Good day, and thank you for standing by. Welcome to the RAPIDe-3 Topline Data webcast. At this time, all participants are in a listen-only mode. After the presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one and one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one, one again. I would now like to hand the conference over to your speaker. Maggie, please go ahead. Thank you, and welcome to the topline data announcement of RAPIDe-3, a phase III clinical study of deucrictibant immediate release capsule for the on-demand treatment of hereditary angioedema attacks. My name is Maggie Beller, Head of Corporate and Investor Communications at Pharvaris. Please note that today's webcast is being recorded, and the slides will be uploaded onto the investor section of our corporate website immediately following this call. Please note that the statements of our guests today are their own and not those of Pharvaris, and Pharvaris makes no representation as to the adequacy, fairness, accuracy, or completeness of the information in their comments. In addition, our presentation today will include forward-looking statements, including but not limited to statements regarding deucrictibant and its potential, as well as our preclinical and clinical studies, regulatory interactions, and future plans. Such forward-looking statements are subject to certain risks and uncertainties that could cause actual results to differ materially from those projected. For additional information regarding the various factors that could cause such differences, please see the section entitled Risk Factors in our annual report on Form 20-F and our other filings available on the SEC's website. In addition, any forward-looking statements represent the company's expectation only of today. While we may elect to update these forward-looking statements, we specifically disclaim any obligation to do so unless required by law. During our call, Pharvaris' Chief Executive Officer, Berndt Modig, will speak to Pharvaris' continued journey to pioneer science for patient choice. We are joined by Dr. Marc Riedl, a Professor of Medicine at the University of California, San Diego, and a Principal Investigator of the RAPIDe-3 study, who will share his perspective on these data as a worldwide-recognized expert treating physician. Thank you, Dr. Riedl, for joining us. Pharvaris' Chief Medical Officer, Dr. Peng Lu, will go through the top-line efficacy and safety findings from the RAPIDe-3 study. Additionally, Pharvaris' Chief Commercial Officer, Wim Souverijns, is available for the Q&A portion of the call. I'd now like to hand the call over to Berndt Modig. Berndt? Thank you, Maggie, and good morning and good afternoon, everybody. Over 20 years ago, I started my career in biotech in HAE at the company that developed icatibant, the current standard of care treatment for HAE attacks, alongside Chief Scientific Officer Jochen Knolle, who's the inventor of icatibant. Shortly after the approval of icatibant in Europe, a person living with HAE approached Jochen at a patient meeting. After declaring icatibant had changed their life, they asked Jochen if he could make icatibant in a pill version. That is the moment Jochen recognized that the good was not good enough. Ten years ago, with this unmet need in mind, Jochen and his lead chemist, Christoph Gibson, designed a highly potent small molecule with poor bioavailability that utilizes the same mechanism of action as icatibant. Also by the initial findings, such as those for the kallikrein challenge studies, Jochen knew this asset could become a game changer, and that is the foundation of Pharvaris. Recognizing deucrictibant's potential as both an on-demand and prophylactic treatment, Jochen and his team went a step further and developed two distinct formulations: an immediate release capsule for on-demand treatment and an extended release tablet for prophylaxis. Following rigorous clinical development, we're proud to announce data from Pharvaris' first pivotal phase 3 study of deucrictibant, in which we met our primary endpoint and all secondary efficacy endpoints with a well-tolerated safety profile. The RAPIDe-3 data potentially positioned the capsule of deucrictibant to deliver the fastest symptom relief of any progression through the complete attack resolution, thereby offering beginning-to-end control of HAE attack treatment. I'd like now to introduce Dr. Marc Riedl, a world-leading HAE expert, to speak to his experience in treating HAE and the unmet needs in acute HAE treatment. Marc. Thanks very much, Berndt, and good morning, good afternoon to everyone. I'm Dr. Marc Riedl. I'm a Professor of Medicine at UCSD, and by way of quick background, I'm an allergist immunologist. I've been managing HAE patients for almost 25 years now, and I've also been very involved in HAE research, particularly in the clinical trials aimed at developing novel and improved therapies for HAE. So it's my pleasure to join the call today, really to provide a clinical perspective on HAE and perhaps provide a few insights for context as we talk about the clinical trial data. So as people are well aware, HAE management has dramatically changed and evolved over the last 20 years or so, and during that time, we've seen great progress in HAE treatment options. There has been considerable growth, particularly in the area