Good day, everyone, and thank you for standing by. Welcome to the CHAPTER-3 Topline Data Webcast. At this time, all participants are on 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 that your hand is raised. To withdraw your question, simply press star one one again. I would now like to hand the conference over to your speaker host. Maggie, please go ahead. Thank you, and welcome to the topline data announcement of CHAPTER-3, a phase III clinical study of deucrictibant extended- release tablet for the prophylactic 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 the call. Please note that 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 insight 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 as of today. While we may elect to update these forward-looking statements, we specifically disclaim any obligation to do so unless required by law. We are joined today by Dr. Marc Riedl, Professor of Medicine at the University of California, San Diego, principal investigator in the CHAPTER-3 study, and a globally recognized expert treating physician who will share his perspective on the CHAPTER-3 data and on their relevance for clinical practice. Thank you, Dr. Riedl, for joining us. During our call, Pharvaris' Chief Executive Officer, Berndt Modig, will speak to Pharvaris' continued commitment to provide medicines that can further advance the management of bradykinin-mediated angioedema. Pharvaris' President, Dr. Peng Lu, will go through the topline efficacy and safety findings from the CHAPTER-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, good afternoon, everybody. Pharvaris prides itself on being a trusted partner to all stakeholders in the HAE community. I am proud to, once again, speak to you as we execute another key milestone for our company. Starting with the on-demand program, positive phase II data were followed by positive phase III results in December 2025. Most recently, the FDA accepted our NDA submission, bringing us one step closer to making deucrictibant IR available for on-demand treatment of HAE attacks. The next catalyst for the on-demand program is the potential approval in April 2027 of deucrictibant IR, which may represent a new standard of care for on-demand HAE attack treatment. Now turning to long-term prophylaxis, we have similarly built a strong foundation. Positive phase II data were announced in December 2023. Today, we build on those with positive phase III results, which support deucrictibant XR as a potential long-term prophylactic therapy. Looking forward, we continue to generate additional evidence for deucrictibant in acquired angioedema through the CREAATE phase III study, which results from the prophylactic part of the study anticipated in the first quarter of 2027. We expect to submit our U.S. NDA in prophylaxis during the first half of 2027. When you step back and take a look at the entire timeline, what is exciting is that we have already crossed several major value inflection points, and the upcoming milestones have the potential to transform Pharvaris into a commercial leader in bradykinin-mediated angioedema. I would now like to hand over the call to Pharvaris President, Dr. Peng Lu, to present the CHAPTER-3 data. Peng? Thanks, Berndt. Before reviewing the data, I would like to take this opportunity to sincerely thank the HAE community, especially study participants, their families, the investigators and the site staff, our study partners, and all Pharvarians for their invaluable contribution to clinical research, especially the CHAPTER-3 study. CHAPTER-3 was a randomized, double-blind, placebo-controlled phase III study of oral administered deucrictibant extended- release tablets, 40 mg once daily, for the prophylaxis of hereditary angioedema attacks. Eligible participants were age 12 and older with HAE type 1, type 2, or HAE with normal C1 inhibitor. Participants were randomized in a 2: 1 ratio, which was stratified by age and baseline attack rate. In total, 85 participants were enrolled, with 55 into the deucrictibant group and 30 with placebo. Baseline demographics and HAE disease characteristics were generally balanced between two groups and are consistent with the overall HAE population. The mean age was about 39 years old, and the four adolescents were enrolled in each group. Most of the participants had HAE type 1 or 2. A total of five participants with HAE normal C1 inhibitor were enrolled. The baseline attack rate was comparable between two groups, with a mean rate approximately three to four attacks per month. After years of dedicated effort, we are proud to announce the CHAPTER-3 study successfully met its primary endpoint, demonstrating a highly statistical significance and clinical meaningful reduction in HAE attack rate. Participants treated with deucrictibant XR experienced substantially fewer HAE attacks during the entire 24-week treatment period, with an estimated attack rate of 0.35 attacks per month with deucrictibant versus 2.06 attacks per month with placebo. This represents an 83% reduction in attack rate with placebo, which was highly statistical significant. Of note, CHAPTER-3 is the first and only pivotal phase III study to enroll patients across the full spectrum of HAE, including participants with HAE with normal C1 inhibitor. In contrast, all other pivotal HAE studies have exclusively enrolled patients with HAE type 1 or 2. Among the 80 participants with HAE type 1 or 2 in CHAPTER-3, deucrictibant XR achieved 87% reduction in monthly attack rate with placebo. Taken together, these findings demonstrate deucrictibant XR provides injectable-like efficacy with the convenience of oral therapy. This slide highlights one of the most important attributes of deucrictibant XR as a prophylactic therapy, its early onset of protection, combined with durable effects over time. Consistent with its pharmacokinetic profile, deucrictibant XR reaches therapeutic exposure within the first day of dosing and achieves