Good morning, and welcome to KalVista Pharmaceuticals conference call and webcast. As a reminder, this webcast is being recorded. My name is Michelle from Notified Conference Call Service, and I will be your operator today. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star one one on your telephone. You will then hear an automated message advising you your hand is raised. To withdraw your question, please press star one one again. I would like to turn the conference over to Ryan Baker, Head of Investor Relations for KalVista. Please go ahead.
Thank you. Good morning, everyone. Earlier this morning, KalVista announced the results from the KONFIDENT Phase 3 clinical trial of sebetralstat as an oral on-demand therapy for hereditary angioedema, HAE. On this conference call today, members of the KalVista management team will make remarks about the KONFIDENT Phase 3 trial results and the accompanying slide presentation in the webcast. Today, speakers from KalVista include Andrew Crockett, Chief Executive Officer, and Dr. Christopher Yea, Chief Development Officer. We are also very pleased to be joined today by Dr. Marc Riedl, a leader in the HAE field. Dr. Riedl will provide his expert perspective on the unmet treatment needs in HAE. Also present on today's call from KalVista is Ben Palleiko, President, Chief Business Officer, and Chief Financial Officer. Following today's prepared remarks, we will open the call for questions. To ask a question at that time, refer to the operator.
Slides to accompany this conference call are posted on the Investors and Media section of our website at www.kalvista.com. The audio webcast with the corresponding presentation slides is also available on the website. Before we get started, I'd like to remind everyone that some of the statements that we make on this call and information presented in the slide deck include forward-looking statements as outlined on this slide. Actual events and results could differ materially from those expressed or implied by any forward-looking statements, including as a result of various risks, uncertainties and other factors, including those set forth in our most recent filings with the SEC and other future filings that we may make with the SEC. We would caution not to place any undue reliance on these forward-looking statements, and they won't disclaim any obligation to update such statements.
I will now turn the call over to Andy Crockett.
Thank you, Ryan. Today is an exciting day for KalVista and also for people living with HAE around the world. Today, we are ushering in a new era of HAE as we've achieved a significant milestone towards bringing the first oral on-demand therapy for safely and effectively treating HAE. We are thrilled with the positive top-line results from the KONFIDENT Phase 3 clinical trial, which we reported in our press release today, which showed that both the 300 mg and 600 mg doses of sebetralstat met their primary endpoint, achieving the beginning of symptom relief from an HAE attack significantly faster than attacks treated with placebo. Of note, the P values were highly statistically significant for both doses. Additionally, both doses met the two key secondary endpoints of the trial and demonstrated an excellent safety and tolerability profile.
KONFIDENT enrolled 136 patients from 66 clinical sites across 20 countries, making it the largest controlled clinical trial conducted in HAE. To begin our presentation, we are pleased to welcome one of the preeminent HAE researchers in the world, Dr. Marc Riedl. Dr. Riedl is Professor of Medicine, Clinical Service Chief and Training Program Director, Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, California, Clinical Director of the U.S. Hereditary Angioedema Association Reference Center and the co-author of U.S. HAEA Medical Advisory Board Guidelines and the International WAO/EAACI Guidelines for the Management of HAE. Dr. Riedl was also an investigator for the KONFIDENT Phase 3 trial. Dr. Riedl, thank you for joining us this morning.
Thank you, Andy, and good morning, everyone. I'm pleased to outline the persisting unmet need in the management of HAE and to provide some context for the KONFIDENT Phase 3 data. Most of you will be familiar with hereditary angioedema or HAE, which is a rare genetic disorder that affects approximately one out of 50,000 people globally. As you can see in the pictures below, patients with HAE experience attacks of swelling in many anatomical locations, including the face and the extremities. Attacks that involve the upper airway may be life-threatening if untreated. HAE is challenging to manage because the attacks are often unpredictable. These attacks can start off mild, but severity can increase quickly. They can also migrate to other anatomical locations, including the larynx. An attack symptoms can last for one or two days, but may persist for up to five days if untreated.
