented at the Quad AI showed the high confidence health care providers have in prescribing actor and the high satisfaction their patients are having with the drug. Momentum to adopt Ekerle continues to build. For January and February 2026, we recorded 384 new start forms, which brings the launch to date start form total to over 1,700. The U.S. HAE population is estimated to include approximately 9,000 patients.

And based on our current start forms, almost 20% of individuals with HAE have initiated Ekerle. We have now received start forms from 49 states and have recently expanded into Puerto Rico, further broadening access to therapy. On the prescriber side, during the first 2 months of 2026, we added 144 prescribers, bringing the launch to date total of unique prescribers to 724. The breadth and depth of actually use across all prescriber tiers continues to grow in a linear fashion, 29 of the top 30 HAE prescribers in the country have prescribed EKTERLY for multiple patients.

As is typical in the early stages of the launch, we expect some quarter-to-quarter variability in certain metrics. The severe winter weather this quarter affected physician office activity and processing of start forms, we believe this is a temporary dynamic and does not reflect any fundamental change in the underlying demand for EKTERLY. Prescriber engagement also continues to expand. On average, we are adding approximately 3 new prescribers each day, and we recently recorded a milestone where 10 new prescribers activated in a single day. These trends reflect increasing awareness and growing physician covenants as experience with EKTERLY builds.

As Ben mentioned earlier, as of Q4, refills represent the majority of units and revenue. This is an important indicator of the real-world utilization patterns and growing satisfaction with EKTERLY. We are seeing uptake among both high burden patients as well as patients with more moderate disease activity. Reflecting the value of an oral therapy that can be used anytime anywhere. This quarter, we conducted a routine market research survey with both patients and health care providers. Health care providers indicated the oral administration and ability to treat attacks early as the top drivers of EKTERLY use.

Further, patients prescribed EKTERLY indicated an increase in attack treatment rate since switching to EKTERLY. It is very encouraging to see initial signals that EKTERLY is delivering on its promise of enabling early treatment and treatment of all attacks for individuals living with HAE. Operationally, we remain focused on enabling broad patient access, importing reimbursement and onboarding and ensuring a high-quality patient experience through our short services. We believe satisfaction is driven not only by the product itself, but also by the services and support we provide to individuals and physicians.

In fact, despite our relatively recent entry, our patient hub services team recently received the highest ratings from health care providers on the quality of patient and access support of any company in the HAE space. Overall, we continue to see growing familiarity with EKTERLY high levels of patient and physician satisfaction and increasing confidence in the role EKTERLY can play in HAE management. We believe EKTERLY is well positioned to become the foundational therapy in the treatment of hereditary angioedema.

With that, I will now turn the call over to Brian to review our financial results.

Thanks, Nicole. As a result of changing our fiscal year end from April 30 to December 31, and -- the results we are reporting today reflect the 8-month transition period from May 1, 2025, through December 31, 2025. For comparability, we are presenting the 2025 results against unaudited financial information for the same period in 2024. As previously announced, net product revenue for the 8-month transition period ended December 31, 2025, was $49.1 million, including $35.4 million generated in the 3 months ended December 31.

Fourth quarter revenue benefited from our specialty pharmacy customers, adding inventory ahead of the holiday shutdowns, which they were able to work through in January. Total operating expenses were $160.2 million compared with $117 million in the prior year period. Cost revenue was $3.1 million and reflects expenses directly associated with product sales. Inventory sold in 2025 is not reflected in the cost of revenue because it was manufactured prior to FDA approval and expense of the R&D line at the time produced. Research and development expenses were $33.4 million compared with $52.2 million in the prior year period.

The decrease primarily reflects lower clinical trial costs as the confident trials wind down reduced discovery activities, the reclassification of certain medical affairs expenses from R&D to SG&A beginning in the fall of 2024 and the capitalization of manufacturing costs following FDA approval in July 2025. SG&A expenses were $124.7 million compared to $64.9 million in the prior year period, driven primarily by commercial launch activities and the continued build-out of infrastructure to support the commercialization of EKERLY.

Operating loss for the period was $112 million compared with $117 million in the prior year period. As of December 31, 2025, we had $300 million in cash and investments which we believe is sufficient to fund the company to profitability under our current operating plan. Overall, this period reflects our transition to a global commercial organization with a direct launch of acute in the United States and Germany. The investments made in 2025 position us to support continued commercial execution.

Looking ahead, we expect operating expenses to remain relatively consistent when adjusted for a 12-month period with the exception that cost of revenue will increase meaningfully as we sell through the remaining Zero cost inventory. With respect to the nonfinancial KPIs, starting with the first quarter 2026 earnings call, we will report patient start forms and unique prescribers for the 3-month period ended that corresponds to the financial results of that reporting period.

With that, I'll turn the call over to Ben for closing remarks. Ben?

Thank you, Brian. We are very encouraged by the early launch trajectory of EKERLY and the strong response from people living with HAE and physicians. With continued U.S. growth, expanding international launches and a pediatric filing ahead, we believe we are well positioned for 2026 and beyond. Our focus remains on disciplined execution expanding access globally and delivering on the full potential of EKERLY for the HAE community. Operator, we'll now open the call for questions.

[Operator Instructions] Our first question comes from Tazeen Ahmad with Bank of America.

Congrats on another strong quarter. Can you talk to us about how do we think about the uptake for the ex U.S. launches. You guys have made it to 20% of U.S. patients in a short amount of time. So -- can you maybe talk about the nuancing in the country specifically, let's say, Germany and Japan? -- to help us with how to think about uptake in general? And then for peak sales, what do you expect the split to be for revenue between U.S.

Sure. Thanks for the question, Tazeen. I'll start off and then take the call can give some more detail. So at a high level, the German trends we've seen are tracking more or less the U.S. trends. It's obviously a much smaller marketplace, but the patient uptake has been quite strong. And I think we're comfortable that growth is going to look a lot like it looks in the U.S., again, just that from a base points. Japan, we did launch, but just factually, it's too early to tell we had our first sale in Japan last week. So it's probably a little early to extrapolate from that trend at this point.

But but more to come here as that launch progresses. And then with regard to peak sales splits, -- in general, the U.S. obviously represents the vast majority of sales for effectively any circles product. And so it will be somewhere in the 85%, 15% plus or minus a few points in either direction. U.S. sales over time. As we've said consistently, ex U.S. -- the vast majority of the world is overwhelmingly on demand only. You don't see a lot of modern prophylaxis use outside the U.S. But again, just because the pricing dynamics tend to be so much different from a unit standpoint, it may be pretty sizable. But from a dollar standpoint, it will always be a relatively small proportion. Nice, don't know if you want to talk about anything more in Germany?

Question comes from Paul Mattis with Stifel.

This is Julien on for Paul. Congrats on the strong progress. Can you just talk a little bit about the types of patients that have started on therapy over the last couple of months in terms of phenotype and how they may compare to the end of last year? And further, you also talked about how the end of the year may have been impacted by the holidays, and you still showed some linear growth in start forms. Just curious, over the next couple of months, if you expect to continue to see increased linear growth? And anything that we should think about going into 1Q with respect to inventory or GTM would be helpful.

Sure. So thanks for your question. In terms of patients adopting actually we're very pleased to continue to see that the high burden segment. We continue to increase our share with that segment in particular as we look at the past few months of 2026. We're also very encouraged to see the broadening though of our patient base of growing both those patients with both mild and moderate burden of disease. And to us, that just really signals the broad appeal of actually to the entire population. And then in terms of the holidays, certainly, we do believe that demand is very strong.

The fundamentals in terms of just the attractiveness of the profile for both patients and physicians. But we did certainly see earlier this year as many companies that -- the severe weather that impacted several states with multiple storms certainly did have a negative impact on demand in terms of the ability for patients to get into the offices to see their physicians as well as for staff to complete administrative steps to complete paperwork for start forms.

Brian, do you want to talk about Q1.

Sure. We, like other high-priced specialty medicines will have a small impact to Q1 gross to net associated with co-pay assistance. It's kind of small and not into the order and temporary in terms of just getting through the deductible reset process.

Our next question comes from Steve Suku with TD Callon.

We have a couple. The first -- maybe could you just comment on how refill trends are progressing in 2026 and where you think things could settle just given really the high demand you're seeing proactively? So that's the first question. And then a couple of quick follow-ups. Are you able to comment on the hyper patients where you are in the penetration of that patient bolus. So that's the second question. And then the third, we appreciate you providing forms through February.

Are you able to comment high level if the rate of pay start form ads is similar in March? Are you seeing kind of the same dynamic that we've seen in Q4? I appreciate you following upon that. And Nicole, aligned with the processing of start forms. Could you just further discuss your comment there? Is it just the normal seasonality around hydrotop resets, per changes, et cetera?

Sure. Sure, absolutely. And I appreciate the question. So in terms of refill, we're very pleased to see that we're really maintaining the trends that we've discussed on previous calls. -- and stack fills we're seeing patients anywhere between 1 to 3 cartons. -- per refill as well as the high burden patients continue to refill more frequently than when we look at those more mild and moderate burden. And we've seen -- again, we've discussed that looking at claims data for some of the other on-demand therapies those more mild to moderate burn patients are refilling just a few times a year, and we see that the high growing patients refilling certainly more frequently. In terms of the share of the high burden patients, we continue to grow.

We're roughly around 1/3 at this point in time. And so we're pleased to see that continue to grow quarter-over-quarter. And really just the attractiveness of the profile continue to draw that particular segment of the market. And then just looking -- could you just remind me of your questions with regards to seasonality, just to make sure that we're answering it appropriately.

I just want to make sure we can either maybe further just dissect your comment of processing of start forms just the processing aspect of it? Is it around the normal seasonality from high resets are changes as we think about kind of the short-term Q1 dynamics?

Stacy, it's Ben. Just I think there's a couple of seasonality things we've tried to highlight here and maybe we're mix them a little bit together. The first is the fact that in Q4, we've said fairly consistently the wholesalers, the PBM -- the wholesale has ended up with higher-than-average stock toward the end of the year. And also, we do think that patients took on more drug in Q4, whether that was for increased need or just in anticipation of the kind of standard Q1 deductible resets, we'll never really know.

But we feel like is said, the volumes were probably higher in Q4, driven by some of these seasonal factors. And that some of that resets in Q1. And so we've just been trying to tell people that, that's kind of a normal course activity. With regard to the starch forms, we've consistently said and we believe this trend we can do that. We expect launch to be consistent and linear. That does not mean -- I think when Nicole is trying to highlight those, it will be consistent linear, but there will be fluctuations quarter-to-quarter, and we don't attach any fundamental significance to them. It's just driven by a number of factors. -- was exactly trying to highlight was the fact in January and February, you had several bouts of extreme weather in the U.S. and that absolutely impacted physicians' offices.

There were certainly days in January and February when we had 0 start forms simply because all the offices were closed. And so that does have a little bit of impact on some numbers we've talked about so far. But again, it's not a fundamental thing. It's just a weather thing. And also, she was trying to like the fact that when physicians offices are closed, the start forms, which the physician's offices have to process, just don't get processed and so to convert in the commercial. And so there's just some factors like that. We're just trying to make sure everyone is aware of as we roll through Q1.

But the high-level message is we believe, in the linear to launch to a greater or lesser degree. And I think we're very comfortable with the way things are progressing and nothing about this, we're trying to suggest any shift in our anticipation of the future growth.

Our next question comes from Maury Raycroft with Jefferies.

This is on for Maury. Congratulations on the strong quarter. We have 2 questions. One is a follow-up. Can you talk more about actually currently the refill rate and the dynamics -- and how do you think the refuel pattern will evolve in 2026 as the patient base broadens. The second question is, can you talk more about how you see the sales shaping up for the rest of the year? And would you be possible to share guidance at some point? And if not, what are the possible gating factors to do that?

Yes, I'll start with the second question, Nicole will pick up on the refill rates. Again, I think as is norm with companies of our stage in the launch and activity level, we're just not in a position to provide guidance point. Again, for us, every quarter is the first quarter we've done this. And so for us to make any long-term projections right now. I think we're -- would probably not be helpful defeating to everybody's activities. So what we do try to do is just convey what we do -- what we are seeing that's been consistent, and that just ties back to what I said to Stacy a minute or 2 ago, just about how the launch continues to be to be quite consistent in terms of patient demand metrics and all the other metrics that flow from that patient commercial starts, refill rates, all that stuff also continues to trend in a favorable direction with really no dramatic shifts noted or expected.

With that, I'll turn it over to Nicole to talk about the refill question.

Sure, absolutely. So as mentioned earlier with Rebuild we typically see 1 to 3 carbons per refill. And so when we discuss our high burden patients, those individuals are typically receiving more on the 2 to 3 cartons. -- on a regular basis on that regular basis being every 1 to 2 months. And then when we take a look at those that have more mild to moderate organic disease, they're really averaging around the lower end of that 1 to 3, so typically 1 to 2 cartons and the frequency of which we would expect would really line up more with what we see with some of the other on-demand therapies in terms of them refilling approximately 3 to 4 times a year.

Our next question comes from Joseph Schwartz with Leerink.

This is Will on for Joe. Congrats on the progress this quarter. So it's great to see the penetration into the U.S. market continue to grow at such a strong rate at this very early stage in the launch. And as we think about it moving forward, where do you expect things to eventually settle out -- and what kind of peak penetration are you targeting? And how does that inform the growth of the on-demand market from $650 million to $1.5 billion?

Yes, sure. Well, -- we don't believe this market over time should overwhelmingly convert to oral therapies. -- the injectables, obviously, everyone knows that they're quite efficacious. They've served patients well for the past decade. But I think it's fairly obvious from just how we actually has done to date. We've entered a new era of therapeutics in HAE and orals that offer all the benefits of the injectables with none of the burdens of the injectables just are a better option for patients, just the classic sort of dominant choice.

And so -- and so we do believe that over the next several years to a very high rate, the market should transition on worlds. So that's a key underlying expectation here. And as part of the transition to orals, what you should also see is treatment rates go higher. Right now, again, it's kind of commonly accepted and this has been talked about many times in many different venues that something between 50% and 65%, call it, 60% plus on mass attacks are treated at all nowadays. So selling is not the fact that late treatment is right. You've only got slightly more than half of the tax under any circumstance that are treated period.

And so -- the point there as that attack rate goes up, obviously, the usage of therapeutics treat will obviously be substantially increased as well. And so the point there is that the right overall just gets larger. And that's really again, just driven by the fact that when you have a better option to treat your tax with, you'll treat more of your attacks. So we think the story of the on-demand market, coming back to your dollar size, is driven largely by just that central fact of the fact that you have now have just a much better choice.

And so when you get to those numbers you just talked about, really that's not even in our minds, an aggressive growth belief. If you took the units that are sold today, which is right around -- last year, it was right around 87,000 units. At the moment, the vast majority of those units are, in fact, generic cataract -- and so that's the reason for the dollar size of the market today isn't anything having to do with lack of demand. It's just the fact that most of that demand is sold at a low price. Clearly, as we've talked about before, we're converting patients this marketplace over to EKTERLY from all the therapies, which includes a lot of folks coming from generic.

And so obviously, every time those folks within the generic, they're moving to a branded therapy. And so the overall market size, if you will, increases with each conversion. And so really, that $1.5 billion TAM you mentioned a minute ago in our minds, an enormous lift, it's really just presuming that you convert the vast majority of the market over 2 walls. So again, a lot of generic moves to branded pricing. And you have some and the number you mentioned doesn't really become terribly ambitious in this manner, but it assumes that there's some growth in the marketplace based upon this higher treatment rate we talked about.

And then on top of that, we've talked about a number of other more marginal impacts, people coming off of prophylaxis, things like that. But fundamentally, that number is really just reflecting more or less the current units carrying over to branded and then some increased treatment share, which, again, I don't believe in the context of that number you talked about is terribly ambitious.

Next question comes from Serge Belanger with Needham.

I guess, first, regarding payer reimbursement and access, any updates there? And I think in the past, you had mentioned that most of the patient starts or prescriptions were being almost universally covered under medical exception. Just curious if there's been any change on that front? Secondly, I think in the past, you've talked about potential use of vector as a short-term prophylactic what does that market opportunity looks like? And you need to conduct clinical trials to capture that opportunity?

Serge, good to hear from you, and thanks for all the questions. I think moving Nicole can talk a bit about the reimbursement metrics. And then I think we'd like to bring Paul into the conversation here and have him talk about the short-term prophylaxis, the work we're doing in that space and why we think it's important.

Sure. Glad to speak to you about the access side of things. We continue to convert paid patients across all the payers right now. We are leveraging a mix of medical exception. as well as the after policies where we have them in place. Those policies commonly are key to label. There are some instances where we do a step through icatibant. But given the experience of we're able to move those patients through without delay. Right now, our payer team is very much focused on really those remaining large PBMs who we expect to formalize policies in the coming months. So from our view, we're very much on track and looking to have really that steady-state access realized later this year in 2026.

Serge, in terms of the SDP opportunity, we currently thinking about this from a research perspective. And so there are ongoing studies. We currently see use in about 50 procedures that are fairly invasive -- and so far medication seems to work quite well. We're going to share the data in the upcoming clinical conference. And we are initiating an additional trial to look at use in short-term prophylaxis. The reality is, today, similar to the or general framework that injectable therapies are challenging us in the setting of short-term prophylaxis, where the recommendation remains strong that for patients undergoing procedures that they have an STP that is typically recommended as an IVC1 inhibitor.

This gives patients an additional option to consider using their oral on-demand therapy in its step. And so we're still evaluating what the opportunity there is. But the data today are pretty encouraging in a space to watch. I don't know don't add anything to that.

Yes. Sorry, it's really just to tie. I mean STP pediatrics, at a high level, what we're really looking to do is continue to provide actually in places where we think it can address a meaningful unmet need. We haven't talked much about pediatrics today. But clearly, that's a space where it's not a lot of patients. But the current options are very much undesirable. And so we think that actually even though it's not going to come for another year or so, still will offer an opportunity for folks to really address the unmet need in this young population in a much better way than they can hardly -- and so it may not be a huge economic pickup for us.

But in terms of just expanding the availability back to lead to the populations that really could get benefit from it we get substantial. And STP is exactly the same thing. I don't think we're presenting this as an enormous step shift in terms of revenue opportunities. But there's high need nowadays for better ways for patients to treat themselves prior to their procedures. Based upon the data we've seen so far, we think actually holds a lot of ones in there. And so this really all just comes under the tent of actually really we do expect to become the foundational therapy for HAE management.

And this is just 2 more ways that we expect to accomplish that.

Our next question comes from Jon Wolleben with Citizens.

I just have kind of a quick follow-up question to the kind of the automation switching from iCAD. Are you seeing any like -- is it too early to be seeing any debt in the amount of prescriptions for generic icatibant. And -- is any of that data going to be kind of captured by you guys have shown us kind of the launch of extra is impacting that generic market -- so a couple of things here. First of all, the vast majority, as you would expect at this point in the launch, people who are or transitioning actually still are in the process of switching over to Echo.

And so it's largely -- when we talk about the 1,700 start for all, it's start form. Not all of those people have moved to commercial. And so you would the number is still small enough that I think you probably wouldn't see a tremendous impact to date in that data if you were to look at it. But I do think that as you play through the year, that will start to become more apparent. But actually, we're still vertically early in the launch from a commercial shipments perspective. And so it's going to take a little bit longer for what you talk about to play through.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

Hi, everyone. My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. I'm happy to introduce Ben Palleiko, the CEO of KalVista. It's a fireside chat format. Thanks so much for joining us today, Ben.

Maury, thanks, as always, for the invite and grateful to Jefferies for all they've done with us over the years. So happy to be here.

And maybe starting off, if you can give a 1-minute intro to the company for people who may not be familiar with the company.

Sure. KalVista Pharmaceuticals is a commercial pharmaceuticals company nowadays. In July, we got FDA approval and then promptly launched our first product, which is called EKTERLY. EKTERLY is approved in the U.S. And actually, multiple other countries now -- for the on-demand treatment of acute attacks of HAE. HAE for those of you who don't know it, is a genetically driven disease where people have these episodic bouts of potentially severe swelling.

There's a number of therapies available for it. They all work reasonably well. But the critical difference effectively is that it allows people to treat it using an oral therapy for the first time ever. And that's a fairly substantial advance in the space that I suspect we'll talk about more.