steady state within two to three days. Correspondingly, CHAPTER-3 shows that the protection of deucrictibant was maximized within the first week of the treatment and then maintained throughout the study duration. Moving on to some of the key secondary endpoints. Deucrictibant XR demonstrated robust and highly consistent treatment benefits in reducing moderate to severe attacks and attacks treated with on-demand medication. In the responder analysis, all but one participant receiving deucrictibant XR achieved at least 50% attack reduction from the baseline. With the most stringent threshold, almost all and two-thirds of participants achieved at least 70% and 90% reduction, respectively. Nearly half of the participants treated with deucrictibant XR remained attack-free throughout the entire 24-week treatment period. These results demonstrate meaningful attack control and reinforce the robust efficacy of deucrictibant XR across multiple clinical relevance measures. Beyond the reduced attacks, we also observed meaningful improvements in how participants felt and functioned in their daily lives. As shown in this slide, participants receiving deucrictibant XR experienced substantial improvements across all domains of Angioedema Quality of Life Questionnaire, including functioning, fatigue and mood, fears and shame, and also nutrition. Across every domain, reductions in AE-QoL scores from baseline to week 24 were consistently greater with deucrictibant XR compared to placebo. These results demonstrate the benefits of deucrictibant XR extend beyond attack prevention alone, translating into broader impacts of the treatment on the meaningful improvements on patients' day-to-day quality of life. From the safety side, deucrictibant was well-tolerated, with most events being mild or moderate in severity. The most common adverse events across both groups were upper respiratory tract infection, nasopharyngitis, and headache. The one treatment emergent serious adverse event also reported in this table as a Grade 4 event was a laryngeal dyskinesia in a patient with a prior history of repeated laryngeal intubation, which was considered not related to study drug by the investigator. The three participants with Grade 3 adverse events included tooth infection and the two people with Level 2 liver enzyme elevation. One of them discontinued study drug, the other remained on treatment and completed the study. The discontinuation in the placebo arm was due to urticaria. There was no evidence of increased risk of gastrointestinal side effects. GI treatment-emergent adverse events were evenly balanced between deucrictibant and the placebo groups, all of them are mild or moderate. As we have shown today, deucrictibant XR demonstrated meaningful and sustained attack prevention starting from week one. CHAPTER-3 study met its efficacy and the patient-reported outcomes endpoints with 83% reduction versus placebo in the overall HAE population and 87% reduction for the type 1 or 2 HAE participants. deucrictibant XR was very well-tolerated. Now, I would like to introduce Dr. Marc Riedl, a world-leading HAE expert, to speak about the existing treatment landscape in the long-term prophylaxis of HAE, the unmet medical need in prevention of HAE attacks, his opinion on the clinical profile of deucrictibant XR, and the potential of deucrictibant as an oral medicine. Marc, please. Thanks very much, Peng, and good morning to everyone. I appreciate the invitation to join the call and giving me the opportunity to just make a few brief comments. I think as the data you've seen, they relate to clinical practice. For a very brief background, I've been working in the HAE space as a specialist for about 25 years now, managing a large group of patients over that time and also conducting research and clinical and translational research in the condition. I would just mention, as people on the call likely know, we've really seen tremendous progress over those years with advances in therapeutics for HAE and an understanding of the condition. That's occurred both for on-demand treatments or treating attacks, but very importantly for the prevention of attacks. I would say in clinical practice, there's been an increasing emphasis on preventing HAE attacks because we do think that's the way to reach the goal of really normalizing people's lives and looking carefully at quality of life, as you just saw was incorporated into this trial. As people know, patients do have increased treatment options. We have achieved a lot over the years. But we've not entirely reached that goal of normalizing life for all patients. I think that's why we continue to see the work that we're seeing, the clinical trials. That's why patients continue to enroll in these studies, and they continue to be completed because we do have unmet needs yet. We do have room for improvement in terms of managing this condition, which as you know, is a lifelong, at this point, lifelong chronic condition. Just a few comments on what we still need in HAE and how the data you've seen on deucrictibant might help us achieve or meet those needs. I would first say that the burden of treatment is a real thing for patients having to take their medicine, the routes, the dosing, the schedule. This is a real issue, and it's something we spend a lot of time talking to patients about. The burden of treatment does affect quality of life. In my experience, many patients are very interested in the oral route, the oral medications, as a more tenable, a more acceptable and tolerable way to take their chronic treatments due to portability and all the things that we know can be advantages of oral treatments. The oral medications for prophylaxis in HAE have had some limitations to this point. That includes reduced efficacy compared to the parenteral medications or limitations due to certain side effects. I think the data that you've just seen is really encouraging. We're seeing the benefits of oral treatments