In order to support shared decision-making between HAE patients and their physicians regarding treatment, clinical experts, along with patient advocates, have collaboratively published treatment guidelines. These have evolved over the past 20 years as the new treatments have become available. Before diving into the specifics, it's worth highlighting that the main goal of treatment in HAE is to achieve total control of the disease and to normalize the lives of patients. In order to realize that goal, there are two main treatment strategies. First, to ensure that all HAE patients have ready access to effective on-demand treatment, and secondly, to consider the addition of long-term prophylaxis, or LTP, in appropriate patients, which means taking into account the frequency and severity of their attacks, the impact of attacks on patients' quality of life, and patient preference.
The global HAE treatment guidelines recommend that all HAE attacks should be considered for treatment, regardless of location or severity, as attacks are unpredictable. However, studies show that 25%-40% of HAE attacks are not treated by patients, including those who have attacks while receiving long-term prophylaxis. The HAE guidelines further recommend that HAE attacks should be treated early to rapidly halt the progression of swelling caused by bradykinin generation and thereby reduce the duration of the attack. However, recent survey data shows that only 20% of patients treat their attacks in less than an hour. Lastly, guidelines recommend that patients have access and carry their on-demand medication for the treatment of at least two attacks.
Here again, we have survey data showing that fewer than 40% of patients carry on-demand treatment outside of the home all the time, some traveling long distances without their on-demand treatment. Now, currently available on-demand treatments are efficacious, but they have limitations. Much of this may be due to the fact that they need to be injected, either intravenously or subcutaneously. Plasma-derived or recombinant C1 inhibitors are not easily portable and require preparation prior to administration in an attack setting. Many patients or their caregivers may have difficulty finding a vein, and patients commonly experience pain at the injection site. Another treatment, ecallantide, has a significant risk of anaphylaxis and is therefore only approved for administration by a healthcare provider in a monitored setting. Finally, the most commonly used on-demand treatment globally, icatibant, is associated with injection site reactions in nearly all patients.
This includes prolonged pain, redness, and swelling in many patients. The picture you see here on the right shows an example of a local skin reaction caused by icatibant. We believe the reason this is so common is that this is a pseudoallergic reaction, which is caused by icatibant binding the MRGPRX2 receptor on mast cells in the skin. Bottom line, the limitations of currently available on-demand treatments likely contribute to patients' decisions to delay or even withhold their injectable on-demand treatment. Now, long-term prophylactic options have grown substantially over the past five or six years. However, it's important to note that although these LTP treatments have been shown to effectively reduce the frequency or number of attacks, a substantial proportion of patients still experience HAE attacks.
As you can see here, this table summarizes findings from the randomized placebo-controlled trials of the approved LTP agents, C1 inhibitor, lanadelumab, and berotralstat. Overall, more than 1/2 of the study population continued to experience HAE attacks over the full duration of these respective trials. Even among those on lanadelumab at steady state, nearly one in four patients continued to experience attacks. So it's reasonable to say that long-term prophylaxis, despite excellent efficacy, does not replace the need for on-demand HAE treatments. Clinical studies have consistently demonstrated that earlier treatment is associated with better outcomes, including rapidly halting the progression of swelling, early symptom relief, and a reduction in the overall severity and duration of the HAE attacks. Sebetralstat is the first potential oral on-demand treatment to reach late-stage development.
In phase I studies, the 300 mg and 600 mg doses were found to result in near complete plasma kallikrein inhibition within 15 minutes, with persistent suppression over more than four hours. The 600 mg dose was chosen for the phase II study that was previously published in The Lancet. Sebetralstat had good safety in the trial versus placebo, and the time to beginning of symptom relief was significantly shorter with sebetralstat compared with placebo, with a median time to beginning of symptom relief of 1.6 hours versus 9.0 hours with placebo. The promising results from the phase II trials set the foundation for KONFIDENT, a Phase 3 crossover trial design to confirm the efficacy and safety of sebetralstat as an on-demand treatment for HAE in both adolescents and adult populations.