Yes. Yes. And launch has been going for about 4.5 months. Understanding it's only been about a week since your third quarter update, but maybe can you give some more -- maybe we'll try to get some more clarity on some of the metrics. So far, you've got 937 start forms. How are you seeing expectations for penetration and cadence of new patients through 2026 as adoption runs?

Sure. Yes. As of today, we're actually over 1,000 patients on therapy. So comfortably over 10% of the marketplace at this point, making our way to whatever that would be 12% or 13%. So the uptake, just given from that statistic alone, you can presume, has been extraordinarily fast.

There's -- again, coming back to what I said in my opening remarks, this is a meaningful therapeutic advance for the category. A lot of people have known over time, they should treat their attacks more frequently and they should treat them earlier in the cycle, but for a lot of reasons, having to do with the fact that all these other therapies that existed in selectively were injected or even IV infused, they just didn't do it enough.

And so the reason for the swift uptake is the fact that for the first time, we've given people something that actually enables them to treat their attacks in the way they're supposed to the treatment guidelines for -- call for.

And again, EKTERLY, the name is carefully picked because it ties to the concept of act early, which is exactly what people with HAE is supposed to do. Treatment guidelines call for patients to, first of all, make their own decisions about treatment of attacks. And second of all, to consider treating all attacks, even mild attacks, can become very significant, they can escalate over time. And then if you're going to treat, you should always treat early.

And so EKTERLY is, among other things, a call to action to remind these folks that they should be treating their attacks early. And based on the evidence we've seen in both the clinical trial program and to date in the marketplace, that's exactly what they're doing and -- which is one of the reasons patient satisfaction so far has been so high.

Got it. Yes, that's helpful. And maybe clarify -- so when patients get their patient start form, they get a free drug sample and then they go on to paid drug. How does that work? And maybe just talk about the expected time to paid drug as payer policies mature.

Absolutely. So the first part, the mechanics can be a little confusing. And so we do try to explain this a little carefully.

When a person goes in and talks to a physician about -- actually and decides it's the right approach for them to take and wants to switch, the physician effectively writes them 2 prescriptions. One is what's called the starch form where they do a lot of data; insurance information, you can find it online, it has a lot of information.

And then the second thing is the physician writes them a prescription for EKTERLY. So they actually will get a standard prescription, right? They're usually written with an initial fill quantity, could be 1 carton, could be more cartons. And then typically, they're written as refill as needed after that. And then they are usually valid for a year.

But the key point here is this is not a sampling program. People don't just get EKTERLY, take it home to try it. People actually agree to switch to EKTERLY to do this. Both those start forms go to our patient services hub. The hub then confirms the person has insurance coverage.

And then once that's been done, we will actually ship them what you said the free drug, this initial carton of EKTERLY because the idea here is let them start getting experience, let them get it in their house. They're probably still going to have -- they're almost certainly still going to have their prior on-demand therapy available to them. Let them get experience using EKTERLY in a low-risk environment.

At the same time, as they're doing that, the team works through to get the commercial coverage. And then as soon as commercial coverage is reached, whether or not they have used their free drug that we sent them earlier, we will then give them the initial commercial fill, called for in the prescription, and then they're on actively and they'll go from there and refill as needed.

So the mechanics are -- it sounds a little complex sometimes. And people, I think, have wondered sometimes, you have to use all the free drug before you can get commercial? There's a lot of questions. That is how it works. And it's very seamless would be, I guess, the right word for the thing. The second part of your question, I forgot, I guess.

Just the expected amount of time to paid drugs payer policy.

Yes. It's -- in the initial start, it does take a little bit of a while. These are -- effectively, it's 100% medical exemption coverage to get going. So that's sort of a 6, 8, maybe a little longer, week process on average. But that does disguise a wide distribution of time frames.

We've had people come in with a prescription and immediately go to commercial. We've had people take meaningfully longer than that as they go through -- because there can be multiple rounds of appeals processes. These all have to be done by the physician offices, which can be onerous, right? So we're not allowed to help them along the way. So it can take longer.

As it matures, what we'd expect is that time frame will compress down, payers get more experience with -- actually, we get more experience of what they require to help make some decisions.

And then as you get to formularies, which is really a 2026 event, that's when the time frames start to become more efficient because now typically, we've gotten some payer coverages already, they've generally been favorable. And generally, they are what's called PA to label, prior authorization to label.

Once you have that, that's a pretty straightforward process because you know what the payer is going to require, you just have to get through it. And then the timing gets more efficient. But in the early innings, it takes a while. And even in the future over time, routinely in the space, companies will always end up with 20% or 25% of folks who are always want medical exception. That's just how it works.

Okay. And can you provide any perspective into refills so far and how the new starts to refill mixture can evolve over time?

Yes. Refills to date are still evolving. We have seen, among all prescriptions, refills. And so one of the questions people had was, well, people just get one box, one carton and then just never use it and never refill again. And I think we've fairly conclusively disproven that. Like we're definitely seeing people of all disease severity levels getting refills.

Of course, factually, the people that have the most refill requirements are the people with the most severe form of disease, and they can be quite high-frequency users. And so we define in our criteria, people with 2 or more attacks a month, we consider to be people with severe disease. And what -- and right now -- and they're probably 15% or 20% of the total patient population.

But at the moment, because they're the highest users of on-demand generally, they're an outsized proportion of our -- of the people that have switched to EKTERLY so far. And so at the end of the September quarter, there were about half of our prescriptions were with people in the severe disease category.

They refill at much faster rates. And so their average refill to date has been something like 3 to 4 weeks, and they're typically refilling with multiple cartons. So that is a very high frequency. Those people will probably continue to go at that rate. But certainly, as we get into the broader population, the refill rate will -- the average refill rate will certainly come down because, again, those folks are 20-or-so percent of the population.

In the long run, when you look at how refill rates work in the space, with FIRAZYR, based on claims data, we think people refill about 3 or 4 times a year, so every 3 or 4 months. Given the fact that we expect them to use more EKTERLY than they use FIRAZYR, that could be a slightly higher frequency for us. But we'll be making our way to something less than 3 or 4 weeks or I guess, longer than 3 or 4 weeks as an average [ refill ] time.

Got it. Okay. So base case is refills could look similar to FIRAZYR. But because you've got an oral drug and more convenient, it could be higher than that.

I think the base is probably higher than that, but we'll -- it's going to take us a while to get to the long term. We do continue to expect that for the foreseeable future, a disproportionate share of the new patient additions will be the severe disease folks. So that number won't shift dramatically probably in the near term. But over time, it will trend downward.

Yes. How long did it take to -- for FIRAZYR to get to like a steady state...

In terms of just the overall -- I mean, I think that -- well, that drug grew all the way until it went generic, I mean, at a pretty substantive rate. I mean, because, again, that was a step-change because until FIRAZYR, all you ever had was IV therapy. So that grew very consistently basically until the genericization, we think actually is the next step-change in this space.

Got it. So it could look -- trajectory could look similar to that.

In the long run. In the long run, this whole market should convert to orals, I mean, just to put it out there, right? I mean that's -- there's no reason to stay on an injectable therapy in the presence of EKTERLY, which requires you to make no trade-offs for the benefit of it. So coming back to this kind of consistent growth, this entire on-demand space should, over time, switch to oral.

Right. Yes. Okay. And maybe going back to your earnings update, so you had $13.7 million in revenue last quarter. Are you putting any additional granularity behind the number in respect to inventory versus patient use? And how should we think about getting to an inventory steady state?

Yes. Most of that's going to be -- I mean, most of that's going to be usage to be flat out. Now whether -- we haven't talked about is a split between new patients and refills. But it is mostly usage.

Certainly, there's some inventory build in there. But this isn't a space where you have massive inventories. I mean our CFO consistently talks about you maybe get 3, 4 weeks of inventory. So the dollar amount, of course, of that will grow over. But as a percentage, it should stay somewhat consistent.

This does reflect actual primarily end-user demand for EKTERLY and then to a lesser extent, just because of the time we've been out there, refills. To your point, Maury, over time, refills will become a more substantial percentage of the overall revenues. But we're still a ways off from that for a time period to come here, just the gross new patient adds are going to be the primary driver.

Got it. Okay. And for refills, do you think some patients could like try to stockpile some of the drug? Is that a possibility? And do you think there could be some payer quantity limit issues as well that you're in?

For sure -- okay, factually, we don't know. But certainly, we expect -- it seems almost certain that people will stockpile this to some level. I mean we've talked about the fact that people don't treat enough attacks. One of the reasons they don't treat enough attacks is, probably the primary reason, they don't like the current injectables. But the other reason is they don't have it with them, they don't carry it.

And so EKTERLY is absolutely -- I mean, the way that it's designed, it's in a -- it comes 2 doses in a carton. The doses are in these really convenient wallets. It's the kind of thing we intentionally made it so you can keep it in your backpack, you can leave it in your office drawer, right? You can have it sort of in the place in your life where you have attacks and up until now, you didn't have the opportunity to treat them.

We have a terrific anecdote of one woman who very quickly, after approval, actually had EKTERLY with her and was driving to work and felt an attack come on. And she actually treated herself at a red light, popped it out, took the tablets, went about her business and said she felt great in a very short period of time afterwards.

So that is a poster example of the benefits of this therapy. She'd had her -- I think she was an Icatibant user beforehand, right? In that case, you're not going to treat with Icatibant to the red light, should have had to take a whole different path to treatment.

So that is -- so yes, there will be some level of patient stocking. Do we think it to be dramatic? Probably not, right? We think a lot of this is going to continue to be kind of recurring usage.

And then quantity limits you asked about as well. payers do typically manage all the branded therapies by quantity limits. Most commonly, they're letting people get around kind of 2 whatever cartons a month, is probably an average quantity limit.

We don't think that's going to infringe on the vast majority of users. And to the extent you have these high-volume users, in particular, they're already well known to the physicians and to the payers. And so they're the kind of people that you can get exceptions for.

So yes, to quantity limits as a probable event, certainly no worse than existing branded therapies and certainly not in a way that we think is going to infringe upon people's reasonable access to the drug.

Got it. Makes sense. And based on what you said so far, it sounds like patients should be pretty sticky to EKTERLY too, where you're not going to have any reason for patients to switch back to injectable or drop off treatment. Is that fair?

Yes, absolutely. Again, this -- there is no downside to EKTERLY compared to the other therapies out there. All it does is make your life better because you have it with you and it's easier to take. And so you'll treat more attacks and you'll treat them earlier.

There's -- and then -- and stickiness also involves other things, including, for example, patient services. We have a -- patient services is sort of a mandated element of this space. Everybody has to have a really robust operation.

We have a terrific one. We actually did an initial survey a few weeks ago just to get initial kind of feedback from patients. And we're rated right up there on par with all the other ones in the space despite the fact that they've been there for 10 years, and we've been there for not much more than 10 weeks.

Got it. And maybe just comment on how safety or adverse events looks post launch compared to your clinical study so far?

Yes. In the real world, you have these FAERS updates that come routinely. Our Chief Medical Officer gets FAERS updates every day. They've transitioned the program. So every single thing goes into FAERS basically. Nothing has shown up of any significance at all. We've seen nothing that looks different or has all alter the safety profile of the drug, which through the entire clinical development program, has been absolutely pristine.

Got it. Okay. And of the 423 unique prescribers, how many are Tier 1? And how should we think about the cadence of new prescribers in 2026?

The majority of the early prescribers will be Tier 1. We've activated those folks at a very high level. Certainly, we've started to move into the Tier 2s and even to a greater extent than we expected into the Tier 3 physicians.

Just so everyone understands, Tier 1s write about half the scripts, Tier 2s write another 40% of the scripts; and Tier 3s, which is 1,000 physicians, write about 10% of the scripts. So it's a really concentrated call point.

We've done extremely well with those Tier 1s and Tier 2s to date, far better than we thought we would. And what's important is they're not only prescribing, but they're repeat prescribing. About 3/4 of the prescriptions in the quarter came from repeat prescribers. And so that goes to both -- the breadth is great. The depth is almost even better because what that means is these folks are just at a fairly steady pace converting their panel over to EKTERLY.

Got it. Okay. And I want to shift gears briefly. In our view, an overhang for your stock is related to [ Pharvaris ] is Phase III data, which is also an on-demand HAE setting that could read out any day by the end of this year. We also think that even if [ Pharvaris ] data appears better numerically than your data, just having the event out of the way should remove no overhang for your stock. How do you see the upcoming [ Pharvaris ] data update? And how should investors contextualize this update versus EKTERLY?

Yes. No surprise. We get these questions a lot. I think this serves as our occasional reminder that events that matter to investors don't always matter to companies. And by which I mean the [ Pharvaris ] data is a data event, and it's going to be what it's going to be and the stocks are going to react in some way. And that's sort of a lot of people now are focused on.

From us -- to us, though, as a commercial company selling product right now, it has actually no influence on our trajectory. Why is that? Kind of three reasons. The first is investors don't really focus on this, but we do and practitioners will as well. Despite the fact that, that study is represented as being comparable to our study, it's actually very, very much different in very important ways.

That study is -- our study was -- well, the largest clinical trial program ever conducted in HAE, but also a very straightforward test of the efficacy of EKTERLY now against placebo. And so we basically told people, if you feel an attack coming on, treat it early, treat it even if it's mild. If you think your symptoms warrant, take another dose and then report these results as you see fit.

Factually, [ RAPEED ] is none of those things. It's a highly engineered study. It requires an extraordinary amount of physician interaction by patients. They're not allowed to treat attacks without calling their physician, they're not allowed to treat mild attacks, they're not allowed to take a second dose without checking with their physician, they're trained on how to report the outcomes measures, and they have another interaction with their physician that is sort of intended to support their decision about whether or not they've reached complete symptom resolution.

The study is -- couldn't be more different in practice from ours. It's engineered to create a clinical outcome where they can claim comparative efficacy. I'm not trying to say that, that shouldn't matter to investors. I'm not an investor, I'm not trying to tell people how they should analyze this.

But what that means, though, is for us from a competitive standpoint, whenever that drug reaches the market, all of that criteria means these results will be viewed in a very different lens, which is going to be -- it's going to be very hard to actually claim in that -- in a commercial setting that you've actually got any kind of differential because everyone knows you designed it to create this differential, right? And that raises questions.

So the first part is the data set, I'm not denying it, it's potential importance to investors. That data set is no importance to us. The second thing is we are in the market since July 7. We are signing up hundreds of new people per month. The patient satisfaction measures on EKTERLY to date have been tremendous. The feedback we've received from the physician community has been outstanding.

That's going to continue at pace. Nothing is going to change that trajectory. So we're just adding people. And so in 2027, we'll have a lot of people on EKTERLY. We'll have a lot of people who are using a lot of EKTERLY.

And there's going to be no compelling -- coming back to the first point, there's going to be really no compelling reason for them to switch. If you're sitting there and you like EKTERLY and it's working well for you and you have your patient services hub that's really treating you well and you have your payer situation all resolved, you're not going to switch EKTERLY.

So we'll be the market leader in '27. I'm confident, as I sit here, we'll remain the market leader post their entry as well.

And then the third thing I'd say is kind of ties back to something I said a few minutes ago, in the presence of oral therapies, this entire market should switch over to orals. Like there's no reason to stay in injectables, which does mean there's plenty of space for two entrants in the market overall. So that's kind of my three-part answer to what do we think about the data.

Okay. Yes, that's helpful. And I guess for the two Phase IIIs, I think it makes sense, two very different Phase III studies. Could -- and it doesn't matter to your commercial opportunity as it stands. But will investors compare this Phase III data set to your Phase II data set? Because I think there could be some similarities just with having the doctor confirmation in there. Are they still very different?

Well, our Phase III, we did have them confirmed, but just to be clear, we had 100% confirmation. And so we didn't -- that's -- and we also allowed them to treat mild attacks in the Phase III. So even there, the distinction.

The only thing that's comparable between our Phase II and their Phase III is we did ask patients to confirm an attack with the physician in the Phase II study. But that was because no one had ever done a study of this type before and no one actually knew what to expect. So we removed that requirement in our Phase III. We literally had no requirements for physician interaction at all in the Phase III study.

So yes, you could say that's one distinction, but all the other things I delineated though, remain the same for the Phase II.

Got it. And maybe talk about the ex U.S. launch. You had the first shipment to Germany in October, and you expect to launch in the U.K. in the first half of '26 and Japan in first quarter '26 with your partner, Kaken. Maybe talk about the opportunity ex U.S. And also EU pricing there, we saw a Germany price listing. I wanted to know if that's finalized yet.

Yes. Yes. The good news about the rest of the world is it's almost entirely an on-demand marketplace. There's very little prophylaxis usage in -- outside the U.S. And even in countries where there appears to be a substantial amount of prophylaxis usage like the U.K., for example, what you actually find is that's not modern prophylaxis, that's things like attenuated androgens, tranexamic acid, like there's a lot of these older therapies those folks mostly use.

So you don't -- you see very little prophylaxis usage, by which I mean modern ones, outside the U.S. The less good news is those markets price at a fraction of the U.S. And so 20% of the U.S. price is probably not a bad estimate. And in some countries, actually, it could be lower than that over time.

The -- specifically the German pricing that Germany has a little bit of a unique system. There's free pricing when the drug is first approved. But then you negotiate and then there's kind of a reimbursement you have to make at the end of the cycle, depending on what price you end up with. We haven't published the German pricing yet. It won't be published for a long time. It won't be finalized for a year.

So we do have a -- we are commercial in Germany, to your point, we have established a price, but that price may or may not be close to what the final price is going to be. We won't know it for a long time.

In the rest of the countries in the world, to your point, we're still working through the pricing mechanisms, whether it's NICE in the U.K. or in Japan, there's a pricing regimen you have to work through as well. So all those -- none of those other countries are even close to having pricing set. But overall, long term, ex U.S. is maybe 20% of your global revenue, just to give a sense of the directionality.

Got it. Okay. That's helpful. And yes, we've heard from some KOLs that some prophy patients are willing to switch to an on-demand only management if an oral on-demand drug is available. Have you seen prophy patients switch to on-demand only since launch? And what does their profile look like?

Right. So factually, if they drop their prophylaxis after switching to EKTERLY in the commercial setting, we wouldn't know, we don't have any indication. I guess, maybe they'd use more, but that would take a while to figure out.

They weren't supposed to do it in the open label, but we have had a few patients who stopped their prophylaxis. That's not again -- we did not recommend it, right? We would not recommend anyone do this, but we have seen it happen.

But certainly, over the long run, there is an interesting question of -- again, we think EKTERLY is a very good drug, we think it can meet the needs of a lot of people. Prophylaxis, whether it's injectable prophylaxis or oral prophylaxis, does bring its own set of burdens. It's either a tablet every day or it's injections every couple of weeks or whatever.

And so if you believe that there is a subset of the prophylaxis patients who maybe don't have such severe form of disease and who maybe had a low baseline attack rate anyway, I think a very interesting question is as they get used to EKTERLY in their on-demand setting, would that make them think about whether they need to continue their prophylaxis? We think that's not an unlikely outcome. But the evidence for that will take a long time to figure out.

Got it. Have you had some patients switch from RUCONEST? Or are they still -- are they using RUCONEST and EKTERLY at the same time? I guess any...

Well, again, coming back to when people switch, they will generally have some leftover on demand of their prior therapy anyway. We have seen switches from all the on-demand therapies, including RUCONEST. We've seen them roughly in proportion to their current market shares. But again, we expect those transitions to continue at a fairly consistent rate.

Got it. Okay. And maybe just briefly talk about the pediatric setting there, you reported some data at ACAAI recently. How big could that market be in the United States?

The end of people is small. There's probably 500 peds in America with the disease. So it's not a huge revenue opportunity, if you will. But it is an important unmet need because the only approved therapy for under age of 12 is actually IV delivered. So which is an enormous problem.

In very brief summary, the data we presented at the college a couple of weeks ago was really important for two reasons. First of all, we showed some initial efficacy data, and what we showed is that the peds results are great. Like kids have roughly the same time of symptom relief. Again, the safety profile remains outstanding. It's all the similar data showed in pediatrics.

Almost more importantly, though, what we showed is the level of unmet need in the pediatric setting has been utterly unrecognized. When we designed this trial, we actually made the criteria for enrollment be that kids had to have 1 attack in the last year to be eligible because they were believed to have attacks at very, very low rates.

What we've discovered in the phase in this trial was actually these kids are attacking on average 0.8 attacks per month, 10 attacks a year, like basically 10x what people thought they had. And what was happening we've discovered is that not that these kids weren't having attacks, it's that in the presence of the only therapy being IV, a lot of these attacks just weren't being treated. Kids didn't want it, parents didn't want to give it to them, right? You just -- you had this dramatic undertreatment.