now with efficacy that looks quite similar to the subcutaneous administered medications. I think this will be very appealing to clinicians and to our patients as an oral medicine that can really achieve a strong efficacy in preventing attacks, and it appears to be very tolerable in terms of side effect profile. The second thing I would say is that we really do work to individualize care to optimize outcomes. By that I mean we do see variable efficacy and tolerability for any and all of the medications that are out there. So having treatment options are very important. I think this will be, if it comes to the clinic, will be a very important treatment option. I'd point out that this is a unique mechanism of action for preventative treatments, the B2 receptor antagonism. That unique mechanism of action makes it a novel treatment option where we might in fact see this improving outcomes for patients who to date have not seen the efficacy or the tolerability that we really aim for. The last thing I would comment on is this group of HAE with normal C1 inhibitor. As you heard, this is a study that enrolled a small group of those patients, and this is a condition that's been very challenging to treat, in part because we understand it has a bit of a variable pathophysiology. But we strongly believe that most, if not all, of these patients have a bradykinin-mediated angioedema. This is, again, a mechanism blocking that bradykinin receptor that may give us real advantages in preventing attacks for this group of patients, the HAE normal C1 inhibitor patients, and really allow us to better manage these patients regardless of the reason, the pathway that there's bradykinin dysregulation. I think in totality, the study data that you've seen today really are encouraging that if approved for use in clinical practice, that deucrictibant will be a very important and a very useful addition to the tools, the options that we have to manage HAE. With that, I'll turn it back over to the Pharvaris team for the next part of the program. Thank you. Yeah. Thank you, Dr. Riedl and Peng, for your insights on the CHAPTER-3 data presented today. I would like to reiterate my appreciation of the people around the world who have collaborated to generate this data. Let me take a step back to share our long-term vision. Our inspired path to bradykinin-mediated angioedema leadership has three steps. First, win on on-demand treatment by combining effective attack control, a well-tolerated profile, oral convenience, and reduce the treatment burden. Second, expanding to long-term prophylaxis with the ambition of offering injectable-like efficacy and a well-tolerated profile with the convenient oral administration as we just heard. Third, leverage the B2 receptor platform beyond HAE, expanding into other bradykinin-mediated diseases and building a differentiated franchise. The opportunity is therefore much bigger than a single product or indication. Building on one foundational mechanism, we aspire to redefine disease management across the spectrum of bradykinin-mediated angioedema and beyond. The upcoming year should be incredibly impactful for Pharvaris. Our PDUFA for deucrictibant in the on-demand setting is in April. We plan to submit our NDA for deucrictibant in a prophylactic setting in the first half of next year, and we plan to announce top-line data from the CREAATE part one phase III study in the first quarter of next year. In closing, Pharvaris is steadfast in our mission to improve the standard of care for people living with bradykinin-mediated angioedema. That concludes 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 one one slowly on your phone to get into the Q&A queue. Please stand by while we compile the Q&A roster. Our first question coming from the line of Maxwell Skor with Morgan Stanley. Great. Thank you very much, and congratulations team on the update. Now with two relatively near-term launches, can you talk about just the commercial builds for both on-demand and prophylactic? How deucrictibant in both formulations are uniquely positioned? Does the dual profile actually change payer conversations or simplify them? Then if I can, just one more follow-up. On CREAATE read-through, how should we think about the relevant comparator from CHAPTER-3, either type 1, 2 patients, or what have we learned from the normal C1 inhibitor patients? Thank you. Thanks, Max, for that great set of questions. We are also going to start off by saying that Pharvaris has the vision of commercializing deucrictibant. We have already early on invested in getting ready for a potential launch and also handing over to Wim Souverijns, Chief Commercial Officer, who actually joined over five years ago. We are well underway in building a very strong team with great experience in this therapeutic space. So over to you, Wim. Thank you, Berndt, and thanks Max for the question. I hope I can answer all of you because there were quite a few in that question. I think first of all, let me say that we're super excited on the commercial side with these data. As you remember, when CHAPTER-1 came out, we were blown away by this very high level of attack reduction, as we call it, injectable-like efficacy, and that's now confirmed in the phase III. So together with RAPIDe-3, we are in a fantastic position with a drug that in both treatments paradigms on-demand and prophylaxis, saw really exceptional data. In terms of our commercial preparation, we are well underway. We know that the target audience in the U.S. is around 2,000 physicians, core physicians. What we've done is we're building a commercial infrastructure that really is going to match that market. By the end of the year, we anticipate to have about 95% of our people in place. Our aim is to really go for an organization that portrays the values of the company, the partnership, the collaboration, people with deep experience in HAE and or rare disease. Based on the interest we get for job