KONFIDENT is now the largest controlled HAE trial conducted to date, and importantly, the first trial designed to align with the on-demand treatment guidelines we discussed earlier: early treatments of all attacks and having ready access to treatment. It's worth noting that KONFIDENT is the first on-demand trial to include patients who are receiving non-androgen long-term prophylactic agents. Lastly, KONFIDENT is the first on-demand trial powered to assess multiple patient-relevant endpoints in a hierarchical fashion. The primary endpoint, time to beginning of symptom relief, the first key secondary endpoint, time to reduction in attack severity, and the second key secondary endpoint, time to complete attack resolution. Thanks for allowing me to provide some clinical context for sebetralstat and KONFIDENT. Now back to the KalVista team to take you through the study results.
Thank you, Dr. Riedl. Now I'd like to hand the call over to Dr. Yea, our Chief Development Officer, to review the Phase 3 top-line results in more detail. Chris?
Thank you, Andy, and good morning, all. The Phase 3 KONFIDENT trial is a well-powered, randomized, double-blind, three-way crossover trial evaluating the efficacy and safety of sebetralstat for the oral on-demand treatment of HAE. The trial investigated two doses of sebetralstat, namely 300 mg and 600 mg. At enrollment, patients were randomized to treat three attacks, with each of sebetralstat, 300 mg, 600 mg, or placebo, in a blinded, randomized sequence. During the study, patients self-administered each treatment as soon as possible after recognition of the onset of an attack. Following treatment, patients recorded response to treatment and adverse events on an electronic diary for up to 48 hours. If needed, patients were able to administer a second dose of the blinded medication, not less than three hours following the first. We have previously reported the results from a phase II clinical trial for sebetralstat.
While these trials are similar in design, the differences are shown on this slide. The key changes were the expansion of the population to include adolescent patients and also patients using long-term prophylaxis. Similarly, the nature of attacks eligible for treatment has also been expanded to include all locations and severities. Finally, while the phase II trial included a single dose of treatment, the Phase 3 trial allows patients to use a second dose. The primary endpoint of the study was time to beginning of symptom relief. This was defined as a rating of a little better for two time points in a row on the Patient Global Impression of Change, or PGIC, scale. This is a seven-point scale on which patients rate their symptoms in comparison to when they first took medication. It was administered every 30 minutes for the first four hours, then hourly to 12 hours.
Two key secondary endpoints were also investigated using a Patient Global Impression of Severity, or PGIS, scale. These assessments recorded the severity of the attack at each time point to identify the first of two time points in a row when severity had reduced, and also the time taken to reach no symptoms. It is important to recognize that this reflects complete resolution of the attack, rather than near complete, as assessed in other trials. KONFIDENT randomized 136 patients to treatment, and by the time the end of the study was called, 110 of those had treated at least one attack prior to our decision to end the trial. All of those attacks are included in the analysis of efficacy.
The study was well-balanced across the treatment groups, and discontinuation rate was low, with no patients withdrawn from the trial due to an adverse event. The distribution of patients enrolled in the trial was typical of an HAE trial population and included multiple geographic regions. Of note, this is the first controlled study to recruit patients in Japan. Of the 110 patients who contributed data to the analyses, 21.8% continued to use long-term prophylaxis while on the trial. During the trial, patients dosed the blinded medication in a median time of 41 minutes following onset of the attack. At baseline, 43.2% of attacks displayed abdominal symptoms. While laryngeal attacks were eligible for treatment in the KONFIDENT study, as anticipated, numbers were low, with eight attacks treated.
This low number precludes any analysis of efficacy, especially given four of the attacks were on placebo treatment. I will talk to this a little later in the call. This slide shows the baseline severity profile of attacks which occurred in patients using LTP compared to those in patients who treat their disease with on-demand only. Representation of all severity grades does not markedly differ between LTP and on-demand patients, including the proportion of severe and very severe attacks. I'll start the review of the safety and efficacy results by looking at the primary endpoint of time to beginning of symptom relief.