And so what I think is really important about EKTERLY is, again, coming back to this change in the whole way this disease is treated is now in the presence of EKTERLY, you're starting to unmask all that. You're seeing these attack rates be much higher, you're seeing the treatment rates go up.

Again, we think the same thing is true in the adult population that will play out over time. But certainly, in pediatrics, it was a very stark example of the fact that it's not that there's unmet need. It was just unrecognized because when you don't have a therapy, you just don't -- you don't do anything, you don't talk about it.

Makes sense. Okay. Well, we're out of time. But Ben, thanks so much for joining today. It's great seeing you.

Always great to see you. Thanks.

Good day, and thank you for standing by. Welcome to KalVista Pharmaceuticals' 2025 Third Quarter Financial Update and Operating Results Conference Call. [Operator Instructions] Please note that today's conference is being recorded.

I will now hand the conference over to your first speaker, Ryan Baker, Head of Investor Relations. Please go ahead.

Thank you, operator. Good morning, everyone, and thank you for joining us to discuss KalVista Pharmaceuticals' 2025 Third Quarter Financial Update and Operating Results.

Please note, we'll be making certain forward-looking statements today. We refer you to KalVista's SEC filings for a discussion of the risks that may cause actual results to differ from the forward-looking statements.

On the call with me today from KalVista are Ben Palleiko, Chief Executive Officer; Nicole Sweeny, Chief Commercial Officer; Brian Piekos, Chief Financial Officer; and Dr. Paul Audhya, our Chief Medical Officer.

Ben will begin with a review of the company's progress during the 3 months ended September 30, including an overview of EKTERLY's early launch, both in the U.S. and abroad as well as other regulatory updates. Paul will give an update on recently presented data from our KONFIDENT-KID trial in HAE for children ages 2 to 11, as well as new patient satisfaction data. Nicole will review the company's commercial progress to date, and Brian will cover the company's financial statements for the most recent quarter. We will then open the call for questions.

With that, I will now turn the call over to Ben.

Thank you, Ryan, and thank you, everyone, for joining us today. And I want to wish a Happy Veterans Day to all my fellow veterans listening in.

We are highly encouraged by EKTERLY's first 3 months on the U.S. market. Adoption has been steady and linear, with real-world utilization tracking as we expected. The takeaways are clear. Demand for EKTERLY is strong. It is being used to treat a significant number of HAE attacks, and it is meeting the expectations of people living with HAE for a highly efficacious and safe therapeutic alternative.

We continue to believe that EKTERLY will evolve to become the foundational treatment for HAE. In addition, we are executing on our mission to bring EKTERLY to people living with HAE globally. The German launch is now underway with initial uptake validating the ex-U.S. interest in EKTERLY. The approval footprint continues to grow, with a recent approval in Australia, adding to the existing authorizations in the U.S., U.K., EU and Switzerland.

In parallel, we continue to evaluate optimal strategies to expand access in geographies where we won't launch on our own. In addition to the collaborations we've previously announced, we anticipate that we will be completing more agreements later this year and in early 2026. We also continue to generate important new data to help educate the HAE community generally, as well as to demonstrate the real-world benefit of EKTERLY to people living with HAE.

Last week, during the American College of Allergy, Asthma and Immunology Meeting, we provided a report on the high satisfaction rates for patients in KONFIDENT-S who had switched to sebetralstat from injectable on-demand therapies. Additionally, interim results from our KONFIDENT-KID trial showed sebetralstat enables early, effective and safe treatment of HAE attacks in children ages 2 to 11. Paul will provide more detail on all of that in a minute.

We've also continued to grow the key capabilities of the company, demonstrated by the recent hires of Bilal Arif as our Chief Operating Officer; and Linea Aspesi as Chief People Officer. Both bring decades of experience that will make them important contributors as we work to evolve KalVista into a leading rare disease company.

Finally, with our recent convertible note offering, we are fully financed through profitability, allowing us to remain sharply focused on executing the EKTERLY launch while evaluating additional growth opportunities.

I will now turn the call over to Paul, who will update you on the latest data from KONFIDENT-S and KONFIDENT-KID.

Thanks, Ben.

I'm pleased to highlight that we continue to generate and publish important insights from our ongoing clinical trials, further building the case for EKTERLY across various patient segments.

Starting with our late-breaker ACAAI, we provided a significant update on our registrational KONFIDENT-KID trial for sebetralstat in children with HAE aged 2 to 11. With 36 children enrolled, this is the largest trial ever conducted in the pediatric HAE population, and we are incredibly proud to have fully recruited it almost a year ahead of schedule. This speaks to the high level of unmet need for these children and their caregivers.

A remarkable finding from the interim analysis is the extent to which this group of children is experiencing attacks. As of June 6, 2025, 65 attacks were treated by 26 children, translating to an attack rate of 0.8 attacks per patient per month. This far exceeds the historical understanding of attack frequency in this population. We believe that the high-attack rate in KONFIDENT-KID reflects an accurate unmasking of the true disease burden that was previously hidden by the difficulties associated with administering and receiving injectable treatments. The invasive and burdensome nature of intravenous and subcutaneous on-demand treatment creates a powerful disincentive for children and their parents to seek treatment for anything but the most severe attacks.

We believe that this has led to significant underreporting of attacks. The availability of an oral on-demand treatment fundamentally lowers the barrier to treatment. This allows for a high-attack rate to be documented because children and their caregivers are no longer faced with the choice of enduring the trauma of an injection versus riding out a potentially worsening attack.

Returning to the results. Treatment was rapid, with caregivers or the children themselves administering sebetralstat ODT in a median of 30 minutes. This option where children can actually treat themselves is a totally unique feature of KONFIDENT-KID and increases the importance of the results as the inability to self-treat attacks by children is such a major issue with injectables.

The median time to symptom relief was a rapid 1.5 hours in the dosing group who experienced the vast majority of attacks. Crucially, there were no treatment-related adverse events or reports of difficulty swallowing the orally disintegrating tablets formulated for kids. These results further highlight EKTERLY's potential to expand to people of all ages living with HAE. We expect to submit the NDA for pediatrics in Q3 of 2026.

Turning now to our long-term open-label extension, KONFIDENT-S. We continue to amass a large volume of data collected under conditions that mimic real-world utilization. For October 31, the trial has accumulated over 2,700 attacks treated with EKTERLY. Notably, this includes 59 laryngeal attacks, 560 attacks in patients receiving long-term prophylaxis and 584 attacks treated by adolescents.

The highest number of attacks treated by an individual participant is 118 over 23 months. As our patient experience has grown, we have observed key changes in dosing behavior. We focus on patients who reached 30 treated attacks, representing about 1/4 of confidence participants. We noted a clear trend. The proportion of patients using a second dose of EKTERLY within 12 hours fell from 22.5% during the first attack to just 13.5% by the 30th attack.

In the same group, the use of conventional injectable therapy dropped from 8% at the beginning of the trial to 0% by attack 30. We believe these marked reductions in the use of a second dose or conventional therapy reflect patients' growing assurance in EKTERLY's reliability. We plan to present this important data in more detail at an upcoming scientific congress.

Coming back to ACAAI, we presented new treatment satisfaction data from KONFIDENT-S in participants who had switched from injectable on-demand treatments to sebetralstat. The median satisfaction score for attacks treated with sebetralstat was 2, or very satisfied on a 7-point scale, ranging from minus 3, which was extremely dissatisfied to 3, which was extremely satisfied. Overall, 84% of attacks treated with sebetralstat were rated by participants as ranging from satisfied to extremely satisfied, with the vast majority being either very or extremely satisfied.

The high-satisfaction scores reported by patients who have successfully transitioned from injectable therapies to sebetralstat speak to the impact of having a simple, effective and reliable oral on-demand treatment readily available. So what are the implications? We know that a patient's decision to switch medication is often a direct measure of their unmet need or dissatisfaction with their current regimen. Therefore, as patients achieve a high level of satisfaction with EKTERLY, the probability of them seeking to switch therapies in the future is expected to decrease. This supports EKTERLY's role as a foundational therapy for HAE for the long term.

To conclude, the breadth and depth of our clinical data, coupled with a high level of patient satisfaction is translating into early commercial momentum. We're seeing strong uptake and growing confidence among the prescribers as awareness of EKTERLY continues to build.

To discuss how the launch is unfolding, I'll now pass the call to Nicole.

Thanks, Paul.

I'm pleased to share that the U.S. launch of EKTERLY continues to accelerate with sustained demand and growing enthusiasm among prescribers and patients. In less than 4 months since launch, we have received 937 start forms, representing more than 10% of the HAE community. This level of early engagement is strong by any launch standard and reflects an extraordinary level of community adoption.

Importantly, this demand is broad-based. We are seeing rapid uptake across all HAE patient segments, including prophylaxis users as well as adolescents. People are switching from all on-demand therapies, but the greatest number have been from FIRAZYR and icatibant as expected, given their market share.

Also, as we expected, the earliest and greatest number of those switching to EKTERLY have been high-burden patients who experienced frequent attacks, whether or not they are on prophylactic therapy. Provider activation is also expanding rapidly. We have 423 unique prescribers and continue to add 3 to 4 new prescribers each day. Awareness levels are exceptionally high with 100% of Tier 1 HCPs and 95% of all-target HCPs reporting awareness of EKTERLY. These metrics reflects both the strength of our field execution and the enthusiasm of the medical community for EKTERLY.

As prescribers gain more experience with EKTERLY and hear from their patients who have switched, their confidence continues to rise. Launch to date, repeat prescribers account for 75% of all EKTERLY start forms, a strong indicator of familiarity and trust in EKTERLY's profile. This provider enthusiasm is matched by a strong depth of utilization in patients. Though the data is early, patients that are refilling their prescriptions, including those on QuickStart and paid therapy, are doing so every 3 to 4 weeks.

For context, most injectable on-demand therapies average only 3 to 4 refills per year. This level of refill frequency is a clear indicator of growing real-world reliance and confidence in EKTERLY. Note that the majority of these refills are driven by patients with a high disease burden. They report experiencing 2 to 4 attacks per month, despite generally also being on prophylaxis therapy, which indicates the lack of adequate disease control. Refill quantities are consistent with this level of burden and higher than our initial expectations.

That all said, as adoption expands beyond to the highest burden patients, we expect refill patterns to normalize in line with the broader HAE community with both a lower frequency of refills and a lower volume of refill quantities. As demand continues to build, payers are actively moving towards formal coverage for EKTERLY. Since approval, patients have been able to leverage medical exception to gain access to EKTERLY. The medical exception approval rate and time to ped shipment are consistent with our expectations less than 6 months following approval. It is very encouraging that we have seen medical exceptions approved by all PBMs, and all large payers for both commercial and Medicare cases.

We continue to advance formal access with multiple regional and national payers already establishing EKTERLY policies. The majority of policies are ped label, which is consistent with other branded on-demand therapies. As expected, the minority of policies require a step through icatibant, which patients are able to move through quickly as most HAE patients have experienced with generic icatibant.

Our market access team is currently engaged with PBMs and remaining national payers, with an aim to formalize access in early 2026. At this point in the launch, we are encouraged to see access to EKTERLY growing as payers recognize the need for EKTERLY as part of an overall HAE treatment plan. Outside the United States, we are seeing early signs of momentum as we expand the reach of EKTERLY.

Following EMA approval, we launched in Germany in mid-October and recorded first-day commercial sales, an immediate validation of both prescriber enthusiasm and the strength of EKTERLY's differentiated oral on-demand profile. In the U.K., with approval now received, we are advancing pricing and reimbursement discussions with NICE in preparation for a first half 2026 launch. And in Japan, we continue to progress towards a PMDA approval and launch in the first quarter of 2026 with our partner, Kaken Pharmaceutical.

Taken together, accelerating utilization, repeat prescribing and growing favorable access provide a clear signal. EKTERLY is quickly on its way to becoming the foundational therapy for HAE treatment. What initially began with the highest burden patients is now expanding in only a few short months across the broader HAE population as physicians gain confidence and patients increasingly choose EKTERLY for their attacks.

I'll now turn the call over to Brian to review our financial performance.

Thanks, Nicole.

Our full financial results were included in the 10-Q filed after the close yesterday. So I'll provide a few highlights for the 3-month period ending September 30. We are pleased to announce sales of EKTERLY were $13.7 million for the launch period through September 30, which includes the $1.4 million recorded in July and previously reported. Subsequent to the July period, our specialty pharmacy partners stocked additional locations and built inventory in a disciplined manner, supporting the growing patient demand.

In the initial 3-month launch period, we are seeing the average number of cartons per shipment on the high end of our expected range, which aligns with utilization among high-burden patients, the core of our early adopter base. When looking at gross to net, I'd note it came in towards the low end of our expected range this quarter, driven largely by lower co-pay utilization typical for this time of year.

Shifting to expenses. Total operating expenses for the period were $59.7 million, consisting of approximately $12 million in R&D expenses and approximately $46.5 million in SG&A expenses. Looking ahead to the remainder of 2025, we expect SG&A expenses to remain relatively consistent as we continue to invest in EKTERLY's global launch. Importantly, with our recent convertible note financing, our cash position is sufficient to fund operations through profitability.

With that, I'll turn the call back to Ben for closing remarks.

Thanks, Brian.

The early momentum and rapid growth we described today reinforce our belief that EKTERLY is positioned for long-term success as market awareness continues to grow. Our near-term focus is on aggressive and disciplined execution, scaling in the U.S., expanding access globally and reinforcing confidence in the role of EKTERLY across the treatment landscape.

We continue to believe that oral on-demand therapy should broadly displace the injectable options and that EKTERLY will be the clear market leader based upon the breadth and depth of the data we have generated that shows EKTERLY can benefit all people living with HAE regardless of their attack location, frequency or severity. We are and will remain the only company that has demonstrated in a clinical trial setting, the effectiveness of our therapy for treatment of HAE attacks in accordance with modern treatment guidelines that call for patients to consider treating all attacks and to treat early.

Through our gold standard design clinical trials and our many publications of the data, we've established a strong position as a patient-focused organization that is dedicated to improving lives, and I expect our reputation will continue to strengthen based upon our early success and our most recent data updates. With strong execution, a clear strategic runway and fully funded path through profitability, we believe we are well on our way to establishing EKTERLY as a foundational therapy for HAE and to generating long-term growth for the company.

With that, we'll open the call for questions. Operator?

[Operator Instructions] Our first question coming from the line of Maury Raycroft with Jefferies.

Congrats on the great quarter. Maybe to start off, wondering if you could talk more about trends for types of patients who are switching to EKTERLY early on, particularly the high-burden patients? Are you putting percentages on how the 937 start forms break down? And how could these trends change over time?

Maury, thanks for joining today, and thanks for the question. Nice to talk to you. I guess I'll start and maybe Nicole will add some other details. What was really important here when we launched EKTERLY was we always presumed that the most rapid adopters would be the people living with HAE who have a very high treatment burden. And we've talked about this for a long time, and I think there's been substantial questions in some quarters about whether that patient population exists and also how severe their attack rates are.

What we found through the third quarter was that, that actually those people do exist and they are transitioning just as we would have expected. Roughly half of all the patients who have switched to EKTERLY to date self-report an attack rate of 2 or more attacks per month, which we consider to be high burden. And that accounts for, obviously, a fair amount of prescriptions, but also those people refill at higher rates and in larger quantities as well.

So clearly, the discovery we've made here is that, that group really does exist that they actually aren't well controlled on prophylaxis and that their needs are being met by EKTERLY. In the longer run, obviously, we expect that number to decline, right? That's a fairly small portion of the population. And as we broaden out EKTERLY's reach, all those items will go down, the refill rates will decline and the number of cartons per refill will also go down. But for now, that group seems to be getting a lot of benefit from EKTERLY just like we anticipated.

Yes. And just to add some further color on the patient base. As Ben was describing, these are patients with a high burden of disease who are also on prophylaxis and continue to have unmanaged HAE. In terms of the product that they've been switching from, we see broad adoption or broad switching across all of the on-demand therapies. The vast majority of patients are switching from Berinert to icatibant, which is very much in line with our expectations as in advance of approval, we often heard about the shortcomings of a subcu injectable. But again, very exciting and encouraging to see just the broad adoption across all of the different on-demand treatments.

Got it. Helpful perspective there. And then maybe one follow-up. Just for the 937 new starts, are you seeing more on what proportion is converting to drug? And are you breaking down paid versus free drug at this time?

Yes. So from an access standpoint, we are very encouraged by the continued increase in paid. Week-to-week, we see the paid rate continue to grow. And we've seen successful use of the medical exception, both in terms of consistency over time, as well as I should add more recently as the EKTERLY policies have started to come into play, we're seeing clarity in terms of path forward for patients to gain access to EKTERLY. So overall, at this point in time, certainly, our paid and the access dynamics are unfolding as we'd expect.

And Maury, for perfect clarity because I don't know if this is where we're going, all those start forms reflect prescriptions. Those are people who are actually switching to EKTERLY. A start form is inherently tied to a prescription for that person to switch.

Our next question coming from the line of Stacy Ku with TD Cowen.

Congrats on a great quarter. So the first is just a follow-up. Are you willing to talk a little bit more about these refill rates or maybe disclose on average number of doses for these high-burden patients? And maybe help us compare that to where you would expect things to normalize, especially given your work with claims data? And of course, as it relates to payer willingness to treat these high-burden patients, maybe talk about the quantity limits that you're seeing for chronic use of EKTERLY? So that's the first question.

And then the second question is just maybe as we look to the commentary, you're kind of trying to highlight for us around those patient bolus dynamics that you're seeing. Just help us understand what that means for the remainder of the year versus what we've seen in Q3? And of course, I'm putting you a little bit on the spot here. As we look to next year, again, still really early days, we totally understand that. But just your level of comfort around consensus as we think about the 937 patient start forms that you've already grabbed in '25?

Thanks, Stacy, for all the questions. We'll work our way around the room here to answer them. So on the first one, you asked about refill rates. Our presumption going into this when you look at claims data is that the average person with HAE is refilling about once every 3 to 4 months. And that will normally be with FIRAZYR or icatibant is typically sold in pack of 3s. So that will typically be at least 3 doses and maybe multiple packs because actually, I think the average rate of refill is higher than that.

What we've seen to date, driven again by this high-burden population has been refill frequencies of probably kind of 1/3 that off frequent, maybe once a month or even more frequently than that. So these people are very high or have, in some cases, very high-attack rates and so they're refilling quite frequently. And they are, when they refill, typically refilling with multiple cartons at a time. So it's many more doses than we would expect on average.

As I said in the last answer, that's because of the subpopulation that has come to EKTERLY early. As we go over time, certainly, we'd expect those rates to normalize more towards what you see in the icatibant type marketplace where you've got refills that are multiple months apart and probably, on average, volumes will be lower.

In terms of quantity limits, actually, you don't you take it from here, Nicole?

Sure. I'm glad to step in. Quantity limits are certainly the norm for the current branded on-demand treatment. And it is something that we're seeing and expected to see with EKTERLY. Having said that, to date, the quantity limits that we're facing with EKTERLY, again, very consistent with the other products and have not created impediment to a patient continuing to gain access to EKTERLY. And historically, there are means to overcome quantity limits should we end up in that situation on a patient basis.

Also, just to transition to your question regarding demand for the remainder of the year, certainly, we recognize going into the holiday season, there are time out of office for physicians and for staff as well as just a very busy time for all of us. So we do anticipate potential disruption to demand in the remainder of 2025.

And then do you want to talk to some of the financials?

Yes. On consensus, Stacy, what we see, there's quite a range in the consensus. I think over a 3-fold gap, we understand the challenges of modeling this new prescription that is an on-demand therapy. It is challenging. It's far more complicated as we change our fiscal year now to a calendar year basis, and I'm not sure all the estimates have caught up to that. And so I think that dispersion in estimates is warranted as we kind of really figure out what utilization will look like over the long term.

Yes. Understood. And then just to confirm, a carton is 2 doses, correct?

Yes.

Our next question coming from the line of Paul Matteis with Stifel.

This is Matthew on for Paul. Congrats on all the progress. I guess I just wanted to better understand with the multiple cartons per shipment, do you think there's any stockpiling behavior within the patients just given how convenient it is to have this oral and the storage is easier? And I guess, how do you see that evolving in the future?