openings at the moment, we feel the excitement within the community of employees as well for the exciting challenge that we have ahead. So we are very well poised to succeed that. In terms of the payer question you asked, the benefit of having ODT and LTP, that absolutely comes through. It's actually not a benefit just for the payer. It's actually fundamentally doctors and also patient and caregivers will tell you having one active drug, one molecule in two formulations that really cover all your needs in HAE is a super advantage. We're going to be leveraging that. We're going to be working on that to make that a real benefit also in the market. From a payer perspective, specifically, yes, that is something that can become an advantage over time. We will obviously launch first with on-demand, but once we have the prophylactic option approved, that would be adding to that armamentarium. Did I cover all your questions, Max? Yes, I believe so. Just finally, just on the CREAATE read-through to, as we're thinking about that trial coming up, anything we've learned from CHAPTER-3. But thank you very much for the commercial side. Yeah, great question, Max. As mentioned, our CREAATE study, the pivotal phase III study for acquired angioedema due to C1 deficiency, is well on track. I think definitely the CHAPTER-3 data is very encouraging and give us more confidence to see the prophylactic treatment effect for part one of the CREAATE study. Meanwhile, Dr. Riedl, maybe I hand it over to you and also maybe introduce more about acquired angioedema patients. Sure, yeah. I think, for the most part, acquired C1 inhibitor deficiency behaves clinically very much like type 1 and type 2 HAE. It is C1 inhibitor deficiency. Of course, the underlying cause is quite different due to consumption and rather than a genetic deficiency in acquired C1 inhibitor deficiency. But clinically speaking, when we manage those patients, the acquired C1 inhibitor deficiency patients, we use really all the same principles and in fact, the same medications. They're off-label in at least in most regions of the world. But point being that we would expect that success in type 1 and type 2 HAE would predict similar results in acquired C1 inhibitor deficiency. Of course, have to do the study to prove that, but that would be the anticipated outcome. Great. Thank you very much. Thank you. Our next question in queue coming from the line of Joe Schwartz with Leerink Partners. The line is now open. Hi. Congrats on the results, and thanks for taking my questions. I have one for the company and one for Dr. Riedl. I think the release notes an increase in the percentage of attack-free participants, but it does not quantify it. I was wondering if you could give us any insight into the proportion of patients on deucrictibant who were attack-free over the 24 weeks and how that compared to placebo. Then, thank you for your perspective, Dr. Riedl. In your clinic, when patients evaluate a prophylactic therapy, what do they anchor on? Is it the percent attack reduction, those that are attack-free, or is it the route and frequency of administration? When there is a once daily pill, how do you think it will set up in the considerations that patients consider when there is monthly or every other month injections in that trade-off? Yes. Thanks so much for the great questions. Within the CHAPTER-3 study altogether, we enrolled five HAE patients with normal C1 inhibitor. Among these five patients, actually three patients received the active treatment, deucrictibant XR. As Dr. Riedl highlighted, for the normal C1 patients, due to the different genetic mutation or underlying different pathophysiology pathways, the response rate relatively higher variability compared to the type 1, 2 HAE patients. Therefore, within these three patients, we observed that one patient with less than 50% reduction, one patient get a 90% reduction, and one patient attack-free. Hopefully, we address your question. Yeah, that is super helpful. Thank you. Dr. Riedl, how do you think that a once daily pill will set up relative to some of the less frequently administered injections that are available? Yeah, thanks for the question. I really like your question because this is the complexity of what goes on in the clinic, and it is a little bit hard to answer, meaning your question, what do patients anchor on? What are they most interested in? I think it is a combination of things, and I sort of always joke, I am notoriously bad at predicting what specific treatment an individual will choose because these conversations are complex with a lot of factors. But I will tell you, this is just my experience, I think efficacy almost always carries the day, meaning that it has got to work. I think we spend a lot of time talking about efficacy. We do discuss from the pivotal trials, the average reduction in attack, percent reduction in attack rate as kind of an important endpoint. I will say that patients are also increasingly interested in this attack-free outcome that I think you mentioned. What are the chances that from the study that I won't have attacks at all for long stretches of time? I think closely behind efficacy, and you touched on it, is the route or the, I call it the schedule, right? What do I have to do to get the benefits of the medicine? My experience is that patients are very, very interested in oral medications. Generally, patients don't like injections or infusions. Of course, as you said, as these become less frequent, it might become more palatable. But we've seen tremendous interest in the oral agents that have been available to date, whether those are prophylaxis on-demand, and I see that continuing. I do think that there's sort of an advantage to the oral route for most patients, perhaps not all, and that that's something that they can picture themselves adhering to over time. A daily pill, it's portable, it's easy to take with them when they travel, and it becomes part of their