of long-term prophylactic treatments, and we have seen, in fact, more patients moving towards preventative treatments. But what hasn't changed in HAE management is that all plans, all treatment plans, must include effective on-demand HAE treatment, and this is without exception because patients continue to have HAE attacks that are unpredictable, that are debilitating, and that are potentially life-threatening. We can never forget that aspect of HAE. So even with more effective long-term prophylactic treatments, our patients with HAE continue to have attacks. They continue to require on-demand treatment, and we see that the treatment responses to the preventative treatments are really quite variable. So this variability in the response to preventative treatment leads to ongoing need for on-demand therapy. We still see attacks occurring, and we need treatment that is rapid, reliably effective. We have current on-demand treatments, and these have generally been effective, though the burden of treatment is relatively high, and this is particularly true with the long-standing subcutaneous and intravenous rescue treatments. So another remaining unmet need in HAE is reduction in the treatment burden for the therapies that we can offer. Historically, treatment burden and side effects have led to treatment delays or even treatment avoidance, and this has long contributed to the morbidity and the risk of these HAE attacks. So the recent development of oral rescue medications for HAE has really been a substantial advance. This has reduced the burden and the barrier to treatment. For patients, the rapid onset of symptom relief, as well as the reduction in attack severity and the durability of the relief, are really the key components to successful on-demand treatment. And this brings me to a final point that I'd like to highlight, that of mechanism of action. So bradykinin B2 receptor antagonism is a well-established and a recognized successful approach to stopping HAE attacks. Both the physicians and the patients in the HAE community are really familiar with this mechanism of action because, as you heard just now, subcutaneous icatibant has the same mechanism of action, and icatibant has been widely used for HAE rescue treatment over the past 14 years or so. So this is a mechanism of action with a proven clinical track record. It's anticipated to be reliably effective for all forms of bradykinin-mediated angioedema. And so as we move towards reviewing the study data, I'll just make a final note that as a clinician, efficacy and safety of a treatment will always carry the day. The most important questions for me and my patients are, number one, does the treatment work? And for HAE rescue medication, that's heavily dependent on how quickly and how durably a treatment works, often assessed by the need for additional doses or additional treatment for that attack. And secondly, is the treatment safe or are there common, substantial side effects? But currently, I would say a third important question is treatment burden. Is the treatment easy to administer? Is it portable? Will it fit into daily work, family, and recreational activities? And it's in these areas where we continue to see progress and advances that really make me optimistic for the future of our HAE patients and their families. So with that, I'd like to turn it over to Dr. Peng Lu. Peng? Thanks, Marc. As Marc highlighted, people living with HAE seek unburdened control of their disease. What has been missing is a combination of simplicity and speed in the moment of attack, coupled with the durable effect of single capsule. Today, that becomes a possibility. Let us walk through the results of the RAPIDe-3 study. RAPIDe-3 was designed as a double-blind crossover study. Each participant received deucrictibant or placebo in a randomized order to treat two qualified attacks, and the licensed patients also received a single dose deucrictibant for PK and safety assessment prior to randomization. Along with new guidelines published early this year, RAPIDe-3 is the first pivotal study to enroll all subtypes of HAE, extending beyond type 1 and 2, also patients with normal C1 inhibitor. In addition, the study enrolled both on-demand and prophylactic patients. Throughout the study, attacks with varying severity and across all body locations were treated to evaluate the therapeutic effect of deucrictibant. RAPIDe-3 was initiated in March 2024. In total, 124 adults and 10 adolescents were recruited within 12 months. Among those enrolled, 88 participants completed treatment and assessments of paired attacks. Therefore, they were included in the primary efficacy analysis. As Pharvaris partnered with centers from 24 countries across six continents, this study included approximately 70% Caucasians, over 14% Asians, and around 7% Black or African Americans, making RAPIDe-3 the most representative HAE study today. For the subtype of HAE patients, in addition to type 1 or 2, RAPIDe-3 also enrolled four HAE patients with normal C1 inhibitors, two with factor XII mutation, and two with the Plasminogen mutation. Among all participants, approximately 23% of patients received long-term prophylactic treatment with lanadelumab most frequently used, accounting for 42%. The demographics of the primary efficacy analysis set 88 participants with paired attacks were comparable