Actually, we don't know. Actually, we don't know. We got put on mute by accident for a second there. People don't have to tell us what's happening. Given that the self-reported attack rate among these folks is quite high, we do think there's obviously a high level of utilization there. But I don't know that we could allocate between how much they're storing it up like as they probably should really to have in places where they can access it when they have attacks versus actually using it.

Again, stepping back a little bit, whether it's because of initial -- some kind of initial stockpile, although again, these refill rates have been pretty consistent or usage. Like I said, as we expand further into the population, we do expect the overall attack rates to normalize more towards what you see in the population as a whole. That means that, again, usage will probably be less on average. Refills will be less frequent on average, and the volumes per refill will come down to some extent. But even people that don't really have high attack rates, when they do refill, seem to be refilling at higher levels than we expected, that's probably maybe more indicative of stockpile than I think the really high-attack rate folks.

I don't know if you have anything to add?

Yes. Just a reminder that the treatment guidelines do -- that physicians have developed both in the U.S. and around the world do encourage that patients keep product on hand to treat multiple attacks, 2 to 3 attacks. And so that is something that is fairly common in terms of practice here with patients in the U.S.

Our next question coming from the line of Joe Schwartz with Leerink Partners.

It's great to see that according to our math, the rate of PSF has stayed fairly constant through your first couple of updates so far. Do you expect this relatively linear PSF growth rate to continue? At what point, either months into the launch or overall penetration-wise, do you expect PSF growth to taper off?

And then ex-U.S., it was great to see the German launch is underway. What is the price you agreed upon in Germany, and how does that compare to the U.S.?

Yes. Thanks for the questions. So the PSF rates have been quite consistent as we've indicated through the first, now 4 months of the launch. As Nicole said a few minutes ago, we do -- the fourth quarter here, especially the November, December as we get to the holidays is definitely a time when we wouldn't be surprised if the numbers slow a bit, right? I mean, people just are not going to be going to their physicians for this type of thing over the holidays. So we would expect that there will be some slowing in the fourth quarter, really just driven by the kind of seasonality of the thing.

As we get into 2026, again, we think the fundamentals on demand are really good, right? People seem to be still getting these appointments at a quite a consistent clip. Inexorably, over time, the rate of start forms will slow down to some extent just as we get deeper into the patient population. But at this point, we really don't have enough information to give an indication of whether that's earlier or later in 2026. But the clip we are on now, while we're quite happy with it, certainly, we wouldn't really expect it to be this fast paced all 2026. So that's the first part.

Certainly, German price, that's something that is not disclosed at this time. We're early in the days of launch there, and we'll be in ongoing negotiations and discussions with German authorities. So that's something certainly we could revisit in the new year.

Okay. What about other European countries in '26? What are the plans there?

Certainly. We certainly have approval in the U.K., and so that is something we're in active discussions with NICE and planning for a launch in the first half of 2026 as well as moving out to some of the other larger countries in Europe towards the end of 2026.

Our next question coming from the line of Jon Wolleben with Citizens Bank.

Congrats on the progress. When you guys talk about kind of normalization of these rates, wondering if you could talk a little bit about your expectations for how many patients do you expect to ultimately be trialing EKTERLY because the high burden makes sense now, but do you think that this is going to be broad across people with low burden as well? Or is it going to be a majority of these high-burden patients over time?

And then in the prepared remarks, you mentioned that gross net towards the low end of your expected range. I was hoping you could just remind us of what that expected range is.

Sure. I'll do the first part. Again, Jon, we do fundamentally expect oral therapies to displace the injectables. I think we've fairly conclusively shown that EKTERLY offers all the benefits of the existing HAE therapies with much better equivalent efficacy in all likelihood, right? We haven't -- it has been shown head-to-head, but I think people generally accept that the safety has been pristine so far. There's really no advantage to anyone using -- continue to use an injectable or an IV therapy.

So on a fundamental level, we do expect orals to overtake the injectables over time. And so there's a sort of high level how the market evolves in our viewpoint. That does -- to your point about whether the rate slows as you move into lower usage people, that's certainly likely. There's definitely just like there's a very high burden population, we presume a commensurate very low burden population that may be less inclined to move over time.

To date, we have seen people across the board switching to EKTERLY. I mean, again, we said -- we've seen certainly the high population be through the third quarter, half of those folks. But the other half are much more of a distribution of attack rates. So the urgency may not be as high as we move deeper into the market, but we do think the fundamentals are that people will switch over time. I mean, a lot -- there's certainly a lot of folks who we believe are still a little bit and see how it's working for someone they know before they switch.

Some of these folks will have tried ORLADEYO before and maybe not have a satisfactory response. And so we do anticipate there could be a little bit of initial caution about another oral therapy. But again, given the anecdotal reports we've seen so far and just the commentary we've heard from physicians who've talked to their patients, we think people are exceedingly satisfied right now. And we do believe that, that will play through over time, and that will bring these people who may be less motivated for whatever reason, right, initially to move, to switch over to EKTERLY in a timely fashion.

I don't know if you want to add anything on that.

Yes, I would just offer that building upon Ben's point, anecdotal feedback as well as market research we've conducted with patients, we see very high satisfaction ratings, both with patients who have a high burden of disease as well as patients with a more moderate or lower burden of disease. And that satisfaction relates specifically to EKTERLY as well as with our patient support services that received high marks in terms of supporting patients to gain access.

And with respect to gross to net, Jon, like other specialty medicines, we expect to see gross to net to be on average, upper teens, low-20s.

Our next question coming from the line of Serge Belanger with Needham & Company.

Congrats on the quarter. First question, I wanted to go back to your initial focus on high-burden patients. Is that just a function of the market or the docs that you -- prescribers that you have initially targeted? And are they using these higher burden patients as leveraging them to get experience with the product and familiarity?

Secondly, when prescribers are writing patient start forms or prescriptions, are these PRNs or are they limiting them to a certain number of boxes or cartons?

Sure. So in terms of the high-burden patients, these are the patients that spend most of their time in with their physician. So these are individuals that are typically on prophylaxis and have HAE that is largely uncontrolled. And so given the high need that they have, they're very much on the physician's radar. Having said that, these are also the patients who are most informed. So in advance of approval, they're actively seeking new treatments. And with the approval of EKTERLY, we know that they made appointments and went into their physicians' offices to discuss.

So, I will say that it's a bit of the patient demand due to the burden of the disease as well as certainly significant awareness on the physician side that they need to support those patients. And yes, I think to some extent, your point, it enables them to test EKTERLY in some of the most difficult cases to really validate that what the profile we saw in the clinical trials really playing out in the real world, which we know has increased confidence of physicians as we see the majority of start forms that are coming from repeat prescribers.

Just in terms of how they write the prescription, typically, a prescription is written for PRN, so that, that allows the flexibility for the patients to gain access to refills at the frequency and the magnitude of which they need. That's historically how it's been done with the other on-demand treatments and what we see with EKTERLY today.

Okay. Great. One quick one for Brian, just on inventory. Out of the $13.7 million that was reported this quarter, how much of that was inventory? And did you exit the quarter at steady state on that front?

Yes. We're seeing, obviously, with the first 2 months of launch, inventory build coming in by the specialty pharmacies, particularly as they add additional locations as the launch gained momentum. We think our specialty pharmacy partners are performing in a disciplined manner with a view of growth. It's not steady state. It's going to continue building in front of expected demand.

Our next question coming from the line of Debanjana Chatterjee with JonesTrading.

Congrats on the quarter. So can you talk a little bit more about how your insurance negotiations are progressing and how we should think about the cadence of payers coming online in the first half of next year?

Sure. Absolutely. Leading into launch, we anticipated that it would take roughly 6 months to both drive demand and for payers to assess EKTERLY and establish policies. What we're seeing at this point in time is that, yes, we are leveraging medical exception on a consistent basis to gain access, but we're also seeing some of the regional and national payers create policies for EKTERLY that are largely favorable. Looking towards the end of this year and into the early part of next year, we are planning to, I would say, wrap up discussions with some of the larger payers and PBMs with an aim to have policies in place again, early in 2026.

Sure. And a quick follow-up. So you've also mentioned that in the early quarters, revenues can be a bit bumpy as refill rates stabilize. So can you talk about how we should think about revenue trajectory in the immediate like next couple of quarters?

I mean, it's a hard question as we just talked about. We continue to expect initial fills to come through. We've talked about that as adoption expands, the burden of disease on patients will, on average, go down. That will impact both initial fill amounts as well as refill rates. This is an on-demand therapy. We're going through a holiday period. It's really hard to understand exactly kind of the nature of the revenue to kind of comment on what trajectory should look like.

And there are no further questions in the queue at this time. Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.

Ladies and gentlemen, thank you for standing by. Welcome to KalVista Pharmaceuticals operational update and first Fiscal quarter financial results. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to turn the conference over to Ryan Baker, Head of Investor Relations. Sir, please go ahead.

Thank you, operator. Good morning, everyone, and thank you for joining us to discuss KalVista Pharmaceuticals fiscal year 2026 first quarter financial update and operating results. Please note we'll be making certain forward-looking statements today. We refer you to KalVista's SEC filings for a discussion of the risks that may cause actual results to differ from the forward-looking statements.

On the call with me today from KalVista are Ben Palleiko, Chief Executive Officer; Nicole Sweeny, Chief Commercial Officer; and Brian Piekos, Chief Financial Officer. Dr. Paul Audhya, our Chief Medical Officer, will be joining us for the Q&A portion of the call. Ben will begin with a review of the company's progress during the 3 months ended July 31, 2025, including FDA approval of EKTERLY and other regulatory updates. Nicole will then review the company's commercial progress to date and Brian will cover the company's financial statements for the most recent quarter. We will then open the call for questions.

With that, I will now turn the call over to Ben.

Thank you, Ryan, and welcome, everyone, to our first ever financial update conference call. It's been a momentous few months for KalVista, highlighted by our announcement on July 7 that the FDA approved EKTERLY as the first and only oral on-demand therapy for acute HAE attacks in adults and pediatric patients aged 12 and older. This approval has positioned EKTERLY to transform the treatment paradigm globally for people living with HAE. We initiated the U.S. launch immediately following approval and are pleased to report today our initial launch metrics.

With EKTERLY, for the first time, people living with HAE had an oral on-demand therapy they can take at the first signs of an attack, achieving symptom relief in the same time frame as injectable therapies with a pristine safety profile. EKTERLY breaks through the barriers imposed by injections, and we believe it is poised to become the foundational HAE treatment globally. It enables people with HAE to adhere to treatment guidelines, which recommend treating attacks early and considering treatment of all attacks with the goal of achieving total disease control and normalizing lives.

Since initiating our U.S. launch, the community response to EKTERLY has been overwhelmingly positive and early uptake is even greater than our expectations. People living with HAE, physicians and payers all have engaged rapidly, which speaks to the unmet need that EKTERLY addresses . In a few moments, I'll turn the call over to Nicole to discuss our commercial progress in more detail, but I will say that we are already seeing the results of the investments we made prior to approval in our commercial infrastructure and we are executing an outstanding fashion on a successful launch. The fact that already almost 5% of the entire U.S. HAE population has submitted a prescription for EKTERLY clearly speaks to all these elements, including the quality of the commercial team we have established.

Beyond the U.S., we continue to make important regulatory progress in our efforts to bring EKTERLY to people living with HAE around the world. In Europe, sebetralstat received a positive CHMP opinion in July for the treatment of acute HAE attacks with a final European Commission decision expected in October. The Committee for Orphan Medicinal products also confirmed maintenance of [ orphan ] designation, underscoring the significant unmet need that sebetralstat addresses in the EU and granting a 10 years of market exclusivity upon approval. We anticipate a staged launch in Europe over the next 12 to 18 months commencing with Germany pending approval.

Also in July, the U.K. MHRA granted marketing authorization of EKTERLY as well as adding it to the agency's orphan register. With regulatory approval secured, the process now moves to [ NICE ] for a health technology assessment to determine patient access and reimbursement. These discussions are essential to ensure broad availability. Based on the current time line, we anticipate a U.K. commercial launch in the first half of 2026.

We continue to progress towards anticipated approval in Japan at the end of this year, and launch through our commercial partner, [ Kaken ] Pharmaceutical in early 2026.

Our Canadian partnership is also progressing towards a regulatory filing and we are currently in discussions with multiple other potential partners worldwide. We believe this progress not only validates the universal need for EKTERLY, but also lays the foundation for meaningful commercial growth and long-term value creation for our shareholders.

With that, I'll now turn the call over to Nicole, who will share more detail on early launch progress and some of the performance indicators we will be building on in the quarters ahead. Nicole?

Thank you, Ben, and good morning, everyone. As Ben mentioned, our launch readiness activities have ensured that we were well positioned to deliver EKTERLY, the first and only oral on-demand therapy to patients as quickly as possible. While we remain in early days of the launch, I am very pleased with the progress we have seen to date. We are observing encouraging signs across several key performance indicators.

From the patient perspective, interest in EKTERLY has been strong and continues to grow. Just days after launch, we attended the HAEA Patient Advocacy Summit in Baltimore were over 1,400 people living with HAE were present. It was an important opportunity to share information and introduce EKTERLY to the community. Within the first few weeks of approval, an additional 500 community members joined our database seeking information and updates on EKTERLY. Through the end of August, more than 4,000 individuals have joined our patient database. Additionally, we continue to host local and virtual education events to increase awareness of EKTERLY among patients and family members.

Following our announcement of the FDA's approval of EKTERLY on July 7, I'm excited to share that in the 8-week period ending August 29, we received 460 patient start forms. Early demand has largely come from patients previously on Firazyr and icatibant as expected, but also from all other on-demand therapies, and we are seeing patients on all prophylactic therapies adopt EKTERLY at similar rates.

On the access front, we know that formal coverage policies typically take up to 6 months to be established. Even so, we are pleased to see some patients gain paid access, consistent with our expectations. The Quickstart program and medical exception processes are proceeding as planned, and we are confident in our ability to secure broad access over time.

For prescribers, our field sales organization is focused on engaging the top 1,000 HAE treating physicians who account for roughly 90% of prescriptions written in the U.S. As expected, early prescriptions have come from KOL to manage the highest number of HAE patients. Importantly, however, adoption has not been limited to the KOLs. We are observing strong interest in prescribing from a broad base of providers, even outside that top 1,000, which underscores the strength of our educational efforts and the clear unmet need EKTERLY is addressing. From launch through August 29, we have activated 253 unique prescribers with 38% of those starting multiple patients on EKTERLY. Over this same time period, our field sales team has reached over 72% of the total physician base, including 96% of the Tier 1 physicians.

In addition to KPIs, our KalVista Care hub services are fully operational, helping patients navigate access and financial support. Early feedback from both patients and offices is very positive.

Taken together, these early signals reinforce our confidence in EKTERLY's potential to become the foundational therapy for people living with HAE. Looking at future quarters as our launch progresses, we expect the launch KPIs will evolve. And so we will adjust our reporting metrics accordingly.

I will now turn the call over to Brian for a review of the company's financial statements for the most recent quarter. Brian?

Thanks, Nicole. Good morning. The press release we issued earlier today contains our full financial results, so I'll provide a few highlights for the 3-month period ended July 31. We are pleased to announce the first sale of EKTERLY reporting $1.4 million in net revenue for the launch period, primarily from stocking awards by the specialty pharmacies and our commercial distribution network. Total operating expenses for the period were $60.4 million, consisting of approximately $15 million in R&D expenses and approximately $45 million in SG&A expenses. The quarter-over-quarter increase in SG&A was driven primarily by external spending related to the EKTERLY launch. Looking ahead to the remainder of 2025, we expect operating expenses to remain relatively consistent as we continue to invest in the EKTERLY launch.

Turning to the balance sheet. We had approximately $191 million of cash and investments as of July 31, 2025. We expect that balance together with forecasted EKTERLY revenue to fund the company's operations into 2027.

Before turning it over to Ben for closing remarks, I'd like to remind everyone that as previously announced in March, we are changing our fiscal year end to December 31. As part of that transition, we will begin reporting on a traditional calendar quarter basis this fall, starting with the quarter ending September 30, which will capture the 3-month period from July through September. Ben?

Thank you, Brian. As Nicole described, we are pleased with the strong response we are seeing in the early days of our U.S. commercial launch. The level of engagement from people living with HAE and physicians underscores both the unmet need in HAE and the transformational potential of EKTERLY. The rapid adoption we are seeing reinforces our belief that EKTERLY can redefine the standard of care for people living with HAE. We remain focused on executing our commercial strategy with discipline, driving global expansion and continuing to deliver on our vision of bringing this meaningful life-changing treatment to people worldwide.

And with that, we will now open the call to your questions. Operator?

[Operator Instructions] And the first question comes from Stacy Ku with TD Cowen.

Congratulations on a wonderful early update. We had a few questions, mostly towards Nicole. Can you just further speak to the Quickstart program? And just maybe help us and other investors understand the process on prior authorizations and medical exemptions, maybe just talk through your expectations for timing to pay drug? And really, how should we think about that translation of the really impressive patient start forms to eventually getting paid drug. So just help us understand that piece.

And then on top of Quickstart program, just maybe if you're willing to -- on top of the details you've provided so far, just talk about the type of prescribing patterns you're seeing. Just help us understand are patients going to be able to have chronic use of EKTERLY as needed. So that's kind of the first question on the Quickstart program and dynamics there.

And then another is maybe another just expectations on timing. We get a lot of questions from investors on that 4,000, let's say, patient and caregivers that have signed up for EKTERLY updates. So just give us a sense of how many are individual patients or caregivers as a new treatment, would you expect [ most commissions ] would want to see their patients in the office? And maybe what's the frequency of current [indiscernible] help us understand that cadence as we think about the high patient demand and how you will have to work through that patient number.

Sure. Thanks so much, Stacy, for the question. So [indiscernible] we've been consistent that we look at the first 6 months [indiscernible] of those months, access may be in [ months 4, 5 and 6, which ] is really why [indiscernible].

And in terms of Quickstart, the mechanics of it, if you will, the Quickstart program immediately provides access to EKTERLY at no charge. The [indiscernible] Quickstart form [indiscernible]. And so when the [indiscernible] form comes in, it allows KalVista to work with the physician office to pursue a medical exception to gain [indiscernible] so the patient has Quickstart, again, while we work with the office to gain paid access. [indiscernible] once the medical exception is approved, the patient's next shipment will be sent without [indiscernible]. If medical exception that time period, [indiscernible], then they contact KalVista [ second expense to be provided ] by KalVista.

So I think in [indiscernible] KalVista team maintained KalVista status [indiscernible] that the patients that [indiscernible]. And obviously, when the [indiscernible] quickly as possible.

I think just a little garbled, by the way, tough for me to and I'm guessing others to hear.

[indiscernible] next question is on the patents.

Sure. Absolutely. In terms of the patient database, [ we're encouraged to ] grow so quickly after approval [indiscernible] And it [ was majority paid ] [indiscernible] caregiver as well [indiscernible] What's most interesting is that when we look at the geography [indiscernible] Tier 2 physicians. So to us, that's very [indiscernible] representatives that are going in are connecting with the physicians that treat these patients and a number of our in-person education programs for patients that [indiscernible] programs so that we can be [indiscernible] same geographies is -- much to engage with those patients at a local level and help them [indiscernible] [ advanced 2 therapy ].

[indiscernible] you had is, I believe, on the visited [indiscernible] a prescriber standpoint and so [indiscernible] that physician [indiscernible] approach in terms of some physicians requiring a visit using [ telehealth ] and some not requiring a visit in order to prescribe therapy.

And our next question comes from Paul Matteis with Stifel.

Really appreciate it. A couple of questions from us. You talked about how the launch metrics may evolve as you move forward with this launch. Just curious what your expectations are moving forward? And I guess, later this year, is it possible that we could be getting actual number of doses prescribed for example, versus just start forms? And also, and again, this may have been answered. It was a little bit difficult with the audio. But just curious, are you able to confirm just sort of what we've heard previously on the insurance process that patients first receive -- doses initially and then also afterwards received 2 doses of paid drug automatically if their insurance is approved? Just wanted to confirm that. And if so, how does that inform your perspective on the launch kinetics moving forward this year?

Sure. So in terms of the script to address your first question, we recognize that as we get into months 4, 5 and 6 later in the year, that certainly some of the KPIs will be evolving and more interest in repeat prescribers as well as refills and certainly talking more about utilization of the product or consumption of our product on a per patient basis. So certainly recognize that. And as the year unfolds, plan to share more in terms of a view into other KPIs.