routine. So I do think that that is attractive to patients. Is this drug going to be for everyone? No. That's why it's nice to have options. But I do think we're going to have a lot of conversations if and when this is in the clinic, a lot of conversations. People will be asking about this because of the considerable interest in the oral route overall. Thank you. Thank you. Our next question in queue coming from the line of Steve Seedhouse with Cantor Fitzgerald. Your line is now open. Great. Thank you so much, and congratulations on the result. First question I had was just hoping you could expand on the safety profile you saw in the study. I think there was a few Grade 3 events, one Grade 4 event that I think you said was a laryngeal HAE attack, which seems fine. Then there was one SAE as well. Would you mind just expanding on those AEs and the overall safety profile observed in the study? Yes. Thanks, Steve. I appreciate the question. As illustrated in the presentation, we do observe one serious adverse event is a laryngeal edema. Actually, this is actually a normal C1 patient. Before joined the CHAPTER-3 study, this patient report 19 oral laryngeal attacks during the screening period. That is why due to the long time laryngeal attack and also multiple times intubation, these patients actually have vocal cord disorder. That is why during this study, actually this patient achieved 90% attack reduction. One time the patient, due to the vocal cord recorder and was hospitalized. During the assessment, there is no swelling during the laryngeal microscopy there. The PI consider it is not treatment-related. Actually, during follow-up with AE, the PI told us the patient is very happy, wants to join the study, even back to work. We really feel proud that deucrictibant can help our patients here. Okay. Thank you. Super helpful. Was hoping also you could comment on prior prophylactic use by patients entering the study. Like what proportion had been on prior prophylaxis versus treatment naive, and did you have representation from prior TAKHZYRO and ORLADEYO use specifically? Yeah. Excellent question. I believe during the demographic slide deck, we show around maybe between 20 to 30 patients on prophylaxis prior during the study. Yes. That actually these patients have that ORLADEYO have the ORLADEYO and also C1 inhibitor use there. Great. Okay. Berndt, you mentioned in the press release and in your closing comments that this encourages the company to develop novel therapies or maybe even deucrictibant for bradykinin-mediated diseases beyond angioedema. You recently published this review summarizing a bunch of indications where B2R may be involved. I was hoping you could expand on your plans going forward in that regard. Yeah, sure. We are, as you also pointed out, evaluating, looking at bradykinin-mediated diseases that could potentially be product extensions of the deucrictibant. That is in the final stages of the evaluation, and we plan to make some decisions on potential starting some clinical development and to generate data for these other indications. We have not publicly disclosed or defined exactly what that is yet. But in due course, we will provide more information about that. Stay tuned. Okay, great. Just last one quickly. Can you say what proportion of the 85 patients enrolled and are continuing in the CHAPTER-4 open-label extension? I guess what is the plan for data disclosure from that going forward? Yeah. Excellent question. As mentioned, 83 patients continue the study. Out of 83, 80 patients go over to the CHAPTER-4 study. Currently, the study is ongoing, and we are continuing monitor long-time efficacy and safety with the CHAPTER-4 study. All right. Thanks so much. Thank you. Our next question coming from the line of Jon Wolleben with Citizens Bank. Your line is now open. Hey, guys. Congrats on the day, and thanks for taking the question. Two for me. Just wondering if you could give us some sense of the most common AEs on deucrictibant, whether it is more than 5% or 10% of the incidence rates. Then for Dr. Riedl, if deucrictibant becomes available in both the on-demand and prophylactic setting, can you walk us through how you think about shared decision-making in introducing this option to patients when they come in or patients thinking about switching to a new therapy? Yeah. As presented data for the safety section, the most common adverse events are upper respiratory, that infection, nasopharyngitis, and also headache, as it shows there. Overall, it is a balance between that procedural and active group. Marc, I believe second question for Dr. Riedl. Do you have any follow-up safety questions? Nope. That was helpful. Yeah. Related to the, if and when this is available in the clinic. I think general practice at our center is, as new medications come to market, to discuss those with patients just as you noted. I do not know the future, but the on-demand treatments or the on-demand indication for deucrictibant looks like it would arrive first. I think as people know, we have some experience with oral on-demand medication already. I think this is not the focus of this discussion, but the on-demand treatment data for deucrictibant looks extremely strong. I think, this mechanism of action, the B2 receptor antagonism is something we have a lot of experience with icatibant over the years. I think that will appeal to patients as an oral route with that mechanism of action to treat attacks. As I already alluded to, I think the long-term prophylactic indication, given the efficacy we are seeing, the tolerability in an oral route will really be an important discussion. I think patients will be very interested in that. Those that are either not on long-term prophylaxis at this point because they have not liked the options or those that actually are on LTP already. Again, the parenteral drugs having some burden of treatment. I think we will see people considering this as a potential switch