The trial met its primary endpoint, showing that attacks treated with both 300 mg and 600 mg, all doses of sebetralstat, achieved beginning of symptom relief significantly faster than attacks treated with placebo, with P values of less than 0.0001 and 0.0013, respectively. The median time to beginning of symptom relief was 1.6 hours with sebetralstat at 300 mg, 1.79 hours with sebetralstat at 600 mg, and 6.72 hours for HAE attacks treated with placebo. While the trial was not powered to detect an effect versus placebo in subgroups of patients and attacks, the trend to treatment effect of sebetralstat was consistent across the groups we have assessed.
As noted previously, we have expanded the population from the phase II trial, and importantly, those new groups, including adolescents and patients on long-term prophylaxis, show a very similar effect to sebetralstat treatment. The trial also shows that sebetralstat has a consistent effect regardless of attack severity. Two key secondary endpoints were tested using a fixed sequence hierarchical approach to support potential labeling discussions. This slide shows the first key secondary endpoint, time to reduction in attack severity. Attacks treated with 300 mg and 600 mg both achieved a significantly faster time to decrease attack severity from baseline compared to placebo. Attacks treated with both doses of sebetralstat reached complete attack resolution significantly faster than placebo. Now turning to safety. This table shows the number of adverse events reported within three days of drug administration.
Consistent with previous studies, sebetralstat was well-tolerated, with a safety profile indistinguishable from placebo. No related adverse event reports were reported in any treatment group by more than one patient. Importantly, gastrointestinal adverse events were similar across all groups. There were no laboratory findings reported as adverse events, including liver-related measurements. Additionally, we continuously monitored all laboratory values throughout the study and saw no signals specifically related to liver or any other parameter. While expanding the treatment population, KONFIDENT delivered similar efficacy results to the phase two trial. Patients chose to use a second dose of medication in around 40% of attacks treated with sebetralstat, in contrast to 55% of attacks treated with placebo. Use of conventional medication was similar between the trials. Our open label extension trial continues to recruit and has enrolled more than 110 patients at the beginning of this month.
To date, more than 640 attacks have been treated with 600 mg sebetralstat, with a median time of 10 minutes from attack onset. As discussed earlier, and as expected, the contribution of laryngeal attacks to the KONFIDENT dataset was limited. The KONFIDENT-S trial has already significantly supplemented the number of laryngeal attacks, which will ultimately be used to support the NDA filing, consistent with previous approvals in the space. In conclusion, the KONFIDENT Phase 3 trial was the largest controlled clinical trial in HAE. This pivotal trial met all primary and key secondary endpoints, which, in combination with the favorable tolerability and safety profile, position us to move forward with filing of an NDA. Sebetralstat was dosed early after attack onset and delivered rapid symptom relief and associated severity reduction and complete attack resolution at both 300 mg and 600 mg dose levels.
Patients administered the formulation soon after attack onset, more closely matching treatment guidelines. Despite the inclusion of a broad population of patients and eligible attacks, efficacy was similar to that reported in the phase II trial. Sebetralstat safety profile was similar to placebo, and there were no safety signals of concern at either dose level. The open-label extension trial will provide a significant quantity of data which supports the safety and efficacy of sebetralstat.
Thank you, Chris. In terms of next steps, we remain on track to file our NDA with the U.S. FDA in the first half of this year, with additional filings in the E.U. and Japan in the second half of 2024. In the very near term, we are planning to present more detail on our Phase 3 data to the medical community at the AAAAI Scientific Conference in Washington, D.C., at the late breaker presentation on Sunday, February 25th. We've also been building our commercial team over the last few years, and our commercialization activities remain on track for a 2025 launch.
In closing, we believe that sebetralstat is positioned to open a new era of HAE therapy and could become the foundational treatment for people living with HAE, offering them an effective, safe, and discreet way to treat HAE attacks without the challenges of injectables or the chronic burdens of long-term prophylaxis. Most importantly, I want to take a moment to thank the people living with HAE, their families, and the investigator teams around the world who supported KONFIDENT and helped us complete this landmark study. Thank you for sharing our vision of the promise of sebetralstat and helping us achieve this important milestone. We look forward to providing further updates and progress to the sebetralstat for the benefit of people living with HAE around the world. With that, let me turn this back to the operator for any questions. Please go ahead, operator.
Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. We ask that you please limit yourself to one question and one follow-up. One moment while we compile our Q&A roster. Our first question is going to come from the line of Maury Raycroft with Jefferies. Your line is open. Please go ahead.
Thank you. Hi, everyone. Good morning. This is Yao on the line for Maury. Congrats on the strong Phase 3 data. The data looks beautiful. Thank you so much for taking our questions. Our first question is on the efficacy. So how does the efficacy look in attacks of different anatomic sites? And what are the characteristics for, of attacks, where a second dose was taken?
Yeah, thanks for the question. So the efficacy of sebetralstat was very consistent across all of those locations that we could identify. I think as one of the slides shows, we've split them to date just by abdominal and peripheral. And we could detect no difference in effective sebetralstat treatment. And we have some further analysis to do with the data to look at, you know, the severity related to location. That work's ongoing. However, I think because we've shown it's a consistent effect across all severities, a consistent effect across all locations, we certainly wouldn't anticipate any difference in efficacy regardless of the location of the attack.
Okay, got it. That makes sense. Oh, do we have a follow-up question? On the, so for the open-label extension study, when do you think you could report the next data cut? And based on the data, how do you think the drug could, this oral on-demand drug could actually change the treatment paradigm in the commercial setting, based on some of the initial feedback you got from doctors?
I'll take the first part of that question. So we're currently making a cut of the 302 open-label extension study to support the NDA. Once we have that, then we'll share information regarding the data at the appropriate time.
Yeah, this is Ben. I'll take the question on the commercial side. I think it's very clear, based on the data you've seen, that the results of the drug are just tremendous. And the flexibility of dosing and the ability to sort of use this has shown itself to be key advantages for patients in the study. And as Chris briefly mentioned, in the open label, it looks like it's even better. I mean, I think what we're really seeing is that patients are able to identify when they're having incipient attacks, and they're taking the drug very quickly. And I think the benefits are, you know, are on pretty full display now and will only get enhanced as we put more of that data out on the open label.
So the point is, we really do believe that with the profile that we've displayed so far, this is the kind of thing where patients could certainly look at this to become their baseline therapy. This could become the first, not really the first line, but effectively the first treatment patients will try to manage their HAE. And to the extent that they still have other challenges or high attack rates, they may consider adding prophylaxis to it. But we do believe at a baseline that sebetralstat offers the opportunity to become the foundation and really to meet patient needs in a very positive and patient-friendly way.
Got it. Congrats again. I'll hop back in the queue.
Thank you.
Thank you. And one moment as we move on to our next question. And our next question is gonna come from the line of Paul Matteis with Stifel. Your line is open. Please go ahead.
Hey, thanks so much for taking my question and congratulations on the data. I had two questions, if you don't mind. On the efficacy side, as we think about redosing rates in this trial, looking that they're lower on drug versus placebo, what do you think the regulatory utility of that analysis is? Like, are you guys thinking about that as an FTC analysis, or is that really just for safety? And ultimately, as you look at these data, what are the kind of implications of redosing on, or I guess, allowing for redosing on a potential label? And then on the safety side, thanks for giving more color on the top-line data here.
I was curious if you can confirm in the open label extension that this all holds true, that there's no signal on anything related to liver enzymes. And maybe just add a little bit more color on kind of what you're seeing on a frequency of use in the real world in terms of, you know, max number of doses or doses per day or things like that. Thank you.
Okay. Okay, Paul. Thanks for those two questions. Yeah, so I think, Paul, we agree with FDA that the treatment in KONFIDENT will be up to two doses. So, you know, a patient is free to use up to those two doses. And I think that's really important. We know that attacks are highly variable in the way they present, you know, anatomic location, severity, speed with which they progress, impact they have on patients' day-to-day activity. Of course, we also know that patients currently use more than one injection to treat an attack. So, from the outset, we felt it was important for patients to be able to maintain that flexibility so that they can decide how they respond to each of those individual attacks.