And then it may be helpful just to -- I know there was an audio glitch. So it may be helpful just to kind of take a step back on Quickstart as well as paid. And so I think it's important to appreciate that when a prescriber -- a physician writes a script for EKTERLY, they write that start form and they send it into the KalVista hub. In parallel, they do send in a request for a Quickstart. And so how this works is that the Quickstart provides immediate access to treatment for EKTERLY at no charge, and then our staff works with the physician office to pursue medical exception and gain paid access.

While a patient is on Quickstart, once that medical exception is approved, the patient's next shipment will be sent without delay and paid by the commercial or the government payer depending on who they have. If that exception requires more time, then we as a company will send a second shipment.

And in terms of the other question, I believe you asked just in terms of script. Yes, patients are typically receiving 2 boxes for their initial prescription. And then it's really -- the refill is very much dependent on how that physician writes the prescription. And so if the refill is written as needed, a patient may receive 2 boxes or they may receive more depending on their burden of disease. And so that is something that, again, it's up to the physician as to how they write. Typically, they prescribe PRN for refills to allow patients flexibility to adjust the number of boxes in the future based on their burden of disease.

Thank you for the color.

And the next question will come from Tazeen Ahmad with Bank of America.

Congrats from me as well and a good start to the launch. I'm sorry if you already said this before, but maybe you can clarify, have you broken down of the 460 start forms? What percent were to a Quickstart, what percent are reimbursed and what percent may be coming from another source? I just want to get a sense of where you are in the early stages of reimbursement. And are we still going to be able to track these numbers quarter-to-quarter?

And then the second question is, is it too early to know what the retreatment rates are? You're just still a few weeks into the launch, but any kind of anecdotes you can share some feedback from your sales force, it would be helpful.

Sure, absolutely. So the -- when we share a start form number of 460, it is that 100% of those individuals also received Quickstart. And so again, as the programs are designed so that the forms come in together, so patients have immediate access to therapy. We certainly were very encouraged and have been encouraged to see that we have started just a few weeks after approval, EKTERLY paid shipments starting to go out to patients where the medical exception process went through rather quickly. Certainly, that's something that we continue to watch, and it does grow week to week. And also even more recently seeing our first refills for on the paid side of things was also very encouraging because to us, that's just signals not only positive sign from the payer side of things, but also that, that individual is really continuing to utilize the product and adopt it as their primary on-demand therapy.

And with regard to treatment, Tazeen, I mean, we've certainly heard some anecdotal feedback from the field already. It's all been, I think, very positive. We haven't really heard anything about any kind of second dosing. We -- but again, we continue to think that's not really an issue. The open label, we've talked about this publicly multiple times, the redose rate somewhere in the [indiscernible] of the low 20s, 22%, 23%, which is actually even below the Firazyr rate. So we don't think that represents any issues with anyone, whether it's patients or payers. And again, because it just absolutely falls to the lower end of what's seen the world nowadays.

Okay. And then last question for me. Any feedback on side effects observed thus far in [indiscernible] or any kind of GI discomfort?

This is Paul Audhya. No, actually, we've been hearing overall consistency between what we observed in the open-label extension. And what we're seeing in terms of just any adverse event reports which have been pretty minimal. Typically in the first 6 months of the launch, that's the period in which is most intense when the prescribers are getting used to the therapy. And so there's nothing that's come forward to date. Certainly, in terms of GI-related adverse events, we haven't heard about any during the course of the launch and actually over the open-label extension, [indiscernible] almost [ 1,000 abdominal attacks ]. And even in that setting, we're seeing extremely low adverse demand rate. So I think really, this is a drug that's not associated with GI adverse events.

I really think the only anecdote we've heard so far has actually been favorable, which was we did have 1 person call our patient hub to let people know that did had a laryngeal attack and we're very pleased with the outcome. They said it have worked quite well for them. So limited stories and top to extrapolate, but everything so far has been favorable.

And the next question is going to come from Maury Raycroft with Jefferies.

Congrats on the progress and the update today. I'll ask 1 about the 460 [ SAR ] forms as well. Just wondering if you can provide a July versus August breakdown just in trying to get a perspective into how much was from rollover from clinical studies or a bolus waiting for the launch. And whether you think this early demand could suggest a linear trajectory?

Nice to hear from you. The -- we chose to put out the August number because we had it, and I think there've been a lot of questions about whether how the trajectory is going to go. I would say is, and we're quite pleased with this. This is -- this doesn't just simply represent a sort of a onetime bolus of rollover people or something. First of all, the open-label extension, even though it's big for HAE, isn't super big. So the people coming off who could [ pop plausible move on ] are measured dozens, not hundreds.

What this really represents is a sustained -- continually growing level of interest from people. And so demand certainly started off, I think, higher than we anticipated and it's continued to go from there. So the curve has been a fairly linear growth from here with really no surges along the way that would represent to us, this was a sort of onetime event. We've been very -- and this a little bit goes to the fact -- and we talked about [indiscernible] the comments, the fact that patient interest has been very broad, certainly even broader than we thought it would be in terms of just people on prophylaxis as well as people with higher lower attack rates. We've seen a really terrific breadth of prescriptions. And again, through -- ever since the launch and even continuing now past August, we've continued to see the same trends.

Got it. That's helpful. And maybe just going forward, as we focus more on revenue numbers going forward, how should we think about just stockpiling as a dynamic there?

That's probably a good question for Brian Piekos.

In terms of inventory at DSPs, like most rare disease launches, we expect long-term averages [indiscernible] 2 to 4 weeks of inventory. I think in the earlier part of the launch, that can move around a bit, but we don't expect anything different as compared to other [indiscernible] launches, specialty medicines.

And the next question will come from Joseph Schwartz with Leerink.

This is Will on for Joe today. Congrats on the great quarter and strong start to the launch. So 1 question for us. Just want to drill down a bit more on the patient profile. So could you share anything beyond what their prior therapy might have been? And are you seeing any meaningful patterns on attack rate severity, attack frequency and what their typical attack rate might have been before initiating treatment?

Sure. I'm glad to take that question. And heading into the launch, I think we had conducted a great deal of market research that indicated those patients with more severe burden of disease that those would be some of our earliest adopters. And certainly, we see adoption across a wide, I would say, array of patient types in terms of the burden of disease. But we have seen and are very pleased with the adoption with those high burden patients. And the profile certainly of the product was attractive to them, and we have certainly seen that population be some of our earliest adopters, but we absolutely have seen adoption across the burden of the disease base, if you will.

And across all prophylaxis therapies.

Yes. Just something else to add is that we've seen -- when we look at the current use of prophylaxis with our patients, we do see that the utilization really lines up with the market share in terms of use of prophy overall. And then we actually see the brand share for prophylaxis lineup as well with the patient base we have launched to date. So again, it's very encouraging to just see this used by a very broad population, whether it's based on burden of disease or previous on-demand or current prophylactic treatment.

And our next question will come from Pete Stavropoulos with Cantor Fitzgerald.

Congratulations on the quarter. Can you just remind us how many patients are in the [ OLE ] are actually U.S.-based? I know you said somewhere in the dozens. And what is the expected cadence or time lines to shift the majority of these patients to reimburse -- commercially reimbursed scripts?

And also from a non-access perspective, I've reached to patient, perhaps educational or informational programs. What's been the outcome to date for those efforts to sort of raise awareness of EKTERLY profile? And do you have a sense of the proportion of patients from the 460 start forms that were directed from these efforts?

I can [indiscernible] the first. Nicole, you can do the second. So Pete, in terms of the OLE rollover, I mean it's important to note that the OLE at least from a U.S. patient perspective, was several dozen patients, not several hundred patients, for example, and some of whom had already gone on to the early access program when they finished and some of them are still actually continuing on the OLE for a while longer. So there is no dramatic sort of burst of people that would immediately switch on the commercial. I think -- and that's why I was saying earlier, our view is that these folks are coming on as part of this generalized demand uptake. And then effectively, their numbers are kind of subsumed by the larger demand we're seeing. So they're certainly out there, and I think we're comfortable they're moving over, but it's very hard for us to track just based upon the fact that, like I said, they're not an enormous immediate transition group.

[indiscernible]

Yes. So in terms of your second question, certainly, we see the earliest patient adopters. As I mentioned earlier, our -- when we've mapped them from a geography standpoint, obviously cluster around our Tier 1 and Tier 2 physicians, which connects back to our marketing list. But also we had a tremendous opportunity with the HAEA Patient Summit. We announced our approval on Monday, we went to that summit on Friday. There were 1,400 members of the community there. So that was also a chance for us to engage with full family members. And so since that time, our education efforts have been very much driven to do local education programs, trying to invite family members to come out certainly with the intent to provide more education and adoption for that individual, but also to help introduce EKTERLY to the family. And so that's certainly something that we've been doing since launch at the in-person conference in the dinner program sense, and we'll carry that approach certainly into the fall in addition to other nonpersonal marketing efforts, e-mails and things like that.

And the next question will come from Serge Belanger with Needham.

First question regarding security and formulary coverage. Maybe just give us an update on where you are and where you expect to be. And then our expectations that you'll still be at parity versus other products in terms of step-throughs, [ prior acts ] and quantity limits.

And then just another quick one. I noticed on Slide 14 of your updated slide deck, you increased the size of the projected market growth by about 25%. Maybe just talk about the assumptions behind that increased growth expectation.

Sure, absolutely. I think in terms of the access side of things, I would say, at this point in time, things are certainly progressing how we would -- how we anticipated utilizing medical exception and that we would see access to paid happen on a more limited basis rather quickly, but certainly that, that would grow over the time. And we certainly anticipate that -- if we think about steady state from the access side of things, yes, we do still anticipate parity access to branded therapies in the market. And certainly going into launch, we were certainly aware that there may be some exceptions where a payer might choose to require a step-through generic [indiscernible] there's been 1 instance that we've seen to date.

But it's really important to note that even where that instance has come up, patients actually have EKTERLY and are getting it paid. And the reason for that is because 80% of patients have either been on generic [indiscernible] or are on generic [ icatibant ] previous to EKTERLY. So even in that instance where we have faced that 1 step at a policy, the patients have been able to move forward and already have their EKTERLY in hand paid for. So certainly, for us, we're continuing to advance our efforts. But again, at this point, we maintain the view that parity access to the other branded therapies will be expected.

And on the market number, Serge, first of all, kudos to you for the reading the deck in detail before the call. Thank you for that.

The second thing would be, it's pretty straightforward. When we've done those numbers, which was a while ago, we had obviously done it based on an estimate of the market size, total market doses, which we talked about a lot and also a branded price, which was down closer to the standard fare 0 price. As part of the update, we revised all that to reflect the fact that the branded prices [ now, our expectation ] is meaningfully higher based upon our WACC and where the market sits nowadays. And so it's just a fairly straightforward exercise to market back to an updated expectation on the pricing and then you grow it a little bit from there. So that's really what it reflects.

And the next question is going to come from Debanjana Chatterjee with Jones.

Congrats the quarter. So you mentioned about the generic step-through that might be required by certain insurers. What do you think these payers would like to see in terms of either safety or efficacy failure on icatibant to approve EKTERLY? And I have a quick follow-up.

Sure. Well, one, as I just mentioned, it's important that the vast majority of patients have experience on generic icatibant, so they can move through that step rather quickly. So for the minority, which would be 20% of patients. The feedback that we hear from physicians is that actually describing a fail or a failure of icatibant to a payer is quite simple, and it could come down to injection site reactions. It could also be, for instance, that someone has a history of abdominal attacks and administering a subcu and the abdomen is difficult and challenging. They could have difficulties with hand swelling, so therefore, administering a subcu is really quite difficult. So again, we see that being an absolute minority of cases where we -- an individual would face it, but there is experience in the market with, again, those examples I gave you for overcoming and establishing that a patient has failed generic icatibant and can quickly move on to EKTERLY in this instance.

That's helpful. And at some point, in terms of the KPI, would you be sharing percentage lives covered?

I think that's something that as we continue through launch, we'll certainly share more progress in terms of our efforts from the payer side of things. The exact details and KPIs, I think that's probably to be determined at this point in time. But certainly, we recognize there's interest and providing more clarity on our efforts to ensure that there's ongoing paid access and establishing those policies. So I would just say stay tuned for further updates from the company, but certainly, we appreciate that there's a need to do so.

And our next question will come from Jon Wolleben with Citizens.

[indiscernible] on for Jon. A quick question about the number of scripts and patients that potentially account for the revenues reported in July is about [ 1.4 million ] reported. And also, when EKTERLY become available in July? Is it immediately post approval?

Brian can answer the second question on the -- with regard to revenues. EKTERLY was available roughly 10 days following approval. We had [indiscernible] .

In respect to revenue...

Just to [indiscernible] start forms, though, just to be clear, we were getting start forms actually the day of approval. Our first start form came in before lunchtime on the day we announced. So start forms did predate actual shipments by 10 days.

And just on the revenue recognition side, we have [ follow 606 and every other functional company ] does. You'll see that our customer base is the specialty pharmacy. So we recognize revenue when a product is received by the specialty pharmacies. And then there is a lag from there when they go out and reach the patients.

I am showing no further questions at this time. This does conclude today's conference call, and thank you for your participation, and you may now disconnect.

Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos, a biotech analyst with 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 description of KalVista for those who are not familiar.

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 in an investor conference actually. Our drug for treatment of acute attacks of hereditary angioedema, which is called EKTERLY, was approved back in early July by the FDA and 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 they'll be launching next year in the U.K. And also at the end of July, the CHMP in the EU recommended approval. That formal approval will come in October. And we're currently pursuing approvals in 4 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.

Yes. So congratulations on the recent approval of EKTERLY. So you're approved for acute HAE attacks. 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 to actually ever execute 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 2 trials, the 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 III 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 2/3 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 the 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.

And 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. The treatment guidelines for HAE say treatment of all attacks and 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 and OLE data sort of suggest about changing patient behavior with EKTERLY?

Right. On-demand -- until EKTERLY was approved, there were 4 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 2 are actually IV delivered. Far and away the market leader, though, is a drug called FIRAZYR. It went generic about 5 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 just of 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. And that's not that these attacks don't need to be treated, except they just choose not to in many cases. And 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. And if you look at the data sets, you will see that commonly people wait 3, 4 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. And so 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 3 or 4 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. And 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. And 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 III 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 and with all the benefits of having a tablet that lets them treat more attacks earlier.

Sort of staying on the theme, when you do go to your website and you go to the publications, you have 10 to 15 per medical conference and you just accumulated a ton of -- and have done a ton of analysis on the data that you have in the Phase III, the open-label study. And again, staying on the 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 a single tablet versus 2 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 probes 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 a conference. In 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 II results were printed in the Lancet and the Phase III in the New England Journal of Medicine, right? So the 2 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 turn 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 will reflect itself as we move into being a commercial company.

In terms of all these other details you asked about, the approved dosing is 600 milligrams on the label, right? So that is 1 of 2 doses we started in Phase III. People typically are going to dose at that level. 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 are going to -- 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, multiple doses, I assume. 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 will 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?

Yes. 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 EKTERLY. Like I said, in our open label, they're treating in something less than 10 minutes on average.

I think the adolescent -- I haven't looked at this data in a little while, but the last time I looked, adolescents were more like 5 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. So if you look at the data nowadays, adolescents historically wait more like 8 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 treated even faster in our study. And yes, I do think that will carry through in the real world. I mean open label is about as real world 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 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 who 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 there would be an attack, they had to call their physician first and confirm it 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 is, 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.

Okay. 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, to payers...

No, it's not at all. Yes. In general, therapy 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 or -- well, 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 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. And I would not expect this to shift 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, can you talk briefly about the label and what differentiates it, like maybe 1 minute, relative to approved agents.

Yes. I think the key thing of the label is it's extraordinarily clean. Our CMO says 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 or 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 U.S. and Europe or where do you peg HAE prevalence?

It seems to be, based upon all the data that's been generated, 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 between 130,000 to 150,000 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 2 markets, acute on-demand and prophylactic treatment, physicians and KOLs 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 2 ways, about 1/3 treat with on-demand only and about 2/3 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% plus. 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 in the on-demand only, who only treat with on-demand are probably having something in the order of 14 attacks a year, kind of a little more than 1 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, 6 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 a higher rate, but it's probably driven by the fact that people with more severe disease go on prophylaxis.

And people talk a lot about attack-free rates, and there's certainly a population that has very frequent attacks, right, half attack or less per month. But it does seem to be less than the majority of folks. And 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 2 attacks a month. And so he's an on-demand primary user. And he was talking to me one time, he said, how he'd been going through a very stressful period. The triggers for HAE are varied. He was going through a very stressful period and all of a sudden he said he was having 7 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 you all of a sudden are 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 5 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 in ROI?

Yes. So we were working on launch almost 2 years ago, and we've been, again, coming back to all the 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 went out talking to people and educating them on the data set. 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 4 or 5 months in advance of approval.

The physician community is right around 2,000 docs in total, about 200 of them, so 10% write about half the scripts. Another 800 write 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 1 and Tier 2s and maybe 95%, 96% of the Tier 3s. So we really got out far and wide to meet this community. Again, we were armed with a truly outstanding data set. And as a result, I think that positioned us really well to go into the launch with a very high degree of physician enthusiasm that 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. And actually, in advance of approval, we'd already built a database that was over 3,000 people. And now, I checked last week, and it was over 4,000 people now. That's almost half the entire HAE population. So 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 biannual HAE patient summit actually was held. So 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, have a lot of work for 2 years prior to approval to get ready to launch and then have some lucky strikes like having the patient meeting happen 10 days later.

So part of the access -- 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 was a good try. Full credit. We're still -- we had a fiscal year that was off calendar. And so we closed our fiscal quarter on July 31. 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 -- frankly, just start forms through July 31. We'll have some other metrics as well. But then after that, we're going to switch to calendar quarter. So we'll also be giving an update in November on the data through September 30.

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 is less than 150 people total. And many of them are ex U.S. 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 made 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 3 approvals issued or pending and another 4 to come in the next 6 months, we can reasonably be a commercial company in 9 countries within 9 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 health care conference and doing the fireside chat. Always nice to see you. And congratulations on the progress.

Thanks for having us.

Good day, and thank you for standing by. Welcome to the KalVista Pharmaceuticals FDA approval call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to Ryan Baker, Head of Investor Relations. Please go ahead.

Thanks for joining us to discuss the U.S. FDA approval of sebetralstat, now known by the brand name EKTERLY, the first and only oral on-demand treatment for hereditary angioedema.

On the call with me today from KalVista are Ben Palleiko, Chief Executive Officer; Dr. Paul Audhya, Chief Medical Officer; and Nicole Sweeny, Chief Commercial Officer. Brian Piekos, Chief Financial Officer, will join us for the Q&A session. Ben will begin with an introduction, followed by Paul, who will provide an overview of the current HAE treatment landscape and highlights from the EKTERLY U.S. package insert. Nicole will then review the company's commercial strategy and launch plans. We will wrap up the call with a Q&A session. Please note that we will review a slide presentation during our webcast today, which will be posted to the KalVista website after the call.

Before we discuss today's news, I remind everyone that we will be making certain forward-looking statements that are based on our current expectations and beliefs. We encourage you to review Slide 2 of the accompanying presentation and our SEC filings, which include detailed discussions of the risks and uncertainties that could cause actual results to differ materially from today's forward-looking statements.

With that, I will now turn the call over to Ben.

Thank you, Ryan. Today is a monumental day for the HAE community and KalVista. We are pleased that the FDA has approved EKTERLY as the first and only oral on-demand treatment for hereditary angioedema attacks in people ages 12 and older. This approval represents a major milestone, not only as the first commercial product for KalVista, but more importantly, as the first new on-demand HAE therapy in over a decade. EKTERLY delivers a long-awaited treatment that is safe, effective and easy to take anytime and anywhere.

I first want to take a moment to thank the patients who participated in our clinical trials, the investigators around the world who conducted those trials, the HAEA and HAEi for their outstanding patient advocacy efforts and my fellow KalVista colleagues for making today possible.

The brand name EKTERLY is a call to action for people living with HAE who act early when treating their attacks. From its inception, EKTERLY was designed to enable people with HAE to comply with global guidelines, which strongly recommend treating attacks as early as possible prior to the progression of swelling, thereby avoiding disabling symptoms caused by HAE attacks.