candidate. Then, as mentioned earlier, I think the appeal of having an oral treatment for both on-demand and long-term prophylaxis is something that could, in some ways, simplify what we are doing. Of course, we have not done that yet. But I think that sort of having one source, if you will, for both types of medications is there is some logistical advantages to that as a clinician, a sort of one-stop shop, if you will, for these little bit complicated treatment plans we developed for individual patients. Anyway, those are just some of my thoughts about what we might see in the clinical space, if and when we are able to prescribe deucrictibant. Thanks for taking the questions. Thank you. Our next question coming from the line of Tazeen Ahmad with Bank of America. You will now open. Hi. Good morning. Thanks for taking my question and congratulations on the positive data. As you think about the world where you will have the options of both on-demand and prophylaxis available, how should we be thinking about a couple of things? First, about the initial ramp for on-demand, and based on that initial ramp, should we assume, based on the evidence presented to date, that the appeal of having both prophy and on-demand options once the prophylaxis indication launches would also accelerate the on-demand? Then I have a follow-up. Thanks. Yeah, thanks for that question. I will hand over also to Wim in a minute. I think basically, as you know, from our launch sequence of on-demand and prophy, that the launch of the on-demand indication basically is a pathfinder or paving the way to support the prophylactic launch that follows afterwards. They are very much integrated. The opportunity for patients to try first deucrictibant with the on-demand, we think, assuming that that would be a positive experience for patients, that they would have a very strong interest in also trying the prophylactic formulation. But Wim, please add to that. Yeah, thanks, Berndt. I would absolutely echo that. I think it's a huge advantage of having these two options. For us, the on-demand launch is critically important because the better we do there, the better we think we can accelerate the prophylactic launch. We basically get a head start on prophylaxis just by getting experience with the therapy. Given that deucrictibant has the same mechanism like icatibant, which is still the standard of care today across the world, that bodes very well, we believe, to convince patients on-demand, whether they're on prophylaxis or only use on-demand therapy to switch to deucrictibant. Once the prophylactic then gets approved, that becomes an amplifier potentially for the on-demand segment too. But we definitely feel this is a huge advantage to have both in our entire. As I said before, this is a feedback we're not getting just from doctors. We're getting it from patients, caregivers. We're getting it from payers. So I think this is a real advantage that we can bring to this market here. Yeah, maybe also add to that, particularly as a new entrant into the market, to basically to find the patient and to be able to address the patients once we have an approved therapy. The on-demand launch then would generate that information for us to fully then also support, and as Wim said, amplify or put an extra boost into the subsequent prophylactic launch. Okay. And then as a follow-up, how long do you think it would take to negotiate with payers once prophylaxis is eventually approved in order to potentially position yourself as a preferred option, having both the on-demand and the prophylaxis options available? So actually, it's a great question. We are very active already. Our plan is to, by the time of on-demand approval is approved, to have more than 90% live coverage conversations with payers, PBMs, states, et cetera. We are very active already kind of educating the payer community on the data. And whenever we speak about the data, we obviously bring forward the phase III data for on-demand with RAPIDe-3. But in the same vein, we are also talking about already our CHAPTER-1 data, which is the phase II for prophylactic, giving those payers already an insight that there is more coming. And obviously that will be accelerating now that we have had the phase III data. So I think we are going to be in a very good spot. As I said before, this is a little bit of the advantage of having the on-demand before the prophylactic launch because, as you know, building a relationship with payer is a thing that takes time. The bigger opportunity ultimately will be the prophylactic market. And we are going to have this time with on-demand to really establish ourselves as a preferred partner there. So I am very positive, very optimistic that we can accelerate what normally, if you would have only on the prophylactic launch, it would probably take more time to get into these formulas and getting the studies that we would aim for. Does that answer your question? Yeah. Thank you very much. Thank you. Our next question coming from the line of Debjit from Guggenheim Securities. Your line is now open. Hey, good morning and thanks for taking the questions. I have one for Dr. Riedl first and then one for the company. Dr. Riedl, if you have patients on ORLADEYO, would you switch them over to deucrictibant, given what we have seen from the data today? To the company, could you sort of clarify the two patients with liver enzyme elevations, were these Grade 3 events or how should we understand it? It wasn't particularly clear to us. Thank you so much. Yeah, thanks for the question. Certainly, we do have patients on ORLADEYO. As people know, that's been a very useful oral preventative drug. The responses are variable to ORLADEYO, and that's true for a lot of medicines. But certainly, for instance, the responder analysis that was done in the ORLADEYO phase III trial showed much more variability than we've seen in some other phase III studies. To answer your question, there are patients