to the all-randomized population presented here. As a reminder, the HAE endpoints are measured by patient-reported outcomes. Today, we will focus on the data from two validated and well-accepted scales: Patient Global Impression of Change (PGIC) and Patient Global Impression of Severity (PGIS). Both scales have been recommended and aligned with the regulators. Evaluating the effectiveness of on-demand treatment requires a holistic view. For people living with HAE, the aspects that matter most: first, fast onset of treatment response; second, short time to substantial symptom relief; and the third, early complete symptom resolution. The RAPIDe-3 study made statistical significance for the primary and all 11 secondary endpoints for the evaluation, which were assessed sequentially under the pre-specified multiplicity control procedure. During today's top-line presentation, we will be sharing data from primary and several secondary efficacy and safety analyses. A comprehensive communication plan has been established for further scientific exchange at the upcoming medical conference. The primary endpoint for RAPIDe-3 is the time to onset of symptom relief, defined as achieving at least a little better at two consecutive time points within 12 hours. Deucrictibant demonstrated a significantly faster onset of symptom relief than placebo, with a median time of 1.28 hours, well beyond 12 hours for placebo, listed as NE, not estimable. As shown in the Kaplan-Meier curve, an evident separation between the deucrictibant and the placebo curve emerged within the first hour. By the four-hour time point, approximately 85% deucrictibant-treated attacks had achieved onset of symptom relief, compared with around 30% of placebo-treated attacks. Subgroup analysis on the onset of symptom relief showed consistent and robust results across subgroups, including patients with normal C1 inhibitor and HAE-nC1-INH, as well as all attack locations and severity. People with HAE and treating physicians report that the point at which attack symptoms stop progressing is the earliest sign that a treatment is working. The worst is over, and things will get better. Based on feedback from patients, advocates, and treating physicians, we designed RAPIDe-3 to include end-of-progression as a pre-specified efficacy endpoint. It is defined as the earliest post-treat time point, after which all subsequent PGIC readings are stable or improved. In the study, we are pleased to observe end-of-progression was achieved within 17 and a half minutes for deucrictibant-treated attacks, confirming the rapid absorption and PK/PD profile of the deucrictibant immediate release capsule. As shown with the full attack trajectory, substantial symptom relief represents a key milestone between onset of response and complete resolution. deucrictibant demonstrated fast and substantial symptom relief with PGIC better, with a median time 2.85 hours. Achieving both a little better and a better quickly shows a robust pattern of treatment effect in the study population, demonstrating deucrictibant's ability to deliver rapid and durable symptom improvement beyond just onset of relief. Substantial symptom relief was also measured by at least one level improvement on the PGIS, Patient Global Impression of Severity sustained for two consecutive time points. Deucrictibant achieved this high bar with a median time of 2.41 hours, showing robust and consistent with the PGIC assessment. When treated with deucrictibant, earlier complete symptom resolution for acute attack had been achieved within 12 hours. What does this mean for patients? Symptoms associated with non-treated HAE attack can negatively impact patients for up to five days. Only one capsule with deucrictibant offered patients the potential to be symptom-free within half a day. During the RAPIDe-3 study, approximately 83% attacks were treated with a single capsule within 12 hours post-treatment with deucrictibant, and 93% attacks did not use rescue medication. In the safety analysis with patients receiving any dose of study drug, deucrictibant was very well tolerated. Overall, a total of 24 and 17 participants observed at least one adverse event for attacks treated with deucrictibant or placebo, respectively. Most adverse events were mild or moderate in severity. There were two serious adverse events reported in each group. One was a miscarriage occurred one and a half months after placebo treatment. The other was non-treated hospitalized HAE attack that occurred about four months after deucrictibant treatment. No participant discontinued study or treatment due to adverse events. No safety signals identified from adverse events, labs, ECG, or vital signs. In summary, the efficacy results clearly show the potential of deucrictibant differentiation. Looking at the strength of the data, I'm truly excited and proud of what the study has accomplished and the impact deucrictibant may have for people living with HAE. After more than a decade working in the HAE space, it has been a privilege to witness and contribute to the remarkable progress in the new treatment development that continues to address our medical need and improve the quality of life for HAE patients. Here, we would like to take this opportunity to sincerely thank the HAE community, especially study participants and their families, investigators