EKTERLY represents our deep commitment to the HAE community. It reflects years of collaboration with people living with HAE to understand their experiences and significant need for an oral treatment that can easily be taken at the onset of an attack regardless of severity or wherever the patient is at the time an attack starts. Paul will discuss the label details in a few minutes. But as a headline, I will note that EKTERLY is approved for all HAE attacks with no restrictions either for severity or regarding the anatomic site of an attack, including the larynx, where speed and ease of administration can make a dramatic difference in treating an attack promptly. Given its unique efficacy and pristine safety profile, we believe EKTERLY is poised to become the foundational therapy for HAE management worldwide.

With that, I will now turn it over to Paul to discuss the current treatment landscape and then review key elements of the EKTERLY label.

Thank you, Ben. I'm Paul Audhya, Chief Medical Officer at KalVista. I'm excited to share some context to the EKTERLY label and take you through some of the key details.

As a reminder, hereditary angioedema or HAE is a rare genetic condition that affects approximately 1 in 35,000 to 50,000 people, roughly 8,000 people in the U.S. As you can see in the pictures, HAE causes unpredictable swelling attacks in various parts of the body, including the face and extremities. Swelling in the airway can be life-threatening if not treated. Attacks most often start as mild, but severity can increase quickly. They can also migrate to other anatomic locations, including larynx. Depending on the tissues affected, attack symptoms can last 1 or 2 days, but may persist for up to 5 days if left untreated.

As noted in the current treatment guidelines, the main goals of treatment in HAE are to achieve total control of the disease and to normalize the lives of patients. To realize those goals, there are 2 main strategies.

Number one, ensure that all HAE patients have ready access to effective on-demand treatment, which ideally offers rapid symptom relief, easy self-administration allowing for early treatment and a good safety profile. And number two, consider the addition of long-term prophylaxis or LTP in appropriate patients, which means evaluating the frequency and severity of attacks, the impact of those attacks on the patient's quality of life and whether adequate control has been achieved with an on-demand treatment. Let's spend some more time on that last one.

Treatment guidelines recommend that patients consider the treatment of all attacks regardless of severity as early as possible after onset to minimize symptoms and reduce attack duration. In order to achieve this, patients should be well trained and have ready access to adequate on-demand medication to treat at least 2 attacks. This translates to carrying the medication at all times when leaving home and within reach at home even at nighttime. However, all approved on-demand treatments require administration by subcutaneous injection or intravenous infusion, which present clear barriers for people living with HAE. Therefore, while injectable treatments may be efficacious, they may not be effective.

Common barriers to early treatment include anxiety associated with pain and injection site reactions, difficulty injecting and especially infusing treatment, the lack of a private and hygienic location to administer medication outside the home and challenges with portability. As a result, patients frequently avoid treatment. And for some, the therapy may be perceived as more painful or challenging than suffering from an attack. Indeed, observational studies revealed that up to half of attacks go untreated.

For attacks that are treated, patients often wait until the swelling becomes severe and thus delay therapy for hours. This is most dramatic in adolescents, a population where icatibant is not approved. And perhaps it's not surprising that given the logistical burden, less than 40% of patients carry their on-demand treatment all the time when traveling outside their homes.

Underutilization of injectable on-demand treatments in the form of delays and denial leads to inadequate control of HAE attacks. As a result, physicians and patients have turned to LTP as an easier alternative. Despite prior advancements in HAE, the promise of total control of disease and normalization of patient lives hasn't yet been achieved.

With the approval of EKTERLY, we believe the treatment paradigm is ready to change. For the first time, people living with HAE can take an oral on-demand treatment at the first sign of an attack and achieve symptom relief in the same time frame as injectable therapies. EKTERLY has the potential to transform the management of HAE, truly empowering patients to comply with the guidelines to help control and normalize their disease. It is reasonable to say that injections will never be normal. By overcoming the barriers imposed by injectables, EKTERLY is poised to become the new foundation of HAE treatment.

So with that background, I'm extremely pleased to share the prescribing highlights from the U.S. package insert. EKTERLY, an oral plasma kallikrein inhibitor is indicated for the treatment of acute attacks of hereditary angioedema in adult and pediatric patients aged 12 and older. EKTERLY has been approved with a recommended dose of 600 milligrams taken orally at the earliest recognition of an HAE attack. A second dose of 600 milligrams can be taken 3 hours after the first dose, if needed. The maximum recommended dose is 1,200 milligrams in any 24-hour period.

Further along, you'll note that there are no contraindications and actually no warnings or precautions at all. The adverse reactions, at the top on the right, only include headaches, which were noted to be uncommon but marginally higher than placebo.

Regarding the potential for drug interactions related to CYP3A4 or in the setting of hepatic impairment, dose reductions were recommended for strong and moderate CYP3A4 inhibitors and in those with moderate hepatic impairment. There are also recommendations to avoid the use of EKTERLY among those taking strong CYP3A4 inhibitors and moderate or strong CYP3A4 inducers as well as those with severe hepatic impairment. Overall, these represent an extremely uncommon group of patients.

Moving on, I'd like to walk you through some key takeaways from different sections in the label. First, in Section 1 on indications and usage, both adolescents and adults were included. Adolescents may be the population with the greatest unmet need as they have the longest treatment delays and difficulty managing their HAE attacks today. There is also no restriction on the type of HAE, so the opportunity to bring actually to all HAE patients in the U.S. with persisting unmet need is possible.

Additionally, you'll note that there are no restrictions with regard to attack severity or location, including laryngeal attacks and no restriction on LTP breakthrough attacks regardless of LTP mechanism of action. This represents the largest number of treated attacks in the U.S. as the majority of HAE patients are receiving LTP and many continue to have attacks in all locations and severities.

In Section 2, dosing and administration, EKTERLY's label is the only one to include at the earliest recognition of an acute HAE attack, which is at the very heart of treatment guidelines and reflects the most significant advance that comes with EKTERLY. We're also pleased that 600 milligrams is the recommended dose as we believe it provides a deeper longer inhibition of plasma kallikrein without any impact on safety. We also believe that 600 milligrams represents optimal dose for HAE attacks based on overall outcomes in the Phase III KONFIDENT trial and the extensive experience to date in the KONFIDENT's open-label extension. The flexibility to use second dose after 3 hours also exemplifies EKTERLY's excellent safety profile. All of this is consistent with Sections 4 and 5, where there are no contraindications, warnings or precautions.

Moving on to Section 6. The table says it all, adverse reactions only comprise headache, which occurred in about 3% of patients receiving EKTERLY 600 milligrams and 1% from placebo. Again, this reflects EKTERLY's pristine safety profile, which underlies the opportunity of 600 milligrams as the recommended dose.

Section 12.3, pharmacokinetics, you'll note 2 important recommendations. First, with 600 milligrams, there is greater than 90% inhibition of plasma kallikrein maintained through 6 hours, which supports optimal management of HAE attacks and increases the potential for low redose rates. The second is that there are no restrictions regarding food intake. In other words, EKTERLY can be taken with or without food. Lastly, in clinical studies, EKTERLY's label is the only one to include statistically significant faster times to begin symptom relief, reduction in attack severity and attack resolution.

Starting in the lower right-hand corner, the prespecified analysis of the primary endpoint of the Phase III KONFIDENT trial was published in the New England Journal of Medicine in May of 2024. There, the median time to beginning of symptom relief for EKTERLY 600 milligrams was 1.79 hours, and 6.72 hours for placebo. However, what you'll note in the clinical study section is that the medians are based on utilization of a more conservative sensoring approach to analyzing the primary endpoint. Basically, for about 5% of total attacks, patients didn't record responses to treatment in their e-diaries.

In the prespecified analysis, for those attacks, we censor them to 0, essentially counting them as neutral in the analysis as we don't know whether they improved or didn't improve over 12 hours. In the alternative analysis, these attacks were considered as not having reached the endpoint within 12 hours, i.e. right censored at 12 hours, which assumes the worst possible outcome.

To clarify this change in methodology, there is a footnote for each of the endpoints under each efficacy figure in the clinical study section. The result of this change was that the separation between EKTERLY 600 milligrams and placebo starts earlier and is wired, but it also shifted out the median slightly for EKTERLY 2.0 hours or about 12 minutes longer, but much further out for placebo, which no longer reached the median within 12 hours.

I'd like to finish this overview with some of the data we've reported this year from KONFIDENT, our ongoing 2-year open-label extension. As a reminder, this trial has many real-world design elements to gain insights on EKTERLY's potential to improve compliance with on-demand treatment guidelines.

First, among 1,706 attacks reported through September 14, 2024, we see a median time to treatment of just 10 minutes. We also observed a median time to end of attack progression of 19.8 minutes. This highlights a rapid response to treatment almost immediately after absorption of EKTERLY. Finally, we've seen a consistent rapid response among attacks that have been highlighted as the most concerning to physicians, including laryngeal, abdominal and LTP breakthrough attacks, all of which have demonstrated a median time to begin symptom relief of 1.3 hours.

On the right, as of June 2025, we've captured approximately 700 additional attacks since September 2024, which now includes 2,323 total attacks, 48 laryngeal attacks, 974 abdominal attacks and 463 LTP breakthrough attacks. Before KONFIDENT completes next year, it will be among the largest treatment experiences ever collected in a clinical trial for an on-demand product. We look forward to sharing new results from KONFIDENT later this year, including data on the very high level of treatment satisfaction among participants treating attacks with EKTERLY in the trial.

I'll now turn the call over to Nicole Sweeny, who will share how we plan to commercialize EKTERLY. Nicole?

Thank you, Paul. I'm Nicole Sweeny, Chief Commercial Officer of KalVista. I'm excited to talk about how we are working to put EKTERLY into patients' hands as soon as possible.

I want to reinforce a point that Ben shared earlier. EKTERLY is based on a call to action for people living with HAE to act early when it comes to treating their attacks. And for the first time ever with EKTERLY, they are able to do so. EKTERLY is the first and only oral on-demand HAE treatment. This allows patients to discreetly carry treatment with them at all times so they are prepared for their next attack. Each dose offers injection-like efficacy. It's proven to halt progression quickly and safely without any needles or pain.

EKTERLY has been demonstrated to be safe and effective in treating all attacks, all attack locations and all attack severity. Additionally, as Paul mentioned, EKTERLY has been FDA approved for use in adults and children 12 years of age and older. This is particularly meaningful for the adolescent population as Firazyr and icatibant are not approved for use.

Our commercial team will be selling EKTERLY in physician offices this morning. Our team is poised to drive swift demand. Our payer team has been educating national and regional payers for the past year. Our field sales team is competitively sized, which provides complete national coverage of HAE prescribers. Our commercial team has decades of combined experience in HAE, rare disease and high-performing product launches. Leadership and field teams include professionals who have successfully launched both prophylactic and on-demand HAE therapies.

As most sales reps have worked in the HAE space, they have strong relationships with target prescribers and knowledge of how these accounts adopt a new HAE therapy. Our field team is focused on driving early EKTERLY adoption with the top 1,000 health care professionals that account for 90% of HAE claims today as this is where the highest patient concentration and unmet need exists. They will reach the remaining 10% of prescribers as the summer progresses.

Our field team has been active in these target accounts since February, providing disease state education and will now pivot to product education. The team has appointments in place for the months following approval with virtual speaker education launches to reach the entire care team within key accounts.

Shifting gears to the patient community, our goal is to introduce EKTERLY and ensure people living with HAE can have informed discussions with their physicians about making a treatment change. Within a few weeks of launch, we will host patient education programs where patients who utilized EKTERLY in the Phase III clinical trial will share personal experience with the HAE community around the country.

In addition, we will participate in the HAEA Patient Summit meeting, which kicks off July 10. This meeting happens every few years and brings together people living with HAE and their families to connect and learn more about developments in HAE. For KalVista, this creates an opportunity to introduce EKTERLY to over 1,200 members of the community. It's a tremendous event and the HAEA is a deeply valued partner to KalVista.

On the access side, both our KalVista patient hub, KalVista Cares and QuickStart programs are live. QuickStart provides patients immediate access to EKTERLY at no charge during the time period their claim for paid access is in process. Each EKTERLY pack includes 2 doses or 4 tablets. Tablets are provided within wallet-sized blister cards, which provide discrete access to therapy. We anticipate product availability in mid-July.

EKTERLY is the first new on-demand treatment approved in over a decade and the first oral option ever. We continue to hear from health care professionals and patients that EKTERLY fills a clear unmet need in HAE treatment. We price EKTERLY competitive to existing branded therapies in the HAE market. We believe this pricing reflects the innovation we're bringing to the community and will support broad utilization.

Lastly, we've taken a comprehensive approach to ensure access support, which includes KalVista Cares, our patient hub. From reimbursement support to QuickStart Access, our infrastructure is built to minimize delays and help people start therapy quickly.

As a company, we understand the importance of delivering accurate and timely visibility into launch progress. Based on historical rare disease launches, we know that third-party data sources can often lag or present an incomplete picture, especially in the early weeks of commercialization. We recognize that we will need to share regular updates externally.

In the early days of launch, KPIs will focus on awareness and engagement efforts in the field as well as QuickStart demand. As launch progresses, we will share greater insights that reflect broad adoption by key stakeholders.

We're incredibly proud to introduce EKTERLY, the first oral on-demand HAE treatment, and believe there's a clear path for EKTERLY to become the foundational treatment in HAE. Our launch strategy is focused and intentional. Today, we will start by driving early demand with patients who have communicated the highest dissatisfaction with current therapies, particularly patients on Firazyr and icatibant. From there, we'll accelerate adoption by converting patients on all on-demand therapies.

As utilization expands and patients experience the benefits of EKTERLY, we expect treatment rates to rise and the on-demand market to grow. The opportunity is significant, and we are ready. The infrastructure is in place. Our field team is deployed, the KalVista Patient Support Hub is live. This is an immediate launch backed by years of preparation and deep expertise in HAE product launches.

I'll close by extending a heartfelt thank you to members of the HAE community who supported our trials and helped us reach this moment. We are excited to bring this life-changing treatment forward to the HAE community.

I'll now pass it back to Ben.

Thanks, Nicole. I'm picking up from where Nicole left off on this slide. We anticipate that the on-demand segment of the HAE market will grow by 70% to $1.2 billion by 2030, a significant portion of which will be fueled by the introduction of EKTERLY.

For the first time, patients have access to an oral on-demand treatment that provides the opportunity to change how and when attacks are treated. As a result, in addition to the general transition to EKTERLY that we expect, we also expect to see an increase in the overall attack treatment rate as people with HAE are more willing and able to treat attacks that currently may go untreated for many reasons.

With FDA approval of EKTERLY now secured in the U.S., we're also preparing for global expansion, beginning with a potential EMA decision and a targeted launch in Germany later this year. In the first half of 2026, we expect to launch in Japan in collaboration with our partner Kaken Pharmaceutical as well as in the U.K., pending local approvals. Additional market launches are planned in 2026 and beyond, including Canada, where we recently entered into a licensing agreement to support approval and commercialization.

As we finish this part of the call, a quick anecdote to highlight how we think EKTERLY can change HAE management. At a recent conference, I met with a physician who relayed to me a real-world story about one of his patients who's been using EKTERLY. She was driving her car to work one day recently when she felt an oncoming abdominal attack. Historically, she was due to the cat event, which would have made treatment of the impending attack impossible without major changes to her day and abdominal attacks are among the most painful to endure.

However, in this case, at the next stoplight, she pulled out her EKTERLY wallet, took her dose and continued to work. She reported to the physician at her next visit that her attack didn't progress further and within about an hour, she felt fine. This is exactly how people with HAE should be able to manage their disease and reflect the results we have seen to date in the data set that is closing in on 2,500 treated attacks.

This is also why we believe EKTERLY is poised to fundamentally transform the HAE treatment landscape. It has the potential to replace injectable, painful and cumbersome on-demand options with an oral therapy that directly addresses treatment burden while providing the necessary efficacy and safety that people living with HAE expect. We believe EKTERLY could become the treatment of choice among adolescents, adults and if approved in the future, pediatrics.

In closing, we're incredibly proud to bring EKTERLY to people living with HAE as an innovative oral therapy that redefines what's possible in HAE management, and we are fully committed to delivering its impact on day 1 and every day after. Our infrastructure, team and strategy are fully in place to deliver a successful launch and sustained performance, and we look forward to providing further updates in the near future.

With that, we'll now open the call for your questions.

[Operator Instructions] Our first question comes from Paul Matteis with Stifel.

Congrats on the approval. I was wondering if you could share more color on the metrics you plan on sharing early in the launch and how those metrics might evolve over time as you get more information? And then I have one follow-up.

Paul, thank you for the question. I'll actually ask Nicole to give the details there.

Sure. Paul, as shared earlier on our call, looking at the early days and weeks of launch, certainly, we plan to share forward information just about engagement with our key accounts in terms of the frequency and engagement with our Tier 1, 2 and 3 accounts as well as engagement with the patient community.

In addition to that, we will provide updates on demand in a general sense in terms of QuickStart requests and start forms that are being processed. And certainly, as the launch takes hold, what will be of keen interest to us as well as I'm sure you and others will be repeat use. So in the weeks and months following that we will share updates as we see repeat prescriptions coming through those key accounts as well as refills on a per patient basis.

In addition to that, during the course of the upcoming months, we will also provide a view into payer engagement and a view into how the formulary process is unfolding.

Okay. Great. And just two quick things to clarify here Nicole. One, in the open-label extension, what did you see in terms of the frequency of use? And do you think that's a good benchmark for real-world use?

And then two, on your point on getting on formulary, I guess, as I understand it right, everything in this category is reimbursed via special -- via medical exemption. So how much is actual formulary access going to matter here? And how much is payer access is really going to change over time?

Sure. And why don't I address your second question first, and then I'll turn it over to Paul.

As with other HAE products, we do anticipate in the early months of launch that medical exception will be the primary means for an individual to gain paid access to EKTERLY. Certainly, the payers have indicated that they typically take about 6 months to see how demand comes in for a new product, and then they'll set their formularies at the close of that 6-month time period. So again, as with other HAE products, we anticipate heavy medical exception for the first 6 months of post approval.

And then on the first question earlier around frequency of use in our open-label extension, we are seeing upwards of 80%, 85% of attacks being treated. So it's exactly what we expected that the rate would be much higher than we see in observational studies with the injectable drugs, which are basically have -- really to a maximum about 2/3. So this is really much higher.

Our next question comes from Maury Raycroft with Jefferies.

Congrats on the approval milestone. Just based on the patient interest you're seeing from your awareness website and doctor interest, how are you setting expectations for the early launch?

And then as a follow-up to Paul's question, can you talk more about how you'll customize drug supply for patients with different monthly attack rates? And what you think the typical prescription and supply will look like for patients?

So Maury, so we -- on the second part at least, going to the last part first, we have the KalVista Cares, as we talked about, set up as an organization that will be in close contact with patients as we go forward. And so the idea here is that patients will get their initial box of EKTERLY, but we'll be checking with them routinely to make sure that their supplies aren't running low and making sure they always have sufficient on hand to be comfortable treating attacks.

We do know that one of the reasons people don't treat attacks is the fact that they worry about not having available when needed. So the idea is to make sure that they're never in that position.

And then on the first part of the question, Nicole can you please take that?

In terms of the prescriptions and how we anticipate the physician writing a prescription for EKTERLY, we anticipate that the initial fill will be for one box of EKTERLY and then they will write similar as they do to other on-demand treatments, PRN, refill as needed. And that is an approach physicians take today, recognizing that the burden of disease and the number of attacks really varies from one of their patients to the next. So therefore, we anticipate, again, they would take that similar PRN approach for EKTERLY.

Our next question comes from Debanjana Chatterjee with Jones.

Congrats on the approval. Could you expand a little bit more on the drug interactions labels and how it might have any influence on the uptake?

So in terms of drug-drug interactions, we did some studies. We see that with moderate CYP3A4 inhibitors or those that have stronger inhibition or induction that it can increase or decrease the concentration. It's overall a relatively small population that have these other drugs on board. So we don't actually think that it's going to have very much impact at all.

In terms of the exposure or experience that we've had with this in doing our open-label extension in our clinical trials, there are very, very few patients who were not eligible due to use of these other therapies. So we don't think it's going to really have any material impact.

And again, just as a reminder, HAE patients are patients who don't have a significant number of other comorbidities. And because of that, they're not really using these drugs in a meaningful way. So we don't think it will have any impairment on uptake.

And I have a quick follow-up. How should we think about the gross to net as the launch progresses?

We're going to bring Brian Piekos in here to pick up those questions.