who are doing extremely well on ORLADEYO, and I think they would probably have little motivation to switch. But there are certainly a substantial number of patients who are getting benefit from ORLADEYO but not seeing quite the efficacy that we'd like. I do think that there's a subset of patients that are all about the oral route. That's their preferred way to go, and that's why they're on ORLADEYO, but would like to see better preventative effects. I think these are conversations we'll have with them, and humans being humans, some will stick with what they know. But a significant number, I think, will say, "Yeah, I like the idea of an oral medicine that may give me better prevention." I think that's certainly a group that I think this would be a very useful medication for. As I mentioned before, there may also certainly be patients on parenteral drugs who like the efficacy of those drugs but would prefer the oral route. I do think these are going to be really important conversations because we do continue to see patients switching from one medicine to another given as data comes out. I think we will continue to see that as these new medicines come to market. Yeah. Maybe I will take over the second question. Appreciate the questions update. Indeed, within the CHAPTER-3 study we have the two patients was observed, as mentioned, a Level 2 enzyme elevation, that is pretty much slightly above fivefold increase from the upper top line limit. For both of patients actually is symptomatic, and we know that elevation of bilirubin was observed. Both patients have co-forming factors with either long-term antigen use or the fatty liver there. So one that actually investigator decided to discontinue the patient from the treatment. As we mentioned, there is one deucrictibant patient discontinued from the study earlier, and another actually continued the treatment and the patients remain on the treatment and complete the study. Thank you. Our next question in queue coming from the line of Laura Chico with Wedbush. Your line is now open. Good morning. Thanks very much for taking the questions. A couple for Dr. Riedl, and then a couple for Pharvaris. Dr. Riedl, how many patients of all your currently managed HAE patients, what proportion are actually on an oral prophylaxis regimen today? I am curious where you think that might go in a couple of years from now once deucrictibant XR reaches the market. Then with respect to switching, switches from ORLADEYO make sense. I guess over time, would you anticipate more switches from TAKHZYRO or ORLADEYO. I am just curious where you think the bulk of the switches would originate from. Then with respect to Pharvaris on pricing, just following up on your earlier commentary, how should we think about the pricing relative to other prophylaxis therapies? I guess I am trying to understand the view of the value delivery here relative to other treatments. Thank you very much. For my part of it, ballpark of patients on the current oral prophylaxis that is out there, we probably have in our big centers probably maybe about 20% of our patients on the oral prophylaxis on berotralstat. As I said, a lot of patients have been very interested in the oral route, but we have seen some move to other things because of efficacy concerns and probably a smaller number due to some of the side effects that occur commonly. There is that group. Your question about switches is a very good one and it is a hard one to answer. I think that we certainly have seen, slowly over time, some of the lanadelumab or TAKHZYRO patients moving to other things. I do think that is a population that, because most of our patients are on every two weeks dosing with that medication. While people will certainly do it is something we hear about that becomes a little bit onerous over time. Some of those patients have switched to the less frequently dosed subcutaneous options that have come along, and so we have already seen a little bit of migration there. To answer your question, I do suspect there are some TAKHZYRO patients that, as this data gets disseminated, have kind of been waiting for oral treatment that might have similar efficacy. I think we may see some switches there. I think, as I already mentioned, I would anticipate some switches from oral ORLADEYO because those patients are really focused on oral medicine but would prefer something that might be somewhat more effective for them. A long way of saying, I think we will see potentially some migration from both of those groups, just based on either the tolerability profile or the efficacy profile. But the final caveat is it is always difficult to predict what individuals or human beings will decide. Those will be really, I think, kind of fascinating conversations to have with our patients. Thanks. On the question on pricing. What we have not seen in this therapeutic area, in any of the entrants, is any disruptive strategies when it comes to pricing. It has to be based on value and patient benefit. We have not talked in detail about our pricing strategy yet, but maybe you can also add something to that. No, I think you are absolutely right, Berndt. I think the beauty of this data is that it puts us, as we said before, it gives injectable-like efficacy in oral convenience therapy, and that provides all the options. What we will be doing, we are looking at payer dynamics, we will be looking at receptivity on the clinical value, and that will then drive our pricing decision ultimately. But we are in a very good position, so I think we can leverage really the data that we have here. Thanks very much. Thank you. Our next question in queue coming from the line of Sushila Hernandez with [Van Lanschot Kempen]. Your line is now open. Hi, team. Thank you for taking our questions. This is Romy on for Sushila. I have two. First for the Pharvaris team. Just a follow-up on the safety, in relation to the liver enzyme elevation. I was wondering if you expect this to be