So, you know, I don't think from a regulatory point of view, there'll be any doubt that this will be seen as, you know, a treatment very similar to the current treatment. You know, you can take a dose and, you know, currently based upon the Phase 3 KONFIDENT trial, you know, patients will be able to use a second dose. So I think that's been, I think it's entirely consistent with current labels, and I think, again, delivers just that flexibility. With respect to the safety, yes, I think it's right to say the 302 study, I personally find fascinating. As you've seen, we've got over 640 attacks.
We have patients who are treating sort of 20 or 30 attacks on study already, and we're collecting attacks at a good rate. As far as the safety we're seeing in the 302, I think it's safe to say it's exactly the same as we've seen in 301. We haven't seen anything in the labs of any concern, either with liver or anything else in the 302 to date. So, you know, I think the 302 is gonna deliver safety and efficacy data, which is entirely consistent with the 302, sorry, with the 301 study.
Yeah, I was just gonna add one more thing, Paul, to Andy. I, you know, I think in terms of, you know, we made a mention earlier of the, the use of sebetralstat in the real world, and I think it's indicative of what we're seeing in the 302 study with, especially that rapid time to dosing of 10 minutes. I just think that is, you know, really important, especially if you think about that in the context of what's happening in the real world with injectables. You know, we know that on average, you know, recent data was showing on average, patients are waiting almost four hours to treat with their injectable therapy. When you compare that to 10 minutes, I think it really highlights the promise of sebetralstat and how that can change the paradigm here.
Thanks, Andy. Appreciate it.
Thank you, and one moment as we move on to our next question. Our next question is gonna come from the line of Joseph Schwartz with Leerink Partners. Your line is open. Go ahead.
Hi. Thanks, and, congratulations. My first question is for Dr. Riedl, and then I have a follow-up for the company. Dr. Riedl, you talked about patients don't treat there too early. I'm wondering how you think about trial set at least to change this behavior in the real world. And, where do you think, sebetralstat could gain the most share from existing on-demand agents, and, how much do you think it could expand the on-demand market?
Yeah, thanks. I, I had a little trouble hearing you. You're breaking up a little bit, but I, I think I got the gist of the question. So we, we do, we do indeed see some hesitancy in the real world for patients to use their on-demand treatments. Certainly, you know, patients will, will do what they need to ultimately to stop these attacks, but because they're either IV infusions or sub-Q injections, that, that can be quite uncomfortable and, and painful at some level. There is, there is some delay in treatment, and so that's a very real phenomenon.
And in fact, some patients will choose not to treat an attack if they think it, you know, might be mild, which is usually a mistake because it leads to more moderate or severe attacks that cause disability and sometimes even, you know, hospital visits. So we do, as the guidelines say, really encourage people to treat early and treat any attack that they anticipate will interfere with their activities. We hear from patients often that, you know, an oral medication is preferred by many of them.
So I do think that this offers the opportunity to give patients a much easier way to treat their attacks, something that's very portable, they can have with them at all times, and they don't have to find a place or a time to do these injections or infusions in the course of their everyday life. So it, you know, remains to be seen. We have to sit down and talk to patients about the data, but I do think this is gonna be very attractive. It may very well make its way to, you know, the top choice for docs and for patients as an on-demand treatment. And it remains to be seen. You know, it could affect the long-term prophylactic use.
I do think there are benefits, clearly, to the long-term prophylaxis in terms of reducing attacks and making life more predictable. But, I think the option to treat attacks early, to easily treat them, with an oral medication, is gonna be a big step forward, you know, for managing patients.
That's very helpful. Thank you. And then, for the company, as your focus evolves towards approval and commercialization, can you talk about your activities there and what kinds of launch prep have been underway? What efforts remain, and what do you foresee your sales and marketing footprint needing to look like in order to leverage the strong clinical data?
Hey, Joe. Thanks for the question. So, to date, we've actually—we've been building for a while, actually a couple of years now, a small commercial activity that we've, over the past six months, really started to beef up. So we have... We hired, as you saw, a very experienced Chief Commercial Officer mid last year. She had experience launching Takhzyro with Takeda, so she knows the world and has succeeded in this space previously. She has built around her a terrific team of folks so far. We've filled all the key slots. We've got heads of sales and marketing in the U.S., and Europe, and in Japan nowadays, to lead those activities.