and site staff, our study partners, and all Pharvaris for their invaluable contribution to HAE clinical research, especially the RAPID 3 study. Thank you, Dr. Riedl and Peng, for your insights on the RAPID 3 data presented today. I'd like to reiterate my appreciation to the team around the world who has collaborated to generate this data. Let me remind us of our journey to this day. Ten years ago, Pharvaris set out to develop an oral bradykinin B2 receptor antagonist using our in vivo bradykinin challenge model. The left part of the slide, we defined the dosing for both on-demand and prophylaxis and subsequently optimized two distinct products, one for each indication by our formulation work. Our aspiration was to show that these products could effectively address the unmet need in both the on-demand and prophylactic settings. Today, we are excited as the results from RAPIDe-3 study represent the step towards realizing that aspiration. We're very proud of the team that made that possible, and we're looking forward to the results of the prophylactic study, CHAPTER-3, in the second half of next year. Additionally, CREATE, the Global Registry Acquired Angioedema Study initiated as planned this quarter, is actively recruiting. Until then, we continue to work towards the planned submission of a first global marketing authorization for deucrictibant in the on-demand treatment of HAE attacks. In closing, Pharvaris is steadfast in our mission to improve the standard of care for people living with bradykinin-mediated angioedema. This has concluded the presentation section of the webcast. We will now open the Q&A portion. If you want to ask a question during the Q&A portion of the webcast, you will need to press star 11 slowly on your phone to get to the Q&A queue. Our first question comes from the line of Maxwell Skor from Morgan Stanley. Please go ahead. Your line is open. Great. Thank you very much for taking my questions, and congratulations on the very encouraging data. So just to start off, could you discuss the strategic advantages of deucrictibant's potential to address both on-demand and prophylactic treatment of HAE? How might this dual indication approach enhance, let's say, market share and patient adoption compared to single indication therapies? And finally, any guidance around which medical meeting we could expect an update and what additional data we could look for in that update? Thank you very much, and congrats again. Yes. So thanks, Max, for the question. And Max, and on that topic, of course, I mentioned in our presentation to have two formulations with the same active ingredient for both on-demand and prophylaxis. Of course, the goal of that is to provide the choice of the patient how to best treat the condition. So that should be a patient benefit potentially in our view. And of course, anything that benefits patients is also good for the company and market share, as you alluded to. So I'd like to also invite Wim Souverijns to comment on that further as we were thinking about that strategy for launch of deucrictibant potentially in the future. So over to you, Wim. Yeah. Thanks, Berndt. I think it's a huge advantage for Pharvaris to have this one active ingredient in two forms that really covers all the needs of patients with bradykinin-mediated angioedema, whether they want to do only on treating their attacks on demand because they have very few of them, or whether they really choose to go for prophylaxis and, as a backup plan, require rescue medication and still use the same molecule. I think this is the wish, desire from the community. They see the benefits of this, and it really plays into our mission as a company. Our tagline is pioneering science for patient choice. Well, this is exactly what we are offering here. We don't really want to force anyone in this market to go left or right. We have the tools for them to treat the way they want to. And I think that will be very appreciated by the community. There is scientific merit to that. So we think this is a big competitive advantage in the market. Yes. Thanks. Yeah. Maybe I can add something. Yeah. Go ahead. Yeah. Exactly. You know that for the next that mentioned the upcoming medical conference, actually, as Dr. Riedl on the call here, actually, our first plan to present top-line data and more detailed information is in the coming AAAAI conference. We will be held in February 2026 in Philadelphia. Great. Thank you. Yes. Thanks for your question. Thank you. We'll now move on to our next question. Our next question comes from the line of Joe Schwartz from Leerink Partners. Please go ahead. Your line is open. Great. Thanks very much, and congrats on the strong data. So question for management and also Dr. Riedl. We've seen actually have a strong launch so far as the first available oral on-demand treatment option for HAE. And since deucrictibant will be entering the market later, I was wondering which specific aspects of its clinical data or product profile do you expect to distinguish it further in the marketplace? And then, Dr. Riedl, similar question. How has your practice been adopting actually now that it's commercially available? And how do you expect market share to break down if and hopefully when deucrictibant's approved? Yeah. Thanks, Joe. And thanks for your question. So what we also discussed here when we