So the gross to net will be on a long-term basis, typical for what you see in rare disease in the upper teens to low 20s. As we're getting to the launch and there are some fixed fees, the gross to net may be slightly higher. But again, it will quickly normalize to that rate we've talked about.

Our next question comes from Joe Schwartz with Leerink Partners.

Congrats on the great achievement. Do you see different phases to EKTERLY launch? For example, are there early, mid and later adopters? And how would you characterize different subgroups as you look at the HAE patient population? And then I have a follow-up.

Yes. So Joe, I'll start, and I think Nicole can [indiscernible] in here.

When we talk to physicians, we do hear that effectively, they believe EKTERLY is appropriate for everybody. So we don't actually see them making distinctions between different populations that might have a greater or lesser need for it. They seems to be very confident that there's a uniform desire among the patient population to have access to this.

And I think the data set we've generated, which shows efficacy in all these important subgroups, right? I mean, abdominal attacks and people on LTP and certainly laryngeal attacks, that has really become the basis of this physician enthusiasm, which is there's effectively no subgroup where we've shown that this doesn't have a substantial improvement in terms of their time to symptom relief and sort of control of their attacks.

So as a general comment, which may be a little bit simple, the physician community, we think is going to want to talk to effectively everybody about this.

Now in terms of -- from the patient side, where the greatest [indiscernible] will be, certainly, Nicole, you've got some thoughts on that, and we can talk a little more detail about who we think will be the first calls to the offices?

Yes, absolutely. With research that we've conducted with patients that are utilizing various on-demand as well as prophylactic plus on-demand treatment, we see that the patients that have experienced and are currently on icatibant and Firazyr see the -- express the greatest interest in adopting EKTERLY swiftly. And that was about 80% of the Firazyr and icatibant patients communicating a high interest in adopting EKTERLY.

And just one other thought going back to the physician side of things. As our sales team has been in the field profiling all of the physicians, all 2,000 physicians, the Tier 1s, 2s and 3s, we see interest -- and high interest to utilize EKTERLY throughout those tiers. But to answer your question, we certainly anticipate the earliest adoption, those earliest prescriptions to come in from the Tier 1 physicians as they manage those patients that have the highest unmet need and really signal that the highest urgency to try something new with EKTERLY.

That's very helpful color. And then as a follow-up, I'm just wondering, it's actually a question we get from investors pretty frequently. What will a patient or their physician need to demonstrate in order for a patient who's on generic icatibant to be eligible for EKTERLY prescription?

Yes. Today, that is -- today, there are patients that -- to move off icatibant. I think that's what you're referring to, to demonstrate that failure on icatibant. It's actually a fairly low bar in terms of what is utilized today. And so really it can be feedback from the physician and the patient, recognizing that the patient doesn't tolerate that product. That can be injection site reactions as well as specific reactions that happen in the abdomen area as that is where the product is administered and oftentimes, individuals have abdominal attacks.

But we most commonly hear that it's just injection site reaction of any kind, which, as you know, being familiar with the Firazyr Phase III study, nearly all patients in the Phase III studies experienced those reactions. So again, fairly common and something that can be moved forward fairly quickly in terms of demonstrating a failure on icatibant.

Our next question comes from the line of Serge Belanger with Needham.

Congrats on the approval. The first question regarding for a potential second dose. I think in the KONFIDENT trial, about 40 patients redosed, I'm not sure what you've been seeing in the KONFIDENT-S open-label trial, but just curious what level of redosing do you expect to see in the real world?

And then secondly, does ORLADEYO represent kind of a potential proxy for what the EKTERLY launch could look like, at least in the initial stage?

I'll take the first part. So with regard to the redose rate, you're correct in KONFIDENT, which was the double-blind study, patients have the option to take an additional dose in 3 hours. And there were very few restrictions in that regard and many patients went in and took advantage of the opportunity to take the additional dose.

In the real-world study KONFIDENT, what we see there is about a 22%, 23% redose rate with the same dose that's approved in the label. So that's what we do expect to see in the real world. We've seen over 2,300 attacks treated. And so the exposure that we've learned is good.

And again, just to remember, as a comparator with Firazyr, that tends to be between 25% and 40%, depending on the observational data that you look at. So this is certainly well in line, if not a little bit less.

I'll turn over the second part around ORLADEYO.

It's important to remember with regard to ORLADEYO launch that prophylaxis has got a fundamentally different sort of revenue profile because obviously, when people start paying commercially, that's a constant number. So I think what we've consistently said to folks is in terms of the uptake, sort of a unit type curve, we do expect it to follow kind of a traditional launch curve. And you can even look back to the Firazyr curve to get a good idea, but the Firazyr curve, frankly, looks a lot like the ORLADEYO curve from a units perspective.

From a revenue perspective, it will certainly be somewhat different. It will be a little bit of a longer initial point to get to the revenue side just because, again, people are refilling as needed and because of the QuickStart program, effectively, everybody will get their initial box without the payment. So again, the curve overall, we think looks about the same, but when we talk about that, we focus really more on the unit curve as opposed to the revenue curve.

Our next question comes from the line of Stacy Ku with TD Cowen.

Congratulations on the EKTERLY approval. And we noticed that it's just in time for the HAE community patient summit, which should be key.

So our first question is on the first-mover advantage that you all have. Can you discuss how you could really fully execute on that? It sounds like you're getting a running start with clinician outreach today. So just remind us what's the expected timing for your sales force to reach and educate the [indiscernible] prescribers, which we believe you said in the past, you've already kind of had a lot of interaction with. So that's the first question.

And then the second is on EKTERLY and Firazyr efficacy. So in general, our KOLs view the Phase III and open-label extension data as showing similar efficacy. But Nicole, kind of based on your commentary on prescriber and patient activation, can you just go into more detail around the launch strategy that you think is key for helping clinicians and patients gain experience just to ensure that the community gets the same conviction as KOLs that EKTERLY is performing similarly to Firazyr?

I'll start and you can [indiscernible]. So in terms of the first-mover advantage, we've got a lot of things we put in place here over the last several years actually and pretty intensively over the last 6 months. As you know, Stacy, we've had a field team out doing physician education and activities since late February. And so of the 2,000 physicians who are in our database, they've contacted all except maybe a relatively small number of the Tier 3 types. All Tier 1, which is about 200 physicians, I'm quite sure we've seen multiple times at this point. The Tier 2s, which is the next 800, we've seen most of them multiple times. And so there's a very high level of awareness in the physician side here that we're comfortable is going to come to play here to our benefit.

On the patient side, obviously, you really can't do any of those activities until approval. But we have, over the past year, developed a database of patients who chose to opt in to communications from the company. And that as of approval is just shy of 3,000 patients, which again is certainly 1/3, maybe closer to 1/2 of the entire population in the U.S. So a very sizable group of people who indicated desire to get more information. And as of today, they will start to get that information. So that's going to very quickly move out to them. And that will only be enhanced by the patient summit that starts at the end of this week. That has between 1,200 and 1,500 attendees typically. And so that's another terrific group for us to get to. So the activities have started today. The field team is actually already out and making calls as of this morning. And a lot of these communications have already been kicked into gear and will sort of escalate here over the next few weeks. So the desire, the goal is to obviously very quickly get as broader reach as we can here with both those populations, get everybody activated and allow us to sort of move at a fairly rapid play. And then I'll bring you to the second part?

Yes. So Stacy, just in terms of the ideal launch and how this all needs to come together. As we've talked about in the past, it's really making sure that we're supporting both the offices and the patients to have that dialogue as soon as possible regarding making a treatment change to EKTERLY.

And from the office side of things, just to expand upon some of the work that's underway. The team is in the field profiling accounts, and they profiled all 2,000 accounts, so all of the prescribing HCPs. They were able to get a sense from the accounts whether or not -- the degree, I should say, to which the accounts saw and recognized a high unmet need for a new on-demand treatment. And so that is what -- those insights are what we've utilized to really prioritize the accounts in particularly for the first 90 days.

As you can imagine, we had lengthy business plan reviews to go through to see where the potential opportunity is for all of those accounts, specifically looking at the first 3 months of launch. In addition to that, as Ben was mentioning, we have planned supportive education programs, not only with the physicians, but with all of the care team members in those accounts. We will be having speaker education programs with key opinion leaders to share their experience from the clinical trials with all of those accounts.

And then on the patient side of things, we'll build upon the Patient Summit, which is coming up this Thursday, where we have a number of educational programs to reach patients throughout the country. And this is important because we will have patients from our Phase III trial share their trial experience with EKTERLY with other members of the patient community. This is something that has been absolutely critical to the success of other launches in HAE.

And the last point that I'll mention is from patients as we've gone and done a number of research, when it comes to adopting a new HAE therapy, some of the common barriers that we've heard relate to concerns about access or potentially the efficacy of the product. And again, this is any HAE therapy. Those are the barriers. And that's really where the QuickStart program plays a key role because it allows not only the physician to prescribe and get that experience, but more importantly, the patient that they can get that real-world experience with the drug to build the trust and really start to fully adopt that product while our team, the KalVista Cares team, works rapidly to ensure paid access. But those are probably some of the key elements.

And as the last point, I'll just say that we didn't want to talk about too much today because it's a future set of presentations for us. But we've obviously started to do some surveys already in terms of patient satisfaction, treatment attacks effect. And suffice to say, they are extraordinarily high. There's a lot of patients with the enthusiasm for how well this works.

So that's the kind of data set that will start to flow out later on this year at scientific conferences and things to start to give more evidence about how well this actually works [indiscernible] compared to their current therapies, which as we've said before, in most cases, [indiscernible] Firazyr.

Our next question comes from Tazeen Ahmad with Bank of America.

A couple for me. Can you clarify whether or not you're going to be doing sampling in the early part of the launch and how we would get color on how much of use could be coming from sampling if you are doing that?

And then secondly, with regards to the label, it's allowing a second 600 mg dose to be used if there's an inadequate response or recurrence after 3 hours. Wanted to ask about how you expect that to work in a real-world setting and how that compared to what you saw in the KONFIDENT study?

For your question regarding sampling. At this time, we are not planning to introduce the sample program into the communities. Our view is that the QuickStart program, which is important to note, allows that free product for that, allowing that immediate utilization of EKTERLY, but that is done in parallel with the start form. And so from our view, we want to make sure that not only we're providing free access to therapy, but also in parallel, moving forward to obtain that paid access for the individual. So again, we do not plan on utilizing a sampling program at this time.

And I'll turn it over to Paul for the second part of your question.

So in KONFIDENT, which is actually our open-label extension kind of set up like a real-world study, where patients make all the decisions as to how they're going to dose and when they're going to use therapy. We've seen that patients will, in fact, choose to use that about 22%, 23% of the time with that 600-milligram dose. So that's what we expect to see in the real world.

Again, this is just going to be pretty typical for these medications. Most of the therapies that are here to allow for redosing. Obviously, the benefit for us is that it can happen in a shorter time frame than Firazyr, for example, which is 6 hours. Here, after about 3 hours, the patient will be educated that they can take additional doses if needed. We've had really no issues with understanding on that front. Over 2,300 attacks have been treated in that open-label extension state. And as I mentioned, in those 20% of cases, there are really no issues with redosing.

They also have portable packs that they could carry with them in the open-label extension, which is quite similar to what we'll have with the launch. Actually, what it will be with the launch will be far easier than what we have in the clinical study. But even there, we had no issues with the understanding as to when to take it and under what circumstances a patient might need it.

Our next question comes from Pete Stavropoulos with Cantor Fitzgerald.

Congratulations on the approval. Nice to see this get over the goal line. So there are about 100, 130 patients in the KONFIDENT-S, the OLE, over 2,300 attacks treated. Curious to hear the feedback that you're getting from treating physicians and patients in terms of the comfort level around using EKTERLY?

And any new trends? I know you mentioned about 23% redosing. Any new trends on taking the second dose to treat an attack as these patients get experience with the drug? And any sense on the impact on the quality of life for these patients? That's the first question.

And the second question I have is, as you touched on different patient populations and expectations for uptake, those on LTP and those on-demand only, do you have a sense of the ease of getting a prior authorization for those different populations? Will they be similar? Or do you expect differences?

Okay. So on the first question with regard to taking the second dose, what we have seen over time is that actually the proportion of patients who take -- or proportion of cats, which is second dose used actually is trending downwards a little bit. And so that's the trend we've detected to date.

We've done 2 interim analyses, one in January of 2024 and then again in September. And we will be cutting that data again later on this year to be able to see if there are any additional changes. But it has kind of stabilized around that 22% number, which again falls into line with what we may have expected.

In terms of quality of life, we didn't have specific quality of life measures set up just because it's an intermittently dosed drug. But what we have observed in our preliminary assessment of satisfaction is that there are very, very high rates of satisfaction among the patients for each attack. So 24 hours, we ask the patient how satisfied are you with basically actually for this attack. And we see very, very high rates. We'll be putting out data later this year to highlight that.

But what we're seeing is that patients are treating large numbers of attacks. We have some patients who have treated over 60 or 70 attacks over the last couple of years and consistently have seen positive results and haven't really opted to change their therapy. Most of them are using it into and through the course of the full 2 years of the study. We'll start seeing all the patients coming off next year. But a number of those have even transitioned to early access. And so there's been a consistent interest in including dosing with EKTERLY. So all positive.

I think the slide that Paul presented really shows everything that's really important, which is all the data continues in the open label to look, if anything, better than it did in Phase III. I mean time to treatment is really short, high proportion of attacks treated. The time initial symptom relief, especially in these important subpopulations we've looked at recently is really impressive, down to about 1.3 hours. We think that's a terrific number.

So the open label, again, being more real world has certainly evolved over the longer time into what we think is an even stronger proposition in terms of the value of the advantage it can offer to people HAE.

Nicole, do you want to cover the other question?

Sure, absolutely. In terms of prior authorization, today, nearly all patients on a prophylactic treatment also have access to an on-demand treatment. And so whether a patient is on prophylaxis or not, the requirements for PA for the on-demand treatment are essentially the same. So we don't anticipate that to be any different relative to EKTERLY.

And it's important to note also that essentially everybody has a prescription for an on-demand medication, whether or not they use prophylaxis. I mean it's probably more than 90% [indiscernible]. So there is no difference in the need for prescription or any way of how one gets it filled.

No. I mean when I say prior authorization, I don't mean for an on-demand treatment itself, but basically, let's say, 2 branded drugs, LTP versus on-demand. Any point...

No. I mean, people have that nowadays. There's quite -- RUCONEST, right; BERINERT, KALBITOR, they're all approved. They're all branded and there's no differential for that.

Our next question comes from Jon Wolleben with Citizens.

I know you guys gave us the metrics you'll be looking at early and mid-launch with the expectation revenue may lag some of those early indicators. I was hoping you could give us some of your internal benchmarks on how things should be tracking so we can see if you guys are hitting your internal targets and how things are progressing relatively early on?

Yes, Jon, we -- as you know, and I think as is extraordinarily common in these kind of situations, we're not really talking about what we expect the numbers to do, especially in the early days where you can have a lot of variability and where a lot of the day-to-day information is not really all that helpful, frankly.

We have, however, committed to providing reasonably fulsome updates when we have the opportunity and certainly as the launch progresses. So we are going to ensure that we give people access to the important information they need to make their own decisions as to how the launch is progressing. But I'm not sure it's particularly helpful at this point to give really granular thoughts on how it might go, especially in the early days. These things take a little bit of time to get started, and we want to give the team the ability to get out there and really start to have some high-quality interactions and build base here in the early days.

Okay. I might have missed this. Can you just talk payer mix and then also your expectations for adolescent use? I'll jump back in the queue.

Sure. So I'm glad to address your question on the payer mix. In HAE today, it's about 70% that are on the commercial payer side, the private payers, and then about 28% that is Medicare, 4% Medicaid and then a single percentage point that is cash. And so that is what we see in the marketplace, and we would expect use of EKTERLY would mirror that.

And in terms of adolescents, it's well known that they have the longest delays in times in terms of time to treatment, in terms of treatment proportion of attacks, like there's a lot of unmet need there. So despite the fact that it's obviously a smaller subpopulation, we do think that the opportunity for adolescents to make use of this is really high, and we expect there to be a pretty significant level of [indiscernible].

That concludes today's question-and-answer session. I'd like to turn the call back to Ben Palleiko for closing remarks.

Again, thank you all for joining us today, and thank you for being part of the journey so far. We do look forward to the next opportunity to provide an update on our progress with EKTERLY. And with that, we're off to work here. And we wish you all the best rest of the day. Thank you. Bye.

This concludes today's conference call. Thank you for participating. You may now disconnect.

Good morning, everyone. My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. It's with great pleasure that I'd like to welcome Ben Palleiko, the CEO of KalVista. Thanks so much for joining us, Ben. And for those who are new to the company, maybe give a 1-minute intro to KalVista.

Absolutely. All right. Well, first off, thanks, Maury, for having us here, and thanks to Jefferies for the continuing support along the way. KalVista Pharmaceuticals is a soon to be commercial company. We are developing sebetralstat for the on-demand treatment of hereditary angioedema. We have a PDUFA date at the FDA of June 17, so right around the corner. And although that's the biggest near-term event for us, we also have multiple other filings around the world, and we expect to be in a position to get a European approval later this year and launch there and get approval and launch in Japan early next year. So on the way to ideally being a global commercial organization here over the course of 2025.

Got it. Yes, it's a great intro, and you're in the home stretch with the approval coming up in less than 2 weeks. And it would make your drug sebetralstat, the first oral on-demand drug to enter the market. What can you share about your latest interactions with FDA? What's been discussed and what still needs to be addressed? And is everything on track for the PDUFA?

As far as we know, everything is on track for the PDUFA. The FDA, despite all the concerns you've kind of heard generally, we've seen no disruptions along the way. Our review team hasn't changed. All the people have always been in the meetings who need to be. All the time lines have been met. So there's been no disruption whatsoever with the FDA. As far as we can tell, we're coming down to the wire, obviously. We've said for a while, we've been in label discussions. There's always a little bit of back and forth on that, but that seems to all be going well from our perspective, and we continue to think they're right on time, and they'll meet the date.

Got it. And what's the latest you can say related to key discussion points and what's going to be included on the label?

At this point, it's really down to some minor details, tables in or out, think the way things are formatted like there's not a lot -- there's no real existential issues involved here from our perspective.

Got it. And you've mentioned in the past, you expect it's going to be a broad label as far as region, attack severity. Anything you could say on redosing and whether that's going to be called out in the label?

Right. So we do expect it to be broadly for the treatment of acute HAE attacks. We do expect it to include adolescents and up. Again, adolescents, we don't talk about much, but that's a group with really high unmet need because functionally, all they have available nowadays under age 18 is intravenous therapies. So a lot of unmet need there. We don't expect to have any restrictions on laryngeal attacks. So we think that will be covered. And obviously, all the other severities would be as well. So I think we do think the label is going to be very favorable. And so we're just kind of -- just sort of selling in on that with them.

Got it. Okay. And what can you say about how packaging is going to work commercially?

It will be boxed with individual doses in wallets. And each box will contain multiple doses. We haven't really talked about that yet. You asked about the redosing in a minute bit, it probably a little bit depends on where the FDA comes in on some of those topics. But we have it all kind of ready to roll here once we get the final label settled.

Got it. Okay. So when you get the approval, we'll learn more of these details, and we'll see the label. We'll...

Yes. Yes. Our plan is to have a post-PDUFA conference call where we'll talk about all these details.

Got it. Okay. That's helpful. And thinking about the launch, can you give us an update on your team's latest efforts in getting ready for the launch in terms of doctor-patient engagement, sales force, supply chain, et cetera? And where are you spending the most time and what else seems to be done?

Yes. Yes, I had the great pleasure of spending the last 2 days actually at an off-site that our commercial team had this week where they're going through their final training to get their certifications to be actually able to go out and start actually talking to offices about the drug post approval. And it's a terrific group. I mean I think I've said before, we've got a -- even though this as a company is our first launch, we have a tremendous amount of experience in HAE. All of our senior leadership have actually launched multiple products in HAE previously. Over half of the field team either has been in HAE or was currently HAE when they joined us. So this is a space we know really well.

The team is really fully prepped and ready to go. They -- again, this week has been all about getting the final training, going through the final marketing materials and the visual aids and things of that sort. So a really granular set of conversations. In terms of what they've done up to now to get ready, I've said before, there's about 2,000 physicians in the space who really ever write a prescription, and we tier them out with being about 200 physicians write half the scripts, about 90% are written by 1,000 physicians and then the other 1,000 are the small numbers.