a potential concern for the label. Then the next for Dr. Riedl. Could you share your experience with enrolling patients in the trial, especially those switching from other therapies? Thank you. Yeah, maybe I can take over the first question. As we explained, we do observe that there is a Level 2 liver enzyme elevation for the deucrictibant that we would expect that from the label part, it may be quite comparable to the other HAE prophylaxis treatment. Maybe potentially there is one section in the label about the level of normality to illustrate the liver enzyme elevation here. Great. Thank you. Yeah. Yeah, just to speak to the enrollments in the study itself, as people might know, enrolling in clinical trials, at least in the U.S., has become a little more challenging. As I mentioned in my comments, we are still seeing patients enroll, because they do recognize there is room for improvement. While it is a little bit slower, a little less brisk than it used to be a decade ago, we are still able to enroll. I think for this trial, it is going to sound repetitive, but I think the real draw was this once a day oral pill, that at least based on the phase II data we had, looked very promising in terms of efficacy. That was for our patients that enrolled, that was the draw. I could take a pill once a day and potentially get the effect that has been seen previously only really with injected medicine. Again, I think that speaks to the advance that this may represent and how that may roll out in the clinic as something that is appealing. That is what drew our patients to the study to begin with. Great. Thank you. Thank you. Our next question in queue coming from the line of Fanyi Zhong with Oppenheimer. Your line is now open. Thanks for taking my question. This is Fanyi Zhong for Jeff Jones. A couple from us. What are the key gating items ahead of your NDA submission? Any strategic plan you could share for ex- U.S. markets going forward? Also, questions to Dr. Riedl. What kind of patient do you see being the first to adopt deucrictibant? Mostly like new patients or patients currently using ORLADEYO or patients on injectable? Thanks. Maybe you repeat that question because it was a little hard, it breaking up in the middle of it. Sure. What are the key gating items ahead of your NDA submission, and any strategic plan you could share for ex-U.S. markets going forward? Yeah, so the NDA submission is also, as we also, prophylaxis, as we have also mentioned earlier, is looking to generate data in acquired angioedema and potentially include that in the filing. That is not really viewed as a gating item, where we will determine the filing date based on the appropriate timing when we have the file ready, and then we will see where we stand with the acquired angioedema data. What we also need in order to complete the package for the filing is also the totality of the safety database, with the CHAPTER-4 study, which is still ongoing. Yeah. As Berndt mentioned, altogether for NDA submission regarding the prophylaxis, we integrate the CHAPTER-3 and also safety package. As mentioned, one year safety data from the CHAPTER-4 and also hopefully the acquired angioedema data from part one clinical results. Then we will put all together for the prophylactic filing for bradykinin mediated angioedema. Your question regarding the ex-U.S. strategy. As you probably have seen, we have a file got validated by the EMA recently. So we have submitted for European approval there as well. Our focus clearly is on the U.S., but we are doing already kind of the critical path activities in preparation for Europe, looking at our value dosage because as you probably know, ex-U.S. payer interactions are very different. So that is the key focus. Then we will look at how we execute on this. We still have options to decide how we want to progress with that. Thank you. Yeah. I think there was a question for me for my part of it. I think the candidates for deucrictibant, first and foremost, any new patients, newly diagnosed or new to prophylaxis. My experience is that given choices, the vast majority of patients will opt for an oral medicine before an injected medicine. I do not see too many patients signing up for injections if there is an oral medicine that will accomplish the same thing. I think that is certainly been our experience, that would be so-called early adopters of this. I think there is, as we have talked about, there is a subgroup of patients that really oral medicine is what they are on or what they are going to tolerate the best. There is a subset of patients on current oral therapies that are not doing as well as we would like. Those would be, I think, prime candidates to switch to an oral medicine with perhaps a better efficacy profile or tolerability profile. Lastly, I think, there is a subset of patients on parenteral drugs who have gone there because of the efficacy of those agents, and some of them are doing really well and will stay on that. There is also a subset of those patients who tolerate those injections because it works for them, it is effective, but given the option, they would rather not have to keep that schedule of injections. Again, I think you sort of see borrowing from these different groups, it becomes a fairly substantial number of people who are going to take a close look at this. That is kind of how I would see it rolling out those kind of groups in that order. Thank you so much to everybody who joined our conference call. This has concluded the Q&A portion of the call. I understand there are still more questions in the queue. I will be reaching out to those people directly. Once again, thank you very much. We are thrilled with these data, and we look forward to continuing to progress new potential treatment options for people living with bradykinin-mediated angioedema. Thank you. Ladies and gentlemen, that does end our conference for today. Thank you for your participation, and you may now disconnect.