showed you the data is what's important for the patient and what really makes an on-demand treatment stand out is, of course, the fast onset of symptom relief, but also extremely important, as Peng also mentioned, the holistic perspective that what a patient is looking for is durability of the efficacy and up to the shortest possible complete resolution of the attack, which is the time point when the patient can resume to normal life and continue what they were doing or going to that meeting or getting on that flight, whatever they would need to do to have the attack behind them as quickly as possible. So onset is important, but of course, also durability is key here. And I think that's where we, based on the data we've seen today, that potentially deucrictibant can stand out. So also hand over to Dr. Riedl also to add some comments on this topic. Sure. Yeah. Thanks for the question. As you might imagine, we've seen really significant interest in the oral rescue medications. And as you noted with the oral kallikrein inhibitor that's now been approved, certainly lots of patient interest. Not surprisingly, people are really keen to use an oral medicine versus having to do an injection or an infusion. And so, as you noted, we've seen pretty robust uptake of patients wanting to try the newly approved medication. I expect that to continue. And I think, as you saw today, the data here looks very favorable for the efficacy and the safety of deucrictibant. So I think in clinical practice, having options is really important. We go through a lot of data with patients and the shared decision-making process. And I think that will certainly be the case if and when deucrictibant is available to us, that we'll be talking through the study data and making sure they understand the pros and cons of any treatment. The only other thing I would add, and I alluded to this in my earlier comments, is that patients are really familiar with bradykinin receptor antagonism. At least in our practice, icatibant has generally been the go-to treatment up until recently for many years. And so I think that may resonate with patients that, "Hey, I used that medicine, and it worked for me, and this is the same mechanism of action." So we do discuss these things with patients. Some patients are more interested in that than others. Mostly, they just want it to work. But I think the familiarity with the mechanism here is something that they will recognize, and we'll talk through as we make treatment decisions. So that's kind of our experience and my view on it. Thanks for the insights. Thank you. We'll now move on to our next question. Our next question comes from the line of Steven Seedhouse from Cantor. Please go ahead. Your line is open. Good morning. Congratulations. What looks like the best onset of action ever reported across every single endpoint. Really impressive. Wanted to ask directly about the competitor here and the comparison, just a couple more details. First, specifically with reference to the drug-drug interactions and CYP3A4 inhibitors in that drug's label, can you comment on the strength of any CYP3A4 interaction with deucrictibant? Is it a substrate? Would you expect similar drug interaction language in an eventual label? And then also the importance of a single capsule here for deucrictibant versus needing two tablets. Do you think that would be, albeit a small but potentially meaningful, difference in the marketplace? Yeah. Thanks, Steve. So I'll hand over to Peng to comment on the CYP3A4 question you had. So start with that. Yeah. Yeah. Sure. Steve, good question here. Indeed, that deucrictibant is mainly metabolized by CYP3A4. Therefore, from the drug-drug interaction part, we would expect to avoid using that deucrictibant with a strong CYP3A4 inhibitor or inducer. That's consistent with for most medications that are metabolized by CYP3A4. Yeah. So on the soft capsule in the single pill, of course, what's relevant here is, of course, in addition to the portability and the ease and simplicity of a very small soft capsule, it's also important here is the need or lack of need for a second dose. I mean, the confidence that the patient is more confident the patient is that taking one pill or tablet is going to take care of it and not have to worry about or have anxiety about, "Should I take a second dose or not?" is the key factor here. So the convenience of a very small, simple soft capsule in combination with the potential of resolving the attack with just one dose, I think, will be the key parameters here that are important. Just to follow up, any chance you have data handy on what percent of the patient demographic breakdown between type 1 versus type 2? Was the vast majority type 1? Just want to confirm that. Yes. Indeed. The majority is that patients, around 90% are type 1 patients. Perfect. Thank you so much. Congrats. Thanks. Thank you. We'll now move on to our next question. Our next question comes from the line of Jeff Jones from Oppenheimer. Please go ahead. Your line is open. Good afternoon, guys, and congrats on the data. Two quick technical questions and then a strategy one. Was there any difference in response rates based on HAE type, although, as you noted, 90% of them were type 1? And can you comment on the average time from the onset of attack to treatment in the study? Peng, over to