When we got started, we'd have been pretty satisfied if the team had really just profiled all of Tier 1 and most of Tier 2. So we were -- we thought that was a fairly ambitious goal. Actually, as I learned this week, they've profiled almost every one of the 2,000 positions. They've gotten virtually all of the Tier 1s like literally with the exception of maybe 1 or 2 docs. Tier 2, 95%, 98% of them, they've done and again, almost all of the Tier 3s even. So we have profiled and actually interacted with essentially all physicians who prescribe in the space at this point. From -- so we're -- and we're very comfortable based upon the enthusiasm we hear with physicians that they'll be supportive here.

From the patient side, obviously, none of that really you can start until post approval. But we've said before that we have been building a database where patients can opt into. And as of this week, I learned we have 2,700 people in that list. So that is probably 1/3 of the addressable population in its entirety. So assuming the FDA approves it on time, we think we're going to be in a really good position to very quickly get out to those folks and start to get the word spread.

From a supply chain perspective, again, we have a really good supply chain team that's very experienced and everything has been settled. We've got the whole chain set. We've got the drug ready to go. I mean all we really need literally is the package insert and then box it up and ship it. So we'll be able to move very quickly post approval to get this out into the marketplace.

Got it. So if you've interacted with most of the 2,000 doctors, you've got 2,700 potential patients signed up. It means there's pretty good awareness overall?

Yes. Yes. We think the awareness is -- among physicians, it's obviously extraordinarily high because, again, we've had a medical affairs team that's been out talking to these people in some cases, for 3 years. So the physician community, I think the awareness is very high. Patient awareness obviously lags a little bit because it has to. But I will say I was fairly astonished to hear that we had that many people already who had shown interest, again, without us actually in any way promoting this to them. So I think that just really indicates how high the organic interest is in the therapy of this kind and how much people are really searching for an oral option. So I think we're quite pleased with where we stand now. And it's important to note, though, that we're not just resting on that. We have a very aggressive plan to get out and raise awareness extraordinarily quickly post approval.

Got it. And you mentioned the experience on the sales team. You've got a Chief Commercial Officer who has pretty strong experience from prior launches. Maybe just talk about her background and what you guys have learned from prior launches and what you want to leverage and avoid.

Yes. So again, tying back to the strength of the team here in place. So right, so our Chief Commercial Officer, Nicole Sweeny, actually has done -- launched both FIRAZYR and TAKHZYRO at Takeda. So -- and she ran the HAE franchise at Takeda. So she's obviously extraordinary experienced in the space. Our Head of U.S. Sales and Marketing also launched both drugs in the space. Our Head of Europe has actually launched 3 drugs. She launched BERINERT as well. Our Head of Japan launched FIRAZYR in Japan. Our Head of the Patient Hub ran a rare disease hub at another large Japanese pharmaceuticals company. We have -- again, I told you that over half the field team has been in HAE or was currently. So there's -- for a first-time launch company, we have an extraordinarily high level of awareness, understanding and just knowledge about this marketplace that I think really positions us well and has put us in a place where even though we're going out with this early drug, we've got field reps who are very well known to the offices they're calling on, have great relationships, and I think that's going to carry through.

Got it. And what feedback have you received from payers on pricing and potential generic step edits?

It's important to note that HAE is a pretty small category for payers generally. And within that category, prophylaxis is the big -- far and away, the biggest expense for payers. So on-demand is a fairly small portion of a fairly small category anyway. The -- however, obviously, we don't take anything for granted. We've gone into the payers over time here with, I think, a very strong value proposition, talking about all the things we've talked about with the investor community as well for years, right? The fact that people don't treat enough attacks that they have all these debilitating symptoms as a result of it, the fact that on occasion, they end up in the emergency room as a result of this, which obviously makes the cost of it skyrocket.

So we've come in with a very strong value proposition. And at this point, we've talked to over 60 payers, just to give you a sense of the number of these pre-approval payer interaction meetings we've had. So we've not taken for granted the fact that this is a very efficacious drug and it's safe. We've really gone in and talked to them about how this is actually going to benefit patients and be worthwhile within the category, even though there's other options in the category. And the reception has been very strong as a result.

We've consistently said that the price range that exists on on-demand therapies, if you look at it on a per dose basis is somewhere between roughly sort of $12,000 and $16,000. We think it's completely appropriate to price within that range. We don't -- we're not -- we don't need to be heroic here about looking for premiums. We think that will yield us with a very favorable access profile, certainly on par with the other therapies out there. And in many cases, I think maybe we might do better. But formulary conversations will roll out over the next 6 months.

And that ties into things like step edits. We don't really -- I mean, obviously, if you talk to 60 people, you get some opinions on everything. But we don't really think step edits are a significant issue. There's definitely a step through to branded FIRAZYR. Most payers have that. So you have to step through generic to get the branded FIRAZYR. But I'm not actually aware of any payers that have -- require a step to current -- through generic icatibant to current branded therapies. And so we don't really expect that to be an issue for us as well.

Got it. And is that the same -- or do you see any trends for that based on the commercial payers versus the Medicare, Medicaid focused payers, on just the step edit question.

Yes. No, I'm thinking about it. No, actually, to date, we don't really see any differentiation at all. People get the fact that people have generic -- I mean, something like 80% of all HAE people have had or currently have generic icatibant. So the exposure to generic icatibant is extremely broad. So the truth is even if people did want to consider a step, pragmatically, people have already kind of gone through it. And that doesn't matter whether they're commercial or government pay, which, again, is not a huge share for us of the overall universe. This is roughly a 70% commercial space. And almost all the rest is actually Medicare.

Right. Okay. Helpful. And wondering if there's a scenario where oral convenience works better than expected and patients are, a, running out of drug too quickly; or b, you start getting payer pushback based on the amount of drug used.

Yes. We thought about this. The -- it is true that when you talk to people about why they don't treat attacks, commonly, it's because basically, I didn't have my whatever, my icatibant with me or I'm just reluctant to use it because of the pain, the logistics, the whatever. But you're spot on that you do hear when you talk to people that there is an issue sometimes that I'm worrying that if they use it up for less severe attacks when they have a really severe attack, a laryngeal attack that they may not have it available. So ensuring that people have constant access to the therapy has, for a long time, been one of our primary concerns. And so as we've set up the patient support services activity, we have talked about that.

And so what -- and the way you deal with that is, especially in this on-demand space where people have to -- there's a refill that's required to sort of get done, we have worked through a plan where there'll be a fairly routine set of our reach to people, especially in the early days when they're trying to settle in and understand how the therapy works, both to make sure they're having a positive experience generally, right, support them as they need, but also to make sure that they're not in a position where they worry about running out of drug. And so our team is prepared to, as part of those conversations, make sure that people always have sufficient amounts on hand. And to the extent they're running out ahead of schedule or there's some other challenge to help them sort through that to make sure they always have what they need. So that's a great question.

In terms of how that works with payers, the truth is we'll see. For the first year or so, realistically, payers are going to sort of roll with it and see how their experience develops. I mean, we expect to start -- I mean, like everyone, it always takes 6 months really to get formulary. So we'll work through that process. But there's going to have to be some water that goes under the bridge here before they actually come to some conclusions about what the usage rates are like. And those may bounce around a little bit as people are experimenting with the drug and finding out what works for them best. So we'll -- if that becomes an issue for payers, we'll work through it. But realistically, that's little ways off for us.

Yes. It could be a good problem to have at that point. And so you commented during your Investor Commercial Day that the plan is to share more insights on launch metrics as the launch advances. What are the metrics that you plan to share early on? And how do you expect these metrics to evolve as the launch advances?

Yes. Yes. The early data set is largely interaction-based, right? It's physician interactions. It's -- there'll be some patient kind of outreach numbers, those kind of things. That will fairly quickly evolve into things like quick start forms, right, that we'll start to talk about. And then as you move a little further in the launch, you start getting into physician -- multiple prescriptions written by physicians. You'll obviously start to move into refill metrics. right? That's probably toward the tail end of the year by the time we get to refills. So we'll have a steady cadence. I don't think it's a whole lot different than what anybody else puts out there nowadays, honestly. But we're cognizant of the fact that we have to provide these metrics for people to understand the launch. And so what we have said is we'll put out whatever we can that's useful to make sure that people have the adequate information to understand where things stand.

Got it. Okay. Makes sense. And any thoughts on just how you're setting expectations for the launch. Consensus numbers, I was looking at those the other day, they're higher than where we're at currently. I don't know what your thoughts are for like the first couple of quarters, if you can comment on that.

Yes. There's probably a little bit more than an average dispersion of views on the launch, right, because it's a little bit -- I mean, there hasn't been a launch like this in a long time. And so I do think one of the challenges people have is trying to model it. That's one of the reasons we tell people we're going to -- we'll provide this kind of fulsome set of data because it is definitely trickier than average because, again, people have to get refills. We haven't guided to any of the numbers. We don't really comment on where the Street stands. I think all we tell people is that we think the fundamentals are good here. I mean, again, it's an efficacious drug. It's utterly been shown to be safe in multiple clinical trials. We think physicians have high awareness and high enthusiasm. We think patients will as well. So we're optimistic. But again, we don't take anything for granted and the plan is to get out there and work hard to make sure that we make this go as well as we'd like it to.

Got it. Okay. And where do you expect first adopters to come from? You mentioned the database already where you've got 2,700 people signed up. But can you talk -- also talk about the use of free drug initially and maybe early launch incentives to get patients to try the drug out?

Yes. Yes. If you talk to physicians, they will -- about who they think is going to be an appropriate patient for this. Almost uniformly, and this almost makes it harder, they say everybody. Like there's really no subset they will point you to. So the question becomes who's going to be more motivated, right, to sort of call their physician and get out there to get it early. There's clearly a subset of patients that have very high on-demand usage rates. And so a priori, I think our expectation would be they're most likely to be the ones who are enthusiastic about getting in.

But certainly, as part of the practice profiling effort, when our team goes in and sits down with physicians to the extent that everyone is willing, we'll talk about in general terms, like what a panel -- what the patient panel looks like, what the need is, right? And physicians will, at some level, create their own list of -- and in fact, some of them explicitly have created their own list of here's my first contacts, right, of people I'll go to. I do think that's generally going to be more likely to be the high burden patients, although the truth is it's kind of -- it's almost anybody's guess.

That's one of the reasons we have said that in the early days, there could -- the uptake curve could be a little jagged because you can certainly see the case, especially when you have small numbers of patients on therapy, where one week you get a bunch of high-use patients and the next week, you get a bunch of lower use patients. And so the numbers kind of may move a little bit. So we will -- I guess, at some level, just like everybody else, we'll see. But we've put a lot of effort into working with the physician offices to help them understand their patient panel, talk about where those people's needs stand and make sure that -- to the extent possible that they're being contacted -- the highest-need people are being contacted early.

Got it. And for prescribers, you mentioned like the Tier 1, Tier 2. Are the Tier 1 prescribers going to be the ones that are prescribing the most initially? Or do you think -- I guess, how do you see that playing out? Are they going to be more reluctant to change all their patients over?

Yes. We -- frankly, Tier 1s probably have the highest level of enthusiasm because they're the ones that have known this drug for the longest, right? That is the group we have been talking to for 3 years. Certainly, the Tier 3s, if anything, are the people who we haven't spent as much time with to date and who may be a little slower on the uptake. But the Tier 1s, again, they're half the prescription volume just by themselves. We think that there's a very high level of enthusiasm. We know a fair number of those people that are proactively planning to call effectively all their patients very quickly and sort of introduce to them as an option. And we'll have some different support mechanisms for them to do that outreach as well. And so I think it's very likely that rather than being reluctant, actually, they're probably the most eager prescribers.

In terms of adoption, to your point, like the risk of it, people tend to have some amount of icatibant or whatever else they use on hand. And so in terms of the transition over, to the extent -- and I think it's not unlikely that there's some concern among patients that they're trying a new therapy and they want to make sure it works for them. But they're all going to have probably to a great extent, this kind of safety net of whatever they were using previously, they'll still have some on hand. And definitely, that's something we're aware of. I mean, when you take icatibant, it hurts, like it hurts to inject yourself, obviously, but the drug is really acidic, right? It hurts as it disseminates. People get a little bit of a pop from it, they say. So there's an absolute physical sensation here.

No one's going to get that with sebetralstat. You take the tablet. It's obviously, everything -- the efficacy is great, but you don't get the same physical sensation. And so we're definitely cognizant of the fact that there's going to be a little bit of a process of getting used to. This sounds a little backwards almost, but getting used to having a therapy that works without being painful.

Yes. Interesting. And as far as what your team can do, I think you mentioned they can work with the doctors to help with outreach to the patients. Can they also help with just the paperwork for facilitating switching from icatibant, too?

Yes. Well, you actually asked about free drug a minute ago, and so this ties into that. We actually have a quick start program that we put in place. And so the mechanics here are that there'll be a form and it will be available either online or printed out. And following the physician visit, whether it's live or it could even be telehealth, that form gets completed by the physician in addition to the prescription. That goes to our patient support services, the patient hub. They process to confirm insurance. And then immediately for everybody, they will ship the first box of sebetralstat to that person.

So people will ideally fairly quickly after they get the prescription written, get their first box to be able to use. And then the idea here is that the expectation is this -- as an average, that this first box probably lasts people plus or minus a month. And that -- during that time is when the payer assistance team is working on getting commercial coverage put into place. And so ideally, in most cases, when they have the next shipment, that's under commercial coverage. But essentially, everybody will be getting free drug on the first go.

Got it. And for getting on to formularies, you're being like 6 to 9 months?

Absolutely average. I mean, I guess if volume really took off, some people might move earlier, but we -- that's kind of what the norm is, and we fully expect to be within that range.

Got it. Okay. And we talked about metrics. Do you have a general sense of when you'd want to provide initial revenue guidance?

Not for a while. The numbers are going to be pretty small for the first quarter or 2, right, to the point of free drug and to kind of getting up to speed. And so realistically, it takes a little bit of time to build. Plus, we have -- we're currently on an April 30 fiscal year. We're in the process of changing that to a calendar year, which is something people have asked us to do for almost a decade, right? So there's going to be some -- a little bit of an offset in how our reporting goes nowadays. The first time we'll -- the first quarter we'll report will be a quarter ending July 31. We'll -- obviously, that will come out in early September. So that will be as good an update as we can give on the first month or 2 after launch. And after that, we'll have another update in December. But again, just to set expectations properly, the first quarter or 2 is not -- are not huge numbers, but then they ideally grow meaningfully after that.

Got it. Okay. And maybe talk about ex U.S. You mentioned Germany, U.K., Japan, and you've got the partnership in Japan. Would you do similar deals like the deal with Kaken in Japan?

Yes. The Japan deal made a lot of sense for us because we have an excellent team in Japan, a really good group. But in terms of the investment -- especially in today's world, the investment required to sort of build the commercial effort and the risk attached to that, Japan is a little bit of a complicated market. So getting an established player in the market that already has the physician call point that has the team that can sort of do it efficiently made a lot of sense for us. So that was the basis of the Kaken deal. And the financial terms were quite favorable compared to where the market sits.

Outside of that -- we've always said we plan to launch in Europe on our own. That continues to be the case. Europe, you can do really efficiently. Again, we've got a lot of experience launching HAE products in Europe. I talked about that a few minutes ago. But Europe is primarily, to be frank, Germany. Germany plus the U.K. together is probably 2/3 of your total European revenues. Germany, you can obviously launch extraordinarily quickly at post approval with this kind of free pricing dynamic they have. So Germany makes a lot of sense to go to immediately, which is why we will. The U.K. also makes a lot of sense to go to and plus the company has a meaningful presence in the U.K.

Beyond that, Europe will kind of roll out over time. The point is we like Europe. We can cover Europe on our own. We think the economics make sense the way we've conceived it. We've got a very lean team in Europe. And so our plan is to continue to move that forward there on our own. And -- but outside of that, by and large, we'll do commercial agreements around the world. We've got a number of those already in process, and I think you'll start to see those roll out over the course of this year to cover some of the other territories.

Got it. Okay. And I wanted to talk more about the market opportunity as well. What are your latest thoughts on just the on-demand market size based on your market research? And what are the key drivers of sebetralstat and what you're going to do that will expand the on-demand market?

Yes. We've put these numbers out a fair bit. If you look at the on-demand doses, if you will, in the U.S., I'm only going to talk about the U.S. right now today, there's right around 84,000 plus or minus doses per year that are prescribed and used. And that accounts for the fact that some things like RUCONEST use multiple vials to treat an attack. So if you look at units, it would give you a bigger number, but the units obviously doesn't account for the fact that some of these drugs use multiple units for -- to treat one attack. So it's basically one attack treatment.

If you put a branded price on that, if you just took that 84,000, you put the FIRAZYR, which is right around $12,000 on that, you're obviously meaningfully north of $1 billion already. So the actual dollar size of the market nowadays is much less than that, largely because you've got generic icatibant, which is majority share and is very low priced. But if you branded the market as a whole, you'd be comfortably north of $1 billion. We think that icatibant users, in particular, will switch at a very high rate to sebetralstat. We think the offering is particularly appealing to them. And so there's some market share expectation on that.

Importantly, though, we also think that the market can grow because it's well known that people only treat about half or maybe 2/3 of their attacks nowadays. And so undertreatment is rife. What we expect is that people will treat meaningful more attacks in the presence of sebetralstat. And that's not to suggest that they treat attacks unnecessarily, but they have attacks now they should treat that they just don't. So to give a comparator, in our open-label extension, right now, people are treating right around 83% of their attacks. So it's, what's that, 25% higher than you see in the real world nowadays. So in addition to the whatever portion of the market we can capture from switches, we do think usage will go up meaningfully, and that will be beneficial. And then over time, I think you start to think about how the market might evolve a little differently.

Everyone assumes that people kind of inexorably come in and go on to prophylaxis and stand prophylaxis. But that's because there's really no better option nowadays. I mean truth is if you're thinking about the trade-offs between treatment benefit and treatment burden, prophylaxis is absolutely your best choice nowadays for almost all -- for many people, which is why 2/3 of the market or more is prophylaxis. In the future, though, in the presence of sebetralstat, we think there's a lot of people who may reconsider that, whether it's actually still the best benefit for them.

No matter how efficacious your prophylaxis is, 30 tablets a month is a lot of tablets and 2 injections a month or even 1 injection a month is a lot of injections. And certainly, there are people who have very severe disease who really need that. And clearly, there's a place for prophylaxis for a meaningful portion of this marketplace.

But in the world today, because of the fact that treatment burden is so high in many cases, there's probably a fairly significant percentage of people who currently use prophylaxis who may start to reconsider that as sebetralstat becomes available. They get some use from it -- get some experience of treating breakthrough attacks with it. They may well decide that actually, this works just fine for their purposes. So there's probably some incremental growth there in a different way than I think people think about nowadays, which is to assume that prophy kind of grows to the sky.

Yes. Yes, a great overview of the market dynamics and how this could play out for on-demand. Quick question, just whether you're having conversations with prophy companies about potentially collaborating in some way to maybe bundle products commercially? Or how do you think about that?

We like sebetralstat. We think it's going to do really well. We don't think we need to tie up with anybody. We're completely happy to be Switzerland here in this case. Prophy is a complicated market. It's probably on the cusp of becoming hypercompetitive, right? You've got 4 therapies approved, 2 more coming this year and 5 more behind that. So the prophy dynamics are probably -- are a little bit tricky nowadays, and I think they're going to get vastly more tricky in the next few years. We think the on-demand dynamics are much more straightforward. We think we have the dominant therapy in the space. The nearest potential competitor is a long way behind us. And so we think we can bring a really high-value offering that people are going to enjoy and appreciate. And we can let the prophylaxis market play out however it does without any regard to us.

Got it. All makes sense. Maybe just in closing, if you want to mention just key financials with cash and where that gets you in...

Yes. So we -- again, we're an April 30 fiscal year. So last -- at this point, the last quarter we reported ended in January, we had right around $250 million on the balance sheet at that point. We've guided that we're funded into at least the second half of 2027. We've also said multiple times that we expect that -- again, we run a lean operation. So we do think we can become cash flow breakeven on the sales of sebetralstat within a few years after launch. So we feel like we're in a financially really strong position. We've got all the resources we need to do the launch very well. And so we don't really foresee any cash limitations here on getting this drug out to people or for the foreseeable future. So I think we're really content with where we stand.

Great. Thank you very much for joining us today, Ben.

Thanks again. Nice talking to you, Maury.