And we've also started to beef up some other key members of the team, and now we're moving down to the next tier of hires. So the core positions have all been filled. The team has really started to put together a lot of early launch activities. We have a very, you know, highly evolved launch checklist that we've been moving through, and we've actually had commercial teams, launch teams, starting to meet over the past few months, even as we get ready to launch in all those geographies. And over the course of the year now, obviously, in the back of this data, we'll start to beef that up more substantially. Switching to the question of, you know, what's the footprint look like?
There will be obviously more hiring to come in that space this year. But one of the terrific things about this indication, and we've said this for a long time, is that it's tailor-made for a biotech company to commercialize. The footprint in the U.S., as a particular example, is really a fraction of what you see in a lot of spaces. I mean, it's something on the order of, you know, a few dozen sales reps and then a few dozen other people. So you're talking somewhere in the 40-50 mark, maybe for the U.S. organization, which is eminently affordable for a company our size.
And the rest of the world commercialization efforts take a little longer to roll out just because of the approval and launch timelines, and the numbers certainly are smaller than that even. So it's the kind of thing that we can cover all the key positions pretty effectively with a team of that size. I think the expense overall is gonna be eminently controllable. And so, you know, we think we can really do this properly and take advantage of the great opportunity before us.
That's very helpful. Congrats again.
Thanks, Joe.
Thank you. And one moment as we move on to our next question. And it looks like our next question is gonna come from the line of Charles Duncan with Cantor Fitzgerald. Your line is open. Please go ahead.
Yes, thanks for taking the question. And Andy and team, congratulations on, very, very nice results. I did have a question for the KOL, Dr. Riedl, first, and that is, Dr. Riedl, when you consider the composition of the patient sample, what is it that you are most impressed with? Is it the fact that there was nice efficacy for on-demand with long-term, long-term, you know, prophylaxis, or in the adolescent, patient population, or severe versus very severe? What most impressed you about that sample?
It's a great question. I would say all of those things were important, but I think the adolescent population is a very important one. This is a time when in the natural history of HAE, we do see an increase in severity for a lot of patients. And at the moment, as people may know, we really only have the IV C1 inhibitors approved in the adolescent population, so it can make on-demand treatment challenging for teenagers. And so I was very happy to see their inclusion and see that, you know, those results looked basically, can't tell any difference compared to the result, the adults.
The other thing that some have had questions about, and I think is an important one, is will this drug work in people that are already on a long-term prophylactic option that has the same mechanism of action, so plasma kallikrein inhibition? And, you know, the answer looks like yes. You can't really tell a difference in the efficacy for those LTP patients on kallikrein inhibitors, with the use of sebetralstat compared to those who aren't on those agents, either, at all. So I think, in my mind, those are sort of, you know, two very important pieces of data, along with the fact that, you know, so far, we haven't, in the analyses, seen any difference in efficacy for different anatomical sites, which is, of course, very important.
You know, we hope to have more look at that as the open label data comes along. But knowing that the drug works for any and all types of attacks is, of course, really important when we're speaking with patients. So I would say those are the important highlights for me.
Very good. Great point and color. For the company, I had a quick question regarding the NDA in terms of gaining steps. Could you help us understand what kind of pace, the timing? It seems like it's fairly acute, so probably not a lot standing in the way. But would you be seeking priority review in addition? And then secondarily, could you just remind us of the ODT? Is that planned for this filing or one in the future? Thank you.
Yeah. So thanks. So yeah, so we are moving full steam ahead with our NDA filing of the NDA in the U.S., as we've said, in the first half of this year. The KONFIDENT trial obviously was the major piece of that. As we've discussed a little bit here, the open label safety trial, we'll take a cut of that data and include that in the NDA as well. But that's really it. So again, we're down to you know the work of you know finalizing it. This is top line data from KONFIDENT. We have additional analyses we'll perform, and then we will prepare that NDA for submission in short order.
As it relates to, you know, we will of course be seeking, you know, all expedited measures to accelerate FDA approval, and so, you know, more to come on that as we find out more and we work on that. And I think, you know, finally, your question about ODT, you know, that will be a separate, it'll be a separate application. We've said that that will be a life cycle extension in the U.S. and will be an sNDA, that will come later. That doesn't... We know that doesn't require any further efficacy data. But the initial launch in the U.S. will be with the tablet formulation.
Thanks, Andy. Congrats on a really well-run study.
Thank you. And one moment for our next question. And as a reminder, ladies and gentlemen, if you would like to ask a question at this time, please press star one one on your telephone. Our next question comes from the line of Serge Belanger with Needham. Your line is open. Please go ahead.
Good morning. Thanks for taking my questions. I wanna offer my congratulations for positive results. I guess first question is, there doesn't seem to be a large difference between the 300- and 600-mg dose, either on efficacy or safety and tolerability. Curious if you agree with that interpretation and whether you'll still seek approval of both doses? And then secondly, for Dr. Riedl, I think you've authored some of the HAE treatment guidelines. Just curious if, assuming this product does get approved, how do you think it'll modify those guidelines, especially as it pertains to prophylaxis? Thank you.
Okay, thanks, Serge. I'll take the first part of that, then hand over to Marc. Yeah, I think that's a very fair sort of, if you will, top-line assessment of the data that we have to date. I think you're right from an efficacy point of view. The two dose levels, I think for all three endpoints, you can see the curves and the confidence intervals around those point estimates look very similar. So I don't think we can differentiate on those. I think really great news, of course, is that we have really good safety profile at the two dose levels. I think as Andy just mentioned, this is just the top-line data.
So we have the full data set, which will be coming in due course, and we'll investigate that data set more fully and see whether we can find an advantage for. I think it'll be the 600 mg over the 300 mg, if there's some data that will support us doing that. Once we have that data, I think we can make a final decision, and then obviously we'll be looking to file the NDA appropriately with the dose or doses that we would then choose. And obviously we'll update at the appropriate time once we've done that. Marc, can I hand over to you to answer the second part?
Sure, happy to.
So the, you know, as far as the evidence-based treatment guidelines, I certainly can't speak for the committees that write those, but I would say that we do, you know, try to actively update those as new treatment options become available, and certainly based on the data we have so far, I, you know, I would expect that sebetralstat will make its way into the guidelines as a, you know, a listed first line on-demand treatment option. That's certainly been the pattern as we get safe and effective treatments for HAE. So I suspect the guidelines will certainly be updated to include sebetralstat, as it's approved in various parts of the world, assuming that occurs.
You know, the question about how it might affect recommendations for treatment strategies, including long-term prophylaxis, is, you know, a very interesting one. I think that I certainly don't see long-term prophylactic options, you know, going away, obviously. I think there are clearly demonstrated benefits, and I think we'll continue to see those, you know, heavily incorporated as an option in the guidelines. But I, you know, I would just, I guess, reiterate that on-demand treatment is recommended for each and every patient, because as we've talked about, even the LTP patients have attacks... And I think more importantly, it'll be important in the clinic as we talk patients through the guidelines and have shared decision-making discussions with them.
You know, how does HAE affect them? What are they most comfortable with in terms of their treatment strategy? You know, that, that's where we may see those discussions being a little bit different. Not that—we certainly will continue to discuss and use long-term prophylactic options, but you may see patients that, you know, are willing to do on-demand treatment only depending on their experience with this oral option and their comfort level with that. So I do think it will certainly. It may change our discussions a little bit. Whether it will ultimately change, you know, the percentage of people that go on long-term prophylactic therapy, I don't know how that'll all sort out.
But I do think it's an option that will be very interesting to talk about with patients and see what their comfort level is.
Great. Thanks for taking my questions.
Thank you, and I'm showing no further questions, and I'd like to turn the conference back over to Ryan Baker for any closing remarks.
Great. Thank you all for taking the time to participate in today's call. Please follow up with us if you have additional questions. Have a great day, everybody.
This concludes today's conference call. Thank you for participating. You may now disconnect.