you. Yeah. Sure. As just a presentation for this study, the majority of patients are type 1 patients and around 5%-7% type 2, and then that 3%-4% type 3 patients. And we indeed did subgroup analysis, and we will be presented in the future conference that actually Dr. Riedl there, and we'll be present that maybe in the AAAAI there. And currently, we can only share that the efficacy is consistent and robust across all the subtypes. Okay. Thank you. Any comment on the time to treatment? Yeah. Currently, because we mainly work on the top-line results, we do not have the detailed information to summarize for the time to treatment because it's not included in the primary and secondary endpoint. But meanwhile, we expect the time to treatment will be consistent as we ever observed for the phase two study. Okay. And then on strategy and next steps, can you comment on estimated timing for regulatory filings and any commentary on commercialization plans? Yeah. So I think we also mentioned that I think in the press release, there's an aim to file here in the next year, in 2026, and in the first half of next year. And of course, the team is working hard to get the file together as already started, of course, and to do that as fast as we can because we get this to the regulatory process and to patients as soon as possible. Maybe to add to that, Jeff, from a commercial perspective, we have had a very prudent resource deployment strategy, which means that we have invested in top talent. So we have, on our leadership, long-standing experience in HAE, hired people that have done the pre-work for the commercial launch. Anything that is on the critical path has been on track. So nothing is lost there. But obviously, the big increase in gearing will be for next quarter and the quarters thereon. But we're going to be launch ready for this product. We're super excited about this. The community is very excited. So it's going to be fun. Great. Thank you very much, guys, and congrats again. Thank you. We'll now move on to our next question. Our next question comes from the line of Laura Chico from Wedbush. Please go ahead. Your line is open. Good morning. Thanks very much for taking the questions. One on the baseline properties of the RAPIDe-3 population. If I contrast on the primary endpoint, the response of the placebo group, the median time to reaching the PGIC endpoint was greater than 12 hours. But if I compare that to the other oral therapies, it just seems like the RAPIDe-3 population might have been a tougher-to-treat population, even though you still did achieve a 1.28-hour median time. So I'm just kind of curious if there's any kind of qualitative comments you can make in terms of the severity of the RAPIDe-3 population. And then I have a follow-up for Dr. Riedl. Thanks, Laura. That's an interesting question. So Peng, can you have some color on that? Yeah. Sure. Actually, good question, Laura. We think this study we covered that attacks that with varying severity and also all location there. And regarding that percentage, we have that around 20% that mild attack and half that 50% moderate attack and about 30% of severe and very severe attack. It's very representative for all the attacks that typically treated with on-demand treatment. And here, indeed, we are also surprised to see that the placebo group even did not achieve that onset within 12 hours. There may be the two factors. The first factor is actually it's 49% patients that achieved onset that around 12 hours. It just missed the median time there. The second is that because you can see from the other that rescue medication use curve, around 44% that the placebo patients actually used rescue medication. Therefore, they will be censored at the end of assessment window. That means that beyond 12 hours there. Okay. That's very helpful. And then one question for Dr. Riedl. There's been a narrative that we've heard from investors, not patients or providers, but that increasing availability of oral on-demand treatments might actually lower prophylaxis use rates. And I'm curious how you see that happening. I know you mentioned the burden of treatment, but do you see prophylaxis rates remaining at this level going forward? Or how are you thinking about that in terms of managing your own patients? Thank you. Yeah. It's an excellent question. It's something I've actually thought about a fair amount. And I also, I will say, had some suspicion that we might see a little bit of erosion of long-term prophylactic therapy as on-demand treatment has become easier recently. I have to say, so far, that hasn't materialized. And so in the clinical space, we still see people very enthusiastic about long-term prophylactic therapy. I think there is a predictability to life that lens that's very attractive and allows them to get on with their lives without worrying so much about attacks. So to answer the question, so far, no. We haven't seen this erosion of long-term prophylactic therapy. And that might also be due to the fact that, as we all know, the long-term prophylactic therapies have continued to evolve also: less burden of treatment, more durable medications, longer duration effect, easier to use, and so forth. So we're still seeing not all, but the majority of patients on long-term prophylaxis. I guess the last piece of commentary, which is just real life, is I don't see people moving away from long-term prophylaxis, but if I put it in a layperson's terms, they're cheating a little bit more, maybe. They're maybe not dosing quite as often as prescribed with their long-term prophylactic therapy. And I think that's just human nature to try to use as little medicine as you might need to. But not going off long-term prophylactic therapy. We really haven't seen that so far. Super helpful. Thank you, guys. Appreciate it. Thank you. We'll now move on to our next question. Our next question comes from the line of Sushila Hernandez from Van Lanschot Kempen. Please go ahead. Your line is open. Yes. Congrats on the data, and thank you for taking my question. Could you elaborate on the importance that the CYP3A4 was explored in all HAE subtypes and what the potential approval means for these patients? And for Dr. Riedl, what are you looking out for for the prophylactic readout next year? Thank you. Yeah. Thanks, Sushila. So it's not the applicability to all forms of angioedema is primarily related, again, to the mechanism of action, bradykinin inhibition at the end of the pathway or the cascade at the receptor level, which enables the treatment of potentially all forms of angioedema. So that's the key point there. And I'm sure Peng also had some comments to add there as well. Yeah. As Dr. Riedl have already highlighted that as a B2 antagonist, that we expect that deucrictibant is able to cover all the angioedema mediated by bradykinin. That's actually have a lot of discussion with the community. But that makes us excited is that for the study, we first actually enrolled really the normal C1 patients in the pivotal study and able to show the data and to really provide more information for the clinical practice that how we can help that normal C1 patients. But Marc, I will also hand it over to you for this question. Yeah. Sorry. The question was related to additional readouts, or could you repeat the specific question? Yes. So the importance of this potential approval for all HAE subtypes and also for the prophylactic readout next year, what are you looking out for? Thank you. Yeah. Sorry. Thanks. So yeah, I think the subtypes of HAE, certainly studies up to this point have largely focused on type one and type two C1 inhibitor deficiency patients. There is this, we think, rarer form of HAE normal C1 inhibitor, which we used to call type 3. We're trying to get away from that terminology because that's clearly an umbrella of probably various different types of mostly bradykinin-mediated angioedema. So I think there's increased interest in looking at that population because there's a huge unmet need there. And you saw the inclusion of a small group of genetically defined HAE normal patients in this study. And there may be some additional studies with that sort of small population looked at. So I think it's always difficult to say much about a few patients, but I do think that it looks that this was a favorable outcome for that subset of HAE as well. And that is a group of patients that need treatment, and we've had very little data to date. So the hope would be that we have data we can point to that will allow us to treat those patients with deucrictibant or other therapies, which will be very positive. As far as additional readouts, I think in the coming year or so, certainly you heard about the oral deucrictibant for long-term prophylactic therapy, the CHAPTER study. I think that will be very important. As I mentioned earlier, we've seen lots of interest in oral therapies, which has been borne out with berotralstat and sebetralstat and now deucrictibant. And I think an oral therapy with high efficacy for long-term prophylaxis would be another big step forward. So we look forward to that data. I think beyond that, as people are aware, there may be additional data on the Intellia CRISPR-Cas9 program we're looking forward to seeing. And then maybe a little further down, but garadacimab as the YTE-modified monoclonal antibody and then siRNA therapies behind that. So I'm not certain on the timeline for when those studies all roll out with their data, but certainly looking forward to seeing what those studies show. Thank you. We'll now move on to our next question. Our next question comes from the line of Thomas Vranken from KBC Securities. Please go ahead. Your line is open. Hi there, and thanks for taking my question and congrats on the data. I have one for Dr. Riedl. Maybe could you share or maybe quantify the proportion of your on-demand patients that you would expect to ultimately switch to oral? And maybe, are there any patients that would still prefer an injectable option? And if so, what are the reasons behind some of those preferences? And then I have a follow-up on maybe the prophylactic program. If you can share any updates with us on the recruitment there, and could you potentially be in a position to accelerate the timeline for this readout as well? Thank you. So maybe start to check around the last question. So our guidance for top-line data for the prophy study is second half of next year, and enrollment is going as expected. And so we are also looking forward to that data readout next year. So that's all on track at this point. And then on the other question, the line was a little bit weak. I couldn't hear exactly what the question would you want repeating the first two questions? Yeah. Sure. I can repeat that. That question was for Dr. Riedl. If you can quantify the proportion of your on-demand patients that you would expect to ultimately switch to oral, and are there any patients that would still prefer an injectable option? And if so, what would be the reasons behind some of those preferences? Yeah. Sure. Happy to share my experience because this is, as you can imagine, something we're actively talking through now that we have some oral options. The vast majority of patients that I manage are interested in oral rescue treatment. It's just my experience, but if I had to put a number on it, I would say 80%-85% are very interested in using oral rescue medicine. And our experience to date is that most, not all, but most of those patients have a good experience with that and tend to stick with it. There is a subset of patients that continue on either subcu or intravenous rescue therapy. It's a small percentage, but there are people that say, "You know what? I'm good with this treatment. I know how to use it. I don't have major intolerable side effects, and I trust this medicine. I know it works for me." So that is a small subset of patients. And then we have had another small subset of patients that have tried the existing oral therapy and decided that for whatever reason, it didn't work fast enough or well enough for them compared to their subcutaneous or intravenous treatment. So there have been some that have trialed it and decided to go back to their previous rescue treatment. It's a small subset. It's not the majority. But those are some of the reasons, I think, either inertia is a strong thing. I'll stick with what I know and what I'm doing, or the injected medicine simply worked better for me faster, more durable, whatever the reason may be. So we have seen a minority, I would say maybe 20% of patients sticking with the older, more conventional therapies versus the oral, but most have pretty quickly adopted the oral rescue medications. All right. Thanks. Very clear. Thank you. We'll now move on to our next question. Our next question comes from the line of Patrick Trucchio from H.C. Wainwright & Co. Please go ahead. Your line is open. Thanks. Good morning and congrats on the data. The first is for Dr. Riedl. Just wondering on the 11 secondary endpoints that met significance, which do you view as the most clinically meaningful: end of progression, substantial relief, or complete resolution? And then just separately, can you share results from the adolescent performance in RAPIDe-3, and was the PK and efficacy profile consistent with adults? And then just lastly, I was wondering what data specifically from this dataset could inform expectations for CHAPTER-3? Yeah. So I think the first question was for Dr. Riedl, so over to you. Yeah. Sure. So of those secondary endpoints, the end of progression is one that we're talking about a lot more and I think has become an important one. And I think Peng talked about this a little bit in her presentation. But if you talk with patients, that's honestly what they're very interested in is at what point does the progression stop, meaning I'm not getting any worse? Because their experience with their attacks is that once that happens, they know that they're going to get better. Of course, they want to get better as quickly as they can. Those other endpoints are important, including up until complete resolution. Psychologically, I think, and I don't want to speak for patients, but this is what they tell me, that end of progression is actually very important. The faster that they can recognize that, the more confident they are that this attack is on its way out, and I can start to get back to my normal activities. Of all the data you saw outside of the primary endpoint, I think that end of progression one is something that's very meaningful to me as a clinician, and also that's what I hear from patients. Peng about the adolescent PK. Yeah. Actually, I will give maybe a similar answer as normal C1 here that we will definitely share that the subgroup analysis data in the future conference. But overall, I think the message is consistent that we did indeed subgroup analysis, and the data that is isolated for primary endpoint and others are consistent for the subgroup compared to overall population. Regarding the detailed data that we will not share today, but we will share soon in the medical conference there. And, regarding your third question, the CHAPTER-3 data, I think that based on today's data and based on the science that to our journey of the clinical research, we do feel that the RAPIDe-3 data that even confirmed with the findings from the RAPID-2, actually, I have to acknowledge beyond my expectation is with a more heterogeneous population of the phase 3 study, we still can demonstrate that as strong data as our phase 2 that even boosts our confidence for the CHAPTER-3 readout. Thanks so much. Thank you. There are no further questions at this time, so I'll hand the call back to Maggie for closing remarks. Thank you very much for joining us for the RAPIDe-3 top-line data presentation. We're grateful to everyone who contributed to the study and to the outcomes that we see here today. If you had any questions, please let us know. You can reach out to